Michelle Williams, ScD

All Publications

• AI-driven evolution of precision population cardiovascular health in cities. Nature reviews. Cardiology Aerts, A., Williams, M. A. 2025; 22 (4): 213-214

  View details for DOI 10.1038/s41569-025-01125-2

  View details for PubMedID 39838100

  View details for PubMedCentralID 11816513

• Early-life menstrual characteristics and gestational diabetes in a large US cohort. Paediatric and perinatal epidemiology Wang, Z., Baird, D. D., Williams, M. A., Jukic, A. M., Wilcox, A. J., Curry, C. L., Fischer-Colbrie, T., Onnela, J. P., Hauser, R., Coull, B. A., Mahalingaiah, S. 2024; 38 (8): 654-665

  Abstract

  Associations between early-life menstrual cycle characteristics (MCC) and gestational diabetes (GDM) remain unclear.To evaluate associations between early-life MCCs and GDM in first pregnancy, across pregnancies and its recurrence.This analysis included participants from a US-based digital cohort enrolled between 11/2019 and 9/2023 who provided consent, completed relevant surveys, were without diabetes and aged ≥18 at first pregnancy (n = 30,473). Age at menarche [<11 (early), 11-15 (referent), ≥16 (late) years] and time from menarche to cycle regularity [<1 (referent), 1-2, 3-4, ≥5 years, not yet regular, regular after hormones] were self-recalled at enrolment. Additionally, the last three categories were considered prolonged time-to-regularity (PTTR). GDM history was recalled at enrolment for each pregnancy. We restricted to pregnancies of ≥24 weeks with a live birth. We evaluated associations of early-life MCCs with GDM at first pregnancy using modified Poisson regression, across pregnancies using cluster-weighted Poisson generalised estimating equation and GDM recurrence using multinomial logistic regression, adjusted for sociodemographic, early-life factors and age at pregnancy. Missing variables were imputed with multiple imputation by chained equations.Among 30,473 participants, 20,591 had eligible first pregnancies, of which 5.9% reported GDM. In 17,512 participants with ≥2 pregnancies, 8.3% had GDM once and 3.7% had recurrent GDM. Early menarche (<11 years, vs. 11-15 years) was associated with GDM in first pregnancy (RR 1.34, 95% CI 1.15, 1.57), across pregnancies (RR 1.24, 95% CI 1.10, 1.39) and recurrence (OR 1.51, 95% CI 1.21, 1.89). PTTR was associated with GDM in the first pregnancy (RR 1.22, 95% CI 1.08, 1.38), across pregnancies (RR 1.16, 95% CI 1.05, 1.27) and recurrence (OR 1.19, 95% CI 0.99, 1.43).Earlier menarche and prolonged time-to-regularity are associated with higher risk of GDM and recurrence, suggesting menstrual characteristics during childhood/adolescence as potential early-life markers for GDM.

  View details for DOI 10.1111/ppe.13129

  View details for PubMedID 39607069

  View details for PubMedCentralID PMC11603761

• Signs of Potential Androgen Excess Across the Lifespan in a US-based Digital Cohort Study. The Journal of clinical endocrinology and metabolism Wolf, A. T., Wang, Z., Onnela, J. P., Baird, D. D., Jukic, A. M., Curry, C. L., Fischer-Colbrie, T., Williams, M. A., Hauser, R., Coull, B. A., Mahalingaiah, S. 2024

  Abstract

  Androgen excess (AE)-related symptoms can vary widely and may appear across the life course.We assessed the prevalence of signs of potential AE and heterogeneity by demographic/health characteristics.We used data of 24 435 participants who consented and enrolled during November 2019 to December 2022 in a US digital cohort to evaluate the prevalence and heterogeneity of self-reported signs of potential AE: possible hirsutism (having thick coarse hair on ≥4 of 8 body locations), hair level on the chin, hair loss on top of the head, and moderate to severe acne.The prevalence of possible hirsutism, having several/a lot of hair on the chin, significantly reduced hair/visible scalp on top of the head, and moderate to severe acne were 6.9%, 12.6%, 1.7%, and 31.8%, respectively. While possible hirsutism and moderate to severe acne decreased with age (range: 18-86 years), hair on the chin and hair loss on the head increased with age. Participants who self-identified as Hispanic or South Asian reported a higher prevalence of possible hirsutism (11.2%, 16.9%, vs 6.3% among non-Hispanic White participants). Participants with higher body mass index had a higher prevalence of possible hirsutism. Moderate to severe acne was more common among those with polycystic ovary syndrome. Possible hirsutism and hair loss were less common among participants using hormones for contraception.In this large cohort, signs of potential AE varied by demographic and health factors. These results could provide a new understanding of how potential AE may appear differently in diverse groups, informing future work to develop more inclusive evaluation at a population level.

  View details for DOI 10.1210/clinem/dgae674

  View details for PubMedID 39388314

• Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood. Science (New York, N.Y.) Daskalakis, N. P., Iatrou, A., Chatzinakos, C., Jajoo, A., Snijders, C., Wylie, D., DiPietro, C. P., Tsatsani, I., Chen, C. Y., Pernia, C. D., Soliva-Estruch, M., Arasappan, D., Bharadwaj, R. A., Collado-Torres, L., Wuchty, S., Alvarez, V. E., Dammer, E. B., Deep-Soboslay, A., Duong, D. M., Eagles, N., Huber, B. R., Huuki, L., Holstein, V. L., Logue, M. W., Lugenbühl, J. F., Maihofer, A. X., Miller, M. W., Nievergelt, C. M., Pertea, G., Ross, D., Sendi, M. S., Sun, B. B., Tao, R., Tooke, J., Wolf, E. J., Zeier, Z., Berretta, S., Champagne, F. A., Hyde, T., Seyfried, N. T., Shin, J. H., Weinberger, D. R., Nemeroff, C. B., Kleinman, J. E., Ressler, K. J. 2024; 384 (6698): eadh3707

  Abstract

  The molecular pathology of stress-related disorders remains elusive. Our brain multiregion, multiomic study of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) included the central nucleus of the amygdala, hippocampal dentate gyrus, and medial prefrontal cortex (mPFC). Genes and exons within the mPFC carried most disease signals replicated across two independent cohorts. Pathways pointed to immune function, neuronal and synaptic regulation, and stress hormones. Multiomic factor and gene network analyses provided the underlying genomic structure. Single nucleus RNA sequencing in dorsolateral PFC revealed dysregulated (stress-related) signals in neuronal and non-neuronal cell types. Analyses of brain-blood intersections in >50,000 UK Biobank participants were conducted along with fine-mapping of the results of PTSD and MDD genome-wide association studies to distinguish risk from disease processes. Our data suggest shared and distinct molecular pathology in both disorders and propose potential therapeutic targets and biomarkers.

  View details for DOI 10.1126/science.adh3707

  View details for PubMedID 38781393

  View details for PubMedCentralID PMC11203158

• Menarche and Time to Cycle Regularity Among Individuals Born Between 1950 and 2005 in the US. JAMA network open Wang, Z., Asokan, G., Onnela, J. P., Baird, D. D., Jukic, A. M., Wilcox, A. J., Curry, C. L., Fischer-Colbrie, T., Williams, M. A., Hauser, R., Coull, B. A., Mahalingaiah, S. 2024; 7 (5): e2412854

  Abstract

  Early menarche is associated with adverse health outcomes. Trends toward earlier menarche have been observed in the US, but data remain limited on differences by sociodemographic factors and body mass index (BMI). Time from menarche to cycle regularity is another understudied early-life characteristic with health implications.To evaluate the temporal trends and disparities in menarche and time to regularity and explore early-life BMI as a mediator.This ongoing cohort study enrolled participants from an ongoing mobile application-based US cohort from November 14, 2019, to March 20, 2023.Birth year (categorized as 1950-1969, 1970-1979, 1980-1989, 1990-1999, and 2000-2005).Main outcomes were age at menarche and time to regularity, which were self-recalled at enrollment. In addition, early (aged <11 years), very early (aged <9 years), and late (aged ≥16 years) age at menarche was assessed.Among the 71 341 female individuals who were analyzed (mean [SD] age at menarche, 12.2 [1.6] years; 2228 [3.1%] Asian, 3665 [5.1%] non-Hispanic Black, 4918 [6.9%] Hispanic, 49 518 [69.4%] non-Hispanic White, and 8461 [11.9%] other or multiple races or ethnicities), 5223 were born in 1950 to 1969, 12 226 in 1970 to 1979, 22 086 in 1980 to 1989, 23 894 in 1990 to 1999, and 7912 in 2000 to 2005. The mean (SD) age at menarche decreased from 12.5 (1.6) years in 1950 to 1969 to 11.9 (1.5) years in 2000 to 2005. The number of individuals experiencing early menarche increased from 449 (8.6%) to 1223 (15.5%), the number of individuals experiencing very early menarche increased from 31 (0.6%) to 110 (1.4%), and the number of individuals experiencing late menarche decreased from 286 (5.5%) to 137 (1.7%). For 61 932 participants with reported time to regularity, the number reaching regularity within 2 years decreased from 3463 (76.3%) to 4075 (56.0%), and the number not yet in regular cycles increased from 153 (3.4%) to 1375 (18.9%). The magnitude of the trend toward earlier menarche was greater among participants who self-identified as Asian, non-Hispanic Black, or other or multiple races (vs non-Hispanic White) (P = .003 for interaction) and among participants self-rated with low (vs high) socioeconomic status (P < .001 for interaction). Within a subset of 9865 participants with data on BMI at menarche, exploratory mediation analysis estimated that 46% (95% CI, 35%-61%) of the temporal trend in age at menarche was explained by BMI.In this cohort study of 71 341 individuals in the US, as birth year increased, mean age at menarche decreased and time to regularity increased. The trends were stronger among racial and ethnic minority groups and individuals of low self-rated socioeconomic status. These trends may contribute to the increase in adverse health outcomes and disparities in the US.

  View details for DOI 10.1001/jamanetworkopen.2024.12854

  View details for PubMedID 38809557

  View details for PubMedCentralID PMC11137638

• Irregular Cycles, Ovulatory Disorders, and Cardiometabolic Conditions in a US-Based Digital Cohort. JAMA network open Wang, Z., Jukic, A. M., Baird, D. D., Wilcox, A. J., Li, H., Curry, C. L., Fischer-Colbrie, T., Onnela, J. P., Williams, M. A., Hauser, R., Coull, B. A., Mahalingaiah, S. 2024; 7 (5): e249657

  Abstract

  Polycystic ovary syndrome (PCOS), characterized by irregular menstrual cycles and hyperandrogenism, is a common ovulatory disorder. Having an irregular cycle is a potential marker for cardiometabolic conditions, but data are limited on whether the associations differ by PCOS status or potential interventions.To evaluate the association of PCOS, time to regularity since menarche (adolescence), and irregular cycles (adulthood) with cardiometabolic conditions.This cross-sectional study used a large, US-based digital cohort of users of the Apple Research application on their iPhone. Eligibility criteria were having ever menstruated, living in the US, being at age of consent of at least 18 years (or 19 years in Alabama and Nebraska or 21 years in Puerto Rico), and being able to communicate in English. Participants were enrolled between November 14, 2019, and December 13, 2022, and completed relevant surveys.Self-reported PCOS diagnosis, prolonged time to regularity (not spontaneously establishing regularity within 5 years of menarche), and irregular cycles.The primary outcome was self-reported cardiometabolic conditions, including obesity, prediabetes, type 1 and 2 diabetes, high cholesterol, hypertension, metabolic syndrome, arrhythmia, congestive heart failure, coronary artery disease, heart attack, heart valve disease, stroke, transient ischemic attack (TIA), deep vein thrombosis, and pulmonary embolism measured using descriptive statistics and logistic regression to estimate prevalence odds ratios (PORs) and 95% CIs. Effect modification by lifestyle factors was also estimated.The study sample (N = 60 789) had a mean (SD) age of 34.5 (11.1) years, with 12.3% having PCOS and 26.3% having prolonged time to regularity. Among a subset of 25 399 participants who completed the hormonal symptoms survey, 25.6% reported irregular cycles. In covariate-adjusted logistic regression models, PCOS was associated with a higher prevalence of all metabolic and several cardiovascular conditions, eg, arrhythmia (POR, 1.37; 95% CI, 1.20-1.55), coronary artery disease (POR, 2.92; 95% CI, 1.95-4.29), heart attack (POR, 1.79; 95% CI, 1.23-2.54), and stroke (POR, 1.66; 95% CI, 1.21-2.24). Among participants without PCOS, prolonged time to regularity was associated with type 2 diabetes (POR, 1.24; 95% CI, 1.05-1.46), hypertension (POR, 1.09; 95% CI, 1.01-1.19), arrhythmia (POR, 1.20; 95% CI, 1.06-1.35), and TIA (POR, 1.33; 95% CI, 1.01-1.73), and having irregular cycles was associated with type 2 diabetes (POR, 1.36; 95% CI, 1.08-1.69), high cholesterol (POR, 1.17; 95% CI, 1.05-1.30), arrhythmia (POR, 1.21; 95% CI, 1.02-1.43), and TIA (POR, 1.56; 95% CI, 1.06-2.26). Some of these associations were modified by high vs low body mass index or low vs high physical activity.These findings suggest that PCOS and irregular cycles may be independent markers for cardiometabolic conditions. Early screening and intervention among individuals with irregular menstrual cycles may be beneficial.

  View details for DOI 10.1001/jamanetworkopen.2024.9657

  View details for PubMedID 38700861

  View details for PubMedCentralID PMC11069087

• Seasonal variations of menstrual cycle length in a large, US-based, digital cohort. International journal of hygiene and environmental health Li, H., Curry, C. L., Fischer-Colbrie, T., Onnela, J. P., Williams, M. A., Hauser, R., Coull, B. A., Jukic, A. M., Mahalingaiah, S. 2024; 256: 114308

  View details for DOI 10.1016/j.ijheh.2023.114308

  View details for PubMedID 38103472

  View details for PubMedCentralID PMC10872302

• Regulations and Funding to Create Enterprise Architecture for a Nationwide Health Data Ecosystem. American journal of public health Seidman, G., AlKasir, A., Ricker, K., Lane, J. T., Zink, A. B., Williams, M. A. 2024; 114 (2): 209-217

  Abstract

  The COVID-19 pandemic highlighted the United States' lack of a nationwide infrastructure for collecting, sharing, and using health data, especially for secondary uses (e.g., population health management and public health). The federal government is taking several important steps to upgrade the nation's health data ecosystem-notably, the Centers for Disease Control and Prevention's Data Modernization Initiative and the Office of the National Coordinator for Health Information Technology's Trusted Exchange Framework and Common Agreement. However, substantial barriers remain. Inconsistent regulations, infrastructure, and governance across federal and state levels and between states significantly impede the exchange and analysis of health data. Siloed systems and insufficient funding block effective integration of clinical, public health, and social determinants data within and between states. In this analytic essay, we propose strategies to develop a nationwide health data ecosystem. We focus on providing federal guidance and incentives to develop state-designated entities responsible for the collection, integration, and analysis of clinical, public health, social determinants of health, claims, administrative, and other relevant data. These recommendations include a regulatory clearinghouse, federal guidance, model legislation and templated regulation, funding to incentive enterprise architecture, regulatory sandboxes, and a 3-pronged research agenda. (Am J Public Health. 2024;114(2):209-217. https://doi.org/10.2105/AJPH.2023.307477).

  View details for DOI 10.2105/AJPH.2023.307477

  View details for PubMedID 38207252

  View details for PubMedCentralID PMC10862221

• Potential causal association between gut microbiome and posttraumatic stress disorder. Translational psychiatry He, Q., Wang, W., Xu, D., Xiong, Y., Tao, C., You, C., Ma, L., Ma, J. 2024; 14 (1): 67

  Abstract

  The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR).The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD's causal effects on the relative abundances of specific features of the gut microbiome.In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability.Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms.

  View details for DOI 10.1038/s41398-024-02765-7

  View details for PubMedID 38296956

  View details for PubMedCentralID PMC10831060

• Discovery of 95 PTSD loci provides insight into genetic architecture and neurobiology of trauma and stress-related disorders. medRxiv : the preprint server for health sciences Nievergelt, C. M., Maihofer, A. X., Atkinson, E. G., Chen, C. Y., Choi, K. W., Coleman, J. R., Daskalakis, N. P., Duncan, L. E., Polimanti, R., Aaronson, C., Amstadter, A. B., Andersen, S. B., Andreassen, O. A., Arbisi, P. A., Ashley-Koch, A. E., Austin, S. B., Avdibegoviç, E., Babic, D., Bacanu, S. A., Baker, D. G., Batzler, A., Beckham, J. C., Belangero, S., Benjet, C., Bergner, C., Bierer, L. M., Biernacka, J. M., Bierut, L. J., Bisson, J. I., Boks, M. P., Bolger, E. A., Brandolino, A., Breen, G., Bressan, R. A., Bryant, R. A., Bustamante, A. C., Bybjerg-Grauholm, J., Bækvad-Hansen, M., Børglum, A. D., Børte, S., Cahn, L., Calabrese, J. R., Caldas-de-Almeida, J. M., Chatzinakos, C., Cheema, S., Clouston, S. A., Colodro-Conde, L., Coombes, B. J., Cruz-Fuentes, C. S., Dale, A. M., Dalvie, S., Davis, L. K., Deckert, J., Delahanty, D. L., Dennis, M. F., deRoon-Cassini, T., Desarnaud, F., DiPietro, C. P., Disner, S. G., Docherty, A. R., Domschke, K., Dyb, G., Kulenovic, A. D., Edenberg, H. J., Evans, A., Fabbri, C., Fani, N., Farrer, L. A., Feder, A., Feeny, N. C., Flory, J. D., Forbes, D., Franz, C. E., Galea, S., Garrett, M. E., Gelaye, B., Gelernter, J., Geuze, E., Gillespie, C. F., Goci, A., Goleva, S. B., Gordon, S. D., Grasser, L. R., Guindalini, C., Haas, M., Hagenaars, S., Hauser, M. A., Heath, A. C., Hemmings, S. M., Hesselbrock, V., Hickie, I. B., Hogan, K., Hougaard, D. M., Huang, H., Huckins, L. M., Hveem, K., Jakovljevic, M., Javanbakht, A., Jenkins, G. D., Johnson, J., Jones, I., Jovanovic, T., Karstoft, K. I., Kaufman, M. L., Kennedy, J. L., Kessler, R. C., Khan, A., Kimbrel, N. A., King, A. P., Koen, N., Kotov, R., Kranzler, H. R., Krebs, K., Kremen, W. S., Kuan, P. F., Lawford, B. R., Lebois, L. A., Lehto, K., Levey, D. F., Lewis, C., Liberzon, I., Linnstaedt, S. D., Logue, M. W., Lori, A., Lu, Y., Luft, B. J., Lupton, M. K., Luykx, J. J., Makotkine, I., Maples-Keller, J. L., Marchese, S., Marmar, C., Martin, N. G., MartÍnez-Levy, G. A., McAloney, K., McFarlane, A., McLaughlin, K. A., McLean, S. A., Medland, S. E., Mehta, D., Meyers, J., Michopoulos, V., Mikita, E. A., Milani, L., Milberg, W., Miller, M. W., Morey, R. A., Morris, C. P., Mors, O., Mortensen, P. B., Mufford, M. S., Nelson, E. C., Nordentoft, M., Norman, S. B., Nugent, N. R., O'Donnell, M., Orcutt, H. K., Pan, P. M., Panizzon, M. S., Pathak, G. A., Peters, E. S., Peterson, A. L., Peverill, M., Pietrzak, R. H., Polusny, M. A., Porjesz, B., Powers, A., Qin, X. J., Ratanatharathorn, A., Risbrough, V. B., Roberts, A. L., Rothbaum, B. O., Rothbaum, A. O., Roy-Byrne, P., Ruggiero, K. J., Rung, A., Runz, H., Rutten, B. P., de Viteri, S. S., Salum, G. A., Sampson, L., Sanchez, S. E., Santoro, M., Seah, C., Seedat, S., Seng, J. S., Shabalin, A., Sheerin, C. M., Silove, D., Smith, A. K., Smoller, J. W., Sponheim, S. R., Stein, D. J., Stensland, S., Stevens, J. S., Sumner, J. A., Teicher, M. H., Thompson, W. K., Tiwari, A. K., Trapido, E., Uddin, M., Ursano, R. J., Valdimarsdóttir, U., van den Heuvel, L. L., Van Hooff, M., van Rooij, S. J., Vermetten, E., Vinkers, C. H., Voisey, J., Wang, Z., Wang, Y., Waszczuk, M., Weber, H., Wendt, F. R., Werge, T., Williams, M. A., Williamson, D. E., Winsvold, B. S., Winternitz, S., Wolf, E. J., Wolf, C., Xia, Y., Xiong, Y., Yehuda, R., Young, R. M., Young, K. A., Zai, C. C., Zai, G. C., Zervas, M., Zhao, H., Zoellner, L. A., Zwart, J. A., Stein, M. B., Ressler, K. J., Koenen, K. C. 2023

  Abstract

  Posttraumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 novel). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (e.g., GRIA1, GRM8, CACNA1E ), developmental, axon guidance, and transcription factors (e.g., FOXP2, EFNA5, DCC ), synaptic structure and function genes (e.g., PCLO, NCAM1, PDE4B ), and endocrine or immune regulators (e.g., ESR1, TRAF3, TANK ). Additional top genes influence stress, immune, fear, and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

  View details for DOI 10.1101/2023.08.31.23294915

  View details for PubMedID 37693460

  View details for PubMedCentralID PMC10491375

• Menstrual cycle length variation by demographic characteristics from the Apple Women's Health Study. NPJ digital medicine Li, H., Gibson, E. A., Jukic, A. M., Baird, D. D., Wilcox, A. J., Curry, C. L., Fischer-Colbrie, T., Onnela, J. P., Williams, M. A., Hauser, R., Coull, B. A., Mahalingaiah, S. 2023; 6 (1): 100

  Abstract

  Menstrual characteristics are important signs of women's health. Here we examine the variation of menstrual cycle length by age, ethnicity, and body weight using 165,668 cycles from 12,608 participants in the US using mobile menstrual tracking apps. After adjusting for all covariates, mean menstrual cycle length is shorter with older age across all age groups until age 50 and then became longer for those age 50 and older. Menstrual cycles are on average 1.6 (95%CI: 1.2, 2.0) days longer for Asian and 0.7 (95%CI: 0.4, 1.0) days longer for Hispanic participants compared to white non-Hispanic participants. Participants with BMI ≥ 40 kg/m2 have 1.5 (95%CI: 1.2, 1.8) days longer cycles compared to those with BMI between 18.5 and 25 kg/m2. Cycle variability is the lowest among participants aged 35-39 but are considerably higher by 46% (95%CI: 43%, 48%) and 45% (95%CI: 41%, 49%) among those aged under 20 and between 45-49. Cycle variability increase by 200% (95%CI: 191%, 210%) among those aged above 50 compared to those in the 35-39 age group. Compared to white participants, those who are Asian and Hispanic have larger cycle variability. Participants with obesity also have higher cycle variability. Here we confirm previous observations of changes in menstrual cycle pattern with age across reproductive life span and report new evidence on the differences of menstrual variation by ethnicity and obesity status. Future studies should explore the underlying determinants of the variation in menstrual characteristics.

  View details for DOI 10.1038/s41746-023-00848-1

  View details for PubMedID 37248288

  View details for PubMedCentralID PMC10226714

• Maternal hair cortisol concentrations and its association with increased insulin resistance in midpregnancy. Annals of epidemiology Juvinao-Quintero, D. L., Larrabure-Torrealva, G. T., Sanchez, S. E., Kirschbaum, C., Williams, M. A., Gelaye, B. 2023; 81: 14-23.e8

  Abstract

  Stress and elevated maternal glycemia have negative effects on pregnancy. We evaluated the association of hair cortisol concentrations (HCC), a marker of chronic stress, with insulin resistance and gestational diabetes (GDM).In total, 527 women from Lima, Peru, provided a hair sample in the second trimester of their pregnancy to measure HCC using liquid chromatography-tandem mass spectrometry. Each 6 cm of hair captured HCC in early (T1=1-12 weeks) and midpregnancy (T2 = 13-24 weeks). GDM diagnosis was conducted in midpregnancy. Multivariable regression models adjusted for putative risk factorsincluding maternal sociodemographic factors, diabetes history, and hair characteristics, were used to estimate the association of HCC with GDM and various glycemic traits.GDM was diagnosed in 122 (23%) women. Mean HCC across pregnancy was T1 = 3.7 (±3.4) pg/mg and T2 = 4.8 (±3.4) pg/mg. HCC was associated with increased log-transformed units of fasting insulin (T1 = 0.15 [0.03, 0.27], T2 = 0.17 [0.04, 0.30]), homeostasis model assessment for insulin resistance (T1 = 0.14 [0.01, 0.26], T2 = 0.17 [0.03, 0.30]), and homeostasis model assessment for β-cell function (T1 = 0.20 [0.05, 0.34], T2 = 0.20 [0.04, 0.36]), but not with GDM (T1 = 0.95 [0.63, 1.40], T2 = 1.11 [0.74, 1.67]).Elevated maternal HCC was associated with abnormal insulin homeostasis in pregnancy. Dysregulation of the hypothalamic-pituitary-adrenal axis, as reflected by high HCC, may also contribute to insulin resistance syndrome in pregnancy.

  View details for DOI 10.1016/j.annepidem.2023.02.011

  View details for PubMedID 36841381

  View details for PubMedCentralID PMC10204096

• The Relationship of Attention-Deficit/Hyperactivity Disorder With Posttraumatic Stress Disorder: A Two-Sample Mendelian Randomization and Population-Based Sibling Comparison Study. Biological psychiatry Wendt, F. R., Garcia-Argibay, M., Cabrera-Mendoza, B., Valdimarsdóttir, U. A., Gelernter, J., Stein, M. B., Nivard, M. G., Maihofer, A. X., Nievergelt, C. M., Larsson, H., Mattheisen, M., Polimanti, R., Meier, S. M. 2023; 93 (4): 362-369

  Abstract

  Attention-deficit/hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD) are associated, but it is unclear if this is a causal relationship or confounding. We used genetic analyses and sibling comparisons to clarify the direction of this relationship.Linkage disequilibrium score regression and 2-sample Mendelian randomization were used to test for genetic correlation (rg) and bidirectional causal effects using European ancestry genome-wide association studies of ADHD (20,183 cases and 35,191 controls) and 6 PTSD definitions (up to 320,369 individuals). Several additional variables were included in the analysis to verify the independence of the ADHD-PTSD relationship. In a population-based sibling comparison (N = 2,082,118 individuals), Cox regression models were fitted to account for time at risk, a range of sociodemographic factors, and unmeasured familial confounders (via sibling comparisons).ADHD and PTSD had consistent rg (rg range, 0.43-0.52; p <  .001). ADHD genetic liability was causally linked with increased risk for PTSD (β = 0.367; 95% CI, 0.186-0.552; p = 7.68 × 10-5). This result was not affected by heterogeneity, horizontal pleiotropy (Mendelian randomization Egger intercept = 4.34 × 10-4, p = .961), or other phenotypes and was consistent across PTSD datasets. However, we found no consistent associations between PTSD genetic liability and ADHD risk. Individuals diagnosed with ADHD were at a higher risk for developing PTSD than their undiagnosed sibling (hazard ratio = 2.37; 95% CI, 1.98-3.53).Our findings add novel evidence supporting the need for early and effective treatment of ADHD, as patients with this diagnosis are at significantly higher risk to develop PTSD later in life.

  View details for DOI 10.1016/j.biopsych.2022.08.012

  View details for PubMedID 36335070

  View details for PubMedCentralID PMC10496427

• A Cross-Sectional Investigation of Preadolescent Cardiometabolic Health: Associations with Fitness, Physical Activity, Sedentary Behavior, Nutrition, and Sleep. Children (Basel, Switzerland) Castro, N., Zieff, G., Bates, L. C., Pagan Lassalle, P., Higgins, S., Faulkner, J., Lark, S., Skidmore, P., Hamlin, M. J., Signal, T. L., Williams, M. A., Stoner, L. 2023; 10 (2)

  Abstract

  Cardiometabolic disease (CMD) risk often begins early in life. Healthy lifestyle behaviors can mitigate risk, but the optimal combination of behaviors has not been determined. This cross-sectional study simultaneously examined the associations between lifestyle factors (fitness, activity behaviors, and dietary patterns) and CMD risk in preadolescent children.1480 New Zealand children aged 8-10 years were recruited. Participants included 316 preadolescents (50% female, age: 9.5 ± 1.1 years, BMI: 17.9 ± 3.3 kg/m2). Fitness (cardiorespiratory fitness [CRF], muscular fitness), activity behaviors (physical activity, sedentary, sleep), and dietary patterns were measured. Factor analysis was used to derive a CMD risk score from 13 variables (adiposity, peripheral and central hemodynamics, glycemic control, and blood lipids).Only CRF (β = -0.45, p < 0.001) and sedentary time (β = 0.12, p = 0.019) were associated with the CMD risk score in the adjusted multivariable analysis. CRF was found to be nonlinear (VO2 max ≤ ≈42 mL/kg/min associated with higher CMD risk score), and thus a CRF polynomial term was added, which was also associated (β = 0.19, p < 0.001) with the CMD risk score. Significant associations were not found with sleep or dietary variables.The findings indicate that increasing CRF and decreasing sedentary behavior may be important public health targets in preadolescent children.

  View details for DOI 10.3390/children10020336

  View details for PubMedID 36832464

  View details for PubMedCentralID PMC9955686

• Pain, mood, and suicidal behavior among injured working adults in Chile. BMC psychiatry Vélez, J. C., Kovasala, M., Collado, M. D., Friedman, L. E., Juvinao-Quintero, D. L., Araya, L., Castillo, J., Williams, M. A., Gelaye, B. 2022; 22 (1): 766

  Abstract

  Chronic pain is comorbid with psychiatric disorders, but information on the association of chronic pain with depressive symptoms, generalized anxiety, and suicidal behavior among occupational cohorts is inadequate. We investigated these associations among employed Chilean adults.A total of 1946 working adults were interviewed during their outpatient visit. Pain was assessed using the Short Form McGill Pain questionnaire (SF-MPG) while depression and generalized anxiety were examined using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. The Columbia-Suicide Severity Rating Scale was used to assess suicidal behavior and suicidal ideation. Multivariable logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (95%CI) for the association of chronic pain with mood disorders, as well as suicidal behavior.High chronic pain (SF-MPG > 11) was reported by 46% of participants. Approximately two-fifths of the study participants (38.2%) had depression, 23.8% generalized anxiety, 13.4% suicidal ideation, and 2.4% suicidal behavior. Compared to those with low pain (SF-MPG ≤11), participants with high chronic pain (SF-MPG > 11) had increased odds of experiencing depression only (aOR = 2.87; 95% CI: 2.21-3.73), generalized anxiety only (aOR = 2.38; 95% CI: 1.42-3.99), and comorbid depression and generalized anxiety (aOR = 6.91; 95% CI: 5.20-9.19). The corresponding aOR (95%CI) for suicidal ideation and suicidal behavior were (aOR = 2.20; 95% CI: 1.58-3.07) and (aOR = 2.18 = 95% CI: 0.99-4.79), respectively.Chronic pain is associated with increased odds of depression, generalized anxiety, and suicidal behavior. Mental health support and appropriate management of patients experiencing chronic pain are critical.

  View details for DOI 10.1186/s12888-022-04391-3

  View details for PubMedID 36471330

  View details for PubMedCentralID PMC9724445

• Abnormal uterine bleeding patterns determined through menstrual tracking among participants in the Apple Women's Health Study. American journal of obstetrics and gynecology Zhang, C. Y., Li, H., Zhang, S., Suharwardy, S., Chaturvedi, U., Fischer-Colbrie, T., Maratta, L. A., Onnela, J., Coull, B. A., Hauser, R., Williams, M. A., Baird, D. D., Jukic, A. M., Mahalingaiah, S., Curry, C. L. 2022

  Abstract

  BACKGROUND: Use of menstrual tracking data to understand abnormal bleeding patterns has been limited because of lack of incorporation of key demographic and health characteristics and confirmation of menstrual tracking accuracy.OBJECTIVE: This study aimed to identify abnormal uterine bleeding patterns and their prevalence and confirm existing and expected associations between abnormal uterine bleeding patterns, demographics, and medical conditions.STUDY DESIGN: Apple Women's Health Study participants from November 2019 through July 2021 who contributed menstrual tracking data and did not report pregnancy, lactation, use of hormones, or menopause were included in the analysis. Four abnormal uterine bleeding patterns were evaluated: irregular menses, infrequent menses, prolonged menses, and irregular intermenstrual bleeding (spotting). Monthly tracking confirmation using survey responses was used to exclude inaccurate or incomplete digital records. We investigated the prevalence of abnormal uterine bleeding stratified by demographic characteristics and used logistic regression to evaluate the relationship of abnormal uterine bleeding to a number of self-reported medical conditions.RESULTS: There were 18,875 participants who met inclusion criteria, with a mean age of 33 (standard deviation, 8.2) years, mean body mass index of 29.3 (standard deviation, 8.0), and with 68.9% (95% confidence interval, 68.2-69.5) identifying as White, non-Hispanic. Abnormal uterine bleeding was found in 16.4% of participants (n=3103; 95% confidence interval, 15.9-17.0) after accurate tracking was confirmed; 2.9% had irregular menses (95% confidence interval, 2.7-3.1), 8.4% had infrequent menses (95% confidence interval, 8.0-8.8), 2.3% had prolonged menses (95% confidence interval, 2.1-2.5), and 6.1% had spotting (95% confidence interval, 5.7-6.4). Black participants had 33% higher prevalence (prevalence ratio, 1.33; 95% confidence interval, 1.09-1.61) of infrequent menses compared with White, non-Hispanic participants after controlling for age and body mass index. The prevalence of infrequent menses was increased in class 1, 2, and 3 obesity (class 1: body mass index, 30-34.9; prevalence ratio, 1.31; 95% confidence interval, 1.13-1.52; class 2: body mass index, 35-39.9; prevalence ratio, 1.25; 95% confidence interval, 1.05-1.49; class 3: body mass index, >40; prevalence ratio, 1.51; 95% confidence interval, 1.21-1.88) after controlling for age and race/ethnicity. Those with class 3 obesity had 18% higher prevalence of abnormal uterine bleeding compared with healthy-weight participants (prevalence ratio, 1.18; 95% confidence interval, 1.02-1.38). Participants with polycystic ovary syndrome had 19% higher prevalence of abnormal uterine bleeding compared with participants without this condition (prevalence ratio, 1.19; 95% confidence interval, 1.08-1.31). Participants with hyperthyroidism (prevalence ratio, 1.34; 95% confidence interval, 1.13-1.59) and hypothyroidism (prevalence ratio, 1.17; 95% confidence interval, 1.05-1.31) had a higher prevalence of abnormal uterine bleeding, as did those reporting endometriosis (prevalence ratio, 1.28; 95% confidence interval, 1.12-1.45), cervical dysplasia (prevalence ratio, 1.20; 95% confidence interval, 1.03-1.39), and fibroids (prevalence ratio, 1.14; 95% confidence interval, 1.00-1.30).CONCLUSION: In this cohort, abnormal uterine bleeding was present in 16.4% of those with confirmed menstrual tracking. Black or obese participants had increased prevalence of abnormal uterine bleeding. Participants reporting conditions such as polycystic ovary syndrome, thyroid disease, endometriosis, and cervical dysplasia had a higher prevalence of abnormal uterine bleeding.

  View details for DOI 10.1016/j.ajog.2022.10.029

  View details for PubMedID 36414993

• Adiposity in preadolescent children: Associations with cardiorespiratory fitness. PloS one Castro, N., Bates, L. C., Zieff, G., Pagan Lassalle, P., Faulkner, J., Lark, S., Hamlin, M., Skidmore, P., Signal, T. L., Williams, M. A., Higgins, S., Stoner, L. 2022; 17 (10): e0275982

  Abstract

  Lifestyle factors contribute to childhood obesity risk, however it is unclear which lifestyle factors are most strongly associated with childhood obesity. The purpose of this cross-sectional study was to simultaneously investigate the associations among dietary patterns, activity behaviors, and physical fitness with adiposity (body fat %, fat mass, body mass index [BMI], and waist to hip ratio) in preadolescent children. Preadolescent children (N = 392, 50% female, age: 9.5 ± 1.1year, BMI: 17.9 ± 3.3 kg/m2) were recruited. Body fat (%) and fat mass (kg) were measured with bioelectrical impedance analysis. Cardiorespiratory fitness (VO2 max), muscular strength (hand-grip strength), activity, sleep, and dietary pattern was assessed. Multivariable analysis revealed that cardiorespiratory fitness associated most strongly with all four indicators of adiposity (body fat (%) (β = -0.2; p < .001), fat mass (β = -0.2; p < .001), BMI (β = -0.1; p < .001) and waist to hip ratio (β = -0.2; p < .001). Additionally, fruit and vegetable consumption patterns were associated with body fat percentage, but the association was negligible (β = 0.1; p = 0.015). Therefore, future interventions should aim to promote the use of cardiorespiratory fitness as a means of reducing the obesity epidemic in children.

