Ayesha Sujan

All Publications

• Validation of Claims-Based Algorithms for Identifying Congenital Urinary Tract, Genital, Gastrointestinal, and Musculoskeletal Malformations. Pharmacoepidemiology and drug safety Fung, K., Leonard, S. A., Huybrechts, K. F., Hernandez-Diaz, S., Bateman, B. T., Straub, L., Sujan, A., Gray, K. J., Andersen, K., Chen, E. Y., El-Tayeb, K., Jeancharles, M., Mootz, A. A., Winkler, A. E., Fernando, A. M., Qin, C. X., Stockert, E. W., Mogun, H., Zhu, Y. 2026; 35 (9): e70461

  Abstract

  Congenital malformations are important outcomes when evaluating medication safety in pregnancy. However, the accuracy of claims-based algorithms for identifying organ-specific malformations remains understudied. We validated algorithms for four malformation groups: urinary tract, genital, gastrointestinal, and musculoskeletal.Using the Mass General Brigham (MGB, 2007-2020) and Stanford Medicine (2016-2023) databases, we identified infants with potential malformations of interest based on diagnosis and procedure codes within 90 days of birth. A total of 150 cases were sampled for each malformation group. Positive predictive values (PPV) were estimated to quantify the validity of the algorithms, separately by site and by International Classification of Diseases (ICD) coding system.For MGB ICD-9, MGB ICD-10, and Stanford ICD-10 algorithms, respectively, PPVs were 100%, 98.0%, and 95.8% for urinary tract malformations; 98.0%, 95.9%, and 93.8% for genital malformations; 76.0%, 78.0%, and 76.0% for gastrointestinal malformations; and 85.4%, 84.0%, and 62.0% for musculoskeletal malformations. False positives were primarily attributed to suspected malformations that were later ruled out and to broader or inaccurate coding for diagnoses that were not major malformations.Claims-based algorithms demonstrated high PPVs for urinary tract and genital malformations and moderate for gastrointestinal malformations, but there was variation in musculoskeletal PPVs between the institutions with different patient populations.

  View details for DOI 10.1002/pds.70461

  View details for PubMedID 42618046

  View details for PubMedCentralID PMC13489719

• Pre-surgical quantitative sensory testing and post-surgical pain among adolescents undergoing spinal fusion surgery: A longitudinal cohort study. The journal of pain Sujan, A. C., Groenewald, C., Li, R., Schreiber, K. L., Palermo, T. M., Kain, Z., Rabbitts, J. A. 2026; 45: 106327

  Abstract

  Pediatric post-surgical pain is common and associated with diminished quality of life and significant medical costs. While quantitative sensory testing (QST) is a promising tool for predicting post-surgical pain in adults, research in youth is lacking. We tested associations between pre-surgical QST indices (pressure and heat pain thresholds, mechanical temporal summation of pain [MTSP], conditioned pain modulation, and cold-pressor painful after-sensations) and average and worst pain severity and pain interference assessed daily during the first week post-hospital discharge (acute outcomes), as well as six-month post-surgical pain intensity and presence of chronic post-surgical pain (CPSP; six-month pain intensity>3/10 and quality-of-life score<74.9). Of 160 enrolled participants, 142 (mean age=14.6 years, 76% female) who completed QST and outcome measures were analyzed. Mean average and worst acute pain severity across the first seven days were 3.5/10 and 5.5/10. Six-month pain intensity was 2.7/10; 30.6% of participants had CPSP. Controlling for sociodemographic and pre-surgical characteristics, higher MTSP (b=0.17, 95% CI=0.02-0.32) and painful after-sensations (b=0.13, 95% CI=0.02-0.23) were associated with greater average acute pain severity. Higher MTSP was also associated with greater worst acute pain severity (b=0.30, 95% CI=0.12-0.47) and six-month pain intensity (b=0.36, 95% CI=0.16-0.55). No QST indices were associated with CPSP. Exploratory analyses revealed that associations were stronger for youth with mild pre-surgical pain. Results suggest QST, particularly MTSP, is a promising pre-surgical marker to identify adolescents who may experience greater post-surgical pain. Future research should evaluate feasibility of pre-surgical bedside QST and QST as a predictor of responsiveness to post-surgical pain management interventions. PERSPECTIVE: Results from this prospective longitudinal study, the largest to date employing preoperative quantitative sensory testing (QST) in adolescents, suggest that pre-surgical QST, particularly mechanical temporal summation of pain, is a promising marker for identifying adolescents at risk for severe acute post-surgical pain.

  View details for DOI 10.1016/j.jpain.2026.106327

  View details for PubMedID 42203052

• Associations Between Neighborhood Opportunity Indicators, Postoperative Pain Outcomes, and Mental Health in Adolescents Undergoing Spinal Fusion Surgery Dionicio, P., Palermo, T., Zhou, C., Aalfs, H., Sujan, A., Querdasi, F. R., Parsons, R., Rabbitts, J. CHURCHILL LIVINGSTONE. 2026

  View details for DOI 10.1016/j.jpain.2025.105904

  View details for Web of Science ID 001744236500097

• National Medical Expenditures Associated With Pediatric Disorders of Gut-Brain Interaction in the United States. Neurogastroenterology and motility Sujan, A. C., Major, J., Groenewald, C. B., Rabbitts, J. A. 2026; 38 (3): e70279

