Elleni Hailu
Postdoctoral Scholar, Neonatal and Developmental Medicine
Contact
https://orcid.org/0000-0002-0879-6176All Publications
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Folate Metabolism and Risk of Childhood Acute Lymphoblastic Leukemia: A Genetic Pathway Analysis from the Childhood Cancer and Leukemia International Consortium
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
2024; 33 (9): 1248-1252
Abstract
Prenatal folate supplementation has been consistently associated with a reduced risk of childhood acute lymphoblastic leukemia (ALL). Previous germline genetic studies examining the one carbon (folate) metabolism pathway were limited in sample size, scope, and population diversity and led to inconclusive results.We evaluated whether ∼2,900 single-nucleotide polymorphisms (SNP) within 46 candidate genes involved in the folate metabolism pathway influence the risk of childhood ALL, using genome-wide data from nine case-control studies in the Childhood Cancer and Leukemia International Consortium (n = 9,058 cases including 4,510 children of European ancestry, 3,018 Latinx, and 1,406 Asians, and 92,364 controls). Each study followed a standardized protocol for quality control and imputation of genome-wide data and summary statistics were meta-analyzed for all children combined and by major ancestry group using METAL software.None of the selected SNPs reached statistical significance, overall and for major ancestry groups (using adjusted Bonferroni P-value of 5 × 10-6 and less-stringent P-value of 3.5 × 10-5 accounting for the number of "independent" SNPs). None of the 10 top (nonsignificant) SNPs and corresponding genes overlapped across ancestry groups.This large meta-analysis of original data does not reveal associations between many common genetic variants in the folate metabolism pathway and childhood ALL in various ancestry groups.Genetic variants in the folate pathway alone do not appear to substantially influence childhood acute lymphoblastic leukemia risk. Other mechanisms such as gene-folate interaction, DNA methylation, or maternal genetic effects may explain the observed associations with self-reported prenatal folate intake.
View details for DOI 10.1158/1055-9965.EPI-24-0189
View details for Web of Science ID 001304222600009
View details for PubMedID 38904462
View details for PubMedCentralID PMC11369612
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Associations between historical and contemporary measures of structural racism and leukocyte telomere length: The Multi-Ethnic Study of Atherosclerosis (MESA).
Social science & medicine (1982)
2024; 360: 117229
Abstract
BACKGROUND: We assessed the link between two manifestations of structural racism-historical redlining and contemporary racial residential segregation-and baseline and 10-year changes in leukocyte telomere length (LTL).METHODS: We used data on Black and Hispanic/Latinx participants from Exams I and V of the Multi-Ethnic Study of Atherosclerosis Stress Ancillary Study (N=741, age range=45-84 years). LTL was defined as the ratio of telomeric DNA to a single copy gene (T/S), and 10-year changes were adjusted for regression to the mean. We used 1930s Home Owners' Loan Corporation maps to assign three historical redlining grades (A&B: best/still desirable, C: declining, D: hazardous/redlined) to participants' neighborhoods (census-tracts) at baseline. The Getis-Ord Gi statistic was used to evaluate census-tract level baseline residential segregation (low/moderate/high).RESULTS: In mixed-effects regression models accounting for neighborhood clustering, individual characteristics, and current neighborhood environments, those living in highly segregated Black neighborhoods had 0.08 shorter baseline LTL (95% CI: -0.13, -0.04), than those residing in the least segregated neighborhoods. We did not find a relationship between residing in segregated neighborhoods and 10-year LTL changes, and associations between residing in historically redlined neighborhoods and both baseline LTL and 10-year changes in LTL were null. Across discriminatory disinvestment trajectories examined, individuals residing in highly segregated but non-redlined neighborhoods had 0.6 shorter baseline LTL than individuals residing in non-redlined neighborhoods with low/moderate segregation (95% CI: -0.12, -0.01).CONCLUSIONS: Our results highlight the impact of racial segregation on cellular aging and underscore the need to ameliorate structural inequities within segregated neighborhoods.