  View details for DOI 10.1371/journal.pone.0275982

  View details for PubMedID 36288267

  View details for PubMedCentralID PMC9605025

• Attempts to conceive and the COVID-19 pandemic: data from the Apple Women's Health Study. American journal of obstetrics and gynecology Fruh, V., Lyons, G., Scalise, A. L., Gallagher, N. J., Jukic, A. M., Baird, D. D., Chaturvedi, U., Suharwardy, S., Onnela, J. P., Williams, M. A., Hauser, R., Coull, B. A., Mahalingaiah, S. 2022; 227 (3): 484.e1-484.e17

  Abstract

  Previous studies have suggested that emergent events may affect pregnancy planning decisions. However, few have investigated the effect of factors related to the COVID-19 pandemic on pregnancy planning, measured by attempting conception, and how attempting conception status may differ by individual-level factors, such as social status or educational level.This study aimed to examine the effects of factors related to the COVID-19 pandemic, until March 2021, on attempting conception status and to assess the effect measure modification by educational level and subjective social status.We conducted a longitudinal analysis within a subgroup of 21,616 participants in the Apple Women's Health Study who enrolled from November 2019 to March 2021, who met the inclusion criteria, and who responded to the monthly status menstrual update question on attempting conception status (yes or no). Participants reporting hysterectomy, pregnancy, lactation, or menopause were excluded. We used generalized estimating equation methodology to fit logistic regression models that estimate odds ratios and 95% confidence intervals for the association between the proportion of participants attempting conception and the month of response (compared with a prepandemic reference month of February 2020) while accounting for longitudinal correlation and adjusting for age, race and ethnicity, and marital status. We stratified the analysis by social status and educational level.We observed a trend of reduced odds of attempting conception, with an 18% reduction in the odds of attempting conception in August 2020 and October 2020 compared with the prepandemic month of February 2020 (August odds ratio: 0.82 [95% confidence interval, 0.70-0.97]; October odds ratio: 0.82 [95% confidence interval, 0.69-0.97). The participants with lower educational level (no college education) experienced a sustained reduction in the odds of attempting to conceive from June 2020 to March 2021 compared with February 2020, with up to a 24% reduction in the odds of attempting to conceive in October 2020 (odds ratio, 0.76; 95% confidence interval, 0.59-0.96). Among participants that were college educated, we observed an initial reduction in the odds of attempting to conceive starting in July 2020 (odds ratio 0.73; 95% confidence interval, 0.54-0.99) that returned near prepandemic odds. Moreover, we observed a reduction in the odds of attempting to conceive among those with low subjective social status, with a decline in the odds of attempting to conceive beginning in July 2020 (odds ratio, 0.83; 95% confidence interval, 0.63-1.10) and continuing until March 2021 (odds ratio, 0.79; 95% confidence interval, 0.59-1.06), with the greatest reduction in odds in October 2020 (odds ratio, 0.67; 95% confidence interval, 0.50-0.91).Among women in the Apple Women's Health Study cohort, our findings suggested a reduction in the odds of attempting to conceive during the COVID-19 pandemic, until March 2021, particularly among women of lower educational level and lower perceived social status.

  View details for DOI 10.1016/j.ajog.2022.05.013

  View details for PubMedID 35568191

  View details for PubMedCentralID PMC9093060

• Maternal-fetal genetic interactions, imprinting, and risk of placental abruption. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians Workalemahu, T., Enquobahrie, D. A., Gelaye, B., Tadesse, M. G., Sanchez, S. E., Tekola-Ayele, F., Hajat, A., Thornton, T. A., Ananth, C. V., Williams, M. A. 2022; 35 (18): 3473-3482

  Abstract

  Abruption cases were more likely to experience preeclampsia, have shorter gestational age, and deliver infants with lower birthweight compared with controls. Models with MFGI effects provided improved fit than models with only maternal and fetal genotype main effects for SNP rs12530904 (p-value = 1.2e-04) in calcium/calmodulin-dependent protein kinase [CaM kinase] II beta (CAMK2B), and, SNP rs73136795 (p-value = 1.9e-04) in peroxisome proliferator-activated receptor-gamma (PPARG), both MB genes. We identified 320 SNPs in 45 maternally-imprinted genes (including potassium voltage-gated channel subfamily Q member 1 [KCNQ1], neurotrimin [NTM], and, ATPase phospholipid transporting 10 A [ATP10A]) associated with abruption. Top hits included rs2012323 (p-value = 1.6E-16) and rs12221520 (p-value1.3e-13) in KCNQ1, rs8036892 (p-value = 9.3E-17) and rs188497582 in ATP10A, rs12589854 (p-value = 2.9E-11) and rs80203467 (p-value = 4.6e-11) in maternally expressed 8, small nucleolar RNA host (MEG8), and rs138281088 in solute carrier family 22 member 2 (SLC22A2) (p-value = 6.8e-9).We identified novel PA-related maternal-fetal MB gene interactions and imprinting effects that highlight the role of the fetus in PA risk development. Findings can inform mechanistic investigations to understand the pathogenesis of PA.

  View details for DOI 10.1080/14767058.2020.1822314

  View details for PubMedID 32972274

  View details for PubMedCentralID PMC8601203

• Association between Ancestry-Specific 6q25 Variants and Breast Cancer Subtypes in Peruvian Women. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Zavala, V. A., Casavilca-Zambrano, S., Navarro-Vásquez, J., Castañeda, C. A., Valencia, G., Morante, Z., Calderón, M., Abugattas, J. E., Gómez, H., Fuentes, H. A., Liendo-Picoaga, R., Cotrina, J. M., Monge, C., Neciosup, S. P., Huntsman, S., Hu, D., Sánchez, S. E., Williams, M. A., Núñez-Marrero, A., Godoy, L., Hechmer, A., Olshen, A. B., Dutil, J., Ziv, E., Zabaleta, J., Gelaye, B., Vásquez, J., Gálvez-Nino, M., Enriquez-Vera, D., Vidaurre, T., Fejerman, L. 2022; 31 (8): 1602-1609

  Abstract

  Breast cancer incidence in the United States is lower in Hispanic/Latina (H/L) compared with African American/Black or Non-Hispanic White women. An Indigenous American breast cancer-protective germline variant (rs140068132) has been reported near the estrogen receptor 1 gene. This study tests the association of rs140068132 and other polymorphisms in the 6q25 region with subtype-specific breast cancer risk in H/Ls of high Indigenous American ancestry.Genotypes were obtained for 5,094 Peruvian women with (1,755) and without (3,337) breast cancer. Associations between genotype and overall and subtype-specific risk for the protective variant were tested using logistic regression models and conditional analyses, including other risk-associated polymorphisms in the region.We replicated the reported association between rs140068132 and breast cancer risk overall [odds ratio (OR), 0.53; 95% confidence interval (CI), 0.47-0.59], as well as the lower odds of developing hormone receptor negative (HR-) versus HR+ disease (OR, 0.77; 95% CI, 0.61-0.97). Models, including HER2, showed further heterogeneity with reduced odds for HR+HER2+ (OR, 0.68; 95% CI, 0.51-0.92), HR-HER2+ (OR, 0.63; 95% CI, 0.44-0.90) and HR-HER2- (OR, 0.77; 95% CI, 0.56-1.05) compared with HR+HER2-. Inclusion of other risk-associated variants did not change these observations.The rs140068132 polymorphism is associated with decreased risk of breast cancer in Peruvians and is more protective against HR- and HER2+ diseases independently of other breast cancer-associated variants in the 6q25 region.These results could inform functional analyses to understand the mechanism by which rs140068132-G reduces risk of breast cancer development in a subtype-specific manner. They also illustrate the importance of including diverse individuals in genetic studies.

  View details for DOI 10.1158/1055-9965.EPI-22-0069

  View details for PubMedID 35654312

  View details for PubMedCentralID PMC9662925

• Covid-19 vaccination and menstrual cycle length in the Apple Women's Health Study. medRxiv : the preprint server for health sciences Gibson, E. A., Li, H., Fruh, V., Gabra, M., Asokan, G., Jukic, A. M., Baird, D. D., Curry, C. L., Fischer-Colbrie, T., Onnela, J. P., Williams, M. A., Hauser, R., Coull, B. A., Mahalingaiah, S. 2022

  Abstract

  COVID-19 vaccination may be associated with change in menstrual cycle length following vaccination.We conducted a longitudinal analysis within a subgroup of 14,915 participants in the Apple Women's Health Study (AWHS) who enrolled between November 2019 and December 2021 and met the following eligibility criteria: were living in the U.S., met minimum age requirements for consent, were English speaking, actively tracked their menstrual cycles, and responded to the COVID-19 Vaccine Update survey. In the main analysis, we included tracked cycles recorded when premenopausal participants were not pregnant, lactating, or using hormonal contraceptives. We used conditional linear regression and multivariable linear mixed-effects models with random intercepts to estimate the covariate-adjusted difference in mean cycle length, measured in days, between pre-vaccination cycles, cycles in which a vaccine was administered, and post-vaccination cycles within vaccinated participants, and between vaccinated and unvaccinated participants. We further compared associations between vaccination and menstrual cycle length by the timing of vaccine dose within a menstrual cycle (i.e., in follicular or luteal phase). We present Bonferroni-adjusted 95% confidence intervals to account for multiple comparisons.A total of 128,094 cycles (median = 10 cycles per participant; interquartile range: 4-22) from 9,652 participants (8,486 vaccinated; 1,166 unvaccinated) were included. The average within-individual standard deviation in cycle length was 4.2 days. Fifty-five percent of vaccinated participants received Pfizer-BioNTech's mRNA vaccine, 37% received Moderna's mRNA vaccine, and 7% received the Johnson & Johnson/Janssen vaccine (J&J). We found no evidence of a difference between mean menstrual cycle length in the unvaccinated and vaccinated participants prior to vaccination (0.24 days, 95% CI: -0.34, 0.82).Among vaccinated participants, COVID-19 vaccination was associated with a small increase in mean cycle length (MCL) for cycles in which participants received the first dose (0.50 days, 95% CI: 0.22, 0.78) and cycles in which participants received the second dose (0.39 days, 95% CI: 0.11, 0.67) of mRNA vaccines compared with pre-vaccination cycles. Cycles in which the single dose of J&J was administered were, on average, 1.26 days longer (95% CI: 0.45, 2.07) than pre-vaccination cycles. Post-vaccination cycles returned to average pre-vaccination length. Estimates for pre vs post cycle lengths were 0.14 days (95% CI: -0.13, 0.40) in the first cycle following vaccination, 0.13 days (95% CI: -0.14, 0.40) in the second, -0.17 days (95% CI: -0.43, 0.10) in the third, and -0.25 days (95% CI: -0.52, 0.01) in the fourth cycle post-vaccination. Follicular phase vaccination was associated with an increase in MCL in cycles in which participants received the first dose (0.97 days, 95% CI: 0.53, 1.42) or the second dose (1.43 days, 95% CI: 1.06, 1.80) of mRNA vaccines or the J&J dose (2.27 days, 95% CI: 1.04, 3.50), compared with pre-vaccination cycles.COVID-19 vaccination was associated with an immediate short-term increase in menstrual cycle length overall, which appeared to be driven by doses received in the follicular phase. However, the magnitude of this increase was small and diminished in each cycle following vaccination. No association with cycle length persisted over time. The magnitude of change associated with vaccination was well within the natural variability in the study population. Menstrual cycle change following COVID-19 vaccination appears small and temporary and should not discourage individuals from becoming vaccinated.

  View details for DOI 10.1101/2022.07.07.22277371

  View details for PubMedID 35860226

  View details for PubMedCentralID PMC9298140

• Poor sleep Quality and Obstructive Sleep Apnea are Associated with Maternal Mood, and Anxiety Disorders in Pregnancy. Maternal and child health journal Rubio, E., Levey, E. J., Rondon, M. B., Friedman, L., Sanchez, S. E., Williams, M. A., Gelaye, B. 2022; 26 (7): 1540-1548

  Abstract

  Previous studies suggest sleep quality and obstructive sleep apnea (OSA) may be associated with psychiatric symptoms, including depression, anxiety, and posttraumatic stress disorder (PTSD). However, few studies have examined the relationship between sleep quality and OSA with maternal psychiatric symptoms during pregnancy, a state of vulnerability to these disorders.The objective of our study is to examine the association between poor sleep quality and sleep apnea with antepartum depression, anxiety, and PTSD among pregnant women.A cross-sectional study was conducted among women seeking prenatal care in Lima, Peru. Sleep quality was measured using the Pittsburgh Sleep Quality Index, and the Berlin questionnaire was used to identify women at high risk for OSA. Depression, generalized anxiety, and PTSD symptoms were measured using the Patient Health Questionnaire-9, Generalized Anxiety Disorder Assessment, and PTSD Checklist - Civilian Version. Multivariate logistic regression procedures were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95% CI).Approximately 29.0X% of women had poor sleep quality, and 6.2% were at high risk for OSA. The prevalence of psychiatric symptoms was high in this cohort with 25.1%, 32.5%, and 30.9% of women reporting symptoms of antepartum depression, antepartum anxiety, and PTSD, respectively. Women with poor sleep quality had higher odds of antepartum depression (aOR = 3.28; 95%CI: 2.64-4.07), generalized anxiety (aOR = 1.94; 95%CI: 1.58-2.38), and PTSD symptoms (aOR = 2.81; 95% CI: 2.28-3.46) as compared with women who reported good sleep quality. Women with a high risk of OSA had higher odds of antepartum depression (aOR = 2.36; 95% CI: 1.57-3.56), generalized anxiety (aOR = 2.02, 95% CI: 1.36-3.00), and PTSD symptoms (aOR = 2.14; 95%CI: 1.43-3.21) as compared with those with a low risk of sleep apnea.Poor sleep quality and high risk of OSA are associated with antepartum depression, generalized anxiety, and PTSD symptoms among pregnant women. Further characterizations of the associations of these prevalent sleep, mood, and anxiety conditions among pregnant women could aid in evaluating and delivering optimal perinatal care to women with these comorbidities.

  View details for DOI 10.1007/s10995-022-03449-8

  View details for PubMedID 35596848

  View details for PubMedCentralID PMC9250423

• Association of morningness-eveningness with psychiatric symptoms among pregnant women. Chronobiology international Ashi, K., Levey, E., Friedman, L. E., Sanchez, S. E., Williams, M. A., Gelaye, B. 2022; 39 (7): 984-990

  Abstract

  In the present study, we examined associations between circadian preference and psychiatric symptoms among 1,796 pregnant women from Lima, Peru. One quarter were classified as evening types. Compared to morning types, evening type pregnant women had increased odds of generalized anxiety (OR = 1.44; 95%CI: 1.12-1.86) and posttraumatic stress disorder (OR = 1.38; 95%CI: 1.07-1.78). Although there was a positive trend, evening chronotype was not significantly associated with elevated odds of depression (OR = 1.23; 95%CI: 0.94-1.61). Future studies are warranted to help understand the underlying behavioral, biological, and genetic pathways of these associations. Assessing circadian preference may help clinicians identify pregnant women at risk for psychiatric symptoms.

  View details for DOI 10.1080/07420528.2022.2053703

  View details for PubMedID 35296206

  View details for PubMedCentralID PMC9177642

• Evaluating the performance of the Pain Interference Index and the Short Form McGill Pain Questionnaire among Chilean injured working adults. PloS one Velez, J. C., Friedman, L. E., Barbosa, C., Castillo, J., Juvinao-Quintero, D. L., Williams, M. A., Gelaye, B. 2022; 17 (5): e0268672

  Abstract

  Chronic pain can lead to economic instability, decreased job productivity, and poor mental health. Therefore, reliable identification and quantification of chronic pain is important for clinical diagnosis and treatment.To determine the psychometric properties of the Spanish language versions of the Pain Interference Index (PII) and the Short Form McGill Pain Questionnaire (SF-MPG) among a population of working adults who experienced injury in Santiago, Chile.A total of 1,975 participants with work-related injuries were interviewed to collect sociodemographic, occupational, and chronic pain characteristics. Construct validity and factorial structure of the PII and SF-MPG were assessed through exploratory factor analyses (EFA). Cronbach's alpha was used to evaluate internal consistency.The PII mean score was 3.84 ± 1.43 among all participants. The SF-MPG median score was 11 [IQR: 6-16] in this study population. Cronbach's alpha for the PII was 0.90 and 0.87 for the SF-MP. EFA resulted in a one factor solution for the PII. A two-factor solution was found for the SF-MPG. The two-factors for SF-MPG were sensory and affective subscales with Cronbach's alpha of 0.82 and 0.714, respectively. When the two scales were combined, an EFA analysis confirmed the PII and SF-MPG measure different aspects of chronic pain.The PII and SF-MPG had good construct validity and reliability for assessing different aspects of chronic pain among working Chilean adults.

  View details for DOI 10.1371/journal.pone.0268672

  View details for PubMedID 35588123

  View details for PubMedCentralID PMC9119477

• Association between omentin-1 and indices of glucose metabolism in early pregnancy: a pilot study. Archives of gynecology and obstetrics Papatheodorou, S., Gelaye, B., Williams, M. A. 2022; 305 (3): 589-596

  Abstract

  Omentin-1 plays an important role in regulating insulin sensitivity outside pregnancy. As an adipokine derived from human placental and adipose tissue, it may be an important contributor in the biological pathway of gestational diabetes.Omentin-1 was measured in a sub-cohort of 50 participants in the Omega study. We aimed to evaluate whether circulating maternal omentin-1 concentrations are associated with fasting serum glucose, insulin, HOMA-IR and maternal obesity as measured by body mass index (BMI) and subcutaneous and intra-abdominal fat thickness measurements in normoglycemic pregnant participants. We performed a subgroup analysis by BMI category.Omentin-1 was negatively correlated with HOMA-IR and insulin and inversely associated with serum glucose concentration in the fully adjusted model (- 47%; slope per tertile increase in concentration - 0.19; P-trend 0.01). This association was significant in non-overweight/obese (< 25 kg/m2) but not among overweight/obese (≥ 25 kg/ m2) participants. The association with serum insulin was not significant in the fully adjusted model.Circulating omentin-1 concentrations are inversely associated with serum glucose concentrations. Although the relevance of these findings remains to be elucidated, they may indicate a mechanism for the development of insulin resistance and gestational diabetes. Follow-up studies with larger sample sizes are warranted.

  View details for DOI 10.1007/s00404-021-06197-2

  View details for PubMedID 34427751

  View details for PubMedCentralID 5860043

• Social Jetlag and Cardiometabolic Risk in Preadolescent Children. Frontiers in cardiovascular medicine Castro, N., Diana, J., Blackwell, J., Faulkner, J., Lark, S., Skidmore, P., Hamlin, M., Signal, L., Williams, M. A., Stoner, L. 2021; 8: 705169

  Abstract

  Objective: Childhood cardiometabolic disease risk (CMD) has been associated with short sleep duration. Its relationship with other aspects of sleep should also be considered, including social jetlag (SJL) which represents the difference between a person's social rhythms and circadian clock. This study investigated whether childhood CMD risk is associated with sleep duration, sleep disturbances, and SJL. Study Design: The observational study included 332 children aged 8-10 years (48.5% female). The three independent variables were sleep duration, sleep disturbances, and SJL. SJL was calculated as the variation in hours between the midpoint of sleep during free (weekend) days and work/school days. Eleven cardiometabolic biomarkers were measured, including central blood pressure, lipids, glycated hemoglobin, arterial wave reflection, and glucose. Underlying CMD risk factors were identified using factor analysis. Results: Four underlying CMD risk factors were identified using factor analysis: blood pressure, cholesterol, vascular health, and carbohydrate metabolism. Neither sleep disturbances nor sleep duration were significantly associated with any of the four CMD factors following adjustments to potential confounders. However, SJL was significantly linked to vascular health (p = 0.027) and cholesterol (p = 0.025). Conclusion: These findings suggest that SJL may be a significant and measurable public health target for offsetting negative CMD trajectories in children. Further studies are required to determine biological plausibility.

  View details for DOI 10.3389/fcvm.2021.705169

  View details for PubMedID 34692778

  View details for PubMedCentralID PMC8529028

• Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information. Biological psychiatry Maihofer, A. X., Choi, K. W., Coleman, J. R., Daskalakis, N. P., Denckla, C. A., Ketema, E., Morey, R. A., Polimanti, R., Ratanatharathorn, A., Torres, K., Wingo, A. P., Zai, C. C., Aiello, A. E., Almli, L. M., Amstadter, A. B., Andersen, S. B., Andreassen, O. A., Arbisi, P. A., Ashley-Koch, A. E., Austin, S. B., Avdibegovic, E., Borglum, A. D., Babic, D., Bakvad-Hansen, M., Baker, D. G., Beckham, J. C., Bierut, L. J., Bisson, J. I., Boks, M. P., Bolger, E. A., Bradley, B., Brashear, M., Breen, G., Bryant, R. A., Bustamante, A. C., Bybjerg-Grauholm, J., Calabrese, J. R., Caldas-de-Almeida, J. M., Chen, C., Dale, A. M., Dalvie, S., Deckert, J., Delahanty, D. L., Dennis, M. F., Disner, S. G., Domschke, K., Duncan, L. E., Dzubur Kulenovic, A., Erbes, C. R., Evans, A., Farrer, L. A., Feeny, N. C., Flory, J. D., Forbes, D., Franz, C. E., Galea, S., Garrett, M. E., Gautam, A., Gelaye, B., Gelernter, J., Geuze, E., Gillespie, C. F., Goci, A., Gordon, S. D., Guffanti, G., Hammamieh, R., Hauser, M. A., Heath, A. C., Hemmings, S. M., Hougaard, D. M., Jakovljevic, M., Jett, M., Johnson, E. O., Jones, I., Jovanovic, T., Qin, X., Karstoft, K., Kaufman, M. L., Kessler, R. C., Khan, A., Kimbrel, N. A., King, A. P., Koen, N., Kranzler, H. R., Kremen, W. S., Lawford, B. R., Lebois, L. A., Lewis, C., Liberzon, I., Linnstaedt, S. D., Logue, M. W., Lori, A., Lugonja, B., Luykx, J. J., Lyons, M. J., Maples-Keller, J. L., Marmar, C., Martin, N. G., Maurer, D., Mavissakalian, M. R., McFarlane, A., McGlinchey, R. E., McLaughlin, K. A., McLean, S. A., Mehta, D., Mellor, R., Michopoulos, V., Milberg, W., Miller, M. W., Morris, C. P., Mors, O., Mortensen, P. B., Nelson, E. C., Nordentoft, M., Norman, S. B., O'Donnell, M., Orcutt, H. K., Panizzon, M. S., Peters, E. S., Peterson, A. L., Peverill, M., Pietrzak, R. H., Polusny, M. A., Rice, J. P., Risbrough, V. B., Roberts, A. L., Rothbaum, A. O., Rothbaum, B. O., Roy-Byrne, P., Ruggiero, K. J., Rung, A., Rutten, B. P., Saccone, N. L., Sanchez, S. E., Schijven, D., Seedat, S., Seligowski, A. V., Seng, J. S., Sheerin, C. M., Silove, D., Smith, A. K., Smoller, J. W., Sponheim, S. R., Stein, D. J., Stevens, J. S., Teicher, M. H., Thompson, W. K., Trapido, E., Uddin, M., Ursano, R. J., van den Heuvel, L. L., Van Hooff, M., Vermetten, E., Vinkers, C., Voisey, J., Wang, Y., Wang, Z., Werge, T., Williams, M. A., Williamson, D. E., Winternitz, S., Wolf, C., Wolf, E. J., Yehuda, R., Young, K. A., Young, R. M., Zhao, H., Zoellner, L. A., Haas, M., Lasseter, H., Provost, A. C., Salem, R. M., Sebat, J., Shaffer, R. A., Wu, T., Ripke, S., Daly, M. J., Ressler, K. J., Koenen, K. C., Stein, M. B., Nievergelt, C. M. 2021

  Abstract

  BACKGROUND: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs).METHODS: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N= 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N= 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms.RESULTS: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program.CONCLUSIONS: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods.

  View details for DOI 10.1016/j.biopsych.2021.09.020

  View details for PubMedID 34865855

• Confronting Our Next National Health Disaster - Long-Haul Covid. The New England journal of medicine Phillips, S., Williams, M. A. 2021; 385 (7): 577-579

  View details for DOI 10.1056/NEJMp2109285

  View details for PubMedID 34192429

• Associations between adverse childhood experiences and migraine among teenage mothers in Peru. Journal of psychosomatic research Siego, C. V., Sanchez, S. E., Jimenez, M. L., Rondon, M. B., Williams, M. A., Peterlin, B. L., Gelaye, B. 2021; 147: 110507

  Abstract

  The objective of this study was to evaluate the association between (1) different types of ACEs and migraine, and (2) the number of ACEs and migraine among adolescent mothers in Lima, Peru.Our cross-sectional study included 787 adolescent mothers (14- to 18-years of age) in Peru. In-person interviews were conducted postpartum, in hospital, within 2-days of delivery. Nine types of ACEs were assessed, including exposure to three categories of abuse, two categories of neglect, and four categories of household dysfunction. Multivariable logistic regression procedures were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) for the association between ACEs and migraine while adjusting for putative confounders.Approximately 75% of adolescent mothers reported having experienced at least one type of ACE. Adolescent mothers who reported any childhood abuse had 1.49-fold increased odds of migraine (aOR = 1.49; 95% CI 1.03-2.18) compared to those with no history of childhood abuse. Adolescent mothers who reported experiencing household dysfunction had 1.56-fold increase odds of migraine (aOR = 1.56; 95% CI 1.09-2.24). Compared to participants who reported no ACE, those who experienced four or more ACEs had 3.09-fold (aOR = 3.09; 95% CI 1.80-5.40) increased odds of migraine (ptrend < 0.001).Exposure to ACEs is highly prevalent in adolescent-aged mothers postpartum and is associated with increased odds of migraine. These findings support the importance of screening for ACEs and migraine among adolescent mothers; and the need for providing culturally appropriate, trauma-informed headache care.

  View details for DOI 10.1016/j.jpsychores.2021.110507

  View details for PubMedID 34020343

  View details for PubMedCentralID PMC8852843

• Design and Methods of the Apple Women's Health Study: A Digital Longitudinal Cohort Study. Mahalingaiah, S., Fruh, V., Rodriguez, E., Konanki, S., Onnela, J., Veiga, A., Jukic, A. Z., Ferguson, K. K., Baird, D. D., Wilcox, A. J., Christine, C. L., Sanaa, S., Tyler, F., Gracee, A., Coull, B. A., Hauser, R. B., Williams, M. A. SPRINGER HEIDELBERG. 2021: 306A

  Abstract

  Prospective longitudinal cohorts assessing women's health and gynecologic conditions have been historically limited.The Apple Women's Health Study was designed to gain a deeper understanding of the relationship between menstrual cycles, health, and behaviors. This paper describes the design and methods of the ongoing Apple Women's Health Study and provides demographic characteristics of the first 10,000 participants.Mobile-application based longitudinal cohort study with survey and sensor-based data. We collected data from 10,000 participants who responded to the demographics survey upon enrollment between November 14, 2019 and May 20, 2020. Participants were asked to complete a monthly follow-up through November 2020. Eligibility criteria include having ever menstruated, installing the Apple Research app on iPhone with iOS version 13.2 or later, living in USA, age of 18 years or older in most states (19 years old in Alabama and Nebraska, 21 years old in Puerto Rico), proficiency in written and spoken English, sole user of an iCloud account or iPhone, and providing informed consent to participate in the study.Mean age at enrollment was 33.6 years old (+/- standard deviation 10.3). Race/ethnicity was representative of the US population [69% White/Non-Hispanic (6,910/10,000)], while 51% (5,089/10,000) had a college education or above. Participant geographic distribution included all U.S. states and Puerto Rico. Seventy-two percent (7,223/10,000) reported use of an Apple Watch, and 24.4% (2,438/10,000) consented to sensor-based data collection. For this cohort, 38% (3,490/9,238) did not respond to the Monthly Survey: Menstrual Update after enrollment. At the six-month follow-up there was a 35% (3,099/8,972) response rate to the Monthly Survey: Menstrual Update. 82.7% (8,266/10,000) of the initial cohort and 95.1% (2,948/3,099) of participants who responded to month 6 of the Monthly Survey: Menstrual Update, tracked at least one menstrual cycle via HealthKit. Participants tracked menstrual bleeding days an average of 4.44 (25-75% range: 3 - 6) calendar months during the study period. Non-White participants were slightly more likely to drop out than White participants; those remaining at 6 months were otherwise similar in demographic characteristics to the original enrollment group.The first 10,000 participants of the Apple Women's Health Study were recruited via the Research app and were diverse in race/ethnicity, educational attainment, and economic status, despite all using an Apple iPhone. Future studies within this cohort incorporating this high-dimensional data may facilitate discovery in women's health in exposure outcome relationships and population-level trends among iPhone users. Retention efforts centered around education, communication, and engagement will be utilized to improve survey response rates, such as the study update feature.

  View details for Web of Science ID 000675441000663

  View details for PubMedID 34610322

• Equitable allocation of COVID-19 vaccines in the United States. Nature medicine Schmidt, H., Weintraub, R., Williams, M. A., Miller, K., Buttenheim, A., Sadecki, E., Wu, H., Doiphode, A., Nagpal, N., Gostin, L. O., Shen, A. A. 2021; 27 (7): 1298-1307

  Abstract

  Many vaccine rationing guidelines urge planners to recognize, and ideally reduce, inequities. In the United States, allocation frameworks are determined by each of the Centers for Disease Control and Prevention's 64 jurisdictions (50 states, the District of Columbia, five cities and eight territories). In this study, we analyzed vaccine allocation plans published by 8 November 2020, tracking updates through to 30 March 2021. We evaluated whether jurisdictions adopted proposals to reduce inequity using disadvantage indices and related place-based measures. By 30 March 2021, 14 jurisdictions had prioritized specific zip codes in combination with metrics such as COVID-19 incidence, and 37 jurisdictions (including 34 states) had adopted disadvantage indices, compared to 19 jurisdictions in November 2020. Uptake of indices doubled from 7 to 14 among the jurisdictions with the largest shares of disadvantaged communities. Five applications were distinguished: (1) prioritizing disadvantaged groups through increased shares of vaccines or vaccination appointments; (2) defining priority groups or areas; (3) tailoring outreach and communication; (4) planning the location of dispensing sites; and (5) monitoring receipt. To ensure that equity features centrally in allocation plans, policymakers at the federal, state and local levels should universalize the uptake of disadvantage indices and related place-based measures.

  View details for DOI 10.1038/s41591-021-01379-6

  View details for PubMedID 34007071

• Air Pollution and Risk of Placental Abruption: A Study of Births in New York City, 2008-2014. American journal of epidemiology Huang, Y., Kioumourtzoglou, M. A., Mittleman, M. A., Ross, Z., Williams, M. A., Friedman, A. M., Schwartz, J., Wapner, R. J., Ananth, C. V. 2021; 190 (6): 1021-1033

  Abstract

  We evaluated the associations of exposure to fine particulate matter (particulate matter with an aerodynamic diameter ≤2.5 μm (PM2.5) at concentrations of <12 μg/m3, 12-14 μg/m3, and ≥15 μg/m3) and nitrogen dioxide (at concentrations of <26 parts per billion (ppb), 26-29 ppb, and ≥30 ppb) with placental abruption in a prospective cohort study of 685,908 pregnancies in New York, New York (2008-2014). In copollutant analyses, these associations were examined using distributed-lag nonlinear models based on Cox models. The prevalence of abruption was 0.9% (n = 6,025). Compared with a PM2.5 concentration less than 12 μg/m3, women exposed to PM2.5 levels of ≥15 μg/m3 in the third trimester had a higher rate of abruption (hazard ratio (HR) = 1.68, 95% confidence interval (CI): 1.41, 2.00). Compared with a nitrogen dioxide concentration less than 26 ppb, women exposed to nitrogen dioxide levels of 26-29 ppb (HR = 1.11, 95% CI: 1.02, 1.20) and ≥30 ppb (HR = 1.06, 95% CI: 0.96, 1.24) in the first trimester had higher rates of abruption. Compared with both PM2.5 and nitrogen dioxide levels less than the 95th percentile in the third trimester, rates of abruption were increased with both PM2.5 and nitrogen dioxide ≥95th percentile (HR = 1.44, 95% CI: 1.15, 1.80) and PM2.5 ≥95th percentile and nitrogen dioxide <95th percentile (HR = 1.43 95% CI: 1.23, 1.66). Increased levels of PM2.5 exposure in the third trimester and nitrogen dioxide exposure in the first trimester are associated with elevated rates of placental abruption, suggesting that these exposures may be important triggers of premature placental separation through different pathways.

  View details for DOI 10.1093/aje/kwaa259

  View details for PubMedID 33295612

  View details for PubMedCentralID PMC8168176

• Adverse intergenerational effects of ethnically-divisive social contexts on children's mental health: A prospective cohort study in the Netherlands. Social science & medicine (1982) Qureshi, F., Derks, I. P., Williams, M. A., Koenen, K. C., Tiemeier, H., Kubzansky, L. D. 2021; 277: 113932

  Abstract

  Around the world, international migration and growing economic inequality have contributed to heightened perceptions of intergroup threat (i.e., feeling that people outside of one's social group are hostile to their physical or emotional well-being). Exposures related to intergroup threat, like negative intergroup contact, are inherently stressful and may contribute to higher levels of psychological distress in the population. This longitudinal study investigated whether maternal experiences of negative intergroup contact are related to poor mental health outcomes among ethnically diverse children in The Netherlands.Data are from 4025 mother-child pairs in the Generation R Study, a multi-ethnic Dutch birth cohort initiated in 2005. Mothers' experiences of negative intergroup contact were assessed during pregnancy. Child mental health was indexed by problem behavior reported by parents and teachers using the Child Behavior Checklist. Linear mixed-effects models tested longitudinal associations of maternal-reported negative intergroup contact with child problem behavior reported by mothers at ages 3, 5, and 9 years, considering a range of potential confounders. Sensitivity analyses examined whether results were replicated using child data from other informants.In fully adjusted models, higher levels of negative intergroup contact were associated with more problem behavior averaged across childhood for both non-Dutch (standardized B = 0.10, 95% CI = 0.05, 0.14) and Dutch children (standardized B = 0.12, 95% CI = 0.08, 0.15). Sensitivity analyses with data from other informants largely supported primary findings.Comparable adverse intergenerational effects on mental health were observed among both ethnic minority and majority children whose mothers experienced negative intergroup contact. These findings suggest that ethnically divisive social contexts may confer widespread risks, regardless of a child's ethnic background. To our knowledge, this study is the first to examine exposures related to intergroup threat from an epidemiologic perspective and provides proof of principle that such exposures may be informative for population health.

  View details for DOI 10.1016/j.socscimed.2021.113932

  View details for PubMedID 33892415

  View details for PubMedCentralID PMC8205087

• Mental Health in Early Childhood and Changes in Cardiometabolic Dysregulation by Preadolescence. Psychosomatic medicine Qureshi, F., Derks, I. P., Jaddoe, V. W., Williams, M. A., Koenen, K. C., Tiemeier, H., Kubzansky, L. D. 2021; 83 (3): 256-264

  Abstract

  Poor mental health in childhood is associated with a greater risk of cardiometabolic disease in adulthood, but less is known about when these associations begin to emerge. This study tests whether poor mental health (indexed by emotional and behavioral problems) in early childhood predicts increases in cardiometabolic dysregulation over 4 years of follow-up.Data are from 4327 participants in the Generation R Study. Problem behaviors were reported by mothers using the Child Behavior Checklist at age 6 years. Repeated measurements of six cardiometabolic parameters were collected at ages 6 and 10 years: high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, systolic and diastolic blood pressures, C-reactive protein, and body mass index. Standardized measures were used to create continuous cardiometabolic dysregulation scores at ages 6 and 10 years. Change in dysregulation was defined as the difference in dysregulation scores over time. Cross-sectional and prospective associations were tested using linear regression, sequentially adjusting for relevant confounders. Additional analyses examined whether prospective relationships were robust to adjustment for baseline levels of dysregulation.There was no association between child problem behaviors and cardiometabolic dysregulation at age 6 years. However, higher levels of problem behaviors predicted increases in cardiometabolic dysregulation (β = 0.12, 95% confidence interval = 0.00-0.23) from ages 6 to 10 years.Worse child mental health may be associated with increases in cardiometabolic dysregulation by preadolescence. To our knowledge, this is the first study to demonstrate that adverse physiologic effects of psychological distress identified in adult populations may be observed as early as childhood.

  View details for DOI 10.1097/PSY.0000000000000927

  View details for PubMedID 33657082

  View details for PubMedCentralID PMC8016708

• Resilience mediates the relationship between household dysfunction in childhood and postpartum depression in adolescent mothers in Peru. Comprehensive psychiatry Carroll, H., Rondon, M. B., Sanchez, S. E., Fricchione, G. L., Williams, M. A., Gelaye, B. 2021; 104: 152215

  View details for DOI 10.1016/j.comppsych.2020.152215

  View details for PubMedID 33242712

  View details for PubMedCentralID PMC8210750

• Is It Lawful and Ethical to Prioritize Racial Minorities for COVID-19 Vaccines? JAMA Schmidt, H., Gostin, L. O., Williams, M. A. 2020; 324 (20): 2023-2024

  View details for DOI 10.1001/jama.2020.20571

  View details for PubMedID 33052391

• Meditation and Yoga Practices as Potential Adjunctive Treatment of SARS-CoV-2 Infection and COVID-19: A Brief Overview of Key Subjects. Journal of alternative and complementary medicine (New York, N.Y.) Bushell, W., Castle, R., Williams, M. A., Brouwer, K. C., Tanzi, R. E., Chopra, D., Mills, P. J. 2020; 26 (7): 547-556

  Abstract

  Editor's Note: As an acute condition quickly associated with multiple chronic susceptibilities, COVID-19 has rekindled interest in, and controversy about, the potential role of the host in disease processes. While hundreds of millions of research dollars have been funneled into drug and vaccine solutions that target the external agent, integrative practitioners tuned to enhancing immunity faced a familiar mostly unfunded task. First, go to school on the virus. Then draw from the global array of natural therapies and practices with host-enhancing or anti-viral capabilities to suggest integrative treatment strategies. The near null-set of conventional treatment options propels this investigation. In this paper, researchers from the Massachusetts Institute of Technology, University of California-San Diego, Chopra Library for Integrative Studies, and Harvard University share one such exploration. Their conclusion, that "certain meditation, yoga asana (postures), and pranayama (breathing) practices may possibly be effective adjunctive means of treating and/or preventing SARS-CoV-2 infection" underscores the importance of this rekindling. At JACM, we are pleased to have the opportunity to publish this work. We hope that it might help diminish in medicine and health the polarization that, like so much in the broader culture, seems to be an obstacle to healing. -John Weeks, Editor-in-Chief, JACM.