  Abstract

  Limited research has evaluated national medical expenditures associated with pediatric disorders of gut-brain interaction (DGBI), despite the high prevalence of these disorders in children and their association with reduced quality of life.We used data from the 2017-2022 Medical Expenditure Panel Survey (MEPS) to estimate the individual- and national-level outpatient, office-based, prescribed medication, emergency room, inpatient, and other medical expenditures, and overall expenditures associated with pediatric DGBI. Pediatric DGBI included International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10) codes associated with irritable bowel syndrome, functional dyspepsia, and other functional intestinal disorders (including constipation) among 40,067 individuals ≤ 18 years receiving medical care in the United States.After controlling for predisposing factors, enabling resources, and co-morbid medical conditions, total per patient annual medical expenditures were $5217 (in 2022 dollars) for pediatric patients with DGBI-an estimate that was $2587 greater than the estimated medical expenditures for children without DGBI. Incremental spending from DGBI patients versus patients without DGBI was highest for outpatient visits followed by office-based visits, prescribed medications, and emergency room visits. Total annual medical expenditures for pediatric patients with DGBI were estimated at $2.08 billion.The results illuminate the significant national medical expenditures associated with pediatric DGBI, suggesting the potential importance of early detection and effective treatment for pediatric DGBI and the need for future research to improve assessment and evidence-based treatment for pediatric DGBI.

  View details for DOI 10.1111/nmo.70279

  View details for PubMedID 41795129

• Country of Birth, Race, Ethnicity, and Prenatal Depression. JAMA network open Kelly-Taylor, K., Aghaee, S., Nugent, J., Oberman, N., Kubo, A., Kurtovich, E., Quesenberry, C. P., Sujan, A. C., Erickson-Ridout, K., Bhalala, M. M., Avalos, L. A. 2025; 8 (9): e2531844

  Abstract

  Non-US-born pregnant individuals have demonstrated better perinatal outcomes compared with their US-born counterparts, yet limited literature has explored this association among mental health conditions in pregnancy and across racial and ethnic groups.To examine the differences in prenatal depression diagnosis and moderate to severe depression symptoms between non-US-born and US-born individuals across racial and ethnic subgroups.Cross-sectional study of members of Kaiser Permanente Northern California (KPNC), an integrated health care delivery system, who attended at least 1 prenatal care visit and delivered a live birth between January 1, 2013, and December 31, 2019. Data were analyzed from September 2023 to January 2024.Self-reported race, ethnicity, and country of birth. Country of birth was used to define maternal nativity (US-born vs non-US-born).Prenatal depression diagnosis (PDD) defined by International Classification of Diseases, Ninth Revision and Tenth Revision codes and moderate to severe depression symptoms defined by self-reported Patient Health Questionnaire-9 (PHQ-9) scores of 10 or greater documented in the KPNC electronic health records (EHR) between the first day of the last menstrual period to the day before live birth.Among the 252 171 participants (168 605 [66.7%] US-born and 83 566 [33.1%] non-US-born), adjusted models showed non-US-born pregnant individuals had an equivalent or significantly lower risk of PDD compared with their US-born counterparts within racial and ethnic subgroups. Non-US-born individuals presented a higher risk of moderate to severe depression symptoms compared with US-born individuals among certain Hispanic (eg, adjusted relative risk [aRR] for other Hispanic individuals, 1.30; 95% CI, 1.01-1.67), and Asian (eg, aRR for Japanese individuals, 3.62; 95% CI, 2.08-6.30) subgroups as well as among White pregnant individuals (aRR, 1.17; 95% CI, 1.10-1.25). Non-US-born Black pregnant individuals presented lower risk of PDD (aRR, 0.30; 95% CI, 0.25-0.36) and moderate to severe depression symptoms (aRR, 0.75; 95% CI, 0.65-0.86) compared with US-born Black individuals.Across racial and ethnic groups, PDD and moderate to severe depression symptoms varied by maternal nativity in this cross-sectional study. The observed advantage among non-US-born individuals across other maternal and neonatal outcomes may not uniformly apply to prenatal mental health conditions when race and ethnicity are considered. Future research should explore sociocultural factors that may influence this association.

  View details for DOI 10.1001/jamanetworkopen.2025.31844

  View details for PubMedID 40952739

  View details for PubMedCentralID PMC12439054

• Prescribed opioid analgesic use in pregnancy and risk of neurodevelopmental disorders in children: A retrospective study in Sweden. PLoS medicine Cleary, E. N., Sujan, A. C., Rickert, M. E., Fischer, F., Lagerberg, T., Chang, Z., Lichtenstein, P., Quinn, P. D., Öberg, A. S., D'Onofrio, B. M. 2025; 22 (9): e1004721