View details for DOI 10.1016/j.socscimed.2024.117229
View details for PubMedID 39303531
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Neighborhood-level Fatal Police Violence and Severe Maternal Morbidity in California.
American journal of epidemiology
2024
Abstract
Police violence is a pervasive issue that may have adverse implications for severe maternal morbidity (SMM). We assessed how the occurrence of fatal police violence (FPV) in one's neighborhood before/during pregnancy may influence SMM risk. Hospital discharge records from California between 2002-2018 were linked with the Fatal Encounters database (N=2,608,682). We identified 2,184 neighborhoods (census-tracts) with at least one FPV incident during the study period and used neighborhood fixed-effects models adjusting for individual sociodemographic characteristics to estimate odds of SMM associated with experiencing FPV in one's neighborhood anytime within the 24-months before childbirth. We did not find conclusive evidence on the link between FPV occurrence before delivery and SMM. However, estimates show that birthing people residing in neighborhoods where one or more FPV events had occurred within the preceding 24-months of giving birth may have a mildly elevated odds of SMM than those residing in the same neighborhoods with no FPV occurrence during the 24-months preceding childbirth (Odds Ratio (OR)=1.02; 95% Confidence Interval (CI): 0.99-1.05), particularly among those living in neighborhoods with fewer (1-2) FPV incidents throughout the study period (OR=1.03; 95% CI:1.00-1.06). Our findings provide evidence for the need to continue to examine the health consequences of police violence.
View details for DOI 10.1093/aje/kwae124
View details for PubMedID 38879741
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Structural Racism, Mass Incarceration, and Racial and Ethnic Disparities in Severe Maternal Morbidity.
JAMA network open
2024; 7 (1): e2353626
Abstract
Importance: Racial and ethnic inequities in the criminal-legal system are an important manifestation of structural racism. However, how these inequities may influence the risk of severe maternal morbidity (SMM) and its persistent racial and ethnic disparities remains underinvestigated.Objective: To examine the association between county-level inequity in jail incarceration rates comparing Black and White individuals and SMM risk in California.Design, Setting, and Participants: This population-based cross-sectional study used state-wide data from California on all live hospital births at 20 weeks of gestation or later from January 1, 1997, to December 31, 2018. Data were obtained from hospital discharge and vital statistics records, which were linked with publicly available county-level data. Data analysis was performed from January 2022 to February 2023.Exposure: Jail incarceration inequity was determined from the ratio of jail incarceration rates of Black individuals to those of White individuals and was categorized as tertile 1 (low), tertile 2 (moderate), tertile 3 (high), with mean cutoffs across all years of 0 to 2.99, 3.00 to 5.22, and greater than 5.22, respectively.Main Outcome and Measures: This study used race- and ethnicity-stratified mixed-effects logistic regression models with birthing people nested within counties and adjusted for individual- and county-level characteristics to estimate the odds of non-blood transfusion SMM (NT SMM) and SMM including blood transfusion-only cases (SMM; as defined by the Centers for Disease Control and Prevention SMM index) associated with tertiles of incarceration inequity.Results: This study included 10 200 692 births (0.4% American Indian or Alaska Native, 13.4% Asian or Pacific Islander, 5.8% Black, 50.8% Hispanic or Latinx, 29.6% White, and 0.1% multiracial or other [individuals who self-identified with ≥2 racial groups and those who self-identified as "other" race or ethnicity]). In fully adjusted models, residing in counties with high jail incarceration inequity (tertile 3) was associated with higher odds of SMM for Black (odds ratio [OR], 1.14; 95% CI, 1.01-1.29 for NT SMM; OR, 1.20, 95% CI, 1.01-1.42 for SMM), Hispanic or Latinx (OR, 1.24; 95% CI, 1.14-1.34 for NT SMM; OR, 1.20; 95% CI, 1.14-1.27 for SMM), and White (OR, 1.02; 95% CI, 0.93-1.12 for NT SMM; OR, 1.09; 95% CI, 1.02-1.17 for SMM) birthing people, compared with residing in counties with low inequity (tertile 1).Conclusions and Relevance: The findings of this study highlight the adverse maternal health consequences of structural racism manifesting via the criminal-legal system and underscore the need for community-based alternatives to inequitable punitive practices.