  View details for DOI 10.1089/acm.2020.0177

  View details for PubMedID 32579021

• Association of stress-related sleep disturbance with psychiatric symptoms among pregnant women. Sleep medicine Sanchez, S. E., Friedman, L. E., Rondon, M. B., Drake, C. L., Williams, M. A., Gelaye, B. 2020; 70: 27-32

  Abstract

  Physiological changes during pregnancy are often accompanied by reduced sleep quality, sleep disruptions, and insomnia. Studies conducted among men and non-pregnant women have documented psychiatric disorders as common comorbidities of insomnia and other sleep disorders. However, no previous study has examined the association between stress-related sleep disturbances and psychiatric disorders among pregnant women.This cross-sectional study included a total of 2051 pregnant women in Peru. The Spanish-language version of the Ford Insomnia Response to Stress Test (FIRST-S) was used to assess sleep disruptions due to stressful situations. Symptoms of antepartum depression, generalized anxiety disorder, and posttraumatic stress disorder (PTSD) were examined using the Patient Health Questionnaire-9, Generalized Anxiety Disorder Scale-7 and PTSD Checklist - Civilian Version, respectively. High risk for psychosis was assessed using the Prodromal Questionnaire. Multivariable logistic regression procedures were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CI).Stress-related sleep disturbance was reported by 33.2% of women. Of all women, 24.9% had antepartum depression, 32.2% had generalized anxiety disorder, 30.9% had PTSD, and 27.6% were assessed as having a high risk of psychosis. After adjusting for confounders, women with stress-related sleep disturbances were more likely to experience antepartum depression (OR = 2.74; 95%CI: 2.22-3.38), generalized anxiety disorder (OR = 2.48; 95%CI: 2.04-3.02), PTSD (OR = 2.36; 95%CI: 1.93-2.88), and high risk for psychosis (OR = 2.07; 95%CI: 1.69-2.54) as compared to women without stress-related sleep disturbances.Stress-related sleep disturbances during pregnancy are associated with increased odds of psychiatric disorders. Inquiring about stress related sleep disturbances during antenatal care may be beneficial for identifying and caring for women at high risk of psychiatric disorders.

  View details for DOI 10.1016/j.sleep.2020.02.007

  View details for PubMedID 32193051

  View details for PubMedCentralID PMC8875285

• Leisure Time Physical Activity, Sedentary Time in Pregnancy, and Infant Weight at Approximately 12 Months. Women's health reports (New Rochelle, N.Y.) Badon, S. E., Littman, A. J., Chan, K. C., Williams, M. A., Kirkegaard, H., Nohr, E. A., Enquobahrie, D. A. 2020; 1 (1): 123-131

  Abstract

  Background: Maternal leisure time physical activity (LTPA) and sedentary time during pregnancy may influence programming of infant growth in a sex-specific manner. Materials and Methods: Participants (N = 35,212) from the Danish National Birth Cohort reported moderate/vigorous LTPA (hours/week) in early (conception to mean 16 weeks of gestation) and late pregnancy (mean 31 weeks of gestation to delivery) during interviews at 16 weeks of gestation and 6 months postpartum. Participants reported screen time at work and time spent watching television/videos (hours/day) in early pregnancy. Infant weight at 12 months of age was reported by mothers. Weight-for-length was categorized using sex-specific international standards. Results: Participants reported on average 1 hour per week of early pregnancy moderate/vigorous LTPA, 0.5 hour per week of late pregnancy LTPA, and 3 hours per day of early pregnancy sedentary time. Early pregnancy LTPA category was not associated with infant weight (p for trend = 0.62). There were suggested associations of early pregnancy sedentary time above the first quartile with greater odds of infant underweight (odds ratio = 1.15-1.27; p for trend = 0.27). Associations were similar in male and female infants. Conclusions: There is no clear relationship between early or late pregnancy LTPA and infant weight at 12 months in our study. Maternal early pregnancy sedentary time may be associated with infant underweight at 12 months.

  View details for DOI 10.1089/whr.2020.0068

  View details for PubMedID 32617532

  View details for PubMedCentralID PMC7325488

• Association of social support and antepartum depression among pregnant women. Journal of affective disorders Friedman, L. E., Gelaye, B., Sanchez, S. E., Williams, M. A. 2020; 264: 201-205

  Abstract

  Few investigators have evaluated the association between early pregnancy social support and depression; however, increased social support may improve mental health during pregnancy. Our objective is to examine whether in early pregnancy there is an association between social support and maternal depression among women in Peru.2,062 pregnant women participated in structured interviews. Early pregnancy social support was measured using the Social Support Questionnaire (SSQ-6). We evaluated the number of individuals that participants could turn to in different situations (Social Support Number Score; SSQN) and their satisfaction with support received (Social Support Satisfaction Score; SSQS). Median SSQN and SSQS characterized participants according to high and low levels of support. SSQN family vs. non-family support were also evaluated separately. Antepartum depression was assessed using the Patient Health Questionnaire-9. Multivariable logistic regression procedures were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).39.6% of women reported high SSQN and 45.5% reported high SSQS. Approximately 25% had antepartum depression. Women with high SSQN had 22% lower odds of antepartum depression (OR = 0.78; 95%CI: 0.63-0.97). Similarly, women with high SSQS scores had 45% lower odds of antepartum depression (OR = 0.55; 95%CI: 0.45-0.68). Women with high SSQN non-family scores had 30% lower odds antepartum depression compared to those with low SSQN non-family scores (OR = 0.70; 95%CI: 0.57-0.86). The association between SSQN family scores and antepartum depression did not reach statistical significance.Increased social support may improve maternal mental health during pregnancy and this association should be assessed in longitudinal studies.

  View details for DOI 10.1016/j.jad.2019.12.017

  View details for PubMedID 32056751

• Pre-marital predictors of marital violence in the WHO World Mental Health (WMH) Surveys. Social psychiatry and psychiatric epidemiology Stokes, C. M., Alonso, J., Andrade, L. H., Atwoli, L., Cardoso, G., Chiu, W. T., Dinolova, R. V., Gureje, O., Karam, A. N., Karam, E. G., Kessler, R. C., Chatterji, S., King, A., Lee, S., Mneimneh, Z., Oladeji, B. D., Petukhova, M., Rapsey, C., Sampson, N. A., Scott, K., Street, A., Viana, M. C., Williams, M. A., Bossarte, R. M. 2020; 55 (3): 393-405

  Abstract

  Intimate partner violence (IPV) is a pervasive public health problem. Existing research has focused on reports from victims and few studies have considered pre-marital factors. The main objective of this study was to identify pre-marital predictors of IPV in the current marriage using information obtained from husbands and wives.Data from were obtained from married heterosexual couples in six countries. Potential predictors included demographic and relationship characteristics, adverse childhood experiences, dating violence, and psychiatric disorders. Reports of IPV and other characteristics from husbands and wives were considered independently and in relation to spousal reports.Overall, 14.4% of women were victims of IPV in the current marriage. Analyses identified ten significant variables including age at first marriage (husband), education, relative number of previous marriages (wife), history of one or more categories of childhood adversity (husband or wife), history of dating violence (husband or wife), early initiation of sexual intercourse (husband or wife), and four combinations of internalizing and externalizing disorders. The final model was moderately predictive of marital violence, with the 5% of women accounting for 18.6% of all cases of marital IPV.Results from this study advance understanding of pre-marital predictors of IPV within current marriages, including the importance of considering differences in the experiences of partners prior to marriage and may provide a foundation for more targeted primary prevention efforts.

  View details for DOI 10.1007/s00127-019-01703-z

  View details for PubMedID 30993376

  View details for PubMedCentralID PMC7410347

• The association between abuse history in childhood and salivary rhythms of cortisol and DHEA in postmenopausal women. Psychoneuroendocrinology Orta, O. R., Huang, T., Kubzansky, L. D., Terry, K. L., Coull, B. A., Williams, M. A., Tworoger, S. S. 2020; 112: 104515

  Abstract

  A history of child abuse (CA) is associated with morbidity and mortality in adulthood, and one proposed mechanism is dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Therefore, we evaluated whether a history of physical and sexual CA was associated with daily rhythms of HPA hormones (cortisol and dehydroepiandrosterone (DHEA)) among postmenopausal women (mean age: 60.6 years). In 2013, 233 participants from the Nurses' Health Study II provided up to 5-timed saliva samples over the course of a day: immediately upon awakening, 45 min, 4 h, and 10 h after waking, and prior to going to sleep. Among these 233 participants, 217 provided ≥4 timed saliva samples. Assessment of physical and sexual CA history occurred in 2001 using the Revised Conflict Tactics Scale. Cumulative CA history was derived by combining reports of physical and sexual abuse prior to age 18. Piecewise linear mixed models compared diurnal rhythms of cortisol and DHEA between participants with none-to-moderate CA (n = 104, reference group) versus high-to-severe CA (n = 113). Models adjusted for characteristics at each saliva collection, health status, sleep quality, medications, and hormone use. Compared to those with none-to-moderate CA, women with high-to-severe CA had different diurnal rhythms in the early and evening hours, including blunted (less steep) early declines in DHEA (% difference (%D) = 10.7, 95 % Confidence Interval (CI) 4.3, 17.5), and steeper late declines in both cortisol and DHEA (cortisol %D = -2.5, 95 % CI -4.8, -0.1, and DHEA %D= -3.9, 95 % CI -6.0, -1.8). In conclusion, high-to-severe abuse history prior to age 18 was more strongly associated with differences in DHEA rather than cortisol, suggesting that early life abuse may be related to dysregulation of stress-response mechanisms later in life.

  View details for DOI 10.1016/j.psyneuen.2019.104515

  View details for PubMedID 31784054

  View details for PubMedCentralID PMC6935398

• Association of antepartum depression, generalized anxiety, and posttraumatic stress disorder with infant birth weight and gestational age at delivery. Journal of affective disorders Gelaye, B., Sanchez, S. E., Andrade, A., Gómez, O., Coker, A. L., Dole, N., Rondon, M. B., Williams, M. A. 2020; 262: 310-316

  Abstract

  Low- and middle-income countries bear a disproportionate burden of preterm birth (PTB) and low infant birth weight (LBW) complications where affective and anxiety disorders are more common in the antepartum period than in industrialized countries.To evaluate the extent to which early pregnancy antepartum depression, generalized anxiety disorder, and posttraumatic stress disorder (PTSD) are associated with infant birth weight and gestational age at delivery among a cohort of pregnant women in Peru.Our prospective cohort study consisted of 4408 pregnant women. Antepartum depression, generalized anxiety, and PTSD were assessed in early pregnancy using the Patient Health Questionnaire-9, Generalized Anxiety Disorder Scale-7 and PTSD Checklist - Civilian Version, respectively. Pregnancy outcome data were obtained from medical records. Multivariable linear and logistic regression procedures were used to estimate adjusted measures of association (β coefficients and odds ratios) and 95% confidence intervals (CI).After adjusting for confounders, women with antepartum generalized anxiety (32.6% prevalence) had higher odds of LBW (adjusted odds ratio (OR)=1.47; 95%CI: 1.10-1.95) and were more likely to deliver small for gestational age (OR = 1.39; 95%CI: 1.01-1.92) infants compared to those without anxiety. Compared to those without PTSD, women with PTSD (34.5%) had higher odds of delivering preterm (OR = 1.28; 95%CI: 1.00-1.65) yet PTSD was not associated with LBW nor gestational age at delivery. Women with antepartum depression (26.2%) were at no increased risk of delivering a preterm, low-birth-weight or small-for-gestational-age infant.Our ability to make casual inferences from this observational study is limited; however, these findings are consistent with prior studies.Generalized anxiety disorder during pregnancy appeared to increase odds of delivering a low-birth-weight or small-for-gestational-age infant, while PTSD was associated with increased odds of delivering preterm. Our findings, and those of others, suggest antenatal care should be tailored to screen for and provide additional mental health services to patients.

  View details for DOI 10.1016/j.jad.2019.11.006

  View details for PubMedID 31733923

  View details for PubMedCentralID PMC7048002

• Metabolomic markers of antepartum depression and suicidal ideation. Journal of affective disorders Mitro, S. D., Larrabure-Torrealva, G. T., Sanchez, S. E., Molsberry, S. A., Williams, M. A., Clish, C., Gelaye, B. 2020; 262: 422-428

  Abstract

  Recent analyses have described metabolomic markers for depression and suicidal ideation in non-pregnant adults. We examined the metabolomic profile of antepartum depression and suicidal ideation during mid-pregnancy, a time of high susceptibility to mood disorders.We collected fasting blood from 100 pregnant Peruvian women and profiled 307 plasma metabolites using liquid chromatography-mass spectrometry. We used the Patient Health Questionnaire 9 to define antepartum depression (score  ≥ 10) and suicidal ideation (having thoughts that you would be better off dead, or of hurting yourself). Logistic regression was used to calculate odds ratios (ORs).Three triacylglycerol metabolites (C48:5 triacylglycerol [OR = =1.89; 95% confidence interval (CI): 1.14-3.14], C50:6 triacylglycerol [OR = =1.88; 95%CI: 1.13-3.14], C46:4 triacylglycerol [OR = =1.89; 95%CI: 1.11-3.21]) were associated with higher odds of antepartum depression and 4 metabolites (betaine [OR = =0.56; 95%CI:0.33-0.95], citrulline [OR = =0.58; 95%CI: 0.34-0.98], C5 carnitine [OR = =0.59; 95%CI: 0.36-0.99], C5:1 carnitine [OR = =0.59; 95%CI: 0.35-1.00]) with lower odds of antepartum depression. Twenty-six metabolites, including 5-hydroxytryptophan (OR = =0.52; 95%CI: 0.30-0.92), phenylalanine (OR = =0.41; 95%CI: 0.19-0.91), and betaine (OR = =0.53; 95%CI: 0.28-0.99) were associated with lower odds of suicidal ideation.Our cross-sectional study could not determine whether metabolites prospectively predict outcomes. No metabolites remained significant after multiple testing correction; these novel findings should be replicated in a larger sample.Antepartum suicidal ideation metabolomic markers are similar to markers of depression among non-pregnant adults, and distinct from markers of antepartum depression. Findings suggest that mood disorder in pregnancy shares metabolomic similarities to mood disorder at other times and may further understanding of these conditions' pathophysiology.

  View details for DOI 10.1016/j.jad.2019.11.061

  View details for PubMedID 31744743

  View details for PubMedCentralID PMC6917910

• Fitness and Fatness Are Both Associated with Cardiometabolic Risk in Preadolescents. The Journal of pediatrics Stoner, L., Pontzer, H., Barone Gibbs, B., Moore, J. B., Castro, N., Skidmore, P., Lark, S., Williams, M. A., Hamlin, M. J., Faulkner, J. 2020; 217: 39-45.e1

  Abstract

  To determine the associations between cardiorespiratory fitness (CRF) and fatness (overweight-obesity) with cardiometabolic disease risk among preadolescent children.This cross-sectional study recruited 392 children (50% female, 8-10 years of age). Overweight-obesity was classified according to 2007 World Health Organization criteria for body mass index. High CRF was categorized as a maximum oxygen uptake, determined using a shuttle run test, exceeding 35 mL·kg-1·minute-1 in girls and 42 mL·kg-1·minute-1 in boys. Eleven traditional and novel cardiometabolic risk factors were measured including lipids, glucose, glycated hemoglobin, peripheral and central blood pressure, and arterial wave reflection. Factor analysis identified underlying cardiometabolic disease risk factors and a cardiometabolic disease risk summary score. Two-way analysis of covariance determined the associations between CRF and fatness with cardiometabolic disease risk factors.Factor analysis revealed four underlying factors: blood pressure, cholesterol, vascular health, and carbohydrate-metabolism. Only CRF was significantly (P = .001) associated with the blood pressure factor. Only fatness associated with vascular health (P = .010) and carbohydrate metabolism (P = .005) factors. For the cardiometabolic disease risk summary score, there was an interaction effect. High CRF was associated with decreased cardiometabolic disease risk in overweight-obese but not normal weight children (P = .006). Conversely, high fatness was associated with increased cardiometabolic disease risk in low fit but not high fit children (P < .001).In preadolescent children, CRF and fatness explain different components of cardiometabolic disease risk. However, high CRF may moderate the relationship between fatness and cardiometabolic disease risk.ACTRN 12614000433606.

  View details for DOI 10.1016/j.jpeds.2019.09.076

  View details for PubMedID 31759583

• Vaginal microbiome diversity and preterm birth: results of a nested case-control study in Peru. Annals of epidemiology Blostein, F., Gelaye, B., Sanchez, S. E., Williams, M. A., Foxman, B. 2020; 41: 28-34

  Abstract

  Preterm birth (PTB) is a major cause of neonatal mortality. The vaginal microbiome is associated with PTB, but results vary across racial/ethnic populations. Some evidence suggests gestational age affects this association. We investigated these associations in a novel population, conducting a post hoc analysis assessing if associations differed between women swabbed at different gestational ages.We compared vaginal microbiomes from women with PTB (n = 25) to a random sample of women with term births (n = 100) among participants in the Pregnancy Outcomes, Maternal and Infant Study, conducted in Lima, Peru. Using DADA2, we identified taxa from 16S DNA sequencing and used Dirichlet multinomial mixture models to group into community state types (CSTs).If gestational age at sampling was not considered, no CST (diverse, Lactobacillus-dominated or Lactobacillus iners-dominated), was associated with PTB. Among women sampled before 12 weeks' gestation, women with Lactobacillus-dominated CSTs were less likely to have a PTB than those with a diverse CST. Among those swabbed between 12 and 16 weeks' gestation, the reverse was true.Our study supports previous literature suggesting that what constitutes a healthy vaginal microbiome varies by race/ethnicity. Longitudinal studies are necessary to disentangle effects of vaginal microbiome differences over gestation.

  View details for DOI 10.1016/j.annepidem.2019.11.004

  View details for PubMedID 31883841

  View details for PubMedCentralID PMC7024011

• Using A Body Shape Index (ABSI) and Body Roundness Index (BRI) to predict risk of metabolic syndrome in Peruvian adults. The Journal of international medical research Stefanescu, A., Revilla, L., Lopez, T., Sanchez, S. E., Williams, M. A., Gelaye, B. 2020; 48 (1): 300060519848854

  Abstract

  We examined the ability of anthropometric measures to predict the risk of metabolic syndrome (MetS) and its components in Peruvian adults.Participants were 1,815 Peruvian adults. Body mass index (BMI), waist circumference (WC), A Body Shape Index (ABSI), Body Roundness Index (BRI) and Visceral Adiposity Index were examined. MetS components were defined using the National Cholesterol Education Program’s Adult Treatment Panel III. Logistic regression was used to calculate odds ratios of MetS and MetS components in relation to increases in anthropometric measures. Receiver operating characteristic curves (and area under the curve) were calculated to compare each measure’s power to predict MetS and MetS components.BRI performed similar to or better than BMI and WC at predicting MetS and MetS components. ABSI underperformed other measures. In men, the odds of MetS and its components increased with unit increases in the anthropometric measures (e.g. a unit increase in BRI was associated with 2.43-fold increased odds of MetS; 95% confidence interval [CI]: 1.95–3.02). A similar association was found for women (odds ratio: 1.89; 95% CI: 1.68–2.12).Our study is the first to identify BRI as a potentially useful clinical predictor of MetS in Peruvian adults.

  View details for DOI 10.1177/0300060519848854

  View details for PubMedID 31144540

  View details for PubMedCentralID PMC7140225

• Secular trends in stillbirth by maternal socioeconomic status in Spain 2007-15: a population-based study of 4 million births. European journal of public health Luque-Fernandez, M. A., Thomas, A., Gelaye, B., Racape, J., Sanchez, M. J., Williams, M. A. 2019; 29 (6): 1043-1048

  Abstract

  Stillbirth, one of the urgent concerns of preventable perinatal deaths, has wide-reaching consequences for society. We studied secular stillbirth trends by maternal socioeconomic status (SES) in Spain.We developed a population-based observational study, including 4 083 919 births during 2007-15. We estimate stillbirth rates and secular trends by maternal SES. We also evaluated the joint effect of maternal educational attainment and the Human Development Index (HDI) of women's country of origin on the risk of stillbirth. The data and statistical analysis can be accessed for reproducibility in a GitHub repository: https://github.com/migariane/Stillbirth.We found a consistent pattern of socioeconomic inequalities in the risk of delivering a stillborn, mainly characterized by a persistently higher risk, over time, among women with lower SES. Overall, women from countries with low HDIs and low educational attainments had approximately a four times higher risk of stillbirth (RR: 4.44; 95%CI: 3.71-5.32). Furthermore, we found a paradoxical reduction of the stillbirth gap over time between the highest and the lowest SESs, which is mostly due to the significant and increasing trend of stillbirth risk among highly educated women of advanced maternal age.Our findings highlight no improvement in stillbirth rates among women of lower SES and an increasing trend among highly educated women of advanced maternal age over recent years. Public health policies developing preventive programmes to reduce stillbirth rates among women with lower SES are needed as well as the necessity of further study to understand the growing trend of age-related stillbirths among highly educated women in Spain.

  View details for DOI 10.1093/eurpub/ckz086

  View details for PubMedID 31121034

  View details for PubMedCentralID PMC6896972

• Relation of outbursts of anger and the acute risk of placental abruption: A case-crossover study. Paediatric and perinatal epidemiology Chahal, H. S., Gelaye, B., Mostofsky, E., Salazar, M. S., Sanchez, S. E., Ananth, C. V., Williams, M. A. 2019; 33 (6): 405-411

  Abstract

  Roughly, a fourth of all placental abruption cases have an acute aetiologic underpinning, but the causes of acute abruption are poorly understood. Studies indicate that symptoms of stress, depression, and anxiety during pregnancy may be associated with a higher risk of abruption.We examined the rate of abruption in the 2 hours immediately following outbursts of anger.In a multicentre case-crossover study, we interviewed 663 women diagnosed with placental abruption admitted to one of the seven Peruvian hospitals between January 2013 and August 2015. We asked women about outbursts of anger before symptom onset and compared this with their usual frequency of anger during the week before abruption.The rate of abruption was 2.83-fold (95% confidence interval [CI] 1.85, 4.33) higher in the 2 hours following an outburst of anger compared with other times. The rate ratio (RR) was lower for women who completed technical school or university (RR 1.38, 95% CI 0.52, 3.69) compared to women with secondary school education or less (RR 3.73, 95% CI 2.32, 5.99, P-homogeneity = .07). There was no evidence that the association between anger episodes and abruption varied by hypertensive disorders of pregnancy (ie preeclampsia/ eclampsia) or antepartum depressive symptoms.There was a higher rate of abruption in the 2 hours following outbursts of anger compared with other times, providing potential clues to the aetiologic mechanisms of abruption of acute onset.

  View details for DOI 10.1111/ppe.12591

  View details for PubMedID 31642555

  View details for PubMedCentralID PMC6823109

• Cerebrovascular disease after placental abruption: A population-based prospective cohort study. Neurology Ananth, C. V., Hansen, A. V., Elkind, M. S., Williams, M. A., Rich-Edwards, J. W., Nybo Andersen, A. M. 2019; 93 (12): e1148-e1158

  Abstract

  To test whether abruption during pregnancy is associated with long-term cerebrovascular disease by assessing the incidence and mortality from stroke among women with abruption.We designed a population-based prospective cohort study of women who delivered in Denmark from 1978 to 2010. We used data from the National Patient Registry, Causes of Death Registry, and Danish Birth Registry to identify women with abruption, cerebrovascular events, and deaths. The outcomes included deaths resulting from stroke and nonfatal ischemic and hemorrhagic strokes. We fit Cox proportional hazards regression models for stroke outcomes, adjusting for the delivery year, parity, education, and smoking.The median (interquartile range) follow-up in the nonabruption and abruption groups was 15.9 (7.8-23.8) and 16.2 (9.6-23.1) years, respectively, among 828,289 women with 13,231,559 person-years of follow-up. Cerebrovascular mortality rates were 0.8 and 0.5 per 10,000 person-years among women with and without abruption, respectively (hazard ratio [HR] 1.6, 95% confidence interval [CI] 0.9-3.0). Abruption was associated with increased rates of nonfatal ischemic stroke (HR 1.4, 95% CI 1.1-1.7) and hemorrhagic stroke (HR 1.4, 95% CI 1.1-1.9). The association of abruption and stroke was increased with delivery at <34 weeks, when accompanied by ischemic placental disease, and among women with ≥2 abruptions. These associations are less likely to have been affected by unmeasured confounding.Abruption is associated with increased risk of cerebrovascular morbidity and mortality. Disruption of the hemostatic system manifesting as ischemia and hemorrhage may indicate shared etiologies between abruption and cerebrovascular complications.

  View details for DOI 10.1212/WNL.0000000000008122

  View details for PubMedID 31420459

• Food Consumption Patterns and Body Composition in Children: Moderating Effects of Prop Taster Status. Nutrients Stoner, L., Castro, N., Kucharska-Newton, A., Smith-Ryan, A. E., Lark, S., Williams, M. A., Faulkner, J., Skidmore, P. 2019; 11 (9)

  Abstract

  This cross-sectional study determined whether 6-n-propylthiouracil (PROP) taster status moderates the relationship between food consumption patterns and body composition in children. Children were recruited (n = 342, 50% female, 8-10 y) from across New Zealand. Using a food frequency questionnaire, these food consumption patterns were derived: Processed Foods, Fruit and Vegetables, and Breakfast Foods. Body composition variables included: body fat (%), fat mass (kg), fat mass index (FMI, kg/m2), body mass index (kg/m2) and waist to height ratio (W:Ht). Following adjustment for confounders, Processed Foods were positively associated with %fat (p = 0.015), fat mass (p = 0.004) and FMI (p = 0.016). Taste test strips determined PROP status. For Breakfast Foods, there were small negative associations with all body composition variables (p ≤ 0.001 to 0.037). The population sample was also stratified by PROP taster status. For the non-tasters, there were small to moderate negative associations between Breakfast Foods and each body composition variable (p = 0.003-0.045) except W:Ht (p = 0.112), and these relationships were stronger for girls compared to boys. For the tasters, there were small to moderate positive associations between Processed Foods with %fat (p = 0.030), fat mass (p ≤ 0.001) and FMI (p = 0.014). In conclusion, sensitivity to bitterness may moderate the relationship between food consumption patterns and body composition in children.

  View details for DOI 10.3390/nu11092037

  View details for PubMedID 31480416

  View details for PubMedCentralID PMC6770641

• Physical Exertion Immediately Before Early Preterm Delivery: A Case-Crossover Study. Epidemiology (Cambridge, Mass.) Chahal, H. S., Gelaye, B., Mostofsky, E., Sanchez, S. E., Mere, J. F., Mercado, F. G., Pacora, P., Williams, M. A. 2019; 30 (4): 582-589

  Abstract

  Occupational exertion is associated with a higher risk of preterm delivery, although studies of leisure time activities generally document reduced risks. Less is known about the risk of preterm delivery immediately following episodes of moderate or heavy physical exertion.We conducted a case-crossover study of 722 women interviewed during their hospital stay for early preterm delivery, defined by a gestational age before 34 weeks, and after 20 weeks. Interviews occurred between March 2013 and December 2015 in seven hospitals in Lima, Peru.The incidence rate ratio (RR) of early preterm delivery was 5.82-fold higher (95% confidence interval [CI] = 4.29, 7.36) in the hour following moderate or heavy physical exertion compared with other times and returned to baseline in the hours thereafter. The RR of early preterm delivery within an hour of physical exertion was lower for exertion at moderate intensity (RR = 2.43; 95% CI = 1.50, 3.96) than at heavy intensity (RR = 23.62; 95% CI = 15.54, 35.91; P-homogeneity < 0.001). The RR of early preterm delivery was lower in the hour following moderate physical exertion among women who habitually engaged in physical exertion >3 times per week in the year before pregnancy (RR = 1.56; 95% CI = 0.81, 3.00) compared with more sedentary women (RR = 6.91; 95% CI = 3.20, 14.92; P-homogeneity = 0.003).Our study showed a heightened risk of early preterm delivery in the hour following moderate or heavy physical exertion.

  View details for DOI 10.1097/EDE.0000000000001008

  View details for PubMedID 31166217

  View details for PubMedCentralID PMC6553497

• Workplace interventions for intimate partner violence: A systematic review. Journal of workplace behavioral health Adhia, A., Gelaye, B., Friedman, L. E., Marlow, L. Y., Mercy, J. A., Williams, M. A. 2019; 34 (3)

  Abstract

  Workplace interventions represent important opportunities to increase awareness of and adherence to disease prevention and health promotion initiatives. However, research on workplace interventions for intimate partner violence (IPV) has not been systematically evaluated. This systematic review summarizes existing studies evaluating workplace interventions for IPV. PubMed, PsycINFO, Business Source Complete, Web of Science, and Social Services Abstracts were systematically searched for English-language studies published before November 2017. Six studies evaluating five interventions were included. Only one study used a randomized design, and only two studies measured whether outcomes were sustained over time. None of the interventions addressed perpetrators of IPV. Interventions focused on recognizing signs of abuse, responding to victims, and providing referrals to community-based resources. Methodological rigor of included studies varied, but all reported at least one intervention-related benefit. Findings included improved awareness of IPV, increased provision of information to victims, and greater willingness to intervene if an employee may be experiencing IPV. Although sparse, available evidence suggests there are potential benefits of workplace interventions for IPV. It is important for future interventions to focus on primary and secondary prevention of IPV and address perpetration, and for investigators to use rigorous study designs and measure whether effects are sustained.

  View details for DOI 10.1080/15555240.2019.1609361

  View details for PubMedID 32322182

  View details for PubMedCentralID PMC7176402

• Associations of antepartum suicidal behaviour with adverse infant and obstetric outcomes. Paediatric and perinatal epidemiology Zhong, Q. Y., Gelaye, B., Karlson, E. W., Avillach, P., Smoller, J. W., Cai, T., Williams, M. A. 2019; 33 (2): 137-144

  Abstract

  Relatively little is known about antepartum suicidal behaviour and pregnancy outcomes. We examined associations of antepartum suicidal behaviour, alone and in combination with psychiatric disorders, with adverse infant and obstetric outcomes.We included 188 925 singleton livebirths from a retrospective cohort (1996-2016). Suicidal behaviour, psychiatric disorders, and outcomes were derived from electronic medical records. We performed multivariable logistic regressions with generalised estimating equations to estimate adjusted odds ratios (aOR) with 95% confidence intervals (95%CI).The prevalence of antepartum suicidal behaviour was 152.44 per 100 000 singleton livebirths. Nearly two-thirds (64.24%) of women with suicidal behaviour also had psychiatric disorders. Compared to women without psychiatric disorders and suicidal behaviour, women with psychiatric disorders alone had 1.3-fold to 1.4-fold increased odds of delivering low birthweight or preterm infants and 1.2-fold increased odds of experiencing obstetric complications. Women with suicidal behaviour alone had increased odds of preterm labour (aOR 2.05, 95% CI 1.16, 3.62). Women with both suicidal behaviour and psychiatric disorders had > twofold increased odds of delivering low birthweight (aOR 2.52, 95% CI 1.40, 4.54), preterm birth (aOR 2.44, 95% CI 1.63, 3.66), and low birthweight/preterm birth (aOR 2.30, 95% CI 1.54, 3.44) infants; the odds of preterm labour (aOR 1.62, 95% CI 1.06, 2.47), placental abruption (aOR 2.33, 95% CI 1.20, 4.51), preterm rupture of membranes (aOR 1.63, 95% CI 1.08, 2.46), and postpartum haemorrhage (aOR 1.93, 95%CI 1.09, 3.40) were elevated.Antepartum suicidal behaviour, when co-occurring with psychiatric disorders, is associated with increased odds of adverse infant and obstetric outcomes. Future studies are warranted to understand the causal roles of suicidal behaviour and psychiatric disorders in pregnancy.

  View details for DOI 10.1111/ppe.12535

  View details for PubMedID 30790331

• Childhood abuse, intimate partner violence, and placental abruption among Peruvian women. Annals of epidemiology Mitro, S. D., Sanchez, S. E., Palomino, H., Gelaye, B., Williams, M. A. 2019; 31: 26-31

  Abstract

  Experiencing childhood abuse (CA) or intimate partner violence (IPV) has been linked to adverse pregnancy outcomes. We examined whether CA history and current IPV are independently and jointly associated with placental abruption (PA).We recruited 662 PA cases and 665 controls in Lima, Peru. We used multivariate logistic regression to calculate odds ratios (OR), adjusting for age, education, and parity.Approximately 42% of cases and controls reported CA; 50% of cases and 49% of controls reported IPV. History of any CA was not associated with PA, but history of severe CA was associated with 38% increased odds of PA (adjusted OR [aOR], 1.38; 95% confidence interval (CI), 1.07-1.80), adjusting for IPV. There was a statistically nonsignificant association between severe IPV and odds of PA (aOR, 1.22; 95% CI, 0.92-1.62), adjusting for CA. Women who experienced severe CA and severe IPV had 2.06-fold (95% CI, 1.25-3.40) increased odds of PA compared with women who did not experience severe abuse. The joint effect of CA and IPV was positive but statistically nonsignificant on the multiplicative (aOR, 1.48; 95% CI, 0.79-2.80) and additive scale (relative excess risk due to interaction, 0.70; 95% CI, -0.39 to 1.78).Preventing exposure to violence may improve maternal outcomes.

  View details for DOI 10.1016/j.annepidem.2018.12.003

  View details for PubMedID 30606468

  View details for PubMedCentralID PMC6420388

• Childhood Assets and Cardiometabolic Health in Adolescence. Pediatrics Qureshi, F., Koenen, K. C., Tiemeier, H., Williams, M. A., Misra, S., Kubzansky, L. D. 2019; 143 (3)

  Abstract

  Research shows that the development of cardiometabolic disease can begin early in life with risk factors accumulating over time, but less is known about protective pathways to positive health. In this study, we use prospective data to test whether childhood assets predict a greater likelihood of being in optimal cardiometabolic health by age 17.Data are from 3074 participants in the Avon Longitudinal Study of Parents and Children (mean age = 17.8). Four childhood assets were prospectively assessed via cognitive tests and parent report when children were between ages 8 and 10: strong executive functioning skills, prosocial behaviors, and low levels of internalizing and externalizing problems. Cardiometabolic health was assessed at ages 9 and 17 by using a composite dysregulation score derived from multiple biological parameters, including cholesterol, blood pressure, C-reactive protein, insulin resistance, and BMI. Associations between assets and optimal health at age 17 (ie, a dysregulation score of ≤1) were evaluated with Poisson regression models with robust error variances.After controlling for covariates (including sociodemographics, correlates of cardiometabolic health, and dysregulation scores at age 9), participants with multiple assets were 1.08 to 1.27 times more likely to be in optimal cardiometabolic health at age 17 compared with those with 0 or 1 asset. Each additional asset conferred a 6% greater likelihood of optimal health over time (relative risk = 1.06 [95% confidence interval: 1.01 to 1.11]).Childhood assets predicted cardiometabolic health with seemingly cumulative impacts. Identifying early assets may provide novel targets for prevention and elucidate pathways to positive adult health.

  View details for DOI 10.1542/peds.2018-2004

  View details for PubMedID 30718380

  View details for PubMedCentralID PMC6398368

• Use of natural language processing in electronic medical records to identify pregnant women with suicidal behavior: towards a solution to the complex classification problem. European journal of epidemiology Zhong, Q. Y., Mittal, L. P., Nathan, M. D., Brown, K. M., Knudson González, D., Cai, T., Finan, S., Gelaye, B., Avillach, P., Smoller, J. W., Karlson, E. W., Cai, T., Williams, M. A. 2019; 34 (2): 153-162

  Abstract

  We developed algorithms to identify pregnant women with suicidal behavior using information extracted from clinical notes by natural language processing (NLP) in electronic medical records. Using both codified data and NLP applied to unstructured clinical notes, we first screened pregnant women in Partners HealthCare for suicidal behavior. Psychiatrists manually reviewed clinical charts to identify relevant features for suicidal behavior and to obtain gold-standard labels. Using the adaptive elastic net, we developed algorithms to classify suicidal behavior. We then validated algorithms in an independent validation dataset. From 275,843 women with codes related to pregnancy or delivery, 9331 women screened positive for suicidal behavior by either codified data (N = 196) or NLP (N = 9,145). Using expert-curated features, our algorithm achieved an area under the curve of 0.83. By setting a positive predictive value comparable to that of diagnostic codes related to suicidal behavior (0.71), we obtained a sensitivity of 0.34, specificity of 0.96, and negative predictive value of 0.83. The algorithm identified 1423 pregnant women with suicidal behavior among 9331 women screened positive. Mining unstructured clinical notes using NLP resulted in a 11-fold increase in the number of pregnant women identified with suicidal behavior, as compared to solely reliance on diagnostic codes.

  View details for DOI 10.1007/s10654-018-0470-0

  View details for PubMedID 30535584

  View details for PubMedCentralID PMC6370493

• Suicide risk assessment: examining transitions in suicidal behaviors among pregnant women in Perú. Archives of women's mental health Levey, E. J., Rondon, M. B., Sanchez, S., Zhong, Q. Y., Williams, M. A., Gelaye, B. 2019; 22 (1): 65-73

  Abstract

  The goals of this research were to characterize suicidal behavior among a cohort of pregnant Peruvian women and identify risk factors for transitions between behaviors. The World Health Organization Composite International Diagnostic Interview suicide questionnaire was employed to assess suicidal behavior. Discrete-time survival analysis was used to study the cumulative age-of-onset distribution. The hazard function was calculated to assess the risk of onset of each suicidal behavior. Among 2062 participants, suicidal behaviors were endorsed by 22.6% of participants; 22.4% reported a lifetime history of suicidal ideation, 7.2% reported a history of planning, and 6.0% reported attempting suicide. Childhood abuse was most strongly associated with suicidal behavior, accounting for a 2.57-fold increased odds of suicidal ideation, nearly 3-fold increased odds of suicide planning, and 2.43-fold increased odds of suicide attempt. This study identified the highest prevalence of suicidal behavior in a population of pregnant women outside the USA. Diverse populations of pregnant women and their patterns of suicidal behavior transition must be further studied. The association between trauma and suicidal behavior indicates the importance of trauma-informed care for pregnant women.