  Abstract

  The extent to which the documented association between prenatal prescribed opioid analgesic (POA) exposure and neurodevelopmental disorders in children is causal or due to confounding is unknown. The objective of this study was to evaluate associations between dose and duration of POA exposure during pregnancy and autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD) in children while minimizing bias due to confounding and other sources.This retrospective study analyzed a population-based cohort of births using national register data from Sweden. The ASD analysis cohort consisted of 1,267,978 children born in Sweden from July 1st, 2007 to December 31st, 2018, with follow-up through 2021. A shorter eligibility period was used to study ADHD given its later age of typical diagnosis, consisting of 918,771 children born through December 31st, 2015. Text-mining algorithms were used to derive cumulative dose and duration of POA exposure during pregnancy from filled POA prescriptions, as well as to identify prescriptions that were to be taken on an "as needed" basis. Outcomes were identified through inpatient or outpatient clinical diagnosis of ASD and ADHD or dispensed ADHD medications. Cox proportional hazards regression models were adjusted for measured covariates from multiple domains. Several designs were used to help address unmeasured confounding: comparisons with children whose birthing parent had a diagnosed painful condition but did not receive POAs, children whose birthing parent received POAs in the year before but not during pregnancy, and siblings who were not exposed to POAs. Of the 1,267,978 children, 48.6% were female and 4.4% were exposed to POAs during pregnancy. At age 10, cumulative incidence of ASD was 2.0% among children unexposed to POAs, 2.9% among children exposed to a low dose across pregnancy, and 3.6% among children exposed to a high dose. In unadjusted models (e.g., hazard ratio [HR]high, 1.74, 95% confidence interval [CI], 1.63, 1.87) and when accounting for measured covariates, cumulative maximum dose was associated with increased risk of ASD (e.g., HRhigh, 1.34, 95% CI, 1.24, 1.44). However, the associations were largely or fully attenuated when using alternative designs (particularly when comparing to children whose birthing parent received POAs before but not during pregnancy: HRhigh, 1.10, 95% CI, 1.00, 1.21). No associations were observed in the sibling comparison (HRhigh, 0.99, 95% CI, 0.81, 1.21). This overall pattern of associations was also observed when considering duration of exposure, and in numerous sensitivity analyses, as well as for analyses of ADHD. A main limitation of this study was that the distribution of dose and duration of POAs prescribed to birthing parents in Sweden limited our ability to explore the effects of extremely high dose and duration on risk for neurodevelopmental disorders.While increased risks with high amounts of POA exposure cannot be ruled out, the results suggest that confounding may largely explain the increased risks of ASD and ADHD associated with prenatal POA exposure at the levels observed in this cohort.

  View details for DOI 10.1371/journal.pmed.1004721

  View details for PubMedID 40956781

  View details for PubMedCentralID PMC12440195

• Buprenorphine and Methadone Discontinuation During Pregnancy and the Postpartum Period: A Nationwide Cohort Study. The American journal of psychiatry Grace Lin, C. W., Bateman, B. T., Straub, L., Hernández-Díaz, S., Vine, S. M., Jones, H. E., Connery, H. S., Davis, J. M., Gray, K. J., Lester, B., Suarez, E. A., Sujan, A. C., Terplan, M., Huybrechts, K. F. 2025: appiajp20241127

  Abstract

  Treatment of pregnant patients with opioid use disorder with methadone or buprenorphine is crucial for maternal and neonatal safety. While several clinical trials have demonstrated higher treatment discontinuation rates for buprenorphine compared with methadone outside of pregnancy, evidence during pregnancy and the postpartum period is limited. The authors compared treatment discontinuation between buprenorphine and methadone during pregnancy and over follow-up through 1 year postpartum.This was a cohort study, using nationwide Medicaid data, of pregnant patients who initiated methadone or transmucosal buprenorphine (with or without naloxone) for opioid use disorder during the first trimester. The primary outcome was treatment discontinuation, defined as a treatment gap ≥60 days; alternative definitions for discontinuation were explored in sensitivity analyses. Hazard ratios were estimated using Cox proportional hazards regression with propensity score overlap weighting to control for confounding. Subgroup analyses were conducted, stratified by buprenorphine alone versus the buprenorphine/naloxone combination, each compared to methadone.Overall, 696 pregnant patients were identified who initiated methadone treatment and 1,538 who initiated buprenorphine treatment in the first trimester. Compared to methadone initiators, buprenorphine initiators were more likely to discontinue treatment during pregnancy (32.8% for buprenorphine vs. 25.6% for methadone; weighted hazard ratio=1.41, 95% CI=1.15, 1.72) and through 1 year postpartum (58.8% vs. 49.0%; hazard ratio=1.37, 95% CI=1.19, 1.57). For patients initiating the buprenorphine/naloxone combination, the hazard ratio was 1.73 (95% CI=1.36, 2.19) during pregnancy and 1.56 (95% CI=1.30, 1.86) through 1 year postpartum. For patients initiating buprenorphine alone, the hazard ratios were 1.14 (95% CI=0.90, 1.46) and 1.23 (95% CI=1.04, 1.46), respectively. Varying the treatment gap used to define discontinuation in sensitivity analyses yielded consistent results.Pregnant patients initiating transmucosal buprenorphine during early pregnancy were more likely to discontinue treatment than those initiating methadone, but treatment discontinuation was high for both treatments. The study findings highlight the importance of identifying and addressing barriers to treatment retention among pregnant patients with opioid use disorder.

  View details for DOI 10.1176/appi.ajp.20241127

  View details for PubMedID 40859701

• Substance use and mental health characteristics among pregnant individuals with medical and non-medical benzodiazepine use early in pregnancy DRUG AND ALCOHOL DEPENDENCE REPORTS Sujan, A. C., Slama, N. E., Bateman, B. T., Ansley, D., Castellanos, C., Young-Wolff, K. C. 2025; 15

  View details for DOI 10.1016/j.dadr.2025.100345

  View details for Web of Science ID 001502158400002

• Substance use and mental health characteristics among pregnant individuals with medical and non-medical benzodiazepine use early in pregnancy. Drug and alcohol dependence reports Sujan, A. C., Slama, N. E., Bateman, B. T., Ansley, D., Castellanos, C., Young-Wolff, K. C. 2025; 15: 100345

  Abstract

  Research to date evaluating the safety of benzodizapine use during pregnancy has shown mixed results and has relied on self-report or filled prescription data, which are unlikely to capture non-medical use and, consequently, could bias results. Therefore, research on non-medical benzodiazepine use during pregnancy is needed.The present study used data from a large, healthcare system with universal screening for prenatal substance use via urine toxicology tests and information on filled prescriptions. We first evaluated the prevalence of pregnancies with non-medical benzodiazepine use (positive urine toxicology test and no filled prescriptions in the past year) and medical benzodiazepine use (positive urine toxicology test and >1 filled prescription in the past year). We also evaluated the presence of co-occurrence of substance use and mental health conditions among these pregnancies.Our results showed that benzodiazepine use during early pregnancy was rare (<1 % had a positive toxicology test). However, more than one-third of those with a positive toxicology test did not have a filled prescription (i.e., had non-medical use) We also found similar rates of substance use and mental health conditions among pregnancies with medical and non-medical benzodiazepine use.Our results suggest that research relying on prescription data alone and the medical system may be missing pregnant individuals using benzodiazepines. This points to a need for additional measures and screenings (e.g., urine toxicology tests) in both research and clinical settings. Our findings also underscore a need for additional services for pregnant individuals with both medical and non-medical benzodiazepine use.