View details for DOI 10.1001/jamanetworkopen.2023.53626
View details for PubMedID 38277143
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Assessing the relationship between census tract rurality and severe maternal morbidity in California (1997-2018).
The Journal of rural health : official journal of the American Rural Health Association and the National Rural Health Care Association
2023
Abstract
PURPOSE: Recent studies have demonstrated an increased risk of severe maternal morbidity (SMM) for people living in rural versus urban counties. Studies have not considered rurality at the more nuanced subcounty census-tract level. This study assessed the relationship between census-tract-level rurality and SMM for birthing people in California.METHODS: We used linked vital statistics and hospital discharge records for births between 1997 and 2018 in California. SMM was defined by at least 1 of 21 potentially fatal conditions and lifesaving procedures. Rural-Urban Commuting Area codes were used to characterize census tract rurality dichotomously (2-category) and at 4 levels (4-category). Covariates included sociocultural-demographic, pregnancy-related, and neighborhood-level factors. We ran a series of mixed-effects logistic regression models with tract-level clustering, reporting risk ratios and 95% confidence intervals (CIs). We used the STROBE reporting guidelines.FINDINGS: Of 10,091,415 births, 1.1% had SMM. Overall, 94.3% of participants resided in urban/metropolitan and 5.7% in rural tracts (3.9% micropolitan, 0.9% small town, 0.8% rural). In 2-category models, the risk of SMM was 10% higher for birthing people in rural versus urban tracts (95% CI: 6%, 13%). In 4-category models, the risk of SMM was 16% higher in micropolitan versus metropolitan tracts (95% CI: 12%, 21%).CONCLUSION: The observed rurality and SMM relationship was driven by living in a micropolitan versus metropolitan tract. Increased risk may result from resource access inequities within suburban areas. Our findings demonstrate the importance of considering rurality at a subcounty level to understand locality-related inequities in the risk of SMM.
View details for DOI 10.1111/jrh.12814
View details for PubMedID 38054697
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Neighborhood Deprivation and Severe Maternal Morbidity in the State of California: An Examination of Effect Modification by Race/Ethnicity.
American journal of obstetrics & gynecology MFM
2023: 100916
Abstract
Social determinants of health, including neighborhood context, may be a key driver of severe maternal morbidity and its related racial/ethnic inequities, but investigations remain limited.We examined associations between neighborhood socioeconomic characteristics and severe maternal morbidity and whether associations were modified by race/ethnicity.This study leveraged a California statewide data resource on all hospital births ≥20 weeks (1997-2018). Severe maternal morbidity was defined as having at least one of 21 diagnoses and procedures (for example, blood transfusion, hysterectomy) as outlined by the Centers for Disease Control and Prevention. Neighborhoods were defined as residential census tracts (N=8,022; average of 1,295 births per neighborhood), and neighborhood deprivation index was a summary measures of 8 census indicators (for example, percent poverty, unemployment, public assistance). Mixed-effects logistic regression models (individuals nested within neighborhoods) were used to compare odds of severe maternal morbidity across quartiles (Quartile 1= least deprived; Quartile 4 = most deprived) of neighborhood deprivation index before and after adjustment for maternal sociodemographic and pregnancy-related factors and co-morbidities. We also created cross-product terms to determine if associations were modified by race/ethnicity.Of 10,384,976 births, the prevalence of severe maternal morbidity was 1.2% (N=120,487). In fully adjusted mixed-effects models, odds of severe maternal morbidity increased with increasing neighborhood deprivation index (Odds Ratios and 95% Confidence Intervals, with Quartile 1 as reference: Quartile 4 =1.23 (1.20-1.26), Quartile 3=1.13 (1.10-1.16), Quartile 2=1.06 (1.03-1.08). Associations were modified by race/ethnicity such that associations (Quartile 4 vs. Quartile 1, 95% C.I.) were strongest among individuals in the "Other" racial/ethnic category (1.39, 1.03-1.86) and weakest among Black individuals (1.07, 0.98-1.16).These findings suggest that neighborhood deprivation contributes to an increased risk of severe maternal morbidity. Future research should examine which aspects of neighborhood environments matter most across racial/ethnic groups.