  View details for DOI 10.1007/s00737-018-0884-4

  View details for PubMedID 29971552

  View details for PubMedCentralID PMC6571105

• Association of antepartum suicidal ideation during the third trimester with infant birth weight and gestational age at delivery. Psychology, health & medicine Gelaye, B., Domingue, A., Rebelo, F., Friedman, L. E., Qiu, C., Sanchez, S. E., Larrabure-Torrealva, G., Williams, M. A. 2019; 24 (2): 127-136

  Abstract

  Antepartum suicidal behaviors are a leading cause of maternal injury and death. Previous research has not investigated associations between antepartum suicidal ideation and perinatal complications. Our study objective was to evaluate the relationship of antepartum suicidal ideation with low infant birthweight, small for gestational age, and preterm birth. A cohort study was conducted among 1,108 women receiving prenatal care in Peru. Suicidal ideation was measured using the Patient Health Questionnaire-9 during pregnancy. Birth outcomes were extracted from medical records. Linear regressions and multivariable logistic regressions were used to estimate were used to investigate associations between suicidal ideation and pregnancy outcomes. The prevalence of suicidal ideation was 8.7%, preterm delivery was 5.7%, low birthweight was 4.4%, and small for gestational age was 3.4%. In an adjusted model, infant birthweight was 94.2 grams lower for mothers with antepartum suicidal ideation (95% CI: -183.0, -5.5, p = 0.037) compared with those without suicidal ideation. After adjusting for confounders including depression, participants with suicidal ideation had a nearly four-fold increased odds of delivering a small for gestational age infant (OR: 3.73; 95% CI: 1.59-8.74). These findings suggest suicidal ideation during pregnancy is associated with adverse perinatal outcomes, especially low infant birthweight.

  View details for DOI 10.1080/13548506.2018.1539235

  View details for PubMedID 30376725

  View details for PubMedCentralID PMC6289591

• International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci. Nature communications Nievergelt, C. M., Maihofer, A. X., Klengel, T. n., Atkinson, E. G., Chen, C. Y., Choi, K. W., Coleman, J. R., Dalvie, S. n., Duncan, L. E., Gelernter, J. n., Levey, D. F., Logue, M. W., Polimanti, R. n., Provost, A. C., Ratanatharathorn, A. n., Stein, M. B., Torres, K. n., Aiello, A. E., Almli, L. M., Amstadter, A. B., Andersen, S. B., Andreassen, O. A., Arbisi, P. A., Ashley-Koch, A. E., Austin, S. B., Avdibegovic, E. n., Babić, D. n., Bækvad-Hansen, M. n., Baker, D. G., Beckham, J. C., Bierut, L. J., Bisson, J. I., Boks, M. P., Bolger, E. A., Børglum, A. D., Bradley, B. n., Brashear, M. n., Breen, G. n., Bryant, R. A., Bustamante, A. C., Bybjerg-Grauholm, J. n., Calabrese, J. R., Caldas-de-Almeida, J. M., Dale, A. M., Daly, M. J., Daskalakis, N. P., Deckert, J. n., Delahanty, D. L., Dennis, M. F., Disner, S. G., Domschke, K. n., Dzubur-Kulenovic, A. n., Erbes, C. R., Evans, A. n., Farrer, L. A., Feeny, N. C., Flory, J. D., Forbes, D. n., Franz, C. E., Galea, S. n., Garrett, M. E., Gelaye, B. n., Geuze, E. n., Gillespie, C. n., Uka, A. G., Gordon, S. D., Guffanti, G. n., Hammamieh, R. n., Harnal, S. n., Hauser, M. A., Heath, A. C., Hemmings, S. M., Hougaard, D. M., Jakovljevic, M. n., Jett, M. n., Johnson, E. O., Jones, I. n., Jovanovic, T. n., Qin, X. J., Junglen, A. G., Karstoft, K. I., Kaufman, M. L., Kessler, R. C., Khan, A. n., Kimbrel, N. A., King, A. P., Koen, N. n., Kranzler, H. R., Kremen, W. S., Lawford, B. R., Lebois, L. A., Lewis, C. E., Linnstaedt, S. D., Lori, A. n., Lugonja, B. n., Luykx, J. J., Lyons, M. J., Maples-Keller, J. n., Marmar, C. n., Martin, A. R., Martin, N. G., Maurer, D. n., Mavissakalian, M. R., McFarlane, A. n., McGlinchey, R. E., McLaughlin, K. A., McLean, S. A., McLeay, S. n., Mehta, D. n., Milberg, W. P., Miller, M. W., Morey, R. A., Morris, C. P., Mors, O. n., Mortensen, P. B., Neale, B. M., Nelson, E. C., Nordentoft, M. n., Norman, S. B., O'Donnell, M. n., Orcutt, H. K., Panizzon, M. S., Peters, E. S., Peterson, A. L., Peverill, M. n., Pietrzak, R. H., Polusny, M. A., Rice, J. P., Ripke, S. n., Risbrough, V. B., Roberts, A. L., Rothbaum, A. O., Rothbaum, B. O., Roy-Byrne, P. n., Ruggiero, K. n., Rung, A. n., Rutten, B. P., Saccone, N. L., Sanchez, S. E., Schijven, D. n., Seedat, S. n., Seligowski, A. V., Seng, J. S., Sheerin, C. M., Silove, D. n., Smith, A. K., Smoller, J. W., Sponheim, S. R., Stein, D. J., Stevens, J. S., Sumner, J. A., Teicher, M. H., Thompson, W. K., Trapido, E. n., Uddin, M. n., Ursano, R. J., van den Heuvel, L. L., Van Hooff, M. n., Vermetten, E. n., Vinkers, C. H., Voisey, J. n., Wang, Y. n., Wang, Z. n., Werge, T. n., Williams, M. A., Williamson, D. E., Winternitz, S. n., Wolf, C. n., Wolf, E. J., Wolff, J. D., Yehuda, R. n., Young, R. M., Young, K. A., Zhao, H. n., Zoellner, L. A., Liberzon, I. n., Ressler, K. J., Haas, M. n., Koenen, K. C. 2019; 10 (1): 4558

  Abstract

  The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.

  View details for DOI 10.1038/s41467-019-12576-w

  View details for PubMedID 31594949

• Stress and hair cortisol concentrations from preconception to the third trimester. Stress (Amsterdam, Netherlands) Orta, O. R., Tworoger, S. S., Terry, K. L., Coull, B. A., Gelaye, B., Kirschbaum, C., Sanchez, S. E., Williams, M. A. 2019; 22 (1): 60-69

  Abstract

  Stress is an important and modifiable determinant of health, and its association with hair cortisol concentrations (HCC) during pregnancy remains unclear. We selected a random sample of 97 participants from a cohort of pregnant participants attending prenatal clinics in Lima, Peru. Each provided a hair sample at enrollment (mean gestational age = 13.1 weeks) and again at full-term delivery. Hair samples were segmented to reflect HCC in preconception and each trimester. At enrollment, measures of stress included: difficulty accessing basic goods, educational attainment, exposure to violence, fair or poor general health, perceived stress, and symptoms of depression, general anxiety, and post-traumatic stress disorder. Linear mixed models evaluated the association between each stress measure and absolute and relative changes in HCC. Pearson correlation coefficients (r) assessed correlations between HCC and continuous stress scores. Educational attainment of ≤12 years was associated with higher HCC in preconception and the 1st trimester, and general anxiety with lower preconception HCC. When modeling HCC patterns across the 4 hair segments, an educational attainment of ≤12 years was associated with higher HCC, high perceived stress with lower HCC, and general anxiety with steeper increases in HCC (group by time p value = .02). Only preconception HCC and GAD scores correlated (r = -0.22, p = .04). We observed few associations between stress and HCC. However, those that were seen were generally restricted to the preconception and 1st trimester. Further investigations into the association between stress and changes in HCC across pregnancy are warranted, and should include the preconception where possible.

  View details for DOI 10.1080/10253890.2018.1504917

  View details for PubMedID 30585520

  View details for PubMedCentralID PMC6453704

• Abruptio placentae risk and genetic variations in mitochondrial biogenesis and oxidative phosphorylation: replication of a candidate gene association study. American journal of obstetrics and gynecology Workalemahu, T., Enquobahrie, D. A., Gelaye, B., Thornton, T. A., Tekola-Ayele, F., Sanchez, S. E., Garcia, P. J., Palomino, H. G., Hajat, A., Romero, R., Ananth, C. V., Williams, M. A. 2018; 219 (6): 617.e1-617.e17

  Abstract

  Abruptio placentae is a complex multifactorial disease that is associated with maternal and neonatal death and morbidity. Abruptio placentae's high recurrence rate, high prevalence of heritable thrombophilia among women with abruptio placentae, and aggregation of cases in families of women with the disease support the possibility of a genetic predisposition. Previous genome-wide and candidate gene association studies have identified single nucleotide polymorphisms in mitochondrial biogenesis and oxidative phosphorylation genes that potentially are associated with abruptio placentae risk. Perturbations in mitochondrial biogenesis and oxidative phosphorylation, which results in mitochondrial dysfunction, can lead to the impairment of differentiation and invasion of the trophoblast and to several obstetrics complications that include abruptio placentae.The purpose of this study was to determine whether the results of a candidate genetic association study that indicated a link between DNA variants (implicated in mitochondrial biogenesis and oxidative phosphorylation) and abruptio placentae could be replicated.The study was conducted among participants (507 abruptio placentae cases and 1090 control subjects) of the Placental Abruption Genetic Epidemiology study. Weighted genetic risk scores were calculated with the use of abruptio placentae risk-increasing alleles of 11 single nucleotide polymorphisms in 9 mitochondrial biogenesis and oxidative phosphorylation genes (CAMK2B, NR1H3, PPARG, PRKCA, THRB, COX5A, NDUFA10, NDUFA12, and NDUFC2), which previously was reported in the Peruvian Abruptio Placentae Epidemiology study, a study with similar design and study population to the Placental Abruption Genetic Epidemiology study. Logistic regression models were fit to examine associations of weighted genetic risk scores (quartile 1, <25th percentile; quartile 2, 25-50th percentile; quartile 3, 50-70th percentile, and quartile 4, >75th percentile) with risk of abruptio placentae, adjusted for population admixture (the first 4 principal components), maternal age, infant sex, and preeclampsia. The weighted genetic risk score was also modeled as a continuous predictor. To assess potential effect modification, analyses were repeated among strata that were defined by preeclampsia status, maternal age (≥35 vs 18-34 years), and infant sex.Abruptio placentae cases were more likely to have preeclampsia, shorter gestational age, and lower infant birthweight. Participants in quartile 2 (score, 12.6-13.8), quartile 3 (score, 13.9-15.0) and quartile 4 (score, ≥15.1) had a genetic risk score of 1.45-fold (95% confidence interval, 1.04-2.02; P=.03), a 1.42-fold (95% confidence interval, 1.02-1.98; P=.04), and a 1.75-fold (95% confidence interval, 1.27-2.42; P=7.0E-04) higher odds of abruptio placentae, respectively, compared with those in quartile 1 (score,<12.6; P-for trend=.0003). The risk of abruptio placentae was 1.12-fold (95% confidence interval, 1.05-1.19; P=3.0×1004) higher per 1-unit increase in the score. Among women with preeclampsia, those in quartile 4 had a 3.92-fold (95% confidence interval, 1.48-10.36; P=.01) higher odds of abruptio placentae compared with women in quartile 1. Among normotensive women, women in quartile 4 had a 1.57-fold (95% confidence interval, 1.11-2.21; P=.01) higher odds of abruptio placentae compared with those in quartile 1 (P-for interaction=.12). We did not observe differences in associations among strata defined by maternal age or infant sex.In this study, we replicated previous findings and provide strong evidence for DNA variants that encode for genes that are involved in mitochondrial biogenesis and oxidative phosphorylation pathways, which confers risk for abruptio placentae. These results shed light on the mechanisms that implicate DNA variants that encode for proteins in mitochondrial function that are responsible for abruptio placentae risk. Therapeutic efforts to reduce risk of abruptio placentae can be enhanced by improved biologic understanding of maternal mitochondrial biogenesis/oxidative phosphorylation pathways and identification of women who would be at high risk for abruptio placentae.

  View details for DOI 10.1016/j.ajog.2018.08.042

  View details for PubMedID 30194050

  View details for PubMedCentralID PMC6497388

• Physical activity and epigenetic biomarkers in maternal blood during pregnancy. Epigenomics Badon, S. E., Littman, A. J., Chan, K. C., Tadesse, M. G., Stapleton, P. L., Bammler, T. K., Sorensen, T. K., Williams, M. A., Enquobahrie, D. A. 2018; 10 (11): 1383-1395

  Abstract

  Investigate associations of leisure time physical activity (LTPA) with DNA methylation and miRNAs during pregnancy. Patients & methods: LTPA, candidate DNA methylation and circulating miRNAs were measured (average 15 weeks gestation) in pregnant women (n = 92).Each additional hour of prepregnancy LTPA duration was associated with hypermethylation in C1orf212 (β = 0.137, 95% CI: 0.004-0.270) and higher circulating miR-146b-5p (β = 0.084, 95% CI: 0.017-0.151). Each additional metabolic equivalent hour of early-pregnancy LTPA energy expenditure was associated with higher circulating miR-21-3p (β = 0.431, 95% CI: 0.089-0.772) in women carrying female offspring, and lower circulating miR-146b-5p (β = -0.285, 95% CI: -0.528 to -0.043) and miR-517-5p (β = -0.406, 95% CI: -0.736 to -0.076) in women carrying male offspring.Our findings suggest that LTPA may influence maternal epigenetic biomarkers, possibly in an offspring sex-specific manner.

  View details for DOI 10.2217/epi-2017-0169

  View details for PubMedID 30324807

  View details for PubMedCentralID PMC6275564

• Chahal et al. Respond to "Physical Exertion and Placental Abruption". American journal of epidemiology Chahal, H. S., Gelaye, B., Williams, M. A. 2018; 187 (10): 2083-2084

  View details for DOI 10.1093/aje/kwy137

  View details for PubMedID 29992300

• Physical Exertion Immediately Prior to Placental Abruption: A Case-Crossover Study. American journal of epidemiology Chahal, H. S., Gelaye, B., Mostofsky, E., Sanchez, S. E., Mittleman, M. A., Maclure, M., Pacora, P., Torres, J. A., Romero, R., Ananth, C. V., Williams, M. A. 2018; 187 (10): 2073-2079

  Abstract

  While there is consistent evidence that episodes of physical exertion are associated with an immediately higher risk of acute ischemic vascular events, the risk of placental abruption immediately following episodes of physical exertion has not been studied. In a multicenter case-crossover study, we interviewed 663 women with placental abruption at 7 Peruvian hospitals between January 2013 and August 2015. We asked women about physical exertion in the hour before symptom onset and compared this with their frequency of physical exertion over the prior week. Compared with times with light or no exertion, the risk of placental abruption was 7.8 (95% confidence interval (CI): 5.5, 11.0) times greater in the hour following moderate or heavy physical exertion. The instantaneous incidence rate ratio of placental abruption within an hour of moderate or heavy physical exertion was lower for women who habitually engaged in moderate or heavy physical activity more than 3 times per week in the year before pregnancy (rate ratio (RR) = 3.0, 95% CI: 1.6, 5.9) compared with more sedentary women (RR = 17.3, 95% CI: 11.3, 26.7; P for homogeneity < 0.001), and the rate ratio was higher among women with preeclampsia/eclampsia (RR = 13.6, 95% CI: 7.0, 26.2) than among women without (RR = 6.7, 95% CI: 4.4, 10.0; P for homogeneity = 0.07).

  View details for DOI 10.1093/aje/kwy138

  View details for PubMedID 29992226

  View details for PubMedCentralID PMC6194205

• Exposures to Air Pollution and Risk of Acute-onset Placental Abruption: A Case-crossover Study. Epidemiology (Cambridge, Mass.) Ananth, C. V., Kioumourtzoglou, M. A., Huang, Y., Ross, Z., Friedman, A. M., Williams, M. A., Wang, S., Mittleman, M. A., Schwartz, J. 2018; 29 (5): 631-638

  Abstract

  Despite abruption's elusive etiology, knowledge of triggers that precede it by just a few days prior to delivery may help to understand the underpinnings of this acute obstetrical complication. We examine whether air pollution exposures immediately preceding delivery are associated with acute-onset abruptions.We applied a bidirectional, time-stratified, case-crossover design to births with an abruption diagnosis in New York City, 2008-2014. We measured ambient fine particulate matter (PM2.5) and nitrogen dioxide (NO2). We fit distributed lag nonlinear models based on conditional logistic regression to evaluate individual exposure and cumulative exposures over lags 0-7 days before abruption, adjusted for temperature and relative humidity (similar lags to the main exposures).We identified 1,190 abruption cases. We observed increased odds of abruption for exposure to PM2.5 (per 10 μg/m) on lag day 3 (odds ratio [OR] 1.19, 95% confidence interval [CI] = 0.98, 1.43), lag day 4 (OR 1.21, 95% CI = 1.01, 1.46), and lag day 5 (OR 1.17, 95% CI = 1.03, 1.33). Similarly, the odds of abruption increased with exposure to NO2 (per 5 ppb) on lag day 3 (OR 1.16, 95% CI = 0.98, 1.37), lag day 4 (OR 1.19, 95% CI = 1.02, 1.39), and lag day 5 (OR 1.16, 95% CI = 1.05, 1.27). Exposures to PM2.5 and NO2 at other lags, or cumulative exposures, were not associated with abruption of acute onset.This case-crossover study showed evidence of an association between short-term ambient air pollution exposures and increased abruption risk of acute onset.

  View details for DOI 10.1097/EDE.0000000000000859

  View details for PubMedID 29863531

  View details for PubMedCentralID PMC6066409

• Maternal intake of fried foods and risk of gestational diabetes mellitus ANNALS OF EPIDEMIOLOGY Osorio-Yanez, C., Gelaye, B., Qiu, C., Bao, W., Cardenas, A., Enquobahrie, D. A., Williams, M. A. 2017; 27 (6): 384-390

  Abstract

  We examined the relationship of maternal periconceptional (i.e., before conception and early pregnancy) intake of fried foods with gestational diabetes mellitus (GDM) risk.In a prospective birth cohort in Seattle and Tacoma, Washington State, USA, we assessed maternal periconceptional fried food intake using a food frequency questionnaire among 3414 participants. We used multivariable generalized linear regression models to derive estimates of relative risks (RRs; and 95% confidence intervals, 95% CIs) of GDM in relation to the intake of different types of fried foods (i.e., fried fish, fried chicken, fried potatoes, chips, and donuts).A total of 169 GDM incident cases were identified in this cohort (4.96%). Compared with no fried fish intake, fried fish intake >1 servings/month was associated with 68% higher GDM risk (adjusted RR and 95% CI; 1.68 [1.16, 2.45]; Ptrend = .019). After adjusting for confounders, the RRs (95% CI) of GDM relative to fried chicken intake were 1.0, 1.44 (0.98, 2.09), and 1.81 (1.22, 2.70) for none, ≤1 and > 1 servings/month intake of fried chicken, respectively (Ptrend = .002). Dietary intake of fried potatoes, snack chips or donuts was not significantly associated with higher GDM risk. Limitations of our study include the lack of information about frying methods and the intake of fried foods at home and away from home.Regular intake of fried fish and fried chicken are associated with elevated GDM risk.

  View details for DOI 10.1016/j.annepidem.2017.05.006

  View details for Web of Science ID 000404807800004

  View details for PubMedID 28641758

  View details for PubMedCentralID PMC5578760

• Should the governments of 'developed' countries be held responsible for equalizing the indigenous health gap? Global health promotion Abdolhosseini, P., Bonner, C., Montano, A., Young, Y. Y., Wadsworth, D., Williams, M., Stoner, L. 2016; 23 (4): 70-72

  Abstract

  Across the globe there is significant variation between and within indigenous populations in terms of world view, culture, and socio-political forces. However, many indigenous groups do share a striking commonality: greater rates of non-communicable diseases and shorter life expectancies than non-indigenous compatriots. Notably, this health gap persists for 'developed' countries, including Australia, Canada, New Zealand and the United States. The question of who is responsible for equalizing the gap is complicated. Using Australia as an exemplar context, this commentary will present arguments 'for' and 'against' the governments of developed nations being held liable for closing the indigenous health gap. We will discuss the history and nature of the health gap, actions needed to 'close the gap', and which party has the necessary resources to do so.

  View details for DOI 10.1177/1757975915574255

  View details for PubMedID 25829406

• Racial/ethnic differences in the associations between obesity measures and severity of sleep-disordered breathing: the Multi-Ethnic Study of Atherosclerosis. Sleep medicine Chen, X., Wang, R., Lutsey, P. L., Zee, P. C., Javaheri, S., Alcántara, C., Jackson, C. L., Szklo, M., Punjabi, N., Redline, S., Williams, M. A. 2016; 26: 46-53

  Abstract

  The objective of this study was to evaluate associations between obesity measures and sleep-disordered breathing severity among White, Black, Hispanic, and Chinese Americans.The method used in this study was a community-based cross-sectional study of 2053 racially/ethnically diverse adults in the Multi-Ethnic Study of Atherosclerosis. Anthropometry and polysomnography were used to measure obesity and apnea-hypopnea index (AHI). Linear regression models were fitted to investigate associations of body mass index (BMI) and waist circumference with AHI (log transformed) with adjustment for sociodemographics, lifestyle factors, and comorbidities.The mean participant age was 68.4 (range: 54-93) years; 53.6% of participants were women. The median AHI was 9.1 events/h. There were significant associations of BMI and waist circumference with AHI in the overall cohort and within each racial/ethnic group. A significant interaction was observed between race/ethnicity and BMI (Pinteraction = 0.017). Models predicted that for each unit increase in BMI (kg/m2), the mean AHI increased by 19.7% for Chinese, 11.6% for Whites and Blacks, and 10.5% for Hispanics. Similarly, incremental changes in waist circumference were associated with larger increases in AHI among Chinese than among other groups.Associations of BMI and waist circumference with AHI were stronger among Chinese than among other racial/ethnic groups. These findings highlight a potential emergence of elevated sleep-disordered breathing prevalence occurring in association with increasing obesity in Asian populations.

  View details for DOI 10.1016/j.sleep.2015.06.003

  View details for PubMedID 26459687

  View details for PubMedCentralID PMC4691213

• Placental telomere length and risk of placental abruption. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians Workalemahu, T., Enquobahrie, D. A., Yohannes, E., Sanchez, S. E., Gelaye, B., Qiu, C., Williams, M. A. 2016; 29 (17): 2767-72

  Abstract

  To investigate the associations of placental telomere length with placental abruption (PA) risk and interactions between placental telomere length and placental mitochondrial DNA (mtDNA) copy number on PA risk.Relative telomere length and mtDNA copy number in placental samples collected from 105 cases and 73 controls were measured in two batches using qRT-PCR. Mean differences in relative telomere length between PA cases and controls were examined. After creating batch-specific median cutoffs for relative telomere length (84.92 and 102.53) and mtDNA copy number (2.32 and 1.42), interaction between the two variables was examined using stratified logistic regression models.Adjusted mean difference in relative telomere length between PA cases and controls was -0.07 (p > 0.05). Among participants with low mtDNA copy number, participants with short relative telomere length had a 3.07-fold higher odds (95% CI: 1.13-8.38) of PA as compared with participants with long relative telomere length (the reference group). Among participants with high mtDNA copy number, participants with short relative telomere length had a 0.71-fold lower odds (95% CI: 0.28-1.83) of PA as compared with the reference group (interaction p values = 0.03).Findings suggest complex relationships between placental telomere length, mtDNA copy number and PA risk which warrant further larger studies.

  View details for DOI 10.3109/14767058.2015.1103224

  View details for PubMedID 26611732

  View details for PubMedCentralID PMC4984533

• Periconceptional seafood intake and pregnancy complications. Public health nutrition Mohanty, A. F., Siscovick, D. S., Williams, M. A., Thompson, M. L., Burbacher, T. M., Enquobahrie, D. A. 2016; 19 (10): 1795-803

  Abstract

  To investigate associations of maternal periconceptional shellfish, lean fish and fatty fish intake with risk of pregnancy complications.In this prospective cohort study, we collected information on intake of seafood subtypes using FFQ. We categorized seafood intake into frequencies of 1 servings/week. We ascertained gestational hypertension, pre-eclampsia, gestational diabetes and preterm birth diagnoses from medical records. Using generalized linear models with a log link, the Poisson family and robust standard errors, we estimated risk ratios and 95 % confidence intervals across seafood intake categories.The Omega study, a study of risk factors for pregnancy complications among women recruited from prenatal clinics in Washington State, USA, 1996-2008.The current study included 3279 participants from the Omega study.Median (interquartile range) shellfish, lean fish and fatty fish intake was 0·3 (0-0·9), 0·5 (0-1·0) and 0·5 (0·1-1·0) servings/week, respectively. Lean fish intake of >1 servings/week (v. <0·2 servings/month) was associated with a 1·55-fold higher risk of preterm birth (95 % CI 1·04, 2·30) and was not associated with the other pregnancy complications. Higher intake of seafood (total or other subtypes) was not associated with pregnancy complications (separately or combined).Higher intake of lean fish, but not fatty fish or shellfish, was associated with a higher risk of preterm birth; these findings may have significance for preterm birth prevention. Studies of mechanisms and potential contributing factors (including seafood preparation and nutrient/contaminant content) are warranted.

  View details for DOI 10.1017/S136898001500316X

  View details for PubMedID 26626702

  View details for PubMedCentralID PMC5500259

• Candidate Gene and MicroRNA Expression in Fetal Membranes and Preterm Delivery Risk. Reproductive sciences (Thousand Oaks, Calif.) Enquobahrie, D. A., Hensley, M., Qiu, C., Abetew, D. F., Hevner, K., Tadesse, M. G., Williams, M. A. 2016; 23 (6): 731-7

  Abstract

  We investigated candidate gene and microRNA (miRNA) expression in amnion and chorion in relation to risk of preterm delivery (PTD). Amnion and chorion were separated from placenta and collected at delivery from participants who delivered at term (N = 10) and from participants who delivered preterm following spontaneous labor (sPTL-PTD; N = 10), premature rupture of membranes (PPROM-PTD; N = 10), and preeclampsia (PE-PTD; N = 10). Expression of genes (metalloproteinase [MMP] 2, MMP-9, and tissue inhibitors of MMP-1) and miRNAs (miR-199a*, -202*, -210, -214, -223, and -338) was profiled using quantitative real-time polymerase chain reaction approaches. Adjusted multinomial logistic regression models were used to calculate relative risk ratios (RRR), 95% confidence intervals, and P values. Among controls, the expression of miR-199a*, -202*, and -214 was lower in the amnion compared with their expression in the chorion, whereas the expression of miR-210 was higher in the amnion compared with its expression in the chorion (all P values < .05). In the amnion, MMP-9 expression was associated with PTD risk (overall P value = .0092), and MMP-9 expression was positively associated with the risk of PPROM-PTD (RRR: 31.10) and inversely associated with the risk of PE-PTD (RRR:6.55e-6), although individual associations were not statistically significant. In addition, in the amnion, the expression of miR-210 (RRR: 0.45; overall P value = .0039) was inversely associated with the risk of PE-PTD, and miR-223 was inversely associated with all subtypes of PTD (overall P value = .0400). The amnion and chorion differ in their miRNA expression. The expression of MMP-9, miR-210, and -223 in the amnion is associated with PTD risk.

  View details for DOI 10.1177/1933719115612925

  View details for PubMedID 26507872

  View details for PubMedCentralID PMC5933148

• Maternal Serum 25-Hydroxyvitamin D Concentrations during Pregnancy and Infant Birthweight for Gestational Age: a Three-Cohort Study. Paediatric and perinatal epidemiology Tian, Y., Holzman, C., Siega-Riz, A. M., Williams, M. A., Dole, N., Enquobahrie, D. A., Ferre, C. D. 2016; 30 (2): 124-33

  Abstract

  In response to inconsistent findings, we investigated associations between maternal serum 25-hydroxyvitamin D [25(OH)D] concentrations and infant birthweight for gestational age (BW/GA), including potential effect modification by maternal race/ethnicity and infant sex.Data from 2558 pregnant women were combined in a nested case-control study (preterm and term) sampled from three cohorts: the Omega study, the Pregnancy, Infection and Nutrition study, and the Pregnancy Outcomes and Community Health study. Maternal 25(OH)D concentrations were sampled at 4 to 29 weeks gestation (80% 14-26 weeks). BW/GA was modelled as sex and gestational age-specific birthweight z-scores. General linear regression models (adjusting for age, education, parity, pre-pregnancy body mass index, season at blood draw, and smoking) assessed 25(OH)D concentrations in relation to BW/GA.Among non-Hispanic Black women, the positive association between 25(OH)D concentrations and BW/GA was of similar magnitude in pregnancies with female or male infants [beta (β) = 0.015, standard error (SE) = 0.007, P = 0.025; β = 0.018, SE = 0.006, P = 0.003, respectively]. Among non-Hispanic White women, 25(OH)D-BW/GA association was observed only with male infants, and the effect size was lower (β = 0.008, SE = 0.003, P = 0.02).Maternal serum concentrations of 25(OH)D in early and mid-pregnancy were positively associated with BW/GA among non-Hispanic Black male and female infants and non-Hispanic White male infants. Effect modification by race/ethnicity may be due, in part, to overall lower concentrations of 25(OH)D in non-Hispanic Blacks. Reasons for effect modification by infant sex remain unclear.

  View details for DOI 10.1111/ppe.12262

  View details for PubMedID 26575943

  View details for PubMedCentralID PMC4749469

• Severe placental abruption: clinical definition and associations with maternal complications. American journal of obstetrics and gynecology Ananth, C. V., Lavery, J. A., Vintzileos, A. M., Skupski, D. W., Varner, M., Saade, G., Biggio, J., Williams, M. A., Wapner, R. J., Wright, J. D. 2016; 214 (2): 272.e1-272.e9

  Abstract

  Placental abruption traditionally is defined as the premature separation of the implanted placenta before the delivery of the fetus. The existing clinical criteria of severity rely exclusively on fetal (fetal distress or fetal death) and maternal complications without consideration of neonatal or preterm delivery-related complications. However, two-thirds of abruption cases are accompanied by fetal or neonatal complications, including preterm delivery. A clinically meaningful classification for abruption therefore should include not only maternal complications but also adverse fetal and neonatal outcomes that include intrauterine growth restriction and preterm delivery.The purpose of this study was to define severe placental abruption and to compare serious maternal morbidity profiles of such cases with all other cases of abruption (ie, mild abruption) and nonabruption cases.We performed a retrospective cohort analysis using the Premier database of hospitalizations that resulted in singleton births in the United States between 2006 and 2012 (n = 27,796,465). Severe abruption was defined as abruption accompanied by at least 1 of the following events: maternal (disseminated intravascular coagulation, hypovolemic shock, blood transfusion, hysterectomy, renal failure, or in-hospital death), fetal (nonreassuring fetal status, intrauterine growth restriction, or fetal death), or neonatal (neonatal death, preterm delivery or small for gestational age) complications. Abruption cases that did not qualify as being severe were classified as mild abruption cases. The morbidity profile included amniotic fluid embolism, pulmonary edema, acute respiratory or heart failure, acute myocardial infarction, cardiomyopathy, puerperal cerebrovascular disorders, or coma. Associations were expressed as rate ratios with 95% confidence intervals that were derived from fitting log-linear Poisson regression models.The overall prevalence rate of abruption was 9.6 per 1000, of which two-thirds of cases were classified as being severe (6.5 per 1000). Serious maternal complications occurred in 15.4, 33.3, and 141.7 per 10,000 among nonabruption cases and mild and severe abruption cases, respectively. In comparison with no abruption, the rate ratio for serious maternal complications were 1.52 (95% confidence interval, 1.35-1.72) and 4.29 (95% confidence interval, 4.11-4.47) in women with mild and severe placental abruption, respectively. Rate ratios for the individual complications were 2- to 7-fold higher among severe abruption cases. Furthermore, the rate ratios for serious maternal complications among severe abruption cases compared with mild abruption cases was 3.47 (95% confidence interval, 3.05-3.95). This association was considerably stronger for virtually all maternal complications among cases with severe abruption compared with mild abruption. Annual rates of mild and severe abruption were fairly constant during the study period. Although the maternal complication rate among non-abruption births was stable from 2006-2012, the rate of complications among mild abruption cases dropped from 2006-2008 and then leveled off thereafter. In contrast, the rate of serious complications among severe abruption cases remained fairly stable from 2006-2010 and increased sharply thereafter.Severe abruption was associated with a distinctively higher morbidity risk profile compared with the other 2 groups. The clinical characteristics and morbidity profile of mild abruption were more similar to those of women without an abruption. These findings suggest that the definition of severe placental abruption based on the proposed specific criteria is clinically relevant and may facilitate epidemiologic and genetic research.

  View details for DOI 10.1016/j.ajog.2015.09.069

  View details for PubMedID 26393335

• Maternal Leisure Time Physical Activity and Infant Birth Size. Epidemiology (Cambridge, Mass.) Badon, S. E., Wander, P. L., Qiu, C., Miller, R. S., Williams, M. A., Enquobahrie, D. A. 2016; 27 (1): 74-81

  Abstract

  Associations of maternal leisure time physical activity with birth size are inconsistent. Roles of infant sex and maternal prepregnancy body mass index (BMI) in these associations have not been studied.Participants (N = 3,310) in the Omega study, a cohort in Washington State (1996-2008), reported leisure time physical activity duration and energy expenditure in the year prepregnancy and in early pregnancy (mean 15 weeks gestation). Regression models estimated mean differences in infant head circumference, birthweight, and ponderal index (birthweight/length) across quartiles of pre- or early-pregnancy leisure time physical activity. We assessed effect modification by infant sex or prepregnancy overweight/obese status (BMI ≥ 25 kg/m).We observed positive associations between prepregnancy leisure time physical activity and head circumference overall and among male infants. Among males, each quartile increase in prepregnancy physical activity duration was associated with 0.14 cm (95% confidence interval = 0.046, 0.24; trend P = 0.004) greater head circumference. We did not observe associations between leisure time physical activity and birthweight or ponderal index overall. Each quartile increase in pre- or early-pregnancy physical activity duration was associated with 17-23 g lower birthweight among female infants and among women with normal prepregnancy BMI.We observed positive associations between prepregnancy leisure time physical activity and head circumference among male infants, and inverse associations of pre- and early-pregnancy physical activity with birthweight among female infants and women with normal prepregnancy BMI. Future studies should confirm results and elucidate mechanisms of observed associations.

  View details for DOI 10.1097/EDE.0000000000000399

  View details for PubMedID 26427724

• Circadian clock-related genetic risk scores and risk of placental abruption. Placenta Qiu, C., Gelaye, B., Denis, M., Tadesse, M. G., Luque Fernandez, M. A., Enquobahrie, D. A., Ananth, C. V., Sanchez, S. E., Williams, M. A. 2015; 36 (12): 1480-6

  Abstract

  The circadian clock plays an important role in several aspects of female reproductive biology. Evidence linking circadian clock-related genes to pregnancy outcomes has been inconsistent. We sought to examine whether variations in single nucleotide polymorphisms (SNPs) of circadian clock genes are associated with PA risk.Maternal blood samples were collected from 470 PA case and 473 controls. Genotyping was performed using the Illumina Cardio-MetaboChip platform. We examined 119 SNPs in 13 candidate genes known to control circadian rhythms (e.g., CRY2, ARNTL, and RORA). Univariate and penalized logistic regression models were fit to estimate odds ratios (ORs); and the combined effect of multiple SNPs on PA risk was estimated using a weighted genetic risk score (wGRS).A common SNP in the RORA gene (rs2899663) was associated with a 21% reduced odds of PA (P < 0.05). The odds of PA increased with increasing wGRS (Ptrend < 0.001). The corresponding ORs were 1.00, 1.83, 2.81 and 5.13 across wGRS quartiles. Participants in the highest wGRS quartile had a 5.13-fold (95% confidence interval: 3.21-8.21) higher odds of PA compared to those in the lowest quartile. Although the test for interaction was not significant, the odds of PA was substantially elevated for preeclamptics with the highest wGRS quartile (OR = 14.44, 95%CI: 6.62-31.53) compared to normotensive women in the lowest wGRS quartile.Genetic variants in circadian rhythm genes may be associated with PA risk. Larger studies are needed to corroborate these findings and to further elucidate the pathogenesis of this important obstetrical complication.

  View details for DOI 10.1016/j.placenta.2015.10.005

  View details for PubMedID 26515929

  View details for PubMedCentralID PMC5010362

• Using the Patient Health Questionnaire (PHQ-9) and the Edinburgh Postnatal Depression Scale (EPDS) to assess suicidal ideation among pregnant women in Lima, Peru. Archives of women's mental health Zhong, Q. Y., Gelaye, B., Rondon, M. B., Sánchez, S. E., Simon, G. E., Henderson, D. C., Barrios, Y. V., Sánchez, P. M., Williams, M. A. 2015; 18 (6): 783-92

  Abstract

  We sought to examine the concordance of two suicidal ideation items from the Patient Health Questionnaire-9 (PHQ-9) and the Edinburgh Postnatal Depression Scale (EPDS), to evaluate the prevalence of suicidal ideation among pregnant women, and to assess the co-occurrence of suicidal ideation with antepartum depressive symptoms. A cross-sectional study was conducted among 1,517 pregnant women attending prenatal care clinics in Lima, Peru. Item 9 of the PHQ-9 assesses suicidal ideation over the last 14 days while item 10 of the EPDS assesses suicidal ideation in the past 7 days. The two suicidal ideation items have a high concordance rate (84.2 %) but a moderate agreement (the Cohen's kappa = 0.42). Based on the PHQ-9 and the EPDS, 15.8 and 8.8 % of participants screened positive for suicidal ideation, respectively. Assessed by the PHQ-9, 51 % of participants with suicidal ideation had probable depression. In prenatal care clinics, screening for suicidal ideation is needed for women with and without depressive symptoms. Future studies are needed to identify additional predictors of antepartum suicidality, determine the appropriate duration of reporting period for suicidal ideation screening, and assess the percentage of individuals with positive responses to the two suicidal ideation items at high risk of planning and attempting suicide.