  View details for DOI 10.1016/j.dadr.2025.100345

  View details for PubMedID 40501494

  View details for PubMedCentralID PMC12152332

• Psychosocial mechanisms underlying the transition from acute to chronic postsurgical pain in youth following spinal fusion: a 6-month longitudinal study. Pain Li, R., Rogers, A. H., Sujan, A. C., Zhou, C., Thiagarajan, P., Palermo, T. M., Kain, Z. N., Rabbitts, J. A. 2025

  Abstract

  Theoretical and empirical work underscores the role of postsurgical acute pain severity and psychosocial factors in the development of chronic postsurgical pain (CPSP). However, evidence on how psychosocial changes in response to acute pain influence CPSP development in adolescents is limited. In this 6-month longitudinal study, adolescents undergoing spinal fusion were assessed presurgery, monitored for 30 days postsurgery, and re-evaluated at 8 weeks and 6 months. We examined changes in adolescent psychosocial factors (depression, anxiety, and pain catastrophizing) and parental distress from presurgery to 8 weeks postsurgery and tested their mediating effects between postsurgical acute pain intensity and interference, and CPSP development at 6 months. Among 160 adolescents included (10-18 years [M = 14.6, SD = 2.1]; 77% female; 17% Hispanic), 34% developed CPSP (pain intensity ≥3 and quality of life impairment) at 6 months. Adolescents who developed CPSP had higher pain intensity, psychological distress, and parental distress presurgery and 8 weeks postsurgery. Longitudinal causal mediation analyses controlling for sex and presurgery pain and psychosocial factors revealed that changes in adolescent anxiety and pain catastrophizing from presurgery to 8 weeks postsurgery mediated the link between postsurgical acute pain intensity and CPSP, explaining 13.8% and 11.0% of the effect, respectively. In addition, changes in adolescent pain catastrophizing mediated the association between acute pain interference and CPSP, explaining 19.6% of the effect. Significant mediation effects were not observed for changes in adolescent depression or parental distress. Anxiety symptoms and pain catastrophizing are actionable targets both before and after surgery to reduce CPSP development in adolescence.

  View details for DOI 10.1097/j.pain.0000000000003631

  View details for PubMedID 40408233

• The Role of Maternal Depression in Racial Disparities and Birth Weight. Journal of racial and ethnic health disparities Eitel, A. E., Witcraft, S. M., Cortese, B., Sujan, A. C., King, C., Guille, C. 2025

  Abstract

  Pregnant people experiencing major depression during pregnancy are at increased risk for premature labor and infants with low birth weight, and there are significant racial disparities in these outcomes. Black women are at higher risk for having premature and low birth weight infants relative to their White counterparts. As such, we sought to examine the relationships between race, depression, and obstetric outcomes (low birth weight and prematurity) in both Black and White women with live births.This study included 185 pregnant women receiving behavioral health services within an Ob/Gyn clinic in an academic medical center in South Carolina. Main and interactive effects on birth weight and gestational age were evaluated with analysis of covariance controlling for maternal age.The association between race and low birth weight was driven primarily by maternal depression. Infants of depressed Black women had significantly reduced birth weight relative to infants of depressed White women, but there was no evidence of racial disparities in birth weight among non-depressed Black women compared to non-depressed White women. Depression symptom severity was not associated with birth outcomes, and there was no effect of depression or race on prematurity.The occurrence of depression during pregnancy may in part account for racial disparities in infant birth weight. Interventions to reduce depression across birthing persons but especially among Black women may be a promising direction to address racial disparities in low birth weight.

  View details for DOI 10.1007/s40615-025-02359-z

  View details for PubMedID 40035952

  View details for PubMedCentralID 5785441

• Prenatal Depression and Symptom Severity by Maternal Race and Ethnicity. JAMA network open Kelly-Taylor, K., Aghaee, S., Nugent, J., Oberman, N., Kubo, A., Kurtovich, E., Quesenberry, C. P., Sujan, A. C., Erickson-Ridout, K., Bhalala, M. M., Avalos, L. A. 2025; 8 (3): e250743

  View details for DOI 10.1001/jamanetworkopen.2025.0743

  View details for PubMedID 40080023

• Validation of Claims-Based Algorithms for Identifying Neonatal Urinary Tract, Genital, Gastrointestinal, and Musculoskeletal Malformations in Healthcare Utilization Databases Fung, K., Leonard, S. A., Huybrechts, K. F., Hernandez-Diaz, S., Bateman, B. T., Straub, L., Sujan, A. C., Gray, K. J., Mogun, H., Zhu, Y. WILEY. 2024: 620

  View details for Web of Science ID 001407925903478

• Associations between Dose of Prescribed Opioid Analgesic Exposure During Pregnancy and Adverse Birth Outcomes and Early Mortality: A Population-Based Study Cleary, E. N., Sujan, A. C., Quinn, P. D., D'Onofrio, B. M., Rickert, M., Lichtenstein, P., Oberg, A. WILEY. 2024: 320