View details for DOI 10.1016/j.ajogmf.2023.100916
View details for PubMedID 36905984
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Structural racism and adverse maternal health outcomes: A systematic review.
Health & place
2022; 78: 102923
Abstract
In the United States, racial disparities in adverse maternal health outcomes remain a pressing issue, with Black women experiencing a 3-4 times higher risk of maternal mortality and a 2-3 times higher risk of severe maternal morbidity. Despite recent encouraging efforts, fundamental determinants of these alarming inequities (e.g. structural racism) remain understudied. Approaches that address these structural drivers are needed to then intervene upon root causes of adverse maternal outcomes and their disparities and to ultimately improve maternal health across the U.S. In this paper, we offer a conceptual framework for studies of structural racism and maternal health disparities and systematically synthesize the current empirical epidemiologic literature on the links between structural racism measures and adverse maternal health outcomes. For the systematic review, we searched electronic databases (Pubmed, Web of Science, and EMBASE) to identify peer-reviewed U.S. based quantitative articles published between 1990 and 2021 that assessed the link between measures of structural racism and indicators of maternal morbidity/mortality. Our search yielded 2394 studies and after removing duplicates, 1408 were included in the title and abstract screening, of which 18 were included in the full text screening. Only 6 studies met all the specified inclusion criteria for this review. Results revealed that depending on population sub-group analyzed, measures used, and covariates considered, there was evidence that structural racism may increase the risk of adverse maternal health outcomes. This review also highlighted several areas for methodological and theoretical development in this body of work. Future work should more comprehensively assess structural racism in a way that informs policy and interventions, which can ameliorate its negative consequences on racial/ethnic disparities in maternal morbidity/mortality.
View details for DOI 10.1016/j.healthplace.2022.102923
View details for PubMedID 36401939
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Racial/ethnic disparities in severe maternal morbidity: An intersectional lifecourse approach.
Annals of the New York Academy of Sciences
2022
Abstract
Despite long-existing calls to address alarming racial/ethnic gaps in severe maternal morbidity (SMM), research that considers the impact of intersecting social inequities on SMM risk remains scarce. Invoking intersectionality theory, we sought to assess SMM risk at the nexus of racial/ethnic marginalization, weathering, and neighborhood/individual socioeconomic disadvantage. We used birth hospitalization records from California across 20 years (1997-2017, N = 9,806,406) on all live births ≥20 weeks gestation. We estimated adjusted average predicted probabilities of SMM at the combination of levels of race/ethnicity, age, and neighborhood deprivation or individual socioeconomic status (SES). The highest risk of SMM was observed among Black birthing people aged ≥35 years who either resided in the most deprived neighborhoods or had the lowest SES. Black birthing people conceptualized to be better off due to their social standing (aged 20-34 years and living in the least deprived neighborhoods or college graduates) had comparable and at times worse risk than White birthing people conceptualized to be worse off (aged ≥35 years and living in the most deprived neighborhoods or had a high-school degree or less). Our findings highlight the need to explicitly address structural racism as the driver of racial/ethnic health inequities and the imperative to incorporate intersectional approaches.
View details for DOI 10.1111/nyas.14901
View details for PubMedID 36166238
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Longitudinal Associations between Discrimination, Neighborhood Social Cohesion, and Telomere Length: The Multi-Ethnic Study of Atherosclerosis (MESA).