  View details for DOI 10.1007/s00737-014-0481-0

  View details for PubMedID 25369907

  View details for PubMedCentralID PMC4635023

• Psychometric properties and factor structure of the General Health Questionnaire as a screening tool for anxiety and depressive symptoms in a multi-national study of young adults. Journal of affective disorders Gelaye, B., Tadesse, M. G., Lohsoonthorn, V., Lertmeharit, S., Pensuksan, W. C., Sanchez, S. E., Lemma, S., Berhane, Y., Vélez, J. C., Barbosa, C., Anderade, A., Williams, M. A. 2015; 187: 197-202

  Abstract

  Globally, common psychiatric disorders such as depression and anxiety are among the leading causes of morbidity and mortality. The 12-item General Health Questionnaire (GHQ-12) is a widely used questionnaire for screening or detecting common psychiatric disorders. The purpose of this study was to examine the reliability, construct validity and factor structure of the GHQ-12 in a large sample of African, Asian and South American young adults.A cross-sectional study was conducted among 9077 undergraduate students from Chile, Ethiopia, Peru and Thailand. Students aged 18-35 years were invited to complete a self-administered questionnaire that collected information about lifestyle, demographics, and GHQ-12. In each country, the construct validity and factorial structures of the GHQ-12 questionnaire were tested through exploratory and confirmatory factor analyses (EFA and CFA).Overall the GHQ-12 items showed good internal consistency across all countries as reflected by the Cronbach's alpha: Chile (0.86), Ethiopia (0.83), Peru (0.85), and Thailand (0.82). Results from EFA showed that the GHQ-12 had a two-factor solution in Chile, Ethiopia and Thailand, although a three-factor solution was found in Peru. These findings were corroborated by CFA. Indicators of goodness of fit, comparative fit index (CFI), root mean square error of approximation (RMSEA), and standardized root mean squared residual, were all in acceptable ranges across study sites. The CFI values for Chile, Ethiopia, Peru and Thailand were 0.964, 0.951, 0.949, and 0.931, respectively. The corresponding RMSEA values were 0.051, 0.050, 0.059, and 0.059.Overall, we documented cross-cultural comparability of the GHQ-12 for assessing common psychiatric disorders such as symptoms of depressive and anxiety disorders among young adults. Although the GHQ-12 is typically used as single-factor questionnaire, the results of our EFA and CFA revealed the multi- dimensionality of the scale. Future studies are needed to further evaluate the specific cut points for assessing each component within the multiple factors.

  View details for DOI 10.1016/j.jad.2015.08.045

  View details for PubMedID 26342172

  View details for PubMedCentralID PMC4587303

• Maternal Early Pregnancy Serum Metabolites and Risk of Gestational Diabetes Mellitus. The Journal of clinical endocrinology and metabolism Enquobahrie, D. A., Denis, M., Tadesse, M. G., Gelaye, B., Ressom, H. W., Williams, M. A. 2015; 100 (11): 4348-56

  Abstract

  Significant gaps remain in the understanding of genetic and environmental risk factors, as well as related mechanisms that contribute to gestational diabetes mellitus (GDM).This study aimed to investigate early pregnancy maternal serum metabolites and subsequent risk of GDM.Information on participant characteristics and GDM diagnosis was collected using in-person interviews and medical record abstraction, respectively. Early pregnancy serum samples were used for nontargeted metabolite profiling using a gas chromatography-mass spectrometry platform. Lasso regression was used to select a set of metabolites that are jointly associated with GDM case-control status. We evaluated the predictive performance of the set of selected metabolites using a receiver operating characteristics curve and area under the curve.A total of 178 GDM cases and 180 controls participated in a pregnancy cohort study.A set of 17 metabolites (linoleic acid, oleic acid, myristic acid, d-galactose, d-sorbitol, o-phosphocolamine, l-alanine, l-valine, 5-hydroxy-l-tryptophan, l-serine, sarcosine, l-pyroglutamic acid, l-mimosine, l-lactic acid, glycolic acid, fumaric acid, and urea) differentiated GDM cases from controls. Fold changes of relative abundance of these metabolites among GDM cases compared with controls ranged from 1.47 (linoleic acid) to 0.78 (5-hydroxy-l-tryptophan). Addition of these selected metabolites to a set of well-known GDM risk factors improved the area under the curve significantly from 0.71 to 0.87 (P = 3.97E-07).We identified combinations of metabolites in early pregnancy that are associated with subsequent risk of GDM. Replication of findings may improve understanding of GDM pathogenesis and may have implications for the design of GDM prevention and early diagnosis protocols.

  View details for DOI 10.1210/jc.2015-2862

  View details for PubMedID 26406294

  View details for PubMedCentralID PMC4702451

• Associations of Early and Late Gestational Weight Gain with Infant Birth Size. Maternal and child health journal Wander, P. L., Sitlani, C. M., Badon, S. E., Siscovick, D. S., Williams, M. A., Enquobahrie, D. A. 2015; 19 (11): 2462-9

  Abstract

  Associations of gestational weight gain (GWG) during specific periods of pregnancy with infant birth size have been inconsistent. Infant sex-specific differences in these associations are unknownInformation on GWG (kg) [total, early (<20 weeks gestation), and late (≥20 weeks gestation)] and indices of infant birth size including birthweight (BW), ponderal index (PI), crown-heel length (CHL), and head circumference (HC) was collected from 3,621 pregnant women. We calculated adjusted mean differences and 95 % confidence intervals (CIs) relating total, early and late GWG to infant birth size using multivariable linear regression procedures. We used stratified analyses and interaction terms to test whether associations differed by infant sex.One-kg increases in total, early or late GWG were associated with BW increases of 17.2 g (95 % CI 13.8-18.9), 14.1 g (95 % CI 10.3-18.0), and 21.0 g (95 % CI 16.7-25.4), respectively. Early GWG-BW and late GWG-BW associations were different (p = 0.026). Sex-stratified total GWG-BW associations were similar to overall results. There were sex-specific differences in early GWG-BW and late GWG-BW associations. Among females, early GWG-BW (12.0 g, 95 % CI 6.7-17.2) and late GWG-BW (24.2 g, 95 % CI 18.2-30.3) associations differed (p = 0.0042); the corresponding associations did not differ among males. Total, early, and late GWG were associated with CHL and HC, but not with PI. Associations did not differ for early or late GWG.For comparable GWG, late-GWG-related BW increase is greater than early-GWG-related BW increase, particularly among female infants.

  View details for DOI 10.1007/s10995-015-1765-3

  View details for PubMedID 26093689

  View details for PubMedCentralID PMC4959808

• Childhood abuse is associated with stress-related sleep disturbance and poor sleep quality in pregnancy. Sleep medicine Gelaye, B., Kajeepeta, S., Zhong, Q. Y., Borba, C. P., Rondon, M. B., Sánchez, S. E., Henderson, D. C., Williams, M. A. 2015; 16 (10): 1274-80

  Abstract

  Childhood abuse is associated with increased risks of adult psychiatric disorders and physical health conditions. Mounting evidence documents associations of childhood abuse with sleep disturbances in adulthood. However, to date, no study has evaluated associations of childhood abuse and sleep disturbances among pregnant women.This cross-sectional study included 634 pregnant Peruvian women. To collect information regarding socio-demographic characteristics, history of childhood abuse, and complaints of sleep disturbances, face-to-face interviews were conducted with women in early pregnancy. Ford Insomnia Response to Stress Test (FIRST-S) and the Pittsburgh Sleep Quality Index (PSQI-S), translated from English to Spanish, were used to assess stress-related sleep disturbance and sleep quality, respectively. Logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95% CIs).Women who experienced any childhood abuse had a 1.65-fold increased odds of stress-related sleep disturbance (aOR = 1.65; 95% CI: 1.15-2.38) and 2.11-fold increased odds of poor sleep quality during early pregnancy (aOR = 2.11; 95% CI: 1.35-3.30) as compared with women who reported no abuse. Women who reported both physical and sexual abuse during childhood were more than twice as likely to suffer from stress-related sleep disturbance (aOR = 2.26; 95% CI: 1.44-3.53) and poor sleep quality (aOR = 2.43; 95% CI: 1.45-4.09) in comparison to women who reported no childhood abuse.A history of childhood abuse is associated with increased odds of stress-related sleep disturbance and poor sleep quality during pregnancy. These findings, if replicated, should be used to inform the development of trauma-informed care for such sleep disturbances induced by childhood trauma.

  View details for DOI 10.1016/j.sleep.2015.07.004

  View details for PubMedID 26429757

  View details for PubMedCentralID PMC4592516

• History of childhood sexual abuse and risk of prenatal and postpartum depression or depressive symptoms: an epidemiologic review. Archives of women's mental health Wosu, A. C., Gelaye, B., Williams, M. A. 2015; 18 (5): 659-71

  Abstract

  The objective of this review is to summarize the literature (and to the extent possible, report the magnitude and direction of the association) concerning history of childhood sexual abuse (CSA) and depression or depressive symptoms among pregnant and postpartum women. Publications were identified through literature searches of seven databases (PubMed, EMBASE, PyscINFO, CINAHL, Web of Science, BIOSIS, and Science Direct) using keywords including "child abuse," "depression," "pregnancy," "prenatal," "pregnancy," and "postpartum." The literature search yielded seven eligible studies on the prenatal period and another seven studies on the postpartum period. All but one prenatal study observed statistically significant positive associations of CSA with depression or depressive symptoms during pregnancy. Findings on the association of CSA with postpartum depression or depressive symptoms were inconsistent; pooled unadjusted and adjusted odds ratios were 1.82 (95 % confidence interval (CI) 0.92, 3.60) and 1.20 (95 % CI 0.81, 1.76). In sum, findings suggest a positive association of history of CSA with depression and depressive symptoms in the prenatal period. Findings on the postpartum period were inconsistent. Clinical and public health implications of evidence from the available literature are discussed, as are desirable study design characteristics of future research.

  View details for DOI 10.1007/s00737-015-0533-0

  View details for PubMedID 25956589

  View details for PubMedCentralID PMC4565760

• Higher Maternal Plasma n-3 PUFA and Lower n-6 PUFA Concentrations in Pregnancy Are Associated with Lower Childhood Systolic Blood Pressure. The Journal of nutrition Vidakovic, A. J., Gishti, O., Steenweg-de Graaff, J., Williams, M. A., Duijts, L., Felix, J. F., Hofman, A., Tiemeier, H., Jaddoe, V. W., Gaillard, R. 2015; 145 (10): 2362-8

  Abstract

  Suboptimal maternal diet during pregnancy might lead to fetal cardiovascular adaptations with persistent consequences in the offspring.We assessed the associations of maternal polyunsaturated fatty acid (PUFA) concentrations during pregnancy with childhood blood pressure.In a population-based prospective cohort study among 4455 mothers and their children, we measured maternal second-trimester n-3 (ω-3) and n-6 (ω-6) PUFA concentrations in plasma glycerophospholipids and expressed n-3 and n-6 PUFAs as proportions of total PUFAs (wt%). Childhood blood pressure was measured at the median age of 6.0 y (95% range: 5.7-7.9 y). We used linear regression models to assess the associations of maternal PUFA wt% with childhood blood pressure at 6 y.Higher total maternal n-3 PUFA wt% and, specifically, docosahexaenoic acid (DHA; 22:6n-3) wt% were associated with lower childhood systolic blood pressure [differences: -0.28 (95% CI: -0.54, -0.03) and -0.29 mm Hg (95% CI: -0.54, -0.03) per SD increase of total n-3 PUFAs and DHA wt%, respectively], but not with childhood diastolic blood pressure. Total maternal n-6 PUFA wt% was positively associated with childhood systolic blood pressure [differences: 0.36 mm Hg (95% CI: 0.09, 0.62) per SD increase of total n-6 PUFA wt%], but not with childhood diastolic blood pressure. A higher n-6:n-3 PUFA ratio was associated with higher childhood systolic blood pressure (P < 0.05). Pregnancy and childhood characteristics only partly explained the observed associations.Higher maternal plasma n-3 PUFA and lower n-6 PUFA concentrations during pregnancy are associated with a lower systolic blood pressure in childhood. Further studies are needed to replicate these findings, explore the underlying mechanisms, and examine the long-term cardiovascular consequences.

  View details for DOI 10.3945/jn.115.210823

  View details for PubMedID 26246325

• Placental mitochondrial DNA content and placental abruption: a pilot study. BMC research notes Qiu, C., Sanchez, S. E., Hevner, K., Enquobahrie, D. A., Williams, M. A. 2015; 8: 447

  Abstract

  Mitochondrial biogenesis and adequate energy production are important for embryogenesis and placentation. Previous studies documented alterations in maternal blood mitochondrial DNA (mtDNA) copy number-a marker of mitochondrial dysfunction-in pregnancies complicated by placental abruption. To further understand the role of mitochondrial dysfunction in the pathogenesis of placental abruption, we conducted a pilot study using placental specimen collected from 103 placental abruption cases and 102 non-abruption controls. Real-time quantitative polymerase chain reaction (PCR) was used to assess the relative copy number of mtDNA in DNA extracted from placental samples collected immediately after delivery. Logistic regression procedures were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI).Higher odds of placental abruption was observed with increasing mtDNA copy number (p value for trend = 0.05). The odds of placental abruption was elevated among women who delivered placentas with higher mtDNA copy number (≥120.5, the median) as compared with those with lower values (<120.5) (adjusted OR = 2.38; 95% CI 1.11-5.08).We found preliminary evidence for associations of target tissue-specific mitochondrial dysfunction with an adverse perinatal outcome, placental abruption. Larger studies and replication of findings in other populations will further our understanding of relationships between cellular and genomic biomarkers of normal and abnormal placental function and vascular placental disorders.

  View details for DOI 10.1186/s13104-015-1340-4

  View details for PubMedID 26377917

  View details for PubMedCentralID PMC4571073

• High risk for obstructive sleep apnea and other sleep disorders among overweight and obese pregnant women. BMC pregnancy and childbirth Rice, J. R., Larrabure-Torrealva, G. T., Luque Fernandez, M. A., Grande, M., Motta, V., Barrios, Y. V., Sanchez, S., Gelaye, B., Williams, M. A. 2015; 15: 198

  Abstract

  Obstructive sleep apnea (OSA), a common and serious disorder in which breathing repeatedly stops during sleep, is associated with excess weight and obesity. Little is known about the co-occurrence of OSA among pregnant women from low and middle-income countries.We examined the extent to which maternal pre-pregnancy overweight or obesity status are associated with high risk for OSA, poor sleep quality, and excessive daytime sleepiness in 1032 pregnant women in Lima, Peru. The Berlin questionnaire was used to identify women at high risk for OSA. The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to examine sleep quality and excessive daytime sleepiness, respectively. Multinomial logistic regression procedures were employed to estimate odds ratios (aOR) and 95% confidence intervals (CI) adjusted for putative confounding factors.Compared with lean women (<25 kg/m(2)), overweight women (25-29.9 kg/m(2)) had 3.69-fold higher odds of high risk for OSA (95% CI 1.82-7.50). The corresponding aOR for obese women (≥30 kg/m(2)) was 13.23 (95% CI: 6.25-28.01). Obese women, as compared with their lean counterparts had a 1.61-fold higher odds of poor sleep quality (95% CI: 1.00-2.63).Overweight or obese pregnant women have increased odds of sleep disorders, particularly OSA. OSA screening and risk management may be indicated among pregnant women in low and middle income countries, particularly those undergoing rapid epidemiologic transitions characterized by increased prevalence of excessive adult weight gain.

  View details for DOI 10.1186/s12884-015-0633-x

  View details for PubMedID 26330183

  View details for PubMedCentralID PMC4557601

• Periconceptional Seafood Intake and Fetal Growth. Paediatric and perinatal epidemiology Mohanty, A. F., Thompson, M. L., Burbacher, T. M., Siscovick, D. S., Williams, M. A., Enquobahrie, D. A. 2015; 29 (5): 376-87

  Abstract

  Previous reports of associations of maternal seafood intake with fetal growth were inconsistent. Further, little is known whether associations differ across seafood subtypes or fetal growth indices.Among 3141 participants of the Omega study, a pregnancy cohort study, we investigated associations of periconceptional shell, lean, and fatty fish intake with fetal growth indices. We categorised food frequency questionnaire reported seafood intake into frequencies of: <0.2 servings/month, 0.2 servings/month -<0.5 servings/week, 0.5-1 servings/week, and >1 servings/week. We abstracted birthweight, birth length, and head circumference from medical records. Using generalised linear models with a log link, the Poisson family, and robust standard errors, we estimated relative risks and 95% confidence intervals (CI) for low birthweight (LBW, <2500 g) and linear regression models to estimate mean differences for continuous fetal growth indices across seafood intake categories.Medians (interquartile range) of shell, lean, and fatty fish intake were 0.3 (0-0.9), 0.5 (0-1.0), and 0.5 (0.1-1.0) servings/week, respectively. Lean fish intake of >1 servings/week (vs. <0.2 servings/month) was associated with a 2.2-fold higher risk of LBW (95% CI 1.2, 4.1). Shellfish intake of >1 servings/week (vs. <0.2 servings/month) was associated with a 0.6 kg/m(3) higher mean ponderal index (95% CI 0.0, 1.2 kg/m(3) ). There was no evidence for associations of total seafood or seafood subtype intake with other fetal growth indices.Higher intakes of lean fish and shellfish were associated with a higher risk of LBW and higher mean ponderal index, respectively. Findings highlight the importance of considerations of seafood subtype in similar investigations.

  View details for DOI 10.1111/ppe.12205

  View details for PubMedID 26147526

  View details for PubMedCentralID PMC4536156

• Morningness/eveningness chronotype, poor sleep quality, and daytime sleepiness in relation to common mental disorders among Peruvian college students. Psychology, health & medicine Rose, D., Gelaye, B., Sanchez, S., Castañeda, B., Sanchez, E., Yanez, N. D., Williams, M. A. 2015; 20 (3): 345-52

  Abstract

  The study was designed to investigate the association between sleep disturbances and common mental disorders (CMDs) among Peruvian college students. A total of 2538 undergraduate students completed a self-administered questionnaire to gather information about sleep characteristics, sociodemographic, and lifestyle data. Evening chronotype, sleep quality, and daytime sleepiness were assessed using the Horne and Ostberg morningness-eveningness questionnaire, Pittsburgh Sleep Quality Index, and Epworth Sleepiness Scale, respectivelty. Presence of CMDs was evaluated using the General Health Questionnaire. Logistic regression procedures were used to examine the associations of sleep disturbances with CMDs while accounting for possible confounding factors. Overall, 32.9% of the participants had prevalent CMDs (39.3% among females and 24.4% among males). In multivariable-adjusted logistic models, those with evening chronotype (odds ratios (OR) = 1.43; 95% CI 1.00-2.05), poor sleep quality (OR = 4.50; 95% CI 3.69-5.49), and excessive daytime sleepiness (OR = 1.68; 95% CI 1.41-2.01) were at a relative increased odds of CMDs compared with those without sleep disturbances. In conclusion, we found strong associations between sleep disturbances and CMDs among Peruvian college students. Early education and preventative interventions designed to improve sleep habits may effectively alter the possibility of developing CMDs among young adults.

  View details for DOI 10.1080/13548506.2014.951367

  View details for PubMedID 25162477

  View details for PubMedCentralID PMC4315718

• Maternal history of childhood sexual abuse and preterm birth: an epidemiologic review. BMC pregnancy and childbirth Wosu, A. C., Gelaye, B., Williams, M. A. 2015; 15: 174

  Abstract

  History of childhood sexual abuse (CSA) is highly prevalent with as many as one in four American women being victims. Exposure to CSA or other early life traumatic experiences has been associated with adverse reproductive and pregnancy outcomes. However, the effects of CSA on preterm delivery (PTB), a leading cause of neonatal mortality, remain poorly understood. The objectives of this review are (i) to synthesize the available research investigating the relationship between maternal history of childhood sexual abuse (CSA) and preterm delivery (PTB); (ii) to provide suggestions for improving future research on this topic; and (iii) to highlight implications for clinical practice and public health.Relevant articles were identified through searches of four electronic databases (PubMed, CINAHL, Web of Science Core Collection and BIOSIS Online) for studies published before March 2014, as well as through reviewing references of published articles.A total of six studies published from 1992 to 2010 were included in this review. Overall, findings were inconsistent. Three studies reported statistically significant associations of CSA with PTB (<37 weeks gestation) or shorter mean gestational age at birth. Women with a history of CSA had 2.6 to 4.8-fold increased odds of PTB as compared with women without a history of CSA. Three other studies did not observe statistically significant differences in rates of PTB or mean gestational age at birth in relation to a history of CSA.Available evidence on this topic is sparse and inconsistent, and limited by a number of methodological challenges. Given the ubiquity of CSA, as well as the clinical and public health significance of PTB, more rigorously designed epidemiologic studies on the association between CSA and PTB are warranted.

  View details for DOI 10.1186/s12884-015-0606-0

  View details for PubMedID 26276498

  View details for PubMedCentralID PMC4537581

• Psychometric Properties of the Pittsburgh Sleep Quality Index (PSQI) in a Cohort of Peruvian Pregnant Women. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine Zhong, Q. Y., Gelaye, B., Sánchez, S. E., Williams, M. A. 2015; 11 (8): 869-77

  Abstract

  We sought to evaluate the construct validity and factor structure of the Spanish-language version of the Pittsburgh Sleep Quality Index (PSQI) among pregnant Peruvian women.A cohort of 642 women were interviewed at ≤ 16 weeks of gestation. During interview, we ascertained information about lifestyles, demographics, sleep characteristics, and mood symptoms. Stress induced sleep disturbance, depressive symptoms, and anxiety symptoms were evaluated using the Ford Insomnia Response to Stress Test (FIRST), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7) assessment scales, respectively. Consistency indices, exploratory and confirmatory factor analyses, correlations, and logistic regressions were used.Both exploratory and confirmatory factor analyses indicated a three-factor solution: sleep quality, sleep efficiency, and sleep medication. We observed significantly positive correlations of the PSQI with the FIRST (0.42), the PHQ-9 (0.49), and the GAD-7 (0.46). Poor sleepers (PSQI global score > 5) had significantly increased odds of experiencing stress-induced sleep disturbance (odds ratio, OR = 3.57; 95% CI: 2.40, 5.31), depression (OR = 5.48; 95% CI: 3.58, 8.37), and generalized anxiety disorder (OR = 4.57; 95% CI: 3.08, 6.76).The Spanish-language version of the PSQI instrument was found to have good construct validity among pregnant Peruvian women. Consistent with some other studies, the PSQI was found to have a three-factor structure. Further assessment and validation studies are needed to determine whether the three, factor-specific scoring of the PSQI is favored over the PSQI global score in diverse populations.

  View details for DOI 10.5664/jcsm.4936

  View details for PubMedID 25845902

  View details for PubMedCentralID PMC4513264

• Reliability of oscillometric central hemodynamic responses to an orthostatic challenge. Atherosclerosis Stoner, L., Bonner, C., Credeur, D., Lambrick, D., Faulkner, J., Wadsworth, D., Williams, M. A. 2015; 241 (2): 761-5

  Abstract

  Monitoring central hemodynamic responses to an orthostatic challenge may provide important insight into autonomic nervous system function. Oscillometric pulse wave analysis devices have recently emerged, presenting clinically viable options for investigating central hemodynamic properties. The purpose of the current study was to determine whether oscillometric pulse wave analysis can be used to reliably (between-day) assess central blood pressure and central pressure augmentation (augmentation index) responses to a 5 min orthostatic challenge (modified tilt-table).Twenty healthy adults (26.4 y (SD 5.2), 55% F, 24.7 kg/m(2) (SD 3.8)) were tested on 3 different mornings in the fasted state, separated by a maximum of 7 days. Central hemodynamic variables were assessed on the left arm using an oscillometric device.Repeated measures analysis of variance indicated a significant main effect of the modified tilt-table for all central hemodynamic variables (P < 0.001). In response to the tilt, central diastolic pressure increased by 4.5 mmHg (CI: 2.6, 6.4), central systolic blood pressure increased by 2.3 (CI: 4.4, 0.16) mmHg, and augmentation index decreased by an absolute - 5.3%, (CI: -2.7, -7.9%). The intra-class correlation coefficient values for central diastolic pressure (0.83-0.86), central systolic blood pressure (0.80-0.87) and AIx (0.79-0.82) were above the 0.75 criterion in both the supine and tilted positions, indicating excellent between-day reliability.Central hemodynamic responses to an orthostatic challenge can be assessed with acceptable between-day reliability using oscillometric pulse wave analysis.

  View details for DOI 10.1016/j.atherosclerosis.2015.06.041

  View details for PubMedID 26142686

• Reliability of oscillometric central blood pressure and wave reflection readings: effects of posture and fasting. Journal of hypertension Young, Y., Abdolhosseini, P., Brown, F., Faulkner, J., Lambrick, D., Williams, M. A., Stoner, L. 2015; 33 (8): 1588-93

  Abstract

  Oscillometric pulse wave analysis devices have recently emerged, presenting suitable options for investigating central hemodynamic properties in clinical practice. This study sought to examine whether the between-day reliability of central SBP (cSBP) and systemic arterial wave reflection (augmentation index, AIx) readings exceed the criterion for acceptable reliability or are affected by posture (supine and seated) and fasting state.Twenty healthy adults (50% female, 27.9 years, 24.2 kg/m) were tested on six different mornings: 3 days fasted and 3 days nonfasted. On each occasion, participants were tested in supine and seated postures. Oscillometric pressure waveforms were recorded on left upper arm.For cSBP, there was nonsignificant main effect for fasting state (P = 0.819) but there was a main effect for posture (P = 0.002). Conversely, for AIx, there was nonsignificant main effect for posture (P = 0.537) but there was a large main effect for fasting state (P = < 0.001). The criterion intraclass correlation coefficient value of 0.75 was exceeded for both variables when participants were assessed under the combined supine-fasted condition. For cSBP, the reliability coefficient was lowest (best) when supine fasted (6.8 mmHg) and greatest (worst) when seated nonfasted (8.6 mmHg). For AIx, the reliability coefficient was lower for the supine (11.4-11.7%) compared with the seated (14.0-15.2%) posture.Findings from this study suggest that oscillometric assessments of central hemodynamic variables exceed the criterion for acceptable reliability and are most reliable when participants are evaluated while supine and fasted.

  View details for DOI 10.1097/HJH.0000000000000604

  View details for PubMedID 26136065

• Paternal Urinary Concentrations of Parabens and Other Phenols in Relation to Reproductive Outcomes among Couples from a Fertility Clinic. Environmental health perspectives Dodge, L. E., Williams, P. L., Williams, M. A., Missmer, S. A., Toth, T. L., Calafat, A. M., Hauser, R. 2015; 123 (7): 665-71

  Abstract

  Human exposure to phenols, including bisphenol A and parabens, is widespread. Evidence suggests that paternal exposure to environmental chemicals may adversely affect reproductive outcomes.We evaluated associations of paternal phenol urinary concentrations with fertilization rate, embryo quality, implantation, and live birth.Male-female couples who underwent in vitro fertilization (IVF) and/or intrauterine insemination (IUI) cycles in a prospective study of environmental determinants of fertility and pregnancy outcomes were included. The geometric mean of males' specific gravity-adjusted urinary phenol concentrations measured before females' cycle was quantified. Associations between male urinary phenol concentrations and fertilization rate, embryo quality, implantation, and live birth were investigated using generalized linear mixed models to account for multiple cycles per couple.Couples (n = 218) underwent 195 IUI and 211 IVF cycles. Paternal phenol concentrations were not associated with fertilization or live birth following IVF. In adjusted models, compared with the lowest quartile of methyl paraben, paternal concentrations in the second quartile were associated with decreased odds of live birth following IUI (adjusted odds ratio = 0.19; 95% CI: 0.04, 0.82).To our knowledge, these are some of the first data on the association of paternal urinary phenol concentrations with reproduction and pregnancy outcomes. Although these results do not preclude possible adverse effects of paternal paraben exposures on such outcomes, given the modest sample size, further understanding could result from confirmation using a larger and more diverse population.

  View details for DOI 10.1289/ehp.1408605

  View details for PubMedID 25767892

  View details for PubMedCentralID PMC4492268

• Early Pregnancy Maternal Blood DNA Methylation in Repeat Pregnancies and Change in Gestational Diabetes Mellitus Status—A Pilot Study. Reproductive sciences (Thousand Oaks, Calif.) Enquobahrie, D. A., Moore, A., Muhie, S., Tadesse, M. G., Lin, S., Williams, M. A. 2015; 22 (7): 904-10

  Abstract

  Repeat pregnancies with different perinatal outcomes minimize underlying maternal genetic diversity and provide unique opportunities to investigate nongenetic risk factors and epigenetic mechanisms of pregnancy complications. We investigated gestational diabetes mellitus (GDM)-related differential DNA methylation in early pregnancy peripheral blood samples collected from women who had a change in GDM status in repeat pregnancies. Six study participants were randomly selected from among women who had 2 consecutive pregnancies, only 1 of which was complicated by GDM (case pregnancy) and the other was not (control pregnancy). Epigenome-wide DNA methylation was profiled using Illumina HumanMethylation 27 BeadChips. Differential Identification using Mixture Ensemble and false discovery rate (<10%) cutoffs were used to identify differentially methylated targets between the 2 pregnancies of each participant. Overall, 27 target sites, 17 hypomethylated (fold change [FC] range: 0.77-0.99) and 10 hypermethylated (FC range: 1.01-1.09), were differentially methylated between GDM and control pregnancies among 5 or more study participants. Novel genes were related to identified hypomethylated (such as NDUFC1, HAPLN3, HHLA3, and RHOG) or hypermethylated sites (such as SEP11, ZAR1, and DDR). Genes related to identified sites participated in cell morphology, cellular assembly, cellular organization, cellular compromise, and cell cycle. Our findings support early pregnancy peripheral blood DNA methylation differences in repeat pregnancies with change in GDM status. Similar, larger, and repeat pregnancy studies can enhance biomarker discovery and mechanistic studies of GDM.

  View details for DOI 10.1177/1933719115570903

  View details for PubMedID 25676578

  View details for PubMedCentralID PMC4565480

• Major depressive disorder and cardiometabolic disease risk among sub-Saharan African adults. Diabetes & metabolic syndrome Gelaye, B., Williams, M. A., Lemma, S., Berhane, Y., Fann, J. R., Vander Stoep, A., Zhou, X. A. 2015; 9 (3): 183-91

  Abstract

  We sought to evaluate the extent to which major depressive disorder (MDD) is associated with cardiometabolic diseases and risk factors.This was a cross-sectional epidemiologic study of 1924 employed adults in Ethiopia. Structured interview was used to collect sociodemographic data, behavioral characteristics and MDD symptoms using a validated Patient Health Questionnaire-9 (PHQ-9) depression scale. Fasting blood glucose, insulin, C-reactive protein, and lipid concentrations were measured using standard approaches. Multivariate logistic regression models were fitted to estimate odds ratios (OR) and 95% confidence intervals (95% CI).A total of 154 participants screened positive for MDD on PHQ-9 (8.0%; 95% CI: 6.7-9.2%). Among women, MDD was associated with more than 4-fold increased odds of diabetes (OR=4.14; 95% CI: 1.03-16.62). Among men the association was not significant (OR=1.12; 95% CI: 0.63-1.99). Similarly, MDD was not associated with metabolic syndrome among women (OR=1.51; 95% CI: 0.69-3.29) and men (OR=0.61; 95% CI: 0.28-1.34). Lastly, MDD was not associated with increased odds of systemic inflammation.The results of our study do not provide convincing evidence that MDD is associated with cardiometabolic diseases among Ethiopian adults. Future studies need to evaluate the effect of other psychiatric disorders on cardiometabolic disease risk.

  View details for DOI 10.1016/j.dsx.2014.05.003

  View details for PubMedID 25470634

  View details for PubMedCentralID PMC4265581

• Early Pregnancy Maternal Hepatocyte Growth Factor and Risk of Gestational Diabetes. British journal of medicine and medical research Dishi, M., Hevner, K., Qiu, C., Fida, N. G., Abetew, D. F., Williams, M. A., Enquobahrie, D. A. 2015; 9 (1)

  Abstract

  We investigated associations of serum hepatocyte growth factor (HGF) with risk of gestational diabetes mellitus (GDM). We also examined whether pre-pregnancy overweight/obesity status or leisure-time physical activity (LTPA) modify these associations.In a nested case-control study (173 GDM cases and 187 controls) among participants of a pregnancy cohort, early pregnancy (16 weeks of gestation, on average) serum HGF was measured using enzyme-linked immunoassay. GDM was diagnosed using American Diabetes Association guidelines. Logistic regression was used to calculate odd ratios (ORs) and 95% confidence intervals (CI). Effect modifications by pre-pregnancy overweight/obesity status or LTPA during pregnancy were examined using stratified analyses and interaction terms.Overall, we did not find significant associations of serum HGF with GDM risk (p-value> 0.05). However, compared with women who had low serum HGF concentrations (<2.29 ng/ml), women with high serum HGF concentrations (≥ 2.29 ng/ml) had 3.8-fold (95%CI: 1.30-10.98) and 4.5-fold (95%CI: 1.28-15.80) higher GDM risk among women who were overweight/obese, pre-pregnancy (body mass index≥25 kg/m2), or did not report LTPA, respectively. These associations were not present among women who were not overweight/obese (interaction p=0.05) or reported LTPA (interaction p=0.05).Overweight/obesity status and LTPA may modify associations of early pregnancy serum HGF with subsequent GDM risk.

  View details for DOI 10.9734/BJMMR/2015/18632

  View details for PubMedID 27158627

  View details for PubMedCentralID PMC4856214

• Racial/Ethnic Differences in Sleep Disturbances: The Multi-Ethnic Study of Atherosclerosis (MESA). Sleep Chen, X., Wang, R., Zee, P., Lutsey, P. L., Javaheri, S., Alcántara, C., Jackson, C. L., Williams, M. A., Redline, S. 2015; 38 (6): 877-88

  Abstract

  There is limited research on racial/ethnic variation in sleep disturbances. This study aimed to quantify the distributions of objectively measured sleep disordered breathing (SDB), short sleep duration, poor sleep quality, and self-reported sleep disturbances (e.g., insomnia) across racial/ethnic groups.Cross-sectional study.Six US communities.Racially/ethnically diverse men and women aged 54-93 y in the Multi-Ethnic Study of Atherosclerosis Sleep Cohort (n = 2,230).N/A.Information from polysomnography-measured SDB, actigraphy-measured sleep duration and quality, and self-reported daytime sleepiness were obtained between 2010 and 2013. Overall, 15.0% of individuals had severe SDB (apnea-hypopnea index [AHI] ≥ 30); 30.9% short sleep duration (< 6 h); 6.5% poor sleep quality (sleep efficiency < 85%); and 13.9% had daytime sleepiness. Compared with Whites, Blacks had higher odds of sleep apnea syndrome (AHI ≥ 5 plus sleepiness) (sex-, age-, and study site-adjusted odds ratio [OR] = 1.78, 95% confidence interval [CI]: 1.20, 2.63), short sleep (OR = 4.95, 95% CI: 3.56, 6.90), poor sleep quality (OR = 1.57, 95% CI: 1.00, 2.48), and daytime sleepiness (OR = 1.89, 95% CI: 1.38, 2.60). Hispanics and Chinese had higher odds of SDB and short sleep than Whites. Among non-obese individuals, Chinese had the highest odds of SDB compared to Whites. Only 7.4% to 16.2% of individuals with an AHI ≥ 15 reported a prior diagnosis of sleep apnea.Sleep disturbances are prevalent among middle-aged and older adults, and vary by race/ethnicity, sex, and obesity status. The high prevalence of sleep disturbances and undiagnosed sleep apnea among racial/ethnic minorities may contribute to health disparities.

  View details for DOI 10.5665/sleep.4732

  View details for PubMedID 25409106

  View details for PubMedCentralID PMC4434554

• Circadian rhythm characteristics, poor sleep quality, daytime sleepiness and common psychiatric disorders among Thai college students. Asia-Pacific psychiatry : official journal of the Pacific Rim College of Psychiatrists Haregu, A., Gelaye, B., Pensuksan, W. C., Lohsoonthorn, V., Lertmaharit, S., Rattananupong, T., Tadesse, M. G., Williams, M. A. 2015; 7 (2): 182-9

  Abstract

  To investigate the relationship between common psychiatric disorders (CPDs) and sleep characteristics (evening chronotype, poor sleep quality and daytime sleepiness) among Thai college students.A cross-sectional study was conducted among 2,970 undergraduate students in Thailand. Students were asked to complete a self-administered questionnaire that collected information about lifestyle and demographic characteristics. The Horne and Ostberg Morningness-Eveningness Questionnaire (MEQ), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to evaluate circadian preference, sleep quality and daytime sleepiness, respectively. The General Health Questionnaire-12 (GHQ-12) was used to evaluate presence of CPDs. Logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) of CPDs in relation to the covariates of interest.A total of 337 students were classified as having CPDs (11.2%; 95% CI 10.1-12.3%). Evening chronotype (OR = 3.35; 95% CI 2.09-5.37), poor sleep quality (OR = 4.89; 95% CI 3.66-6.54) and excessive daytime sleepiness (OR = 1.95; 95% CI 1.54-2.47) were statistically significantly associated with CPDs.Our study demonstrated that CPDs are common among Thai college students. Further, evening chronotype, poor sleep quality and excessive daytime sleepiness were strongly associated with increased risk of CPDs. These findings highlight the importance of educating students and school administrators about the importance of sleep and their impact on mental health.

  View details for DOI 10.1111/appy.12127

  View details for PubMedID 24664948

  View details for PubMedCentralID PMC4176528

• An international contrast of rates of placental abruption: an age-period-cohort analysis. PloS one Ananth, C. V., Keyes, K. M., Hamilton, A., Gissler, M., Wu, C., Liu, S., Luque-Fernandez, M. A., Skjærven, R., Williams, M. A., Tikkanen, M., Cnattingius, S. 2015; 10 (5): e0125246

  Abstract

  Although rare, placental abruption is implicated in disproportionately high rates of perinatal morbidity and mortality. Understanding geographic and temporal variations may provide insights into possible amenable factors of abruption. We examined abruption frequencies by maternal age, delivery year, and maternal birth cohorts over three decades across seven countries.Women that delivered in the US (n = 863,879; 1979-10), Canada (4 provinces, n = 5,407,463; 1982-11), Sweden (n = 3,266,742; 1978-10), Denmark (n = 1,773,895; 1978-08), Norway (n = 1,780,271, 1978-09), Finland (n = 1,411,867; 1987-10), and Spain (n = 6,151,508; 1999-12) were analyzed. Abruption diagnosis was based on ICD coding. Rates were modeled using Poisson regression within the framework of an age-period-cohort analysis, and multi-level models to examine the contribution of smoking in four countries.Abruption rates varied across the seven countries (3-10 per 1000), Maternal age showed a consistent J-shaped pattern with increased rates at the extremes of the age distribution. In comparison to births in 2000, births after 2000 in European countries had lower abruption rates; in the US there was an increase in rate up to 2000 and a plateau thereafter. No birth cohort effects were evident. Changes in smoking prevalence partially explained the period effect in the US (P = 0.01) and Sweden (P<0.01).There is a strong maternal age effect on abruption. While the abruption rate has plateaued since 2000 in the US, all other countries show declining rates. These findings suggest considerable variation in abruption frequencies across countries; differences in the distribution of risk factors, especially smoking, may help guide policy to reduce abruption rates.