  View details for Web of Science ID 001407925902144

• Z-Drug Use in the First Trimester and Risk of Congenital Malformations in the US Fung, K., Straub, L., Bateman, B. T., Sujan, A. C., Brill, G., Hernandez-Diaz, S., Huybrechts, K. F. WILEY. 2024: 40-41

  View details for Web of Science ID 001407925900079

• Retention in Buprenorphine vs. Methadone Treatment for Opioid Use Disorder in Pregnancy and Postpartum Lin, C., Bateman, B. T., Straub, L., Vine, S., Sujan, A. C., Suarez, E. A., Hernandez-Diaz, S., Huybrechts, K. F. WILEY. 2024: 56-57

  View details for Web of Science ID 001407925900109

• Chronic Hypertension During Pregnancy: Prevalence and Treatment in the United States, 2008-2021. Hypertension (Dallas, Tex. : 1979) Leonard, S. A., Siadat, S., Main, E. K., Huybrechts, K. F., El-Sayed, Y. Y., Hlatky, M. A., Atkinson, J., Sujan, A., Bateman, B. T. 2024

  Abstract

  Treatment of chronic hypertension during pregnancy has been shown to reduce the risk of adverse perinatal outcomes. In this study, we examined the prevalence and treatment of chronic hypertension during pregnancy and assessed changes in these outcomes following the release of the updated 2017 hypertension guidelines of the American College of Cardiology and American Heart Association.We analyzed the MerativeTM Marketscan® Research Database of United States commercial insurance claims from 2007 to 2021. We assessed the prevalence of chronic hypertension during pregnancy and oral antihypertensive medication use over time. We then performed interrupted time series analyses to evaluate changes in these outcomes.The prevalence of chronic hypertension steadily increased from 1.8% to 3.7% among 1 900 196 pregnancies between 2008 and 2021. Antihypertensive medication use among pregnant individuals with chronic hypertension was relatively stable (57%-60%) over the study period. The proportion of pregnant individuals with chronic hypertension treated with methyldopa or hydrochlorothiazide decreased (from 29% to 2% and from 11% to 5%, respectively), while the proportion treated with labetalol or nifedipine increased (from 19% to 42% and from 9% to 17%, respectively). The prevalence or treatment of chronic hypertension during pregnancy did not change following the 2017 American College of Cardiology and American Heart Association hypertension guidelines.The prevalence of chronic hypertension during pregnancy doubled between 2008 and 2021 in a nationwide cohort of individuals with commercial insurance. Labetalol replaced methyldopa as the most commonly used antihypertensive during pregnancy. However, only about 60% of individuals with chronic hypertension in pregnancy were treated with antihypertensive medications.

  View details for DOI 10.1161/HYPERTENSIONAHA.124.22731

  View details for PubMedID 38881466

• Patient vs Parent Proxy Reports: The Asian Experience in Pediatric Chronic Pain Ma, R., Bhandari, R., Kim, Y. K., Sujan, A. C. OXFORD UNIV PRESS INC. 2024: 149

  View details for Web of Science ID 001271423400304

• Differences in Parent Protective Behaviors in Pediatric Chronic Pain between Asian and Non-Hispanic White Families Kim, Y. K., Sujan, A. C., Bhandari, R., Ma, R. OXFORD UNIV PRESS INC. 2024: 145-146

  View details for Web of Science ID 001271423400296

• Agreement Between Self-reports and Urine Toxicology Measures of Illicit Methamphetamine and Cocaine Use During Early Pregnancy. Journal of addiction medicine Sujan, A. C., Alexeeff, S. E., Slama, N. E., Goler, N., Avalos, L. A., Adams, S. R., Conway, A., Ansley, D., Pal, A., Gunn, R. L., Micalizzi, L., Young-Wolff, K. C. 2023

  Abstract

  OBJECTIVE: This study aimed to assess agreement between self-report and urine toxicology measures assessing use of 2 illicit simulants (methamphetamine and cocaine) during early pregnancy.METHODS: This cross-sectional study of 203,053 pregnancies from 169,709 individuals receiving prenatal care at Kaiser Permanente Northern California between January 1, 2011, and December 31, 2019, assessed agreement (kappa, sensitivity, and specificity) between self-reported frequency and urine toxicology measures of methamphetamine and cocaine early in pregnancy.RESULTS: Prenatal use of the illicit stimulants was rare according to toxicology (n = 244 [0.12%]) and self-report measures (n = 294 [0.14%]). Agreement between these measures was low (kappa < 0.20). Of the 498 positive pregnancies, 40 (8.03%) screened positive on both measures, 204 (40.96%) screened positive on toxicology tests only, and 254 (51.00%) screened positive by self-report only. Relative to toxicology tests, sensitivity of any self-reported use was poor with 16.39% (95% confidence interval [CI], 11.75%-21.04%) of pregnancies with a positive toxicology test self-reporting any use in pregnancy. Relative to self-report, sensitivity of toxicology tests was also poor with 13.61% (95% CI, 9.69%-17.52%) of pregnancies who self-reported any use having positive urine toxicology tests. The sensitivity improved slightly at higher frequencies of self-reported use: daily, 17.50% (95% CI, 5.72%-29.29%); weekly, 25.00% (95% CI, 11.58%-38.42%); and monthly or less, 11.06% (95% CI, 6.89%-15.23%). Specificity was high (>99%), reflecting the high negative rate of use.CONCLUSIONS: Findings suggest that using self-report and toxicology measures in combination likely provides the most accurate information on methamphetamine and cocaine use in early pregnancy. Findings also highlight the need to provide supportive nonstigmatizing environments in which pregnant individuals feel comfortable disclosing substance use without fear of punishment.