The journals of gerontology. Series A, Biological sciences and medical sciences
2021; 77 (2): 365-74
Abstract
We aimed to examine if neighborhood social cohesion moderated longitudinal associations between baseline reports of discrimination and 10-year changes in Leukocyte Telomere Length (LTL).Data are from the Multi-Ethnic Study of Atherosclerosis (MESA; N=1,064; age range 45-84 years). Baseline discrimination was measured using the Major Experiences of Discrimination Scale (MDS; none, 1 domain, ≥2 domains) and the Experiences of Discrimination Scale (EDS; none, moderate, high). Neighborhood social cohesion at baseline was assessed via a community survey within census tract defined neighborhoods. 10-year change in LTL was defined as Regression to the Mean corrected 10-year difference in the ratio of telomeric DNA to a single copy gene (T/S).In linear mixed effects models, we found that neighborhood social cohesion modified the effect of baseline reports of MDS on 10-year changes in LTL, independent of sociodemographic characteristics, health behaviors, and health conditions (p(χ 2)=0.01). Among those residing in neighborhoods with low social cohesion, experiencing major discrimination in ≥2 domains was associated with faster LTL attrition over 10-years, compared to reporting no discrimination (β=-0.03; 95% CI: -0.06, -0.003). We found no main associations for either discrimination measure and no interaction between EDS and neighborhood social cohesion.Results indicate that neighborhood social cohesion is an important dimension of the neighborhood context that may moderate the impact of major experiences of discrimination on telomere length attrition. These findings help advance our understanding of the integral role that neighborhood environments play in attenuating the effect of discrimination on accelerated cell aging.
View details for DOI 10.1093/gerona/glab193
View details for PubMedID 34282826
View details for PubMedCentralID PMC8824602
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Neighborhood social environment and changes in leukocyte telomere length: The Multi-Ethnic Study of Atherosclerosis (MESA)
HEALTH & PLACE
2021; 67: 102488
Abstract
Given limited research on the impact of neighborhood environments on accelerated biological aging, we examined whether changes in neighborhood socioeconomic and social conditions were associated with change in leukocyte telomere length using 10 years of longitudinal data from the Multi-Ethnic Study of Atherosclerosis (years 2000-2011; N = 1031; mean age = 61, SD = 9.4). Leukocyte telomere length change was corrected for regression to the mean and neighborhood was defined as census tract. Neighborhood socioeconomic indicators (factor-based score of income, education, occupation, and wealth of neighborhood) and neighborhood social environment indicators (aesthetic quality, social cohesion, safety) were obtained from the U.S Census/American Community Survey and via study questionnaire, respectively. Results of linear mixed-effects models showed that independent of individual sociodemographic characteristics, each unit of improvement in neighborhood socioeconomic status was associated with slower telomere length attrition over 10-years (β = 0.002; 95% Confidence Interval (CI): 0.0001, 0.004); whereas each unit of increase in safety (β = -0.043; 95% CI: -0.069, -0.016) and overall neighborhood social environment score (β = -0.005; 95% CI: -0.009, -0.0004) were associated with more pronounced telomere attrition, after additionally adjusting for neighborhood socioeconomic status. This study provides support for considerations of the broader social and socioeconomic contexts in relation to biological aging. Future research should explore potential psychosocial mechanisms underlying these associations using longitudinal study designs with repeated observations.
View details for DOI 10.1016/j.healthplace.2020.102488
View details for Web of Science ID 000616070900010
View details for PubMedID 33276262
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Birth Hospital and Racial/Ethnic Differences in Severe Maternal Morbidity in the State of California.