  View details for DOI 10.1371/journal.pone.0125246

  View details for PubMedID 26018653

  View details for PubMedCentralID PMC4446321

• Association of poor subjective sleep quality with suicidal ideation among pregnant Peruvian women. General hospital psychiatry Gelaye, B., Barrios, Y. V., Zhong, Q. Y., Rondon, M. B., Borba, C. P., Sánchez, S. E., Henderson, D. C., Williams, M. A. 2015; 37 (5): 441-7

  Abstract

  To examine the independent and joint relationships of poor subjective sleep quality and antepartum depression with suicidal ideation among pregnant women.A cross-sectional study was conducted among 641 pregnant women attending prenatal care clinics in Lima, Peru. Antepartum depression and suicidal ideation were assessed using the Patient Health Questionnaire-9 scale. Antepartum subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Logistic regression procedures were performed to estimate odds ratios (aOR) and 95% confidence intervals (95% CI) adjusted for confounders.Overall, the prevalence of suicidal ideation in this cohort was 16.8% and poor subjective sleep quality was more common among women endorsing suicidal ideation as compared to their counterparts who did not (47.2% vs. 24.8%, P<.001). After adjustment for confounders including maternal depression, poor subjective sleep quality (defined using the recommended criteria of PSQI global score of >5 vs. ≤5) was associated with a 1.7-fold increased odds of suicidal ideation (aOR=1.67; 95% CI 1.02-2.71). When assessed as a continuous variable, each 1-unit increase in the global PSQI score resulted in an 18% increase in odds for suicidal ideation, even after adjusting for depression (aOR=1.18; 95% CI 1.08-1.28). Women with both poor subjective sleep quality and depression had a 3.5-fold increased odds of suicidal ideation (aOR=3.48; 95% CI 1.96-6.18) as compared with those who had neither risk factor.Poor subjective sleep quality was associated with increased odds of suicidal ideation. Replication of these findings may promote investments in studies designed to examine the efficacy of sleep-focused interventions to treat pregnant women with sleep disorders and suicidal ideation.

  View details for DOI 10.1016/j.genhosppsych.2015.04.014

  View details for PubMedID 25983188

  View details for PubMedCentralID PMC4558240

• Fasting lipid and lipoproteins concentrations in pregnant women with a history of migraine. Headache Gelaye, B., Larrabure-Torrealva, G. T., Qiu, C., Luque-Fernandez, M. A., Peterlin, B. L., Sanchez, S. E., Williams, M. A. 2015; 55 (5): 646-57

  Abstract

  Migraine is associated with a number of cardiometabolic risk factors including abnormalities in lipid metabolism. However, little is known about these associations among pregnant migraineurs. We conducted the present study to evaluate the extent to which altered lipid profiles are associated with history of migraine among pregnant women.A cohort of 1062 Peruvian women were interviewed at 24-28 weeks of gestation. Migraine status was classified based on the International Classification of Headache Disorders-II diagnostic criteria. Serum lipid concentrations were measured enzymatically using standardized assays. Multivariable logistic regression was used to estimate adjusted odds ratios (AORs) and 95% confidence intervals (CIs) as measures of associations of migraine status with varying concentrations of lipids and lipoproteins during pregnancy.Approximately 18.5% of the study participants were identified as migraineurs (196 of 1062). Maternal serum total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, and total cholesterol : HDL ratio were all statistically significantly elevated among pregnant migraineurs compared with pregnant non-migraineurs. In multivariate adjusted models, pregnant women with migraine had higher odds of elevated total cholesterol, LDL, and total cholesterol : HDL ratio as compared with pregnant women without migraine. For instance, the AOR and 95% CI for successive quartiles of the total cholesterol associated with history of migraine were Q2 (219-247 mg/dL): 1.05 (0.64-1.70), Q3 (248-281 mg/dL): 1.16 (0.72-1.86), and Q4 (≥282 mg/dL): 1.87 (1.20-2.91) with the lowest quartile (<219 mg/dL) as the referent group (P value for trend = .003). Obese women with elevated total cholesterol (≥282 mg/dL) were more likely to be migraineurs (OR = 3.71; 95% CI 1.58-8.71) as compared with non-obese women with lower total cholesterol (<219 mg/dL). Similar elevated odds of migraine were observed for obese women with elevated LDL cholesterol, elevated triglycerides and high total cholesterol : HDL ratio.Pregnant migraineurs had elevated odds of dyslipidemia, particularly hypercholesterolemia, elevated LDL, and total cholesterol : HDL ratio as compared with pregnant non-migraineurs. The observed associations were more pronounced among obese migraineurs. Our findings add to the accumulating evidence of adverse cardiometabolic risk profiles among migraineurs and extend these associations to pregnant women.

  View details for DOI 10.1111/head.12571

  View details for PubMedID 25904286

  View details for PubMedCentralID PMC4439363

• Plasma vitamin D is associated with fasting insulin and homeostatic model assessment of insulin resistance in young adult males, but not females, of the Jerusalem Perinatal Study. Public health nutrition Moore, A., Hochner, H., Sitlani, C. M., Williams, M. A., Hoofnagle, A. N., de Boer, I. H., Kestenbaum, B., Siscovick, D. S., Friedlander, Y., Enquobahrie, D. A. 2015; 18 (7): 1324-31

  Abstract

  To examine cross-sectional relationships between plasma vitamin D and cardiometabolic risk factors in young adults.Data were collected from interviews, physical examinations and biomarker measurements. Total plasma 25-hydroxyvitamin D (25(OH)D) was measured using LC-tandem MS. Associations between 25(OH)D and cardiometabolic risk factors were modelled using weighted linear regression with robust estimates of standard errors.Individuals born in Jerusalem during 1974-1976.Participants of the Jerusalem Perinatal Study (n 1204) interviewed and examined at age 32 years. Participants were oversampled for low and high birth weight and for maternal pre-pregnancy obesity.Mean total 25(OH)D concentration among participants was 21·7 (sd 8·9) ng/ml. Among males, 25(OH)D was associated with homeostatic model assessment of insulin resistance (natural log-transformed, β=-0·011, P=0·004) after adjustment for BMI. However, these associations were not present among females (P for sex interaction=0·005).We found evidence for inverse associations of 25(OH)D with markers of insulin resistance among males, but not females, in a healthy, young adult Caucasian population. Prospective studies and studies conducted on other populations investigating sex-specific effects of vitamin D on cardiometabolic risk factors are warranted.

  View details for DOI 10.1017/S1368980014001475

  View details for PubMedID 25145881

  View details for PubMedCentralID PMC4592940

• Molecular Regulation of Parturition: The Role of the Decidual Clock. Cold Spring Harbor perspectives in medicine Norwitz, E. R., Bonney, E. A., Snegovskikh, V. V., Williams, M. A., Phillippe, M., Park, J. S., Abrahams, V. M. 2015; 5 (11)

  Abstract

  The timing of birth is a critical determinant of perinatal outcome. Despite intensive research, the molecular mechanisms responsible for the onset of labor both at term and preterm remain unclear. It is likely that a "parturition cascade" exists that triggers labor at term, that preterm labor results from mechanisms that either prematurely stimulate or short-circuit this cascade, and that these mechanisms involve the activation of proinflammatory pathways within the uterus. It has long been postulated that the fetoplacental unit is in control of the timing of birth through a "placental clock." We suggest that it is not a placental clock that regulates the timing of birth, but rather a "decidual clock." Here, we review the evidence in support of the endometrium/decidua as the organ primarily responsible for the timing of birth and discuss the molecular mechanisms that prime this decidual clock.

  View details for DOI 10.1101/cshperspect.a023143

  View details for PubMedID 25918180

  View details for PubMedCentralID PMC4632866

• Diagnostic Validity of the Generalized Anxiety Disorder - 7 (GAD-7) among Pregnant Women. PloS one Zhong, Q. Y., Gelaye, B., Zaslavsky, A. M., Fann, J. R., Rondon, M. B., Sánchez, S. E., Williams, M. A. 2015; 10 (4): e0125096

  Abstract

  Generalized anxiety disorder (GAD) during pregnancy is associated with several adverse maternal and perinatal outcomes. A reliable and valid screening tool for GAD should lead to earlier detection and treatment. Among pregnant Peruvian women, a brief screening tool, the GAD-7, has not been validated. This study aims to evaluate the reliability and validity of the GAD-7.Of 2,978 women who attended their first perinatal care visit and had the GAD-7 screening, 946 had a Composite International Diagnostic Interview (CIDI). The Cronbach's alpha was calculated to examine the reliability. We assessed the criterion validity by calculating operating characteristics. The construct validity was evaluated using factor analysis and association with health status on the CIDI. The cross-cultural validity was explored using the Rasch Rating Scale Model (RSM).The reliability of the GAD-7 was good (Cronbach's alpha = 0.89). A cutoff score of 7 or higher, maximizing the Youden Index, yielded a sensitivity of 73.3% and a specificity of 67.3%. One-factor structure of the GAD-7 was confirmed by exploratory and confirmatory factor analysis. Concurrent validity was supported by the evidence that higher GAD-7 scores were associated with poor self-rated physical and mental health. The Rasch RSM further confirmed the cross-cultural validity of the GAD-7.The results suggest that the Spanish-language version of the GAD-7 may be used as a screening tool for pregnant Peruvian women. The GAD-7 has good reliability, factorial validity, and concurrent validity. The optimal cutoff score obtained by maximizing the Youden Index should be considered cautiously; women who screened positive may require further investigation to confirm GAD diagnosis.

  View details for DOI 10.1371/journal.pone.0125096

  View details for PubMedID 25915929

  View details for PubMedCentralID PMC4411061

• Medications as a source of paraben exposure. Reproductive toxicology (Elmsford, N.Y.) Dodge, L. E., Kelley, K. E., Williams, P. L., Williams, M. A., Hernández-Díaz, S., Missmer, S. A., Hauser, R. 2015; 52: 93-100

  Abstract

  Parabens are used as antimicrobial excipients in some pharmaceuticals. Parabens may adversely affect reproduction.Determine whether paraben-containing medication contributes to high urinary paraben concentrations.Individuals at a fertility clinic provided multiple urine samples during evaluation/treatment and reported 24-h use of medications and personal care products (PCP). Repeated measures models compared specific gravity-adjusted urinary methyl, propyl, and butyl paraben concentrations between samples "exposed" and "unexposed" to paraben-containing medication.Eleven participants contributed 12 exposed and 45 unexposed samples, among which paraben concentrations did not differ. Use within 7h was associated with 8.7-fold and 7.5-fold increases in mean methyl (P=0.11) and propyl (P=0.10) paraben concentrations, respectively, after adjusting for PCP use. However, these associations decreased to 1.3-fold (P=0.76) and 2.6-fold (P=0.34), respectively, after removal of one influential individual.Paraben-containing medications contributed to higher urinary paraben concentrations within hours of use.

  View details for DOI 10.1016/j.reprotox.2015.02.002

  View details for PubMedID 25728410

  View details for PubMedCentralID PMC4426043

• Is the fetoplacental ratio a differential marker of fetal growth restriction in small for gestational age infants? European journal of epidemiology Luque-Fernandez, M. A., Ananth, C. V., Jaddoe, V. W., Gaillard, R., Albert, P. S., Schomaker, M., McElduff, P., Enquobahrie, D. A., Gelaye, B., Williams, M. A. 2015; 30 (4): 331-41

  Abstract

  Higher placental weight relative to birthweight has been described as an adaptive mechanism to fetal hypoxia in small for gestational age (SGA) infants. However, placental weight alone may not be a good marker reflecting intrauterine growth restriction. We hypothesized that fetoplacental ratio (FPR)-the ratio between birthweight and placental weight-may serve as a good marker of SGA after adjustment for surrogates of fetal hypoxemia (maternal iron deficiency anemia, smoking and choriodecidual necrosis). We conducted a within-sibling analysis using data from the US National Collaborative Perinatal Project (1959-1966) of 1,803 women who delivered their first two (or more) consecutive infants at term (n = 3,494). We used variance-component fixed-effect linear regression models to explore the effect of observed time-varying factors on placental weight and conditional logistic regression to estimate the effects of the tertiles of FPRs (1st small, 2nd normal and 3rd large) on the odds of SGA infants. We found placental weights to be 15 g [95 % confidence interval (CI) 8, 23] higher and -7 g (95 % CI -13, -2) lower among women that had anemia and choriodecidual necrosis, respectively. After multivariable adjustment, newborns with a small FPR (1st-tertile ≤7) had twofold higher odds of being SGA (OR 2.0, 95 % CI 1.2, 3.5) than their siblings with a large FPR (3nd-tertile ≥9). A small FPR was associated with higher odds of SGA, suggesting that small FPR may serve as an indicator suggestive of adverse intrauterine environment. This observation may help to distinguish pathological from constitutional SGA.

  View details for DOI 10.1007/s10654-015-9993-9

  View details for PubMedID 25630563

• Infant sex-specific placental cadmium and DNA methylation associations. Environmental research Mohanty, A. F., Farin, F. M., Bammler, T. K., MacDonald, J. W., Afsharinejad, Z., Burbacher, T. M., Siscovick, D. S., Williams, M. A., Enquobahrie, D. A. 2015; 138: 74-81

  Abstract

  Recent evidence suggests that maternal cadmium (Cd) burden and fetal growth associations may vary by fetal sex. However, mechanisms contributing to these differences are unknown.Among 24 maternal-infant pairs, we investigated infant sex-specific associations between placental Cd and placental genome-wide DNA methylation.We used ANOVA models to examine sex-stratified associations of placental Cd (dichotomized into high/low Cd using sex-specific Cd median cutoffs) with DNA methylation at each cytosine-phosphate-guanine site or region. Statistical significance was defined using a false discovery rate cutoff (<0.10).Medians of placental Cd among females and males were 5 and 2 ng/g, respectively. Among females, three sites (near ADP-ribosylation factor-like 9 (ARL9), siah E3 ubiquitin protein ligase family member 3 (SIAH3), and heparin sulfate (glucosamine) 3-O-sulfotransferase 4 (HS3ST4) and one region on chromosome 7 (including carnitine O-octanoyltransferase (CROT) and TP5S target 1 (TP53TG1)) were hypomethylated in high Cd placentas. Among males, high placental Cd was associated with methylation of three sites, two (hypomethylated) near MDS1 and EVI1 complex locus (MECOM) and one (hypermethylated) near spalt-like transcription factor 1 (SALL1), and two regions (both hypomethylated, one on chromosome 3 including MECOM and another on chromosome 8 including rho guanine nucleotide exchange factor (GEF) 10 (ARHGEF10). Differentially methylated sites were at or close to transcription start sites of genes involved in cell damage response (SIAH3, HS3ST4, TP53TG1) in females and cell differentiation, angiogenesis and organ development (MECOM, SALL1) in males.Our preliminary study supports infant sex-specific placental Cd-DNA methylation associations, possibly accounting for previously reported differences in Cd-fetal growth associations across fetal sex. Larger studies are needed to replicate and extend these findings. Such investigations may further our understanding of epigenetic mechanisms underlying maternal Cd burden with suboptimal fetal growth associations.

  View details for DOI 10.1016/j.envres.2015.02.004

  View details for PubMedID 25701811

  View details for PubMedCentralID PMC4385453

• Association of decreased serum brain-derived neurotrophic factor (BDNF) concentrations in early pregnancy with antepartum depression. BMC psychiatry Fung, J., Gelaye, B., Zhong, Q. Y., Rondon, M. B., Sanchez, S. E., Barrios, Y. V., Hevner, K., Qiu, C., Williams, M. A. 2015; 15: 43

  Abstract

  Antepartum depression is one of the leading causes of maternal morbidity and mortality in the prenatal period. There is accumulating evidence for the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of depression. The present study examines the extent to which maternal early pregnancy serum BDNF levels are associated with antepartum depression.A total of 968 women were recruited and interviewed in early pregnancy. Antepartum depression prevalence and symptom severity were assessed using the Patient Health Questionnaire-9 (PHQ-9) scale. Maternal serum BDNF levels were measured using a competitive enzyme-linked immunosorbent assay (ELISA). Logistic regression procedures were performed to estimate odds ratios (OR) and 95% confidence intervals (95% CI) adjusted for confounders.Maternal early pregnancy serum BDNF levels were significantly lower in women with antepartum depression compared to women without depression (mean ± standard deviation [SD]: 20.78 ± 5.97 vs. 21.85 ± 6.42 ng/ml, p = 0.024). Lower BDNF levels were associated with increased odds of maternal antepartum depression. After adjusting for confounding, women whose serum BDNF levels were in the lowest three quartiles (<17.32 ng/ml) had 1.61-fold increased odds (OR = 1.61, 95% CI: 1.13, 2.30) of antepartum depression as compared with women whose BDNF levels were in the highest quartile (>25.31 ng/ml). There was no evidence of an association of BDNF levels with depression symptom severity.Lower maternal serum BDNF levels in early pregnancy are associated with antepartum depression. These findings may point toward new therapeutic opportunities and BDNF should be assessed as a potential biomarker for risk prediction and monitoring response to treatment for antepartum depression.

  View details for DOI 10.1186/s12888-015-0428-7

  View details for PubMedID 25886523

  View details for PubMedCentralID PMC4364091

• Sleep disturbances and quality of life in Sub-Saharan African migraineurs. The journal of headache and pain Morgan, I., Eguia, F., Gelaye, B., Peterlin, B. L., Tadesse, M. G., Lemma, S., Berhane, Y., Williams, M. A. 2015; 16: 18

  Abstract

  Although in the past decade occidental countries have increasingly recognized the personal and societal burden of migraine, it remains poorly understood in Africa. No study has evaluated the impact of sleep disturbances and the quality of life (QOL) in sub-Saharan Africans with migraine.This was a cross-sectional study evaluating adults, ≥ 18 years of age, attending outpatient clinics in Ethiopia. Standardized questionnaires were utilized to collect demographic, headache, sleep, lifestyle, and QOL characteristics in all participants. Migraine classification was based on International Classification of Headache Disorders (ICHD)-II criteria. The Pittsburgh Sleep Quality Index (PSQI) and the World Health Organization Quality of Life (WHOQOL-BREF) questionnaires were utilized to assess sleep quality and QOL characteristics, respectively. Multivariable logistic regression models were fit to estimate adjusted odds ratio (OR) and 95% confidence intervals (95% CI).Of 1,060 participants, 145 (14%) met ICHD-II criteria for migraine. Approximately three-fifth of the study participants (60.5%) were found to have poor sleep quality. After adjustments, migraineurs had over a two-fold increased odds (OR = 2.24, 95% CI 1.49-3.38) of overall poor sleep quality (PSQI global score >5) as compared with non-migraineurs. Compared with non-migraineurs, migraineurs were also more likely to experience short sleep duration (≤7 hours) (OR = 2.07, 95% CI 1.43-3.00), long sleep latency (≥30 min) (OR = 1.97, 95% CI 1.36-2.85), daytime dysfunction due to sleepiness (OR = 1.51, 95% CI 1.12-2.02), and poor sleep efficiency (<85%) (OR = 1.93, 95% CI 1.31-2.88). Similar to occidental countries, Ethiopian migraineurs reported a reduced QOL as compared to non-migraineurs. Specifically Ethiopian migraineurs were more likely to experience poor physical (OR = 1.56, 95% CI 1.08-2.25) and psychological health (OR = 1.75, 95% CI 1.20-2.56), as well as poor social relationships (OR = 1.56, 95% CI 1.08-2.25), and living environments (OR = 1.41, 95% CI 0.97-2.05) as compared to those without migraine.Similar to occidental countries, migraine is highly prevalent among Ethiopians and is associated with poor sleep quality and a lower QOL. These findings support the need for physicians and policy makers to take action to improve the quality of headache care and access to treatment in Ethiopia.

  View details for DOI 10.1186/s10194-015-0504-x

  View details for PubMedID 25902831

  View details for PubMedCentralID PMC4385231

• Adverse childhood experiences are associated with adult sleep disorders: a systematic review. Sleep medicine Kajeepeta, S., Gelaye, B., Jackson, C. L., Williams, M. A. 2015; 16 (3): 320-30

  Abstract

  Adverse childhood experiences (ACEs) represent substantial threats to public health and affect about 58% of youth in the US. In addition to their acute effects such as injury and physical trauma, ACEs are associated with an increased risk of several negative health outcomes throughout the life course. Emerging evidence suggests that sleep disorders may be one such outcome, but existing studies have not been systematically reviewed and summarized. We conducted a systematic review to summarize the evidence concerning the relationship between ACEs and sleep disorders and disturbances, with a focus on adult women. Original publications were identified through searches of the electronic databases MEDLINE, Embase, and Web of Science using the keywords "childhood," "adversity," "abuse," and "sleep" as well as searches of the reference lists of eligible studies. Studies evaluating ACEs that occurred before 18 years of age and sleep outcomes that were assessed at 18 years or older were adjudicated and included. A total of 30 publications were identified. Of the 30 studies, 28 were retrospective analyses and there was vast heterogeneity in the types of ACEs and sleep outcomes measured. The majority of retrospective studies (N = 25 of 28) documented statistically significant associations between sleep disorders including sleep apnea, narcolepsy, nightmare distress, sleep paralysis, and psychiatric sleep disorders with a history of childhood adversity. In many studies, the strengths of associations increased with the number and severity of adverse experiences. These associations were corroborated by the two prospective studies published to date. Notably, investigators have documented statistically significant associations between family conflict at 7-15 years of age and insomnia at 18 years of age (odds ratio, OR = 1.4; 95% confidence interval, CI = 1.2-1.7) and between childhood sexual abuse and sleep disturbances 10 years later in adult women (β = 0.24, p <0.05). There is a growing scientific body of knowledge suggesting an association between ACEs and multiple sleep disorders in adulthood. The available evidence indicates the need to develop treatment strategies such as trauma-informed care for survivors of abuse who suffer from sleep disorders and disturbances. Further, longitudinal studies among diverse populations are needed to improve the overall understanding of this association and to investigate potential gender and racial/ethnic disparities in the strength of the association.

  View details for DOI 10.1016/j.sleep.2014.12.013

  View details for PubMedID 25777485

  View details for PubMedCentralID PMC4635027

• Dimitrios Trichopoulos: in memoriam (1938-2014). Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Mucci, L. A., Hunter, D. J., Williams, M. 2015; 24 (3): 483

  View details for DOI 10.1158/1055-9965.EPI-14-1412

  View details for PubMedID 25750250

• Caregivers' hair cortisol: a possible biomarker of chronic stress is associated with obesity measures among children with disabilities. BMC pediatrics Chen, X., Gelaye, B., Velez, J. C., Barbosa, C., Pepper, M., Andrade, A., Gao, W., Kirschbaum, C., Williams, M. A. 2015; 15: 9

  Abstract

  The stress of caring for a loved one with chronic illness has been associated with childhood obesity. Hair cortisol has been proposed as a novel biomarker of chronic psychological stress. This study aimed to evaluate the associations between caregivers' chronic stress evaluated by hair cortisol concentrations (HCC) and obesity measures among children with disabilities such as autism.Eighty-five dyads of children with disabilities and their primary caregivers participated in the study between April and July 2013 in the Patagonia Region, Chile. Trained research staff conducted anthropometric measurements of children and caregivers. Cortisol concentrations, extracted from hair samples with methanol, were quantified using liquid chromatography tandem mass spectrometry. Pearson's correlation coefficients and linear regression models were used to examine the associations between caregiver HCC (log-transformed) and child obesity measures with adjustment for covariates.Caregiver HCC were positively and significantly correlated with child weight (child age- and sex-adjusted r =0.23, P = 0.036), body mass index (BMI) (r = 0.23, P = 0.035), circumferences of neck (r = 0.30, P = 0.006), waist (r = 0.27, P = 0.014), and hip (r = 0.22, P = 0.044). After adjustment for children's age and sex, caregiver HCC were significantly related to child weight (kg) (beta = 4.47, standard error (SE) = 2.09), BMI (kg/m(2)) (beta = 1.52, SE = 0.71), neck circumference (cm) (beta = 1.20, SE = 0.43), waist circumference (cm) (beta = 3.75, SE = 1.50), and hip circumference (cm) (beta = 3.02, SE = 1.48). Caregiver HCC were also positively but not statistically significantly associated with child waist-to-hip ratio (beta = 0.01, SE = 0.01; P = 0.191) or body fat percentage (%) (beta = 2.11, SE = 1.28; P = 0.104). Further adjustment for other covariates including child disability diagnosis and caregiver age, sex, education, current smoking, perceived stress, and caregiver BMI did not change the results substantially.Chronic stress of caregivers, evaluated by increased cortisol concentrations in hair, was positively associated with obesity measures among children with disabilities.

  View details for DOI 10.1186/s12887-015-0322-y

  View details for PubMedID 25886364

  View details for PubMedCentralID PMC4339433

• Childhood abuse and early menarche among Peruvian women. The Journal of adolescent health : official publication of the Society for Adolescent Medicine Barrios, Y. V., Sanchez, S. E., Nicolaidis, C., Garcia, P. J., Gelaye, B., Zhong, Q., Williams, M. A. 2015; 56 (2): 197-202

  Abstract

  Childhood abuse has been associated with age of menarche in some studies, but not all, and few have assessed the independent associations of sexual and physical abuse with early menarche. We examined the association between childhood abuse and early menarche among pregnant women in Lima, Peru.Multinomial logistic regression procedures were used to estimate odds ratios (OR) and 95% confidence intervals (CIs) for early menarche (≤11 years) in relation to any physical or sexual childhood abuse, physical abuse only, sexual abuse only, and both physical and sexual abuse in a cohort of 1,499 pregnant (first trimester) women.Approximately 69% of participants reported experiencing physical or sexual abuse in childhood. The frequencies of physical abuse only, sexual abuse only, and both physical and sexual abuse were 37.4%, 7.7%, and 24.5%, respectively. Compared with women who reported no childhood abuse, those who reported any childhood abuse had a 1.38-fold increased odds of early menarche (95% CI, 1.01-1.87). Compared with no abuse, the odds of early menarche was 1.60-fold among women with childhood sexual abuse only (OR, 1.60; 95% CI, .93-2.74) and 1.56-fold for those with both physical and sexual abuse (OR, 1.56; 95% CI, 1.07-2.25) during childhood. Isolated physical abuse was weakly associated with early menarche (OR, 1.23; 95% CI, .87-1.74). There was no clear evidence of association of childhood abuse with late menarche (≥15 years).Childhood abuse, particularly joint physical and sexual abuse, is associated with early menarche. Our findings add to an expanding body of studies documenting the enduring adverse health consequences of childhood abuse.

  View details for DOI 10.1016/j.jadohealth.2014.10.002

  View details for PubMedID 25620302

  View details for PubMedCentralID PMC4306809

• Childhood sexual abuse and posttraumatic stress disorder among pregnant and postpartum women: review of the literature. Archives of women's mental health Wosu, A. C., Gelaye, B., Williams, M. A. 2015; 18 (1): 61-72

  Abstract

  The aims of this review are (i) to summarize and evaluate current knowledge on the association between childhood sexual abuse (CSA) and posttraumatic stress disorder (PTSD) in pregnant and postpartum women, (ii) to provide suggestions for future research on this topic, and (iii) to highlight some clinical implications. Relevant publications were identified through literature searches of four databases (PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, and PsycARTICLES) using keywords such as "child abuse," "posttraumatic stress," "pregnancy," and "postpartum". Five studies were included in this review. Findings across all studies were consistent with higher prevalence of PTSD diagnosis or symptomatology among women with history of CSA. However, only findings from two studies were statistically significant. One study observed higher overall PTSD scores in women with CSA history compared to women with non-CSA trauma history or no trauma history during pregnancy (mean ± SD 1.47 (0.51) vs. 1.33 (0.41) vs. 1.22 (0.29), p < 0.001), at 2 months postpartum (mean ± SD 1.43 (0.49) vs. 1.26 (0.38) vs. 1.19 (0.35), p < 0.001), and at 6 months postpartum (mean ± SD 1.36 (1.43) vs. 1.20 (0.33) vs. 1.14 (0.27), p < 0.001). Another study observed that the prevalence of PTSD during pregnancy was 4.1 % in women with no history of physical or sexual abuse, 11.4 % in women with adult physical or sexual abuse history, 16.0 % in women with childhood physical or sexual abuse history, and 39.0 % in women exposed to both childhood and adult physical or sexual abuse (p < 0.001); in a subsequent analysis, the investigators reported that pregnant women with PTSD had over 5-fold odds of having a history of childhood completed rape compared to counterparts without PTSD (OR = 5.3, 95 % CI 3.2, 8.7). Overall, available evidence suggests positive associations of CSA with clinical PTSD or PTSD symptomatology among pregnant and postpartum women.

  View details for DOI 10.1007/s00737-014-0482-z

  View details for PubMedID 25380784

  View details for PubMedCentralID PMC4308508

• Depression, anxiety and stress among pregnant migraineurs in a pacific-northwest cohort. Journal of affective disorders Orta, O. R., Gelaye, B., Qiu, C., Stoner, L., Williams, M. A. 2015; 172: 390-6

  Abstract

  The co-occurrence of migraine and unipolar psychiatric disorders has been well documented in non-pregnant populations, however little is known in pregnant populations.A cohort of 1321 women was interviewed during the first trimester of pregnancy. At the time of interview lifetime migraine status was ascertained using International Classification of Headache Disorders diagnostic criteria (ICHD-II). Information regarding unipolar depression, anxiety and stress during pregnancy was collected using the Patient Health Questionnaire Depression Module-9 (PHQ-9), and the Depression Anxiety Stress Scales 21-item Short Form (DASS-21). Multivariable logistic regression procedures were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of migraine and mood disorders during pregnancy.Approximately 28.2% (N=372) were classified as having a lifetime history of migraine; among migraineurs 122 were classified as migraineurs with aura and 250 as migraineurs without aura. Compared with non-migraineurs, migraineurs were associated with 1.60-fold increased odds of depression as measured by a PHQ-9 score ≥10 (AOR=1.60; 95% CI: 1.12-2.31). Overall, migraine with aura was more strongly associated with depression than was migraine without aura. Migraineurs, as compared with non-migraineurs, also had higher odds of mood disorders as measured by the DASS-21.The comorbidity of mood and migraine disorders in pregnant populations supports the need for integrated mental and physical clinical evaluation, increased vigilance, and treatment of patients with such disorders.

  View details for DOI 10.1016/j.jad.2014.10.032

  View details for PubMedID 25451442

  View details for PubMedCentralID PMC4406774

• Hair cortisol in relation to sociodemographic and lifestyle characteristics in a multiethnic US sample. Annals of epidemiology Wosu, A. C., Gelaye, B., Valdimarsdóttir, U., Kirschbaum, C., Stalder, T., Shields, A. E., Williams, M. A. 2015; 25 (2): 90-5, 95.e1-2

  Abstract

  We investigated the feasibility of obtaining hair samples from men and women at community-based barbershops and hair salons for analysis of cortisol and assessed sociodemographic and lifestyle correlates of hair cortisol concentrations (HCCs). A total of 102 participants completed the study.Research staff interviewed participants using a structured questionnaire, and samples of hair were collected. HCCs were determined using liquid chromatography-tandem mass spectrometry. Age- and sex-adjusted linear regression models were used to evaluate the association of HCC with covariates.Analyses by race/ethnicity showed highest median HCC in blacks (12.5 [6.9-29.3]) pg/mg) followed by Hispanics (10.7 [5.8-14.9] pg/mg), whites (5.0 [3.8-10.8] pg/mg), and other participants (4.2 [3.3-15.7] pg/mg), P < .01. Current smokers had significantly higher median HCC (11.7 [8.8-18.9] pg/mg) compared with former smokers (4.6 [3.5-14.6] pg/mg) and those who had never smoked (6.9 [4.7-12.8] pg/mg), P = .04. After adjustment for age and sex, geometric mean HCC was 0.72 pg/mg lower in dyed hair compared with hair that was not dyed (β = -0.72, standard error = 0.30, 95% confidence interval, -1.29 to -0.15, P = .02).HCC can be assessed in community-based studies. Future HCC studies should consider cosmetic hair treatment, cigarette smoking, and the potential role of psychosocial stressors in the association between race/ethnicity and HCC.

  View details for DOI 10.1016/j.annepidem.2014.11.022

  View details for PubMedID 25534254

  View details for PubMedCentralID PMC4306631

• Association of childhood physical and sexual abuse with intimate partner violence, poor general health and depressive symptoms among pregnant women. PloS one Barrios, Y. V., Gelaye, B., Zhong, Q., Nicolaidis, C., Rondon, M. B., Garcia, P. J., Sanchez, P. A., Sanchez, S. E., Williams, M. A. 2015; 10 (1): e0116609

  Abstract

  We examined associations of childhood physical and sexual abuse with risk of intimate partner violence (IPV). We also evaluated the extent to which childhood abuse was associated with self-reported general health status and symptoms of antepartum depression in a cohort of pregnant Peruvian women.In-person interviews were conducted to collect information regarding history of childhood abuse and IPV from 1,521 women during early pregnancy. Antepartum depressive symptomatology was evaluated using the Patient Health Questionnaire-9. Multivariable logistic regression procedures were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95%CI).Any childhood abuse was associated with 2.2-fold increased odds of lifetime IPV (95%CI: 1.72-2.83). Compared with women who reported no childhood abuse, those who reported both, childhood physical and sexual abuse had a 7.14-fold lifetime risk of physical and sexual IPV (95%CI: 4.15-12.26). The odds of experiencing physical and sexual abuse by an intimate partner in the past year was 3.33-fold higher among women with a history of childhood physical and sexual abuse as compared to women who were not abused as children (95%CI 1.60-6.89). Childhood abuse was associated with higher odds of self-reported poor health status during early pregnancy (aOR = 1.32, 95%CI: 1.04-1.68) and with symptoms of antepartum depression (aOR = 2.07, 95%CI: 1.58-2.71).These data indicate that childhood sexual and physical abuse is associated with IPV, poor general health and depressive symptoms in early pregnancy. The high prevalence of childhood trauma and its enduring effects of on women's health warrant concerted global health efforts in preventing violence.

  View details for DOI 10.1371/journal.pone.0116609

  View details for PubMedID 25635902

  View details for PubMedCentralID PMC4312043

• Smoking and perceived stress in relation to short salivary telomere length among caregivers of children with disabilities. Stress (Amsterdam, Netherlands) Chen, X., Velez, J. C., Barbosa, C., Pepper, M., Andrade, A., Stoner, L., De Vivo, I., Gelaye, B., Williams, M. A. 2015; 18 (1): 20-8

  Abstract

  Telomere length (TL), the length of repeated DNA sequence that forms protective caps at the end of chromosomes, has emerged as a novel biomarker of cell aging and oxidative stress. There is increasing research exploring the associations of smoking and perceived stress with TL, and the results are inconsistent. This study aimed to examine whether smoking and perceived stress were associated with shortened salivary TL among primary caregivers of children with disabilities. Using a quantitative polymerase chain reaction method, salivary TL was assessed among 89 caregivers aged 19-69 years (87% were women) who took care of disabled children in the Patagonia Region, Chile. Interviewer-administered questionnaires were used to collect information on sociodemographic and lifestyle factors. The 14-item Perceived Stress Scale was used to assess perceived stress. Mean relative TL was 0.92 (standard error = 0.03). Smokers had age-adjusted mean TL that was 0.07 units lower (β = -0.07, standard error = 0.03; p = 0.012) than non-smokers. Smokers were 2.17 times more likely to have shorter TL ( < 0.73, the lowest quartile of TL) than non-smokers (odds ratio = 3.17; 95% confidence interval = 1.05-9.52) with adjustment for age and perceived stress. Caregivers with higher perceived stress were 2.13 times more likely to have shorter TL (odds ratio = 3.13; 95% confidence interval = 1.03-9.55) than caregivers with lower perceived stress after adjustment for age and smoking. This study provides the first evidence of strong associations between smoking and perceived stress and shortened salivary TL among caregivers of children with disabilities. Larger studies with detailed information on smoking status are warranted to confirm our findings.

  View details for DOI 10.3109/10253890.2014.969704

  View details for PubMedID 25256607

  View details for PubMedCentralID PMC4344384

• Construct validity and factor structure of the pittsburgh sleep quality index and epworth sleepiness scale in a multi-national study of African, South East Asian and South American college students. PloS one Gelaye, B., Lohsoonthorn, V., Lertmeharit, S., Pensuksan, W. C., Sanchez, S. E., Lemma, S., Berhane, Y., Zhu, X., Vélez, J. C., Barbosa, C., Anderade, A., Tadesse, M. G., Williams, M. A. 2014; 9 (12): e116383

  Abstract

  The Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) are questionnaires used to assess sleep quality and excessive daytime sleepiness in clinical and population-based studies. The present study aimed to evaluate the construct validity and factor structure of the PSQI and ESS questionnaires among young adults in four countries (Chile, Ethiopia, Peru and Thailand).A cross-sectional study was conducted among 8,481 undergraduate students. Students were invited to complete a self-administered questionnaire that collected information about lifestyle, demographic, and sleep characteristics. In each country, the construct validity and factorial structures of PSQI and ESS questionnaires were tested through exploratory and confirmatory factor analyses (EFA and CFA).The largest component-total correlation coefficient for sleep quality as assessed using PSQI was noted in Chile (r = 0.71) while the smallest component-total correlation coefficient was noted for sleep medication use in Peru (r = 0.28). The largest component-total correlation coefficient for excessive daytime sleepiness as assessed using ESS was found for item 1 (sitting/reading) in Chile (r = 0.65) while the lowest item-total correlation was observed for item 6 (sitting and talking to someone) in Thailand (r = 0.35). Using both EFA and CFA a two-factor model was found for PSQI questionnaire in Chile, Ethiopia and Thailand while a three-factor model was found for Peru. For the ESS questionnaire, we noted two factors for all four countries.Overall, we documented cross-cultural comparability of sleep quality and excessive daytime sleepiness measures using the PSQI and ESS questionnaires among Asian, South American and African young adults. Although both the PSQI and ESS were originally developed as single-factor questionnaires, the results of our EFA and CFA revealed the multi- dimensionality of the scales suggesting limited usefulness of the global PSQI and ESS scores to assess sleep quality and excessive daytime sleepiness.