  View details for DOI 10.1097/ADM.0000000000001230

  View details for PubMedID 37801372

• Benzodiazepine use early in pregnancy and risk of congenital malformations Sujan, A. C., Bateman, B. T., Straub, L., Hernandez-Diaz, S., Zhu, Y., Brill, G., Huybrechts, K. F. WILEY. 2023: 69

  View details for Web of Science ID 001091511700128

• Maternal prescribed opioid analgesic use during pregnancy and associations with neurodevelopmental disorders in offspring Cleary, E. N., Sujan, A. C., Quinn, P. D., Rickert, M., Lichtenstein, P., Oberg, A., D'Onofrio, B. WILEY. 2023: 134

  View details for Web of Science ID 001091511700253

• A systematic review of in utero cannabis exposure and risk for structural birth defects. Frontiers in pediatrics Sujan, A. C., Pal, A., Avalos, L. A., Young-Wolff, K. C. 2023; 11: 1149401

  Abstract

  Cannabis use among pregnant women has increased over time. Therefore, there is a great public health need to understand the consequences of in utero cannabis exposure. While several meta-analyses and reviews have summarized the evidence of in utero cannabis exposure on adverse obstetric outcomes (e.g., low birth weight and preterm birth) and long-term offspring development, there has not been a focus on in utero cannabis exposure and risk for structural birth defects.We conducted a systematic review using PRISMA guidelines to evaluate the association between in utero cannabis exposure and structural birth defects.We identified 20 articles to include in our review and focused on interpreting findings from the 12 that adjusted for potential confounders. We report findings by seven organ systems. Within the 12 articles, four reported on cardiac malformations, three reported on central nervous system malformations, one reported on eye malformations, three reported on gastrointestinal malformations, one reported on genitourinary malformations, one reported on musculoskeletal malformations, and two reported on orofacial malformations.Findings on associations between in utero cannabis exposure and birth defects reported in more than two articles were mixed (i.e., findings for cardiac, gastrointestinal, central nervous system malformations). Findings for associations between in utero cannabis exposure and birth defects reported in two articles (i.e., orofacial malformations) or in a single article (eye, genitourinary, and musculoskeletal) suggested that cannabis exposure was not associated with these types of malformations, but strong conclusions cannot be drawn from such sparce research. We review the limitations and gaps in the existing literature and call for more research to rigorously evaluate associations between in utero cannabis exposure and structural birth defects.identifier CRD42022308130.

  View details for DOI 10.3389/fped.2023.1149401

  View details for PubMedID 37303758

  View details for PubMedCentralID PMC10248236

• Racial and ethnic differences in perinatal depression and anxiety. Journal of affective disorders Sujan, A. C., Nance, N., Quesenberry, C., Ridout, K., Bhalala, M., Avalos, L. A. 2023

  Abstract

  Findings on racial and ethnic differences in perinatal depression/anxiety are mixed.We assessed racial and ethnic differences in depression, anxiety, and comorbid depression/anxiety diagnoses in the year before, during, and the year after pregnancy (n = 116,449) and depression severity during (n = 72,475) and in the year after (n = 71,243) pregnancy among patients in a large, integrated healthcare delivery system.Compared to Non-Hispanic White individuals, Asian individuals had lower risk of perinatal depression and anxiety (e.g., depression during pregnancy relative risk [RR] = 0.35, 95 % confidence interval [CI]:0.33-0.38) and postpartum moderate/severe (RR = 0.63, 95 % CI:0.60-0.67) and severe (RR = 0.66, 95 CI:0.61-0.71) depression but higher risk of moderate/severe depression during pregnancy (RR = 1.18, 95 % CI:1.11-1.25). Non-Hispanic Black individuals had higher risk of perinatal depression, comorbid depression/anxiety, and moderate/severe and severe depression (e.g., depression diagnoses during pregnancy RR = 1.35, 95 % CI:1.26-1.44). Hispanic individuals had lower risk of depression during pregnancy and perinatal anxiety (e.g., depression during pregnancy RR = 0.86, 95 % CI:0.82-0.90) but higher risk of postpartum depression (RR = 1.14, 95 % CI:1.09-1.20) and moderate/severe and severe depression during and after pregnancy (e.g., severe depression during pregnancy RR = 1.59, 95 % CI:1.45-1.75).Information on depression severity was unavailable for some pregnancies. Findings may not generalize to individuals without insurance or outside of Northern California.Non-Hispanic Black individuals of reproductive age should be targeted with prevention and intervention efforts aimed at reducing and treating depression and anxiety. Asian and Hispanic individuals of reproductive age should be targeted with campaigns to destigmatize mental health disorders and demystify treatments and systematically screened for depression/anxiety.