American journal of obstetrics and gynecology
2020
Abstract
BACKGROUND: Birth hospital has recently emerged as a potentially key contributor to disparities in severe maternal morbidity, but investigations remain limited.OBJECTIVES: We leveraged state-wide data from California to examine whether birth hospital explained racial/ethnic differences in severe maternal morbidity.METHODS: This cohort study used data on all births ≥20 weeks in California (2007-2012). Severe maternal morbidity during birth hospitalization was measured using the Centers for Disease Control and Prevention index of having at least one of 21 diagnoses and procedures (e.g. eclampsia, blood transfusion, hysterectomy). Mixed effects logistic regression models (i.e. women nested within hospitals) were used to compare racial/ethnic differences in severe maternal morbidity before and after adjustment for maternal sociodemographic and pregnancy-related factors, co-morbidities, and hospital characteristics. We also estimated risk-standardized severe maternal morbidity rates for each hospital (N=245) and the percent reduction in severe maternal morbidity if each group of racially/ethnically minoritized women gave birth at the same distribution of hospitals as non-Hispanic White women.RESULTS: Of the 3,020,525 women who gave birth, 39,192 (1.3%) had severe maternal morbidity (2.1% Black; 1.3% US-born Hispanic; 1.3% foreign-born Hispanic; 1.3% Asian/Pacific Islander; 1.1% White; 1.6% American Indian/Alaska Native and Mixed Race referred to as "Other"). Risk-standardized rates of severe maternal morbidity ranged from 0.3 to 4.0 per 100 births across hospitals. After adjusting for covariates, odds of severe maternal morbidity was greater among non-White women compared to Whites in a given hospital (Odds Ratios and 95% Confidence Intervals; Black =1.25 (1.19-1.31), US-born Hispanic=1.25 (1.20-1.29), Foreign-born Hispanic=1.17 (1.11-1.24), Asian/Pacific Islander=1.26 (1.21-1.32), "Other"=1.31 (1.15-1.50). Among the studied hospital factors, only teaching status was associated with severe maternal morbidity in fully adjusted models. Although 33% of White women delivered in hospitals with the highest tertile of severe maternal morbidity rates compared to 53% of Black women, birth hospital only accounted for 7.8% of the differences in severe maternal morbidity comparing Black and White women and accounted for 16.1-24.2% of the differences for all other racial/ethnic groups.CONCLUSION: In California, excess odds of severe maternal morbidity among racially/ethnically minoritized women was not fully explained by birth hospital. Structural causes of racial/ethnic disparities in severe maternal morbidity may vary by region, which warrants further examination to inform effective policies.
View details for DOI 10.1016/j.ajog.2020.08.017
View details for PubMedID 32798461
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Discrimination, social support, and telomere length: the Multi-Ethnic Study of Atherosclerosis (MESA)
ANNALS OF EPIDEMIOLOGY
2020; 42: 58-63
Abstract
We sought to assess the association of reports of discrimination with leukocyte telomere length (LTL) and effect measure modification by social support.This study used data from the Multi-Ethnic Study of Atherosclerosis Stress Ancillary Study (n = 1153). Discrimination was measured using the everyday discrimination and the major experiences of discrimination scales. LTL was defined as the ratio of telomeric DNA to single-copy control gene (mean = 0.916, SD = 0.205). Linear regression models were used to examine the relationship between discrimination and LTL.We found no association between either measure of discrimination and LTL, but there was evidence of effect modification by social support (P (χ2) = 0.001) for everyday discrimination only. Among those with low social support, reporting moderate and high everyday discrimination was associated with a 0.35 (95% CI: -0.54 to -0.16) and a 0.17 (95% CI: -0.34 to -0.01) shorter telomere length, respectively, compared to reporting no discrimination, after adjusting for demographic factors, health behaviors, and health conditions. There were no associations between discrimination and LTL among those reporting moderate or high social support.These findings underscore the importance of continued investigation of the potential health consequences of chronic unfair treatment in the absence of supportive resources.
View details for DOI 10.1016/j.annepidem.2019.12.009
View details for Web of Science ID 000519149800009
View details for PubMedID 32070634
View details for PubMedCentralID PMC11019778