  View details for DOI 10.1371/journal.pone.0116383

  View details for PubMedID 25551586

  View details for PubMedCentralID PMC4281247

• Placental genome and maternal-placental genetic interactions: a genome-wide and candidate gene association study of placental abruption. PloS one Denis, M., Enquobahrie, D. A., Tadesse, M. G., Gelaye, B., Sanchez, S. E., Salazar, M., Ananth, C. V., Williams, M. A. 2014; 9 (12): e116346

  Abstract

  While available evidence supports the role of genetics in the pathogenesis of placental abruption (PA), PA-related placental genome variations and maternal-placental genetic interactions have not been investigated. Maternal blood and placental samples collected from participants in the Peruvian Abruptio Placentae Epidemiology study were genotyped using Illumina's Cardio-Metabochip platform. We examined 118,782 genome-wide SNPs and 333 SNPs in 32 candidate genes from mitochondrial biogenesis and oxidative phosphorylation pathways in placental DNA from 280 PA cases and 244 controls. We assessed maternal-placental interactions in the candidate gene SNPS and two imprinted regions (IGF2/H19 and C19MC). Univariate and penalized logistic regression models were fit to estimate odds ratios. We examined the combined effect of multiple SNPs on PA risk using weighted genetic risk scores (WGRS) with repeated ten-fold cross-validations. A multinomial model was used to investigate maternal-placental genetic interactions. In placental genome-wide and candidate gene analyses, no SNP was significant after false discovery rate correction. The top genome-wide association study (GWAS) hits were rs544201, rs1484464 (CTNNA2), rs4149570 (TNFRSF1A) and rs13055470 (ZNRF3) (p-values: 1.11e-05 to 3.54e-05). The top 200 SNPs of the GWAS overrepresented genes involved in cell cycle, growth and proliferation. The top candidate gene hits were rs16949118 (COX10) and rs7609948 (THRB) (p-values: 6.00e-03 and 8.19e-03). Participants in the highest quartile of WGRS based on cross-validations using SNPs selected from the GWAS and candidate gene analyses had a 8.40-fold (95% CI: 5.8-12.56) and a 4.46-fold (95% CI: 2.94-6.72) higher odds of PA compared to participants in the lowest quartile. We found maternal-placental genetic interactions on PA risk for two SNPs in PPARG (chr3:12313450 and chr3:12412978) and maternal imprinting effects for multiple SNPs in the C19MC and IGF2/H19 regions. Variations in the placental genome and interactions between maternal-placental genetic variations may contribute to PA risk. Larger studies may help advance our understanding of PA pathogenesis.

  View details for DOI 10.1371/journal.pone.0116346

  View details for PubMedID 25549360

  View details for PubMedCentralID PMC4280220

• Adiponectin and leptin levels in migraineurs in the Atherosclerosis Risk in Communities Study. Neurology Dearborn, J. L., Schneider, A. L., Gottesman, R. F., Kurth, T., Pankow, J. S., Couper, D. J., Rose, K. M., Williams, M. A., Peterlin, B. L. 2014; 83 (24): 2211-8

  Abstract

  To evaluate adiponectin and leptin levels in older men and women with migraine.Fasting total and high molecular weight (HMW) adiponectin and leptin levels were evaluated in a case-cohort study of nondiabetic older migraine and nonmigraine control participants from the ongoing, longitudinal, general population, Atherosclerosis Risk in Communities Study at visit 1 (1987-1989). A standardized headache questionnaire was completed at visit 3 (1993-1995). Logistic regression models adjusted for age, sex, race, center, body mass index, and fasting glucose were used to evaluate the association of each adipocytokine with migraine.Of the 981 participants, the mean age at baseline was 52.8 years (SE 0.3); 131 fulfilled migraine criteria. Crude, mean total adiponectin levels were greater in men and women with migraine (8.1 µg/mL, SE 0.5) as compared to those without migraine (7.0 µg/mL, SE 0.2) (p = 0.031). After adjustments, the odds of migraine were increased by 88% with each SD increase in total adiponectin in men (odds ratio [OR] 1.86; 95% confidence interval [CI] 1.15, 3.01; p = 0.011), but not in women (OR 1.05; 95% CI 0.80, 1.37; p = 0.728; p interaction = 0.029). Similar results were demonstrated for HMW adiponectin. Crude and adjusted leptin levels were not associated with migraine.Although crude, total adiponectin levels were higher in older men and women with migraine than controls, after adjustments, the prevalence of migraine was significantly associated with total adiponectin only in older men, suggesting the association may be confounded or absent in older women. Leptin was not associated with migraine in older men or women.

  View details for DOI 10.1212/WNL.0000000000001067

  View details for PubMedID 25378672

  View details for PubMedCentralID PMC4277678

• Vitamin D Deficiency Treatment Patterns in Academic Urban Medical Center. The American journal of pharmacy benefits Chandler, P. D., Giovannucci, E. L., Williams, M. A., LeBoff, M. S., Bates, D. W., Hicks, L. S. 2014; 6 (1): e1-e8

  Abstract

  Assess racial/ethnic and sex differences in treatment of vitamin D deficiency with high dose ergocalciferol ('vitamin D2') or other forms of vitamin D in a northeastern U.S. ambulatory clinic of an academic urban medical center.Cross-sectional observational review of electronic medication prescribing records of patients with 25-hydroxyvitamin D (25OHD) deficiency (25OHD < 20 ng/ml) from 2004-2008.Using multivariable logistic regression adjusting for patients' demographics, and Elixhauser comorbidity score, we examined the association of sex and race/ethnicity with prescription for at least one dose of vitamin D.Among 2,140 patients without renal disease and tested for 25OHD deficiency (25OHD < 20 ng/ml), 66.2% received no vitamin D prescription for vitamin D deficiency. Blacks and Hispanics received vitamin D prescriptions at a higher frequency than whites, 37.8% 38.4% and 30.9%, respectively, p=0.003. The vitamin D prescription rate for women versus men was 26.3% and 7.5%, respectively, p=0.04. In a fully adjusted model, no difference in prescription likelihood for blacks and whites [OR=1.18 95% CI, 0.88-1.58; p=0.29] or Hispanics and whites was noted [OR=1.01 95% CI, 0.70-1.45;p=0.73]. Similarly, fully adjusted model showed no difference in prescription likelihood for females and males [OR=1.23 95% CI, 0.93-1.63; p=0.12].Among primary care patients with vitamin D deficiency, vitamin D supplementation was low and white patients were less likely to receive vitamin D treatment than blacks or Hispanics. Interventions to correct the high prevalence of vitamin D deficiency should address the markedly low rate of vitamin D prescribing when 25OHD levels are measured.

  View details for PubMedID 25328637

  View details for PubMedCentralID PMC4199332

• Attitudes, beliefs, and perceptions of caregivers and rehabilitation providers about disabled children's sleep health: a qualitative study. BMC pediatrics Chen, X., Gelaye, B., Velez, J. C., Pepper, M., Gorman, S., Barbosa, C., Zafonte, R. D., Redline, S., Williams, M. A. 2014; 14: 245

  Abstract

  Children with disabilities are more likely to have sleep disturbances than children without disabilities. Identifying attitudes, beliefs, knowledge, and perceptions of caregivers and health professionals is essential in developing effective intervention programs to improve disabled children's sleep health. However, no such qualitative data about adults who have key roles in the life and daytime activities of children with disabilities are available. This qualitative study aimed to understand attitudes, beliefs, knowledge, and perceptions about disabled children's sleep hygiene among caregivers and rehabilitation providers of children with disabilities.Twenty seven adults, including nine primary caregivers and eighteen rehabilitation providers, participated in five focus group discussions between September and December 2012 at the Rehabilitation Center in Punta Arenas, Chile. A trained facilitator guided focus group discussions using a semi-structured script. Audiotapes and transcripts of focus group discussions were reviewed and analyzed for recurrent themes.Participants identified seven themes related to children's sleep hygiene: lifestyle behaviors, family factors, children's disabilities and/or comorbidities, environmental factors, adults' responsibilities for children's sleep, perception of good sleep, and parental distress about children's sleep problems. While both caregivers and rehabilitation providers recognized the importance of sleep for children's health and functioning, they differed in their understanding of how sleep hygiene practices influence sleep. Rehabilitation providers recognized the negative influence of electronics on sleep and the positive influence of sleep routines. In contrast, caregivers reported use of television/movie watching and stimulants as coping strategies for managing children's sleep problems.Caregivers may benefit from better understanding the influence of electronics and stimulant use on child sleep health. Rehabilitation providers are well positioned to provide educational messages to both children and caregivers in order to change their attitudes, perceptions, and practices surrounding sleep. These qualitative data are valuable in developing intervention programs aimed at improving sleep health among children with disabilities.

  View details for DOI 10.1186/1471-2431-14-245

  View details for PubMedID 25273034

  View details for PubMedCentralID PMC4194412

• Sleep duration, vital exhaustion, and odds of spontaneous preterm birth: a case-control study. BMC pregnancy and childbirth Kajeepeta, S., Sanchez, S. E., Gelaye, B., Qiu, C., Barrios, Y. V., Enquobahrie, D. A., Williams, M. A. 2014; 14: 337

  Abstract

  Preterm birth is a leading cause of perinatal morbidity and mortality worldwide, resulting in a pressing need to identify risk factors leading to effective interventions. Limited evidence suggests potential relationships between maternal sleep or vital exhaustion and preterm birth, yet the literature is generally inconclusive.We examined the relationship between maternal sleep duration and vital exhaustion in the first six months of pregnancy and spontaneous (non-medically indicated) preterm birth among 479 Peruvian women who delivered a preterm singleton infant (<37 weeks gestation) and 480 term controls who delivered a singleton infant at term (≥37 weeks gestation). Maternal nightly sleep and reports of vital exhaustion were ascertained through in-person interviews. Spontaneous preterm birth cases were further categorized as those following either spontaneous preterm labor or preterm premature rupture of membranes. In addition, cases were categorized as very (<32 weeks), moderate (32-33 weeks), and late (34- <37 weeks) preterm birth for additional analyses. Logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs).After adjusting for confounders, we found that short sleep duration (≤6 hours) was significantly associated with preterm birth (aOR = 1.56; 95% CI 1.11-2.19) compared to 7-8 hours of sleep. Vital exhaustion was also associated with increased odds of preterm birth (aOR = 2.41; 95% CI 1.79-3.23) compared to no exhaustion (Ptrend <0.001). These associations remained significant for spontaneous preterm labor and preterm premature rupture of membranes. We also found evidence of joint effects of sleep duration and vital exhaustion on the odds of spontaneous preterm birth.The results of this case-control study suggest maternal sleep duration, particularly short sleep duration, and vital exhaustion may be risk factors for spontaneous preterm birth. These findings call for increased clinical attention to maternal sleep and the study of potential intervention strategies to improve sleep in early pregnancy with the aim of decreasing risk of preterm birth.

  View details for DOI 10.1186/1471-2393-14-337

  View details for PubMedID 25261975

  View details for PubMedCentralID PMC4190429

• Pre-Adolescent Cardio-Metabolic Associations and Correlates: PACMAC methodology and study protocol. BMJ open Castro, N., Faulkner, J., Skidmore, P., Williams, M., Lambrick, D. M., Signal, L., Thunders, M., Muller, D., Lark, S., Hamlin, M., Lane, A. M., Kingi, T. K., Stoner, L. 2014; 4 (9): e005815

  Abstract

  Although cardiovascular disease is typically associated with middle or old age, the atherosclerotic process often initiates early in childhood. The process of atherosclerosis appears to be occurring at an increasing rate, even in pre-adolescents, and has been linked to the childhood obesity epidemic. This study will investigate the relationships between obesity, lifestyle behaviours and cardiometabolic health in pre-pubescent children aged 8-10 years, and investigates whether there are differences in the correlates of cardiometabolic health between Māori and Caucasian children. Details of the methodological aspects of recruitment, inclusion/exclusion criteria, assessments, statistical analyses, dissemination of findings and anticipated impact are described.Phase 1: a cross-sectional study design will be used to investigate relationships between obesity, lifestyle behaviours (nutrition, physical activity/fitness, sleep behaviour, psychosocial influences) and cardiometabolic health in a sample of 400 pre-pubescent (8-10 years old) children. Phase 2: in a subgroup (50 Caucasian, 50 Māori children), additional measurements of cardiometabolic health and lifestyle behaviours will be obtained to provide objective and detailed data. General linear models and logistic regression will be used to investigate the strongest correlate of (1) fatness; (2) physical activity; (3) nutritional behaviours and (4) cardiometabolic health.Ethical approval will be obtained from the New Zealand Health and Disabilities Ethics Committee. The findings from this study will elucidate targets for decreasing obesity and improving cardiometabolic health among preadolescent children in New Zealand. The aim is to ensure an immediate impact by disseminating these findings in an applicable manner via popular media and traditional academic forums. Most importantly, results from the study will be disseminated to participating schools and relevant Māori health entities.

  View details for DOI 10.1136/bmjopen-2014-005815

  View details for PubMedID 25234509

  View details for PubMedCentralID PMC4170204

• Associations of allostatic load with sleep apnea, insomnia, short sleep duration, and other sleep disturbances: findings from the National Health and Nutrition Examination Survey 2005 to 2008. Annals of epidemiology Chen, X., Redline, S., Shields, A. E., Williams, D. R., Williams, M. A. 2014; 24 (8): 612-9

  Abstract

  To examine whether allostatic load (AL), a measure of cumulative physiologic dysregulation across biological systems, was associated with sleep apnea, insomnia, and other sleep disturbances.Data from the National Health and Nutrition Examination Survey 2005-2008 were used. AL was measured using nine biomarkers representing cardiovascular, inflammatory, and metabolic system functioning. A total of 3330 US adults aged 18 years and older were included in this study.The prevalence of high AL (AL score  ≥3) was the highest among African Americans (26.3%), followed by Hispanic Americans (20.3%), whites (17.7%), and other racial/ethnic group (13.8%). After adjustment for sociodemographic and lifestyle factors, high AL was significantly associated with sleep apnea (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.40-2.63), snoring (OR, 2.20; 95% CI, 1.79-2.69), snorting/stop breathing (OR, 2.16; 95% CI, 1.46-3.21), prolonged sleep latency (OR, 1.42; 95% CI, 1.08-1.88), short sleep duration (<6 hours) (OR, 1.35; 95% CI, 1.00-1.82), and diagnosed sleep disorder (OR, 2.26; 95% CI, 1.66-3.08). There was no clear evidence that observed associations varied by sociodemographic characteristics.This study suggests significant associations of high AL with sleep apnea, sleep apnea symptoms, insomnia component, short sleep duration, and diagnosed sleep disorder among US adults.

  View details for DOI 10.1016/j.annepidem.2014.05.014

  View details for PubMedID 24985316

  View details for PubMedCentralID PMC4188508

• Coronary artery calcification is increased in patients with COPD and associated with increased morbidity and mortality. Thorax Williams, M. C., Murchison, J. T., Edwards, L. D., Agustí, A., Bakke, P., Calverley, P. M., Celli, B., Coxson, H. O., Crim, C., Lomas, D. A., Miller, B. E., Rennard, S., Silverman, E. K., Tal-Singer, R., Vestbo, J., Wouters, E., Yates, J. C., van Beek, E. J., Newby, D. E., MacNee, W. 2014; 69 (8): 718-23

  Abstract

  Coronary artery calcification is pathognomonic of coronary artery disease (CAD). Whether CAD in patients with COPD is linked to lung function, functional capacity and/or clinically relevant outcomes is unknown. The objective was to assess the association between CAD and disease severity, functional capacity and outcomes in patients with COPD.Coronary artery calcium score (CACS; Agatston score) was measured using chest CT in patients with COPD, smokers with normal spirometry and non-smokers from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study.CACS was measured in 942 subjects: 672 with COPD (mean age±SD, 63±7 years; FEV1 49±16% predicted), 199 smokers with normal spirometry (54±9 years; FEV1 110±12% predicted) and 71 non-smokers (55±9 years; FEV1 114±14% predicted). CACS was higher in patients with COPD than smokers or non-smokers (median (IQR), 128 (492) vs 0 (75) vs 0 (3) Agatston units (AU), p<0.001). In patients with COPD, CACS correlated with age, pack-years, 6 min walking distance, modified Medical Research Council Dyspnoea score and circulating levels of interleukin (IL)-6, IL-8, Clara Cell protein 16, surfactant protein D and peripheral blood neutrophil count, but not with emphysema, exacerbation frequency, % predicted FEV1 or decline in FEV1. CACS was higher in patients with COPD who died than in those who survived until 3-year follow-up (CACS 406 vs 103 AU, p<0.001), and was associated with mortality in a Cox proportional hazards model (p=0.036).Patients with COPD have more CAD than controls and this is associated with increased dyspnoea, reduced exercise capacity and increased mortality. These data indicate that the presence of CAD in patients with COPD is associated with poor clinical outcomes.

  View details for DOI 10.1136/thoraxjnl-2012-203151

  View details for PubMedID 24473329

• Obstructive Sleep Apnea and Multiple Anthropometric Indices of General Obesity and Abdominal Obesity among Young Adults. International journal of social science studies Chen, X., Pensuksan, W. C., Lohsoonthorn, V., Lertmaharit, S., Gelaye, B., Williams, M. A. 2014; 2 (3): 89-99

  Abstract

  This study aimed to examine the association between obstructive sleep apnea (OSA) and obesity among young adults. A total of 2911 college students in Thailand participated in the study. Anthropometric measurements and blood pressure were taken by trained research staff. Overall, 6.3% of college students had OSA determined by the Berlin Questionnaire, 9.6% were overweight (BMI: 25-29 kg/m2), 4.5% were obese (BMI≥30 kg/m2); 12.4% had abdominal obesity (men: waist circumference≥90 cm; women: waist circumference≥80 cm). There were significant associations between OSA and overweight (odds ratio (OR)=1.72; 95% confidence interval (CI)=1.04-1.85) and obesity (OR=24.23; 95% CI=15.20-38.61), independent of demographic and lifestyle factors, blood pressure, and psychological distress. Students with OSA were more likely to have abdominal obesity than those without OSA (OR=2.09; 95% CI=1.19-3.67). OSA was significantly related to joint effects of general and abdominal obesity. The OSA-obesity associations were robust and evident for both genders, individuals with normal and elevated blood pressure, and those with and without psychological distress. This study shows independent associations of OSA with general and abdominal obesity among young adults. OSA could be a risk factor for obesity and consequent cardiovascular morbidities. OSA screening and treatment might be important for young adults.

  View details for DOI 10.11114/ijsss.v2i3.439

  View details for PubMedID 25530977

  View details for PubMedCentralID PMC4270013

• Assessing validity of a depression screening instrument in the absence of a gold standard. Annals of epidemiology Gelaye, B., Tadesse, M. G., Williams, M. A., Fann, J. R., Vander Stoep, A., Andrew Zhou, X. H. 2014; 24 (7): 527-31

  Abstract

  We evaluated the extent to which use of a hypothesized imperfect gold standard, the Composite International Diagnostic Interview (CIDI), biases the estimates of diagnostic accuracy of the Patient Health Questionnaire-9 (PHQ-9). We also evaluate how statistical correction can be used to address this bias.The study was conducted among 926 adults where structured interviews were conducted to collect information about participants' current major depressive disorder using PHQ-9 and CIDI instruments. First, we evaluated the relative psychometric properties of PHQ-9 using CIDI as a gold standard. Next, we used a Bayesian latent class model to correct for the bias.In comparison with CIDI, the relative sensitivity and specificity of the PHQ-9 for detecting major depressive disorder at a cut point of 10 or more were 53.1% (95% confidence interval: 45.4%-60.8%) and 77.5% (95% confidence interval, 74.5%-80.5%), respectively. Using a Bayesian latent class model to correct for the bias arising from the use of an imperfect gold standard increased the sensitivity and specificity of PHQ-9 to 79.8% (95% Bayesian credible interval, 64.9%-90.8%) and 79.1% (95% Bayesian credible interval, 74.7%-83.7%), respectively.Our results provided evidence that assessing diagnostic validity of mental health screening instrument, where application of a gold standard might not be available, can be accomplished by using appropriate statistical methods.

  View details for DOI 10.1016/j.annepidem.2014.04.009

  View details for PubMedID 24935465

  View details for PubMedCentralID PMC4104527

• Daytime Sleepiness, Circadian Preference, Caffeine Consumption and Use of Other Stimulants among Thai College Students. Journal of public health and epidemiology Tran, J., Lertmaharit, S., Lohsoonthorn, V., Pensuksan, W. C., Rattananupong, T., Tadesse, M. G., Gelaye, B., Williams, M. A. 2014; 8 (6): 202-210

  Abstract

  We conducted this study to evaluate the prevalence of daytime sleepiness and evening chronotype, and to assess the extent to which both are associated with the use of caffeinated stimulants among 3,000 Thai college students. Demographic and behavioral characteristics were collected using a self-administered questionnaire. The Epworth Sleepiness Scale and the Horne and Ostberg Morningness-Eveningness Questionnaire were used to evaluate prevalence of daytime sleepiness and circadian preference. Multivariable logistic regression models were used to evaluate the association between sleep disorders and consumption of caffeinated beverages. Overall, the prevalence of daytime sleepiness was 27.9 % (95% CI: 26.2-29.5%) while the prevalence of evening chronotype was 13% (95% CI: 11.8-14.2%). Students who use energy drinks were more likely to be evening types. For instance, the use of M100/M150 energy drinks was associated with a more than 3-fold increased odds of evening chronotype (OR 3.50; 95% CI 1.90-6.44), while Red Bull users were more than twice as likely to have evening chronotype (OR 2.39; 95% CI 1.02-5.58). Additionally, those who consumed any energy drinks were more likely to be daytime sleepers. For example, Red Bull (OR 1.72; 95% CI 1.08-2.75) or M100/M150 (OR 1.52; 95% CI 1.10-2.11) consumption was associated with increased odds of daytime sleepiness. Our findings emphasize the importance of implementing educational and prevention programs targeted toward improving sleep hygiene and reducing the consumption of energy drinks among young adults.

  View details for DOI 10.5897/JPHE2014.0620

  View details for PubMedID 25356368

  View details for PubMedCentralID PMC4209847

• Early pregnancy urinary biomarkers of fatty acid and carbohydrate metabolism in pregnancies complicated by gestational diabetes. Diabetes research and clinical practice Qiu, C., Enquobahrie, D. A., Frederick, I. O., Sorensen, T. K., Fernandez, M. A., David, R. M., Bralley, J. A., Williams, M. A. 2014; 104 (3): 393-400

  Abstract

  Alterations in organic acid biomarkers from fatty acid and carbohydrate metabolism have been documented in type 2 diabetes patients. However, their association with gestational diabetes mellitus (GDM) is largely unknown.Participants were 25 GDM cases and 25 non-GDM controls. Biomarkers of fatty acid (adipate, suberate and ethylmalonate) and carbohydrate (pyruvate, l-lactate and β-hydroxybutyrate) metabolism were measured in maternal urine samples collected in early pregnancy (17 weeks) using liquid chromatography-mass spectrometry methods. Logistic regression were used to calculate odds ratios (OR) and 95% confidence intervals (CI).GDM cases and controls differed in median urinary concentrations of ethylmalonate (3.0 vs. 2.3μg/mg creatinine), pyruvate (7.4 vs. 2.1μg/mg creatinine), and adipate (4.6 vs. 7.3μg/mg creatinine) (all p-values <0.05). Women in the highest tertile for ethylmalonate or pyruvate concentrations had 11.4-fold (95%CI 1.10-117.48) and 3.27-fold (95%CI 0.72-14.79) increased risk of GDM compared with women in the lowest tertile for ethylmalonate and pyruvate concentrations, respectively. Women in the highest tertile for adipate concentrations, compared with women in the lowest tertile, had an 86% reduction in GDM risk (95%CI 0.02-0.97).These preliminary findings underscore the importance of altered fatty acid and carbohydrate metabolism in the pathogenesis of GDM.

  View details for DOI 10.1016/j.diabres.2014.03.001

  View details for PubMedID 24703806

  View details for PubMedCentralID PMC4077203

• Comparative performance of Patient Health Questionnaire-9 and Edinburgh Postnatal Depression Scale for screening antepartum depression. Journal of affective disorders Zhong, Q., Gelaye, B., Rondon, M., Sánchez, S. E., García, P. J., Sánchez, E., Barrios, Y. V., Simon, G. E., Henderson, D. C., Cripe, S. M., Williams, M. A. 2014; 162: 1-7

  Abstract

  We sought to evaluate the psychometric properties of two widely used screening scales: the Patient Health Questionnaire (PHQ-9) and Edinburgh Postnatal Depression Scale (EPDS) among pregnant Peruvian women.This cross-sectional study included 1517 women receiving prenatal care from February 2012 to March 2013. A structured interview was used to collect data using PHQ-9 and EPDS. We examined reliability, construct and concurrent validity between two scales using internal consistency indices, factor structures, correlations, and Cohen׳s kappa.Both scales had good internal consistency (Cronbach׳s alpha>0.8). Correlation between PHQ-9 and EPDS scores was fair (rho=0.52). Based on exploratory factor analysis (EFA), both scales yielded a two-factor structure. EFA including all items from PHQ-9 and EPDS yielded four factors, namely, "somatization", "depression and suicidal ideation", "anxiety and depression", and "anhedonia". The agreement between the two scales was generally fair at different cutoff scores with the highest Cohen׳s kappa being 0.46.Both the PHQ-9 and EPDS are reliable and valid scales for antepartum depression assessment. The PHQ-9 captures somatic symptoms, while EPDS detects depressive symptoms comorbid with anxiety during early pregnancy. Our findings suggest simultaneous administration of both scales may improve identification of antepartum depressive disorders in clinical settings.

  View details for DOI 10.1016/j.jad.2014.03.028

  View details for PubMedID 24766996

  View details for PubMedCentralID PMC4040145

• Daytime sleepiness, poor sleep quality, eveningness chronotype, and common mental disorders among Chilean college students. Journal of American college health : J of ACH Concepcion, T., Barbosa, C., Vélez, J. C., Pepper, M., Andrade, A., Gelaye, B., Yanez, D., Williams, M. A. 2014; 62 (7): 441-8

  Abstract

  To evaluate whether daytime sleepiness, poor sleep quality, and morningness and eveningness preferences are associated with common mental disorders (CMDs) among college students.A total of 963 college students completed self-administered questionnaires that collected information about sociodemographic characteristics, sleep quality characteristics, CMDs, and other lifestyle behaviors.The prevalence of CMDs was 24.3% (95% confidence interval [CI] [21.5%, 27.1%]) among all students. Prevalence estimates of both excessive daytime sleepiness and poor sleep quality were higher among females (35.4% and 54.4%) than males (22.0% and 45.8%). Cigarette smoking was statistically significantly and positively associated with having CMDs (p = .034). Excessive daytime sleepiness (odds ratio [OR] = 3.65; 95% CI [2.56, 4.91]) and poor sleep quality (OR = 4.76; 95% CI [3.11, 7.29]) were associated with increased odds of CMDs.Given the adverse health consequences associated with both sleep disorders and CMDs, improving sleep hygiene among college students is imperative to public health.

  View details for DOI 10.1080/07448481.2014.917652

  View details for PubMedID 24810953

  View details for PubMedCentralID PMC4207264

• Sleep Disturbances and Common Mental Disorders in College Students. Health behavior and policy review Byrd, K., Gelaye, B., Tadessea, M. G., Williams, M. A., Lemma, S., Berhanec, Y. 2014; 1 (3): 229-237

  Abstract

  To estimate the prevalence of common mental disorders (CMDs) and examine the association of sleep disorders with presence of CMDs.A self-administered questionnaire was used to ascertain demographic information and behavioral characteristics among 2,645 undergraduate students in Ethiopia. Standard questionnaires were used to assess CMDs, evening chronotype, sleep quality and daytime sleepiness.A total of 716 students (26.6%) were characterized as having CMDs. Female students had higher prevalence of CMDs (30.6%) compared to male students (25.4%). After adjusting for potential confounders, daytime sleepiness (OR=2.02; 95% CI 1.64-2.49) and poor sleep quality (OR=2.36; 95% CI 1.91-2.93) were associated with increased odds of CMDs.There is a high prevalence of CMDs comorbid with sleep disorders among college students.

  View details for DOI 10.14485/HBPR.1.3.7

  View details for PubMedID 25309939

  View details for PubMedCentralID PMC4190836

• Maternal and cord blood hormones in relation to birth size. European journal of epidemiology Lagiou, P., Samoli, E., Hsieh, C. C., Lagiou, A., Xu, B., Yu, G. P., Onoyama, S., Chie, L., Adami, H. O., Vatten, L. J., Trichopoulos, D., Williams, M. A. 2014; 29 (5): 343-51

  Abstract

  Birth size has been associated with adult life diseases, but the endocrine factors that are likely involved are not established. We evaluated the associations of maternal and cord blood hormones with birth size in normal pregnancies, and examined possible effect modification by maternal height, on the basis of prior suggestive evidence. In a prospective study of normal singleton pregnancies in Boston, USA and Shanghai, China, maternal hormone levels at the 27th gestational week were available for 225 pregnancies in Boston and 281 in Shanghai and cord blood measurements for 92 pregnancies in Boston and 110 in Shanghai. Pearson partial correlation coefficients of log-transformed hormone levels with birth weight and length were calculated. Overall, positive correlations with birth weight were found for maternal estriol (r = 0.19; p < 0.001) and progesterone (r = 0.15; p < 0.001) and these associations were more evident among taller mothers. There was an inverse association of cord blood progesterone (r = -0.16; p < 0.03) with birth weight. In Boston, cord blood IGF-1 was positively associated with birth weight (r = 0.22; p < 0.04) and length (r = 0.25; p < 0.02), particularly among taller mothers (r = 0.43 and 0.38, respectively; p < 0.02), whereas among taller mothers in Shanghai the associations of IGF-2 with birth size appeared to be at least as strong as those of IGF-1. In conclusion, maternal estriol and progesterone, and cord blood IGF-1 were positively correlated with birth size. All correlations tended to be more pronounced among offspring of taller mothers. Among taller mothers in Shanghai, IGF-2 appeared to be at least as strongly associated with birth size as IGF-1.

  View details for DOI 10.1007/s10654-014-9914-3

  View details for PubMedID 24848607

• The Relationship between High Risk for Obstructive Sleep Apnea and General and Central Obesity: Findings from a Sample of Chilean College Students. ISRN obesity Wosu, A. C., Vélez, J. C., Barbosa, C., Andrade, A., Frye, M., Chen, X., Gelaye, B., Williams, M. A. 2014; 2014: 871681

  Abstract

  This cross-sectional study evaluates the prevalence and extent to which high risk for obstructive sleep apnea (OSA) is associated with general obesity and central obesity among college students in Punta Arenas, Chile. Risk for OSA was assessed using the Berlin Questionnaire and trained research nurses measured anthropometric indices. Overweight was defined as body mass index (BMI) of 25-29.9 kg/m(2) and general obesity was defined as BMI ≥ 30 kg/m(2). Central obesity was defined as waist circumference ≥90 centimeters (cm) for males and ≥80 cm for females. Multivariate logistic regression models were fit to obtain adjusted odds ratios (OR) and 95% confidence intervals (CI). Prevalence of high risk for OSA, general obesity, and central obesity were 7.8%, 12.8%, and 42.7%, respectively. Students at high risk for OSA had greater odds of general obesity (OR 9.96; 95% CI: 4.42-22.45) and central obesity (OR 2.78; 95% CI 1.43-5.40). Findings support a strong positive association of high risk for OSA with obesity.

  View details for DOI 10.1155/2014/871681

  View details for PubMedID 24944841

  View details for PubMedCentralID PMC4040193

• Cross-cultural validity of the Spanish version of PHQ-9 among pregnant Peruvian women: a Rasch item response theory analysis. Journal of affective disorders Zhong, Q., Gelaye, B., Fann, J. R., Sanchez, S. E., Williams, M. A. 2014; 158: 148-53

  Abstract

  We sought to evaluate the validity of the Spanish language version of the patient health questionnaire-9 (PHQ-9) depression scale in a large sample of pregnant Peruvian women using Rasch item response theory (IRT) approaches. We further sought to examine the appropriateness of the response formats, reliability and potential differential item functioning (DIF) by maternal age, educational attainment and employment status.This cross-sectional study was conducted among 1520 pregnant women in Lima, Peru. A structured interview was used to collect information on demographic characteristics and PHQ-9 items. Data from the PHQ-9 were fitted to the Rasch IRT model and tested for appropriate category ordering, the assumptions of unidimensionality and local independence, item fit, reliability and presence of DIF.The Spanish language version of PHQ-9 demonstrated unidimensionality, local independence, and acceptable fit for the Rasch IRT model. However, we detected disordered response categories for the original four response categories. After collapsing "more than half the days" and "nearly every day", the response categories ordered properly and the PHQ-9 fit the Rasch IRT model. The PHQ-9 had moderate internal consistency (person separation index, PSI=0.72). Additionally, the items of PHQ-9 were free of DIF with regard to age, educational attainment, and employment status.The Spanish language version of the PHQ-9 was shown to have item properties of an effective screening instrument. Collapsing rating scale categories and reconstructing three-point Likert scale for all items improved the fit of the instrument. Future studies are warranted to establish new cutoff scores and criterion validity of the three-point Likert scale response options for the Spanish language version of the PHQ-9.

  View details for DOI 10.1016/j.jad.2014.02.012

  View details for PubMedID 24655779

  View details for PubMedCentralID PMC4004697

• Eveningness Chronotype, Daytime Sleepiness, Caffeine Consumption, and Use of Other Stimulants Among Peruvian University Students. Journal of caffeine research Whittier, A., Sanchez, S., Castañeda, B., Sanchez, E., Gelaye, B., Yanez, D., Williams, M. A. 2014; 4 (1): 21-27

  Abstract

  Objectives: The aims of this study were to evaluate patterns of circadian preferences and daytime sleepiness, and to examine the extent to which the consumption of stimulant beverages is associated with daytime sleepiness and evening chronotype among Peruvian college-age students. Methods: A total of 2,581 undergraduate students completed a self-administered comprehensive questionnaire that gathered information about sleep habits, sociodemographic and lifestyle characteristics, and the use of caffeinated beverages. The Morningness-Eveningness Questionnaire (MEQ) and Epworth Sleepiness Scale (ESS) were used to assess chronotype and daytime sleepiness. We used multivariable linear and logistic regression procedures to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the associations of sleep disorders with sociodemographic and behavioral factors. Results: The prevalence of daytime sleepiness was 35% [95% CI 32.7-36.4] and eveningness chronotype was 10% [95% CI 8.8-11.1%]. Age, sex, cigarette smoking, and alcohol consumption were significantly associated with an evening chronotype. After adjusting for age, sex, smoking, body mass index, and physical activity, students who reported consumption of any stimulant beverages had 1.25 increased odds of excessive daytime sleepiness (OR=1.25 [95% CI 1.03-1.53]) compared with students who did not consume stimulant beverages. Consumption of any stimulant beverages was not statistically significantly associated with being an evening chronotype (OR=1.30 [95% CI 0.86-1.96]). Conclusions: Excessive daytime sleepiness and eveningness chronotype are common among Peruvian college students. MEQ scores were associated with age, sex, smoking, and alcohol consumption. Regular stimulant beverage consumption tended to be positively associated with excessive daytime sleepiness.

  View details for DOI 10.1089/jcr.2013.0029

  View details for PubMedID 24868492

  View details for PubMedCentralID PMC4026101

• Sleep characteristics and health-related quality of life among a national sample of American young adults: assessment of possible health disparities. Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation Chen, X., Gelaye, B., Williams, M. A. 2014; 23 (2): 613-25

  Abstract

  The aim of the study is to examine the associations of sleep characteristics with health-related quality of life (HRQOL) and sleep health disparities among US young adults using national survey data.The study sample consisted of 2,391 young adults aged 20-39 years from the National Health and Nutrition Examination Survey 2005-2008. HRQOL was assessed using the Centers for Disease Control and Prevention's HRQOL-4 scale. Multivariable logistic regression models were applied to evaluate the sleep-HRQOL associations. Stratified analyses were conducted to examine whether the associations varied by sociodemographic characteristics.Approximately 35.6 % of young adults slept <7 h, 41.9 % had insomnia, 4.4 % had sleep disorder, and 8.5 % had sleep apnea. More females had insomnia than males (48.6 vs. 35.9 %, P < 0.001). US-born young adults had more sleep disturbances than their foreign-born counterparts. Compared with those sleeping 7-8 h, the adjusted odds ratio of poor general health was 1.60 (95 % confidence interval, 1.08-2.35) for individuals sleeping 6-7 h and 1.88 (1.23-2.86) for those sleeping <6 h. Similar results were found for low mental HRQOL and overall HRQOL. Insomnia, long sleep latency, troubling falling asleep, daytime sleepiness, and frequent sleeping pill use were significantly associated with low mental HRQOL and overall HRQOL. The associations between sleep disturbances and low HRQOL varied little by sex, race/ethnicity, and country of birth.Sleep disturbances are common among US young adults and are significantly associated with low HRQOL. Objective measures of sleep are warranted to confirm our findings.