  View details for DOI 10.1016/j.jad.2023.04.123

  View details for PubMedID 37156281

• Patterns of Substance Use During Early Pregnancy and Associations With Behavioral Health Characteristics. Journal of addiction medicine Sujan, A. C., Alexeeff, S. E., Slama, N., Avalos, L. A., Adams, S. R., Conway, A., Ansley, D., Young-Wolff, K. C. 2022

  Abstract

  OBJECTIVES: The aims of the study are to identify patterns of early pregnancy substance use and to examine how these patterns relate to behavioral health conditions measured in early pregnancy.METHODS: We conducted a retrospective observational study (N= 265,274 pregnancies) screened for alcohol, cannabis, nicotine, pharmaceutical opioids, and stimulants during the first trimester via self-report and urine toxicology tests in Kaiser Permanente Northern California from January 1, 2012, to December 31, 2019. To identify patterns of prenatal substance use, we conducted latent class analysis. We then calculated the prevalence of depression, anxiety, intimate partner violence, and family drug use history for each prenatal substance use group and compared the prevalences by estimating prevalence ratios using modified Poisson regression, adjusting for sociodemographic characteristics.RESULTS: We identified the following 4 latent groups with different patterns of substance use: (a) predominantly alcohol and no other substances (9.30%), (b) predominantly cannabis and no other substances (4.88%), (c) predominantly nicotine and some pharmaceutical opioids (1.09%), and (d) high-polysubstance (alcohol, cannabis, nicotine, and stimulants; 0.36%); these pregnancies were compared with (e) no prenatal substance use (84.37%). The prevalence of all behavioral health conditions was elevated in all prenatal substance use groups compared with the no substance use group. Furthermore, the prevalence of depressive and anxiety disorders, intimate partner violence and family drug use history were greater in the high-polysubstance cluster than the alcohol and cannabis clusters.CONCLUSIONS: Results highlight the importance of screening and interventions for all types of substance use during early pregnancy and suggest a particularly high need to prioritize targeting early interventions to pregnant and reproductive age individuals with polysubstance use.

  View details for DOI 10.1097/ADM.0000000000001090

  View details for PubMedID 36255108

• Patterns of Substance Use During Early Pregnancy and Associations With Behavioral Health Characteristics. Journal of addiction medicine Sujan, A. C., Alexeeff, S. E., Slama, N., Avalos, L. A., Adams, S. R., Conway, A., Ansley, D., Young-Wolff, K. C. 2022; 17 (3): e141-e147

  Abstract

  The aims of the study are to identify patterns of early pregnancy substance use and to examine how these patterns relate to behavioral health conditions measured in early pregnancy.We conducted a retrospective observational study (N= 265,274 pregnancies) screened for alcohol, cannabis, nicotine, pharmaceutical opioids, and stimulants during the first trimester via self-report and urine toxicology tests in Kaiser Permanente Northern California from January 1, 2012, to December 31, 2019. To identify patterns of prenatal substance use, we conducted latent class analysis. We then calculated the prevalence of depression, anxiety, intimate partner violence, and family drug use history for each prenatal substance use group and compared the prevalences by estimating prevalence ratios using modified Poisson regression, adjusting for sociodemographic characteristics.We identified the following 4 latent groups with different patterns of substance use: ( a ) predominantly alcohol and no other substances (9.30%), ( b ) predominantly cannabis and no other substances (4.88%), ( c ) predominantly nicotine and some pharmaceutical opioids (1.09%), and ( d ) high-polysubstance (alcohol, cannabis, nicotine, and stimulants; 0.36%); these pregnancies were compared with ( e ) no prenatal substance use (84.37%). The prevalence of all behavioral health conditions was elevated in all prenatal substance use groups compared with the no substance use group. Furthermore, the prevalence of depressive and anxiety disorders, intimate partner violence and family drug use history were greater in the high-polysubstance cluster than the alcohol and cannabis clusters.Results highlight the importance of screening and interventions for all types of substance use during early pregnancy and suggest a particularly high need to prioritize targeting early interventions to pregnant and reproductive age individuals with polysubstance use.

  View details for DOI 10.1097/ADM.0000000000001090

  View details for PubMedID 37267164

• In-utero cannabis exposure and long-term psychiatric and neurodevelopmental outcomes: The limitations of existing literature and recommendations for future research BIRTH DEFECTS RESEARCH Sujan, A. C., Young-Wolff, K. C., Avalos, L. A. 2022; 114 (13): 689-713

  Abstract

  Given increases in cannabis use in pregnancy and animal model research showing effects of in-utero cannabis exposure, high-quality information on long-term consequences of in-utero cannabis exposure in humans is needed. While reviews have summarized findings from observational studies with humans, reviews have not focused on limitations of these studies and recommendations for future research. Therefore, we critically reviewed observational research on in-utero cannabis exposure and psychiatric and neurodevelopmental outcomes measured at or after age 3 and provided recommendations for future research. We used Web of Science, Google Scholar, and work cited from relevant identified publications to identify 46 papers to include in our review. Our review includes two main sections. The first section highlights the extensive limitations of the existing research, which include small and nongeneralizable samples, reliance on self-reported data, lack of detail on timing and amount of exposure, inclusion of older exposure data only, not accounting for important confounders, inclusion of potential mediators as covariates, not including outcome severity measures, and not assessing for offspring sex differences. The second section provides recommendations for future research regarding exposure and outcome measures, sample selection, confounder adjustment, and other methodological considerations. For example, with regard to exposure definition, we recommend that studies quantify the amount of cannabis exposure, evaluate the influence of timing of exposure, and incorporate biological measures (e.g., urine toxicology measures). Given that high-quality information on long-term consequences of in-utero cannabis exposure in humans does not yet exit, it is crucial for future research to address the limitations we have identified.

  View details for DOI 10.1002/bdr2.2060

  View details for Web of Science ID 000811526600001

  View details for PubMedID 35708102

  View details for PubMedCentralID PMC9357094

• Maternal Serotonergic Antidepressant Use in Pregnancy and Risk of Seizures in Children NEUROLOGY Wiggs, K., Sujan, A. C., Rickert, M. E., Quinn, P. D., Larsson, H., Lichtenstein, P., D'Onofrio, B. M., Oberg, A. 2022; 98 (23): E2329-E2336

  Abstract

  To evaluate whether children born to women who use serotonergic antidepressants during pregnancy have higher risk of neonatal seizures and epilepsy.We used Swedish register-based data to examine associations between maternal reported use of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in pregnancy and diagnosis of neonatal seizures or epilepsy in >1.2 million children. To account for systematic differences between exposed and unexposed children, we adjusted for a wide range of measured confounders. After first evaluating the role of maternal indication for SSRI/SNRI use (i.e., depression or anxiety) and parental epilepsy, we adjusted for remaining parental background factors (e.g., age, comorbidities, education, and family socioeconomic indices) and pregnancy-specific characteristics (e.g., maternal use of other psychotropic medications and tobacco smoking in early pregnancy).Compared with all other children, children of women who reported use of SSRI/SNRI in pregnancy had an elevated risk of neonatal seizures and epilepsy (risk ratio [RR] 1.41, 95% CI 1.03-1.94; hazard ratio [HR] 1.21, 95% CI 1.03-1.43, respectively). The estimates of association were attenuated by adjustment for maternal indications for SSRI/SNRI use (RR 1.30, 95% CI 0.94-1.80; HR 1.13, 95% CI 0.95-1.33), but not by additional adjustment for parental history of epilepsy. Full adjustment for all measured parental and pregnancy-specific factors resulted in substantial attenuation of the remaining associations (RR 1.10, 95% CI 0.79-1.53; HR 0.96, 95% CI 0.81-1.14).We found no support for the concern that maternal SSRI/SNRI use in pregnancy increases children's risk for neonatal seizures or epilepsy.This study provides Class II evidence that exposure to SSRIs/SNRIs in the first trimester of pregnancy is not associated with an increased incidence of neonatal seizures/epilepsy.

  View details for DOI 10.1212/WNL.0000000000200516

  View details for Web of Science ID 000804246800014

  View details for PubMedID 35545445

  View details for PubMedCentralID PMC9202527

• Listening to women and pregnant and postpartum people: Qualitative research to inform opioid use disorder treatment for pregnant and postpartum people. Drug and alcohol dependence reports Guille, C., Hall, C., King, C., Sujan, A., Brady, K., Newman, R. 2022; 3: 100064

  Abstract

  Background: The diagnosis of Opioid Use Disorder (OUD) during pregnancy has increased 2-to-5-fold over the past decade and barriers to treatment are significant. Technology-based solutions have the potential to overcome these barriers and deliver evidence-based treatment. However, these interventions need to be informed by end-users. The goal of this study is to gain feedback from peripartum people with OUD and obstetric providers about a web-based OUD treatment program.Methods: Qualitative interviews were conducted with peripartum people with OUD (n=18) and focus groups were conducted with obstetric providers (n=19). Feedback from these interviews informed the development of text message-based screening, brief phone-based intervention and referral to treatment program, called Listening to Women and Pregnant and Postpartum People (LTWP). Once developed, further qualitative interviews with peripartum people with OUD (n=12) and obstetric providers (n=21) were conducted to gather feedback about the LTWP program.Results: Patients reported that a relationship with a trusted provider is paramount for treatment engagement. Providers reported that time constraints and complex patient needs prohibit them from treating OUD and that evidence-based Screening, Brief Intervention and Referral to Treatment (SBIRT) are not implemented effectively in routine prenatal care. Neither patients nor providers were enthusiastic about our web-based intervention for OUD; thus, results were used to guide the development of LTWP to improve implementation of SBIRT during prenatal care.Conclusions: End-user informed, technology-enhanced SBIRT has the potential to improve the implementation of SBIRT during routine prenatal care, and in turn, improve maternal and child health.

  View details for DOI 10.1016/j.dadr.2022.100064

  View details for PubMedID 36845990

• What do we know about in-utero antidepressant exposure, and are these medications safe to use during pregnancy? ACTA PSYCHIATRICA SCANDINAVICA Sujan, A. C. 2022; 145 (6): 541-543

  View details for DOI 10.1111/acps.13437

  View details for Web of Science ID 000787046000001

  View details for PubMedID 35426123

• Initiation of Opioid Prescription and Risk of Suicidal Behavior Among Youth and Young Adults PEDIATRICS Fine, K. L., Rickert, M. E., O'Reilly, L. M., Sujan, A. C., Boersma, K., Chang, Z., Franck, J., Lichtenstein, P., Larsson, H., D'Onofrio, B. M., Quinn, P. D. 2022; 149 (3)

  Abstract

  Opioids are involved in an increasing proportion of suicide deaths. This study examined the association between opioid analgesic prescription initiation and suicidal behavior among young people.We analyzed Swedish population-register data on 1 895 984 individuals ages 9 to 29 years without prior recorded opioid prescriptions. We identified prescriptions dispensed from January 2007 onward and diagnosed self-injurious behavior and death by suicide through December 2013. We first compared initiators with demographically matched noninitiators. To account for confounding, we applied an active comparator design, which examined suicidal behavior among opioid initiators relative to prescription nonsteroidal antiinflammatory drug (NSAID) initiators while inverse-probability-of-treatment weighting with individual and familial covariates.Among the cohort, 201 433 individuals initiated opioid prescription. Relative to demographically matched noninitiators, initiators (N = 180 808) had more than doubled risk of incident suicidal behavior (hazard ratio = 2.64; 95% confidence interval [CI], 2.47-2.81). However, in the active comparator design, opioid initiators (N = 86 635) had only 19% relatively greater risk of suicidal behavior compared with NSAID initiators (N = 255 096; hazard ratio = 1.19; 95% CI,: 1.11-1.28), corresponding to a weighted 5-year cumulative incidence of 2.2% (95% CI, 2.1-2.4) for opioid and 1.9% (95% CI, 1.9-2.0) for NSAID initiators. Most