  View details for DOI 10.1007/s11136-013-0475-9

  View details for PubMedID 23860850

  View details for PubMedCentralID PMC4015621

• Seasonal variation of 25-hydroxyvitamin D among non-Hispanic black and white pregnant women from three US pregnancy cohorts. Paediatric and perinatal epidemiology Luque-Fernandez, M. A., Gelaye, B., VanderWeele, T., Ferre, C., Siega-Riz, A. M., Holzman, C., Enquobahrie, D. A., Dole, N., Williams, M. A. 2014; 28 (2): 166-76

  Abstract

  Vitamin D deficiency during pregnancy has been associated with increased risk of complications and adverse perinatal outcomes. We evaluated seasonal variation of 25-hydroxyvitamin D [25(OH)D] among pregnant women, focusing on patterns and determinants of variation.Data came from three cohort studies in the US that included 2583 non-Hispanic Black and White women having prenatal 25(OH)D concentrations determined. Fourier time series and generalised linear models were used to estimate the magnitude of 25(OH)D seasonality. We modelled seasonal variability using a stationary cosinor model to estimate the phase shift, peak-trough difference, and annual mean of 25(OH)D.We observed a peak for 25(OH)D in summer, a nadir in winter, and a phase of 8 months, which resulted from fluctuations in 25(OH)D3 rather than 25(OH)D2. After adjustment for covariates, the annual mean concentrations and estimated peak-trough difference of 25(OH)D among Black women were 19.8 ng/mL [95% confidence interval (CI) 18.9, 20.5] and 5.8 ng/mL [95% CI 4.7, 6.7], and for non-Hispanic White women were 33.0 ng/mL [95% CI 32.6, 33.4] and 7.4 ng/mL [95% CI 6.0, 8.9].Non-Hispanic Black women had lower average 25(OH)D concentrations throughout the year and smaller seasonal variation levels than non-Hispanic White women. This study's confirmation of 25(OH)D seasonality over a calendar year has the potential to enhance public health interventions targeted to improve maternal and perinatal outcomes.

  View details for DOI 10.1111/ppe.12103

  View details for PubMedID 24354847

  View details for PubMedCentralID PMC3946392

• Women's experience of abuse in childhood and their children's smoking and overweight. American journal of preventive medicine Roberts, A. L., Galea, S., Austin, S. B., Corliss, H. L., Williams, M. A., Koenen, K. C. 2014; 46 (3): 249-58

  Abstract

  Smoking and overweight are principal determinants of poor health for which individual-level interventions are at best modestly effective. This limited effectiveness may be partly because these risk factors are patterned by parents' experiences preceding the individual's birth.To determine whether women's experience of abuse in childhood was associated with smoking and overweight in their children.In 2012, data were linked from two large longitudinal cohorts of women (Nurses' Health Study II [NHSII], n=12,666) and their children (Growing Up Today [GUTS] Study, n=16,774), 1989-2010. ORs of children following higher-risk smoking trajectories and risk ratios (RRs) of children's overweight and obesity by their mother's childhood experience of physical, emotional, and sexual abuse were calculated. The extent to which mother's smoking and overweight, socioeconomic indicators, family characteristics, and child's abuse exposure accounted for possible associations was ascertained.Children of women who experienced severe childhood abuse had greater likelihood of higher-risk smoking trajectories (OR=1.40, 95% CI=1.21, 1.61), overweight (RR=1.21, 95% CI=1.11, 1.33), and obesity (RR=1.45, 95% CI=1.21, 1.74) across adolescence and early adulthood compared with children of women who reported no abuse. Mother's smoking and overweight and children's abuse exposure accounted for more than half of the elevated risk of following the highest-risk smoking trajectory and overweight in children of women abused.These findings raise the possibility that childhood abuse may not only adversely affect the health of the direct victim but may also affect health risk factors in her children decades after the original traumatic events.

  View details for DOI 10.1016/j.amepre.2013.11.012

  View details for PubMedID 24512863

  View details for PubMedCentralID PMC3962663

• Risk of spontaneous preterm birth in relation to maternal experience of serious life events during pregnancy. International journal of women's health Barrios, Y. V., Sanchez, S. E., Qiu, C., Gelaye, B., Williams, M. A. 2014; 6: 249-57

  Abstract

  The purpose of this study was to examine the risk of preterm birth (PTB) in relation to serious life events experienced during pregnancy in Peruvian women.This case-control study included 479 PTB cases and 480 term controls. In-person interviews asked information regarding sociodemographics, medical and reproductive histories, and serious life events experienced during pregnancy. Multivariate logistic regression procedures were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs).Compared with women who did not experience a serious life event during pregnancy, those who experienced the following life events had a more than two-fold increased odds of PTB: death of first-degree relative (adjusted OR 2.10; 95% CI 1.38-3.20), divorce or separation (adjusted OR 2.09; 95% CI 1.10-4.00), financial troubles (adjusted OR 2.70; 95% CI 1.85-3.94), or serious fight with partner (adjusted OR 2.40; 95% CI 1.78-3.17). Women who experienced any serious life events during pregnancy had higher odds (adjusted OR 2.29; 95% CI 1.65-3.18) of suffering spontaneous preterm labor and preterm premature rupture of membranes (adjusted OR 2.19; 95% CI 1.56-3.08), compared with women who did not experience any such events. Associations of similar directions and extent were observed for severity of PTB (ie, very, moderate, or late PTB). The magnitude of the associations increased as increased frequency of serious life events (P trend <0.001).Experiencing serious life events during pregnancy was associated with increased odds of PTB among Peruvian women. Interventions aimed at assisting women experiencing serious life events may reduce the risk of PTB. Future studies should include objective measures of stress and stress response to understand better the biological underpinnings of these associations.

  View details for DOI 10.2147/IJWH.S54269

  View details for PubMedID 24591850

  View details for PubMedCentralID PMC3938466

• Modifiable cardiovascular disease risk factors among indigenous populations. Advances in preventive medicine Lucero, A. A., Lambrick, D. M., Faulkner, J. A., Fryer, S., Tarrant, M. A., Poudevigne, M., Williams, M. A., Stoner, L. 2014; 2014: 547018

  Abstract

  Objective. To identify modifiable cardio-metabolic and lifestyle risk factors among indigenous populations from Australia (Aboriginal Australians/Torres Strait Islanders), New Zealand (Māori), and the United States (American Indians and Alaska Natives) that contribute to cardiovascular disease (CVD). Methods. National health surveys were identified where available. Electronic databases identified sources for filling missing data. The most relevant data were identified, organized, and synthesized. Results. Compared to their non-indigenous counterparts, indigenous populations exhibit lower life expectancies and a greater prevalence of CVD. All indigenous populations have higher rates of obesity and diabetes, hypertension is greater for Māori and Aboriginal Australians, and high cholesterol is greater only among American Indians/Alaska Natives. In turn, all indigenous groups exhibit higher rates of smoking and dangerous alcohol behaviour as well as consuming less fruits and vegetables. Aboriginal Australians and American Indians/Alaska Natives also exhibit greater rates of sedentary behaviour. Conclusion. Indigenous groups from Australia, New Zealand, and the United States have a lower life expectancy then their respective non-indigenous counterparts. A higher prevalence of CVD is a major driving force behind this discrepancy. A cluster of modifiable cardio-metabolic risk factors precede CVD, which, in turn, is linked to modifiable lifestyle risk factors.

  View details for DOI 10.1155/2014/547018

  View details for PubMedID 24649368

  View details for PubMedCentralID PMC3933231

• School-Based Intervention: Evaluating the role of Water, Latrines and Hygiene Education on Trachoma and Intestinal Parasitic Infections in Ethiopia. Journal of water, sanitation, and hygiene for development : a journal of the International Water Association Gelaye, B., Kumie, A., Aboset, N., Berhane, Y., Williams, M. A. 2014; 4 (1): 120-130

  Abstract

  We sought to evaluate the impact of a hygiene and sanitation intervention program among school-children to control active trachoma and intestinal parasitic infections.This longitudinal epidemiologic study was conducted among 630 students in rural Ethiopia. Baseline and follow-up surveys were conducted to evaluate the impact of a three pronged intervention program i) constructing of ventilated improved pit latrines, ii) provision of clean drinking water, and iii) and hygiene education. Socio-demographic information was collected using a structured questionnaire. Presence of trachoma and intestinal parasitic infections were evaluated using standard procedures.At baseline 15% of students had active trachoma while 6.7% of them were found to have active trachoma post intervention (p<0.001). Similar improvements were noted for parasitic infections. At baseline 7% of students were reported to have helminthic infections and 30.2% protozoa infections. However, only 4% of students had any helminthic infection and 13.4% (p<0.001) of them were found to have any protozoa infection. Improvements were noted in students' knowledge and attitudes towards hygiene and sanitation.The results of our study demonstrated that provision of comprehensive and targeted sanitation intervention program was successful in reducing the burden of trachoma and intestinal parasitic infection among school children.

  View details for DOI 10.2166/washdev.2013.060

  View details for PubMedID 25859318

  View details for PubMedCentralID PMC4387890

• Daytime Sleepiness, Circadian Preference, Caffeine Consumption and Khat Use among College Students in Ethiopia. Journal of sleep disorders-- treatment & care Robinson, D., Gelaye, B., Tadesse, M. G., Williams, M. A., Lemma, S., Berhane, Y. 2013; 3 (1)

  Abstract

  To estimate the prevalence of daytime sleepiness and circadian preferences, and to examine the extent to which caffeine consumption and Khat (a herbal stimulant) use are associated with daytime sleepiness and evening chronotype among Ethiopian college students.A cross-sectional study was conducted among 2,410 college students. A self-administered questionnaire was used to collect information about sleep, behavioral risk factors such as caffeinated beverages, tobacco, alcohol, and Khat consumption. Daytime sleepiness and chronotype were assessed using the Epworth Sleepiness Scale (ESS) and the Horne & Ostberg Morningness /Eveningness Questionnaire (MEQ), respectively. Linear and logistic regression models were used to evaluate associations.Daytime sleepiness (ESS≥10) was present in 26% of the students (95% CI: 24.4-27.8%) with 25.9% in males and 25.5% in females. A total of 30 (0.8%) students were classified as evening chronotypes (0.7% in females and 0.9% in males). Overall, Overall, Khat consumption, excessive alcohol use and cigarette smoking status were associated with evening chronotype. Use of any caffeinated beverages (OR=2.18; 95%CI: 0.82-5.77) and Khat consumption (OR=7.43; 95%CI: 3.28-16.98) increased the odds of evening chronotype.The prevalence of daytime sleepiness among our study population was high while few were classified as evening chronotypes. We also found increased odds of evening chronotype with caffeine consumption and Khat use amongst Ethiopian college students. Prospective cohort studies that examine the effects of caffeinated beverages and Khat use on sleep disorders among young adults are needed.

  View details for DOI 10.4172/2325-9639.1000130

  View details for PubMedID 24818170

  View details for PubMedCentralID PMC4015623

• Validity of the Patient Health Questionnaire-9 for depression screening and diagnosis in East Africa. Psychiatry research Gelaye, B., Williams, M. A., Lemma, S., Deyessa, N., Bahretibeb, Y., Shibre, T., Wondimagegn, D., Lemenhe, A., Fann, J. R., Vander Stoep, A., Andrew Zhou, X. H. 2013; 210 (2): 653-61

  Abstract

  Depression is often underdiagnosed and undertreated in primary care settings, particularly in developing countries. This is, in part, due to challenges resulting from lack of skilled mental health workers, stigma associated with mental illness, and lack of cross-culturally validated screening instruments. We conducted this study to evaluate the reliability and validity of the Patient Health Questionnaire-9 (PHQ-9) as a screen for diagnosing major depressive disorder among adults in Ethiopia, the second most populous country in sub-Saharan Africa. A total of 926 adults attending outpatient departments in a major referral hospital in Ethiopia participated in this study. We assessed criterion validity and performance characteristics against an independent, blinded, and psychiatrist administered semi-structured Schedules for Clinical Assessment in Neuropsychiatry (SCAN) interview. Overall, the PHQ-9 items showed good internal (Cronbach's alpha=0.81) and test re-test reliability (intraclass correlation coefficient=0.92). A factor analysis confirmed a one-factor structure. Receiver Operating Characteristics (ROC) analysis showed that a PHQ-9 threshold score of 10 offered optimal discriminatory power with respect to diagnosis of major depressive disorder via the clinical interview (sensitivity=86% and specificity=67%). The PHQ-9 appears to be a reliable and valid instrument that may be used to diagnose major depressive disorders among Ethiopian adults.

  View details for DOI 10.1016/j.psychres.2013.07.015

  View details for PubMedID 23972787

  View details for PubMedCentralID PMC3818385

• Correlates of cortisol in human hair: implications for epidemiologic studies on health effects of chronic stress. Annals of epidemiology Wosu, A. C., Valdimarsdóttir, U., Shields, A. E., Williams, D. R., Williams, M. A. 2013; 23 (12): 797-811.e2

  Abstract

  Assessment of cortisol concentrations in hair is one of the latest innovations for measuring long-term cortisol exposure. We performed a systematic review of correlates of cortisol in human hair to inform the design, analysis, and interpretation of future epidemiologic studies. Relevant publications were identified through electronic searches on PubMed, WorldCat, and Web of Science using keywords, "cortisol," "hair," "confounders," "chronic," "stress," and "correlates." Thirty-nine studies were included in this review. Notwithstanding scarce data and some inconsistencies, investigators have found hair cortisol concentrations to be associated with stress-related psychiatric symptoms and disorders (e.g., post-traumatic stress disorder), medical conditions indicating chronic activation of the hypothalamic-pituitary-adrenal axis (e.g., Cushing's syndrome), and other life situations associated with elevated risk of chronic stress (e.g., shiftwork). Results from some studies suggest that physical activity, adiposity, and substance abuse may be correlates of hair cortisol concentrations. In contrast to measures of short-term cortisol release (saliva, blood, and urine), cigarette smoking and use of oral contraceptives appear not to be associated with hair cortisol concentrations. Studies of pregnant women indicate increased hair cortisol concentrations across successive trimesters. The study of hair cortisol presents a unique opportunity to assess chronic alterations in cortisol concentrations in epidemiologic studies.

  View details for DOI 10.1016/j.annepidem.2013.09.006

  View details for PubMedID 24184029

  View details for PubMedCentralID PMC3963409

• Unemployment and stillbirth risk among foreign-born and Spanish pregnant women in Spain, 2007-2010: a multilevel analysis study. European journal of epidemiology Luque-Fernandez, M. A., Franco, M., Gelaye, B., Schomaker, M., Garitano, I. G., D'Este, C., Williams, M. A. 2013; 28 (12): 991-9

  Abstract

  We describe stillbirth and unemployment rates by autonomous region in Spain and analyse whether women who gave birth in regions with high unemployment rates were more likely to have a stillborn. We designed a multilevel population-based observational study of births from 2007 to 2010. We defined stillbirth as the outcome, individual maternal socioeconomic and pregnancy-related characteristics as covariates, and maternal autonomous region of residence as the contextual covariate. We used mixed-logistic regression models to account for differences across regions. In total, 1,920,235 singleton births and 5,560 stillbirths were included in the study. Women residing in autonomous regions with the highest rates of unemployment had a two-times-greater chance of delivering a stillborn (adjusted OR 2.60; 95 % CI 2.08-3.21). The region where women resided explained 14 % of the total individual differences in the risk of delivering a stillborn. The odds of stillbirth were 1.82 (95 % CI 1.62-2.05) times higher for African-born women than for Spanish-born women and 1.90 (95 % CI 1.68-2.15) times higher for women with low educational attainment than for women with higher education. In conclusion, regional disparities in stillbirth rates in Spain in the period 2007-2010 were mainly associated with mothers who had low levels of education, were African-born, and lived in regions with higher unemployment.

  View details for DOI 10.1007/s10654-013-9859-y

  View details for PubMedID 24142267

• Associations of placental weight with maternal and cord blood hormones. Annals of epidemiology Lagiou, P., Hsieh, C. C., Samoli, E., Lagiou, A., Xu, B., Yu, G. P., Onoyama, S., Chie, L., Vatten, L. J., Adami, H. O., Trichopoulos, D., Williams, M. A. 2013; 23 (11): 669-73

  Abstract

  Placental weight has been associated with mammographic pattern and coronary heart disease in the adult offspring, but the mechanisms are unknown. We evaluated the associations of maternal and cord blood hormones with placental weight in normal pregnancies.Prospective study of 167 normal singleton pregnancies in Boston, USA and 256 in Shanghai, China. Maternal hormone levels at the 27th gestational week were available for all pregnancies. Cord blood measurements were available for 86 pregnancies in Boston and 104 in Shanghai. Pearson partial correlation coefficients of log-transformed hormone levels with placental weight were calculated.Maternal levels of estriol, testosterone, and progesterone (P < .05) were positively associated with placental weight. There was no such evidence for adiponectin, prolactin, and insulin-like growth factor (IGF)-I. Cord blood steroids tended to be inversely associated with placental weight, the results being statistically significant for testosterone (P < .05). There was a marginally significant positive association of cord blood IGF-I with placental weight. Reported results were adjusted for study center.Placental weight appears to be positively correlated with maternal steroids. Its correlation with cord blood steroids, however, appears inverse, compatible with negative feedback mechanisms. There is also a suggestion for placental weight to be positively associated with cord blood IGF-I.

  View details for DOI 10.1016/j.annepidem.2013.08.003

  View details for PubMedID 24099689

• Episodic migraine and obesity and the influence of age, race, and sex. Neurology Peterlin, B. L., Rosso, A. L., Williams, M. A., Rosenberg, J. R., Haythornthwaite, J. A., Merikangas, K. R., Gottesman, R. F., Bond, D. S., He, J. P., Zonderman, A. B. 2013; 81 (15): 1314-21

  Abstract

  To evaluate the episodic migraine (EM)-obesity association and the influence of age, race, and sex on this relationship.We examined the EM-obesity association and the influence of age, race, and sex in 3,862 adult participants of both black and white race interviewed in the National Comorbidity Survey Replication. EM diagnostic criteria were based on the International Classification of Headache Disorders. Body mass index was classified as underweight (<18.5 kg/m(2)), normal (18.5-24.9 kg/m(2)), overweight (25-29.9 kg/m(2)), or obese (≥30 kg/m(2)). Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for EM were estimated using logistic regression. Models were stratified by age (<50/≥50 years), race (white/black), and sex (male/female).A total of 188 participants fulfilled criteria for EM. In all participants, the adjusted odds of EM were 81% greater in individuals who were obese compared with those of normal weight (OR 1.81; 95% CI: 1.27-2.57; p = 0.001), with a significant trend of increasing odds of EM with increasing obesity status from normal weight to overweight to obese (p = 0.001). In addition, stratified analyses demonstrated that the odds of EM were greater in obese as compared with normal-weight individuals who were 1) younger than 50 years of age (OR 1.86; 95% CI: 1.20-2.89; p for trend = 0.008), 2) white (OR 2.06; 95% CI: 1.41-3.01; p for trend ≤0.001), or 3) female (OR 1.95; 95% CI: 1.38-2.76; p for trend ≤0.001).The odds of EM are increased in those with obesity, with the strongest relationships among those younger than 50 years, white individuals, and women.

  View details for DOI 10.1212/WNL.0b013e3182a824f7

  View details for PubMedID 24027060

  View details for PubMedCentralID PMC3806922

• Sleep-disordered breathing and gestational diabetes mellitus: a meta-analysis of 9,795 participants enrolled in epidemiological observational studies. Diabetes care Luque-Fernandez, M. A., Bain, P. A., Gelaye, B., Redline, S., Williams, M. A. 2013; 36 (10): 3353-60

  Abstract

  Recently, sleep-disordered breathing (SDB) has been reported to be associated with the development of gestational diabetes mellitus (GDM). Accordingly, as this is emergent area of research that has significant clinical relevance, the objective of this meta-analysis is to examine the relationship between SDB with GDM.We searched several electronic databases for all of the studies published before January 2013 and reviewed references of published articles. Meta-analytic procedures were used to estimate the unadjusted and BMI-adjusted odds ratios (ORs) using a random effects model. Significant values, weighted effect sizes, and 95% CIs were calculated, and tests of homogeneity of variance were performed.Results from nine independent studies with a total of 9,795 pregnant women showed that SDB was significantly associated with an increased risk of GDM. Women with SDB had a more than threefold increased risk of GDM, with a pooled BMI-adjusted OR 3.06 (95% CI 1.89-4.96).These findings demonstrate a significant association between SDB and GDM that is evident even after considered confounding by obesity. This meta-analysis indicates a need to evaluate the role of early recognition and treatment of SDB early during pregnancy.

  View details for DOI 10.2337/dc13-0778

  View details for PubMedID 24065843

  View details for PubMedCentralID PMC3781575

• Genome-wide and candidate gene association studies of placental abruption. International journal of molecular epidemiology and genetics Workalemahu, T., Enquobahrie, D. A., Moore, A., Sanchez, S. E., Ananth, C. V., Pacora, P. N., Liang, L., Salazar, M., Williams, M. A. 2013; 4 (3): 128-39

  Abstract

  Placental abruption (PA), a pregnancy-related vascular disorder, is a leading cause of maternal and perinatal morbidity and mortality. The success of identifying genetic susceptibility loci for PA, a multi-factorial heritable disorder, has been limited. We conducted a genome-wide association study (GWAS) and candidate gene association study using 470 PA cases and 473 controls from Lima, Peru. Genotyping for common genetic variations (single nucleotide polymorphisms, SNPs) was conducted using the Illumina Cardio-Metabo Chip platform. Common variations in 35 genes that participate in mitochondrial biogenesis (MB) and oxidative phosphorylation (OS) were selected for the candidate gene study. Regression models were fit to examine associations of each SNP with risk of PA. In pathway analyses, we examined functions and functional relationships of genes represented by the top GWAS hits. Genetic risk scores (GRS), based on top hits of the GWAS and candidate gene analyses, respectively, were computed using the risk allele counting method. The top hit in the GWAS analyses was rs1238566 (empirical P-value=1.04e-4 and FDR-adjusted P-value=5.65E-04) in FLI-1 gene, a megakaryocyte-specific transcription factor. Networks of genes involved in lipid metabolism and cell signaling were significantly enriched by the 51 genes whose SNPs were among the top 200 GWAS hits (P-value <2.1e-3). SNPs known to regulate MB (e.g. CAMK2B, NR1H3, PPARG, PRKCA, and THRB) and OP (e.g., COX5A, and NDUF family of genes) were associated with PA risk (P-value <0.05). GRS was significantly associated with PA risk (trend P-value <0.001 and 0.01 for GWAS and candidate gene based GRS, respectively). Our study suggests that integrating multiple analytical strategies in genetic association studies can provide opportunities for identifying genetic risk factors and novel molecular mechanisms that underlie PA.

  View details for PubMedID 24046805

  View details for PubMedCentralID PMC3773564

• Sleep Quality, Sleep Patterns and Consumption of Energy Drinks and Other Caffeinated Beverages among Peruvian College Students. Health Sanchez, S. E., Martinez, C., Oriol, R. A., Yanez, D., Castañeda, B., Sanchez, E., Gelaye, B., Williams, M. A. 2013; 5 (8B): 26-35

  Abstract

  To evaluate sleep quality in relation to lifestyle characteristics including consumption of energy drinks and other caffeinated beverages among Peruvian college students.A total of 2,458 college students were invited to complete a self-administered questionnaire that collected information about a variety of behaviors including consumption of energy drinks, caffeinated and alcoholic beverages. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. Logistic regression procedures were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for poor sleep quality in relation to lifestyle characteristics.A total of 965 males and 1,493 female students were enrolled in the study. 52.0% of males and 58.4% of females experienced poor sleep quality (p=0.002). Females (OR=1.28; 95% CI 1.08-1.51) and those who reported consuming ≥ 3 stimulant beverages per week (OR=1.88; 95% CI 1.42-2.50) had higher odds of poor sleep quality. Students who consumed 1-19 alcoholic beverages monthly (OR=1.90; 95% CI 1.46-2.49) had a higher odds of long sleep latency. Consumption of ≥ 3 stimulant beverages per week was associated with daytime dysfunction due to sleep loss (OR=1.45; 95% CI 1.10-1.90), short sleep duration (OR= 1.49; 95% CI 1.14-1.94), and use of sleep medication (OR= 2.10; 95% CI 1.35-3.28).Consumption of energy drinks, other caffeinated beverages and alcoholic beverages are risk factors of poor sleep quality. Increased awareness of these associations should promote interventions to improve students' lifestyle habits, including consumption of alcoholic and caffeinated beverages, and overall health.

  View details for DOI 10.4236/health.2013.58A2005

  View details for PubMedID 25243056

  View details for PubMedCentralID PMC4169115

• Maternal blood mitochondrial DNA copy number and placental abruption risk: results from a preliminary study. International journal of molecular epidemiology and genetics Williams, M. A., Sanchez, S. E., Ananth, C. V., Hevner, K., Qiu, C., Enquobahrie, D. A. 2013; 4 (2): 120-7

  Abstract

  Oxidative stress and impaired placental function - pathways implicated in the pathogenesis of placental abruption - have their origins extending to mitochondrial dysfunction. To the best of our knowledge, there are no published reports of associations of placental abruption with circulating mitochondrial DNA (mtDNA) copy number - a novel biomarker of systemic mitochondrial dysfunction. This pilot case-control study was comprised of 233 placental abruption cases and 238 non-abruption controls. Real-time quantitative polymerase chain reaction (PCR) was used to assess the relative copy number of mtDNA in maternal whole blood samples collected at delivery. Logistic regression procedures were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). There was some evidence of an increased odds of placental abruption with the highest quartile of mtDNA copy number (P for trend = 0.09) after controlling for confounders. The odds of placental abruption was elevated among women with higher mtDNA copy number (≥336.9) as compared with those with lower values (<336.9) (adjusted OR = 1.60; 95% CI 1.04-2.46). Women diagnosed with preeclampsia and with elevated mtDNA copy number had a dramatically increased odds of placental abruption as compared with normotensive women without elevated mtDNA copy number (adjusted OR = 6.66; 95% CI 2.58-17.16). Maternal mitochondrial dysfunction appears to be associated with placental abruption in the presence of preeclampsia. Replication in other studies, particularly prospective cohort studies and those that allow for tissue specific assessment of mitochondrial dysfunction (e.g., the placenta) are needed to further understand cellular and genomic biomarkers of normal and abnormal placental function.

  View details for PubMedID 23875065

  View details for PubMedCentralID PMC3709116

• Physical activity and metabolic syndrome among Ethiopian adults. American journal of hypertension Workalemahu, T., Gelaye, B., Berhane, Y., Williams, M. A. 2013; 26 (4): 535-40

  Abstract

  BACKGROUND The global prevalence of chronic noncommunicable diseases (NCDs) is on the rise, with the majority of the growth occurring among populations in developing countries. Few studies have quantified the health benefits for physical activity among sub-Saharan African adults. We examined associations of physical activity with the prevalence of metabolic syndrome (MetS) and its components in Ethiopian men and women. METHODS This cross-sectional study of 1,843 individuals (1,117 men and 726 women) was conducted among working adults (public schools and bank employees) in Addis Ababa, Ethiopia. The study was conducted in accordance with the STEPwise approach of the World Health Organization. Physical activity was assessed using a previously validated Global Physical Activity Questionnaire. MetS was defined according to the International Diabetes Federation criteria. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI). RESULTS The odds of MetS was inversely associated with physical activity in men (P trend = 0.02) but not women (P trend = 0.85). Among men, the OR of MetS comparing those with high vs. low levels of physical activity was 0.56 (95% CI = 0.33-0.97). For women, the corresponding OR was 1.07 (95% CI = 0.57-2.01). Physical activity was significantly and inversely associated with high waist circumference and hypertriglyceridemia among men, but no such associations were observed among women. CONCLUSIONS Higher levels of physical activity were inversely associated with MetS and several individual components among men. No similar trends were observed among women in this cohort, in part because of the small sample size.

  View details for DOI 10.1093/ajh/hps079

  View details for PubMedID 23422933

  View details for PubMedCentralID PMC3626042

• Migraine and psychiatric comorbidities among sub-saharan african adults. Headache Gelaye, B., Peterlin, B. L., Lemma, S., Tesfaye, M., Berhane, Y., Williams, M. A. 2013; 53 (2): 310-21

  Abstract

  Despite being a highly prevalent disorder and substantial cause of disability, migraine is understudied in Africa. Moreover, no previous study has investigated the effects of stress and unipolar psychiatric comorbidities on migraine in a sub-Saharan African cohort.To evaluate the prevalence of migraine and its association with stress and unipolar psychiatric comorbidities among a cohort of African adults.This was a cross-sectional epidemiologic study evaluating 2151 employed adults in sub-Saharan Africa. A standardized questionnaire was used to identify sociodemographic, headache, and lifestyle characteristics of participants. Migraine classification was based on the International Classification of Headache Disorders-2 diagnostic criteria. Depressive, anxiety, and stress symptoms were ascertained with the Patient Health Questionnaire and the Depression Anxiety Stress Scale, respectively. Multivariable logistic regression models were used to estimate adjusted odds ratio (OR) and 95% confidence intervals (CIs).A total of 9.8% (n=212) of study participants fulfilled criteria for migraine (9.8%, 95% CI 8.6-11.1) with a higher frequency among women (14.3%, 95% CI 11.9-16.6) than men (6.9%, 95% CI 5.5-8.3). Similar to predominantly Caucasian migraine cohorts, sub-Saharan African migraineurs were more likely to be younger, have a lower education, and more likely to report a poor health status than non-migraineurs. However, in contrast with historical reports in predominantly Caucasian migraine cohorts, sub-Saharan African migraineurs were less likely to report smoking than non-migraineurs. Participants with moderately severe depressive symptoms had over a 3-fold increased odds of migraine (OR=3.36, 95% CI 1.30-8.70) compared with those classified as having minimal or no depressive symptoms, and the odds of migraine increased with increasing severity of depressive symptoms (P trend<0.001). Similarly, those with mild, moderate, and severe anxiety symptoms had increased odds of migraine (OR=2.28, 95% CI 1.24-4.21; OR=1.77, 95% CI 0.93-3.35; and OR=5.39, 95% CI 2.19-13.24, respectively). Finally, those with severe stress had a 3.57-fold increased odds of migraine (OR=3.57, 95% CI 1.35-9.46).Although historically it has been reported that migraine prevalence is greater in Caucasians than African Americans, our study demonstrates a high migraine prevalence among urban-dwelling Ethiopian adults (9.9%) that is comparable with what is typically reported in predominantly Caucasian cohorts. Further, among employed sub-Saharan African adults and similar to predominantly Caucasian populations, migraine is strongly associated with stress and unipolar psychiatric symptoms. The high burden of migraine and its association with stress and unipolar psychiatric symptoms in our study of well-educated and urban-dwelling African adults has important clinical and public health implications pending confirmation in other African populations.

  View details for DOI 10.1111/j.1526-4610.2012.02259.x

  View details for PubMedID 23095087

  View details for PubMedCentralID PMC3556345

• Maternal plasma advanced glycation end products concentrations in response to oral 50-gram glucose load in mid-pregnancy: a pilot study. Clinical laboratory Williams, M. A., Enquobahrie, D. A., Zimmer, J., Qiu, C. F., Hevner, K., Abetew, D., Christianson, C., Sheaff, C. 2012; 58 (9-10): 1045-50

  Abstract

  Accumulating evidence documents the initiation of diverse physiologic and biochemical responses subsequent to an oral glucose load.We sought to evaluate the extent to which acute hyperglycemia, resulting from a 50-gram glucose load, contributes to changes in maternal plasma concentrations of advanced glycation end products (AGEs), a heterogeneous group of molecules formed from the non-enzymatic reaction of reducing sugars with free amino groups of proteins, lipids, and nucleic acids.Blood specimens were collected from each participant in mid-pregnancy using standard procedures before and after a 50-gram oral glucose load. Maternal plasma methylglyoxal (MG), pentosidine and N(epsilon)-(carboxymethyl)lysine (CML) (free and bound) were measured by HPLC-MS/MS method. Non-parametric methods were employed for statistical analysis.Median plasma MG increased 1.27 fold as a result of acute hyperglycemia. Median bound CML concentrations were elevated 21% in post-load plasma samples as compared with pre-load samples, while median free pentosidine concentrations were 51% lower (both p-values < 0.05). Future studies of larger populations and longer periods of follow-up are warranted to investigate the consequences of acute and chronic hyperglycemia on placental function and fetal development.

  View details for PubMedID 23163122

• Prevalence and correlates of mental distress among working adults in ethiopia. Clinical practice and epidemiology in mental health : CP & EMH Gelaye, B., Lemma, S., Deyassa, N., Bahretibeb, Y., Tesfaye, M., Berhane, Y., Williams, M. A. 2012; 8: 126-33

  Abstract

  To evaluate the prevalence of mental distress and its correlates among working Ethiopian adults.This cross-sectional study of 2,180 individuals (1,316 men and 864 women) was conducted among working adults in Addis Ababa, Ethiopia. A structured questionnaire was used to collect information on socio-demographic and lifestyle characteristics of participants. Mental distress was assessed using the self-reporting questionnaire (SRQ). Logistic regression was employed to estimate adjusted odds ratios (OR) and 95% confidence intervals (95% CI).The prevalence of mental distress in the study sample was 17.7% (25.9% in women and 12.4% in men). Younger participants (age ≤24 years) had the highest prevalence of mental distress (35.5% in women and 16.7% in men). The odds of mental distress was 2.47-fold higher among women as compared with men (OR=2.47, 95% CI 1.97-3.09). Participants reporting excellent health status had a 50% reduced odds of mental distress (OR=0.47; 95%CI: 0.38-0.59); and moderate alcohol consumption was associated with a slight increased odds of mental distress (OR=1.26; 95%CI: 1.00-1.67).A high prevalence of mental distress was observed among working adults in Ethiopia. Our findings suggest that the workforce institutions should provide targeted prevention and intervention programs to improve the mental health state of their employees. National mental health policy that clearly outlines and addresses mental distress among working adults is also warranted.

  View details for DOI 10.2174/1745017901208010126

  View details for PubMedID 23166564

  View details for PubMedCentralID PMC3496909

• Association of Age at Menarche and Menstrual Characteristics with Adult Onset Asthma among Reproductive Age Women. Reproductive system & sexual disorders : current research Fida, N. G., Williams, M. A., Enquobahrie, D. A. 2012; 1 (3)

  Abstract

  Observations of increasing asthma incidence, decreasing age at menarche, and common risk factors have led investigators to hypothesize potential associations of age at menarche or menstrual characteristics with incidence of adult onset asthma. We evaluated these associations among reproductive age women.Study participants were selected from among women enrolled in a pregnancy cohort study. Information on age at menarche, menstrual characteristics, and history of asthma was collected using interviewer-administered questionnaires. Adult onset asthma was defined as asthma first diagnosed after onset of menarche. Women who had no information on asthma and menstrual history and those who were diagnosed with asthma before menarche were excluded. A total of 3,461 women comprised the analytic population. Logistic regression was used to estimate adjusted relative risk (aRR) and 95% confidence intervals (95% CI) relating age at menarche and menstrual characteristics with adult onset asthma.Mean age at menarche was 12.8 years (standard deviation=1.46). Among study participants, 7.5% were diagnosed with asthma after the onset of menarche. After controlling for potential confounders (age, race, body mass index, and socio-economic status), women who had early menarche (<12 years old) had 60% higher risk of being diagnosed with adult onset asthma as compared with women who did not have early menarche (≥ 12 years old) (aRR= 1.59, 95% CI 1.19 - 2.13). Menstrual irregularities or abnormal (short or long) cycle length were not associated with risk of adult onset asthma. In addition, no significant interaction was observed between age at menarche or menstrual characteristics with body mass index or physical activity (in adolescence) in relation to adult onset asthma.Early menarche is associated with a higher risk of developing adult onset asthma among reproductive age women. Mechanisms for this association are potential areas of future research.

  View details for DOI 10.4172/2161-038X.1000111

  View details for PubMedID 25309820

  View details for PubMedCentralID PMC4192656

• Differential Expression of HrtA1 and ADAM12 in Placentas from Preeclamptic and Normotensive Pregnancies. Reproductive system & sexual disorders : current research Enquobahrie, D. A., Hevner, K., Qiu, C., Abetew, D. F., Sorensen, T. K., Williams, M. A. 2012; 1 (3): 1000110

  Abstract

  High temperature requirement factor A 1 (HtrA1) and a disintegrin and metalloproteinase 12 (ADAM12), which play roles in placental implantation and placental growth, have been implicated in the pathogenesis of preeclampsia.We investigated relative mRNA expression of both genes in placental tissues from women with preeclampsia (N=18) (average gestational age 36 weeks) and an equal number of women with normotensive pregnancies (average gestational age 39 weeks). Real-time polymerase chain reaction was used to measure mRNA extracted from term placental biopsies. Differential gene expression was evaluated using Student's T-test and fold change analyses.Statistically significant increases in placental HtRA1 (1.69-fold, p=0.030) and ADAM12 (1.48-fold, p=0.010) mRNA expression were observed among preeclamptic cases as compared with normotensive controls. HtrA1 expression was correlated with maternal age (p-value <0.01) among preeclampsia cases.Increases in HtRA1 and ADAM12 placental gene expression in placentas from preeclamptic pregnancies are consistent with some earlier reports of altered serum protein concentrations in preeclamptic pregnancies. This adds to the literature suggesting that defects in placentation (e.g. involving trophoblast invasion) are of etiologic importance in preeclampsia.

  View details for DOI 10.4172/2161-038X.1000110

  View details for PubMedID 24860691

  View details for PubMedCentralID PMC4031672

• Global placental gene expression in gestational diabetes mellitus. American journal of obstetrics and gynecology Enquobahrie, D. A., Williams, M. A., Qiu, C., Meller, M., Sorensen, T. K. 2009; 200 (2): 206.e1-13

  Abstract

  Gestational diabetes mellitus (GDM) is thought to modify the pattern of placental transcriptome. In a microarray study and a confirmatory quantitative real-time reverse transcription-polymerase chain reaction study, we investigated global placental gene expression in GDM.Ribonucleic acid was extracted from placental samples collected from 19 GDM cases and 21 controls. Oligonucleotide probes representing 22,000 genes were used to measure gene expression. Differential gene expression was evaluated using the Student t test, fold change assessment, and significance analysis of microarrays. Path analysis was used to assess functions and functional relationships of differentially expressed genes.Sixty-six genes participating in cell functions involving cell activation, immune response, organ development, and regulation of cell death were differentially expressed in GDM placentas. These genes include previously described candidate genes (eg, LEP, CEBPA, and MIF), genes with related functions (eg, ADFP), and novel genes (eg, AQP3).Expression of genes responsible for diverse biologic processes are modified in GDM.

  View details for DOI 10.1016/j.ajog.2008.08.022

  View details for PubMedID 18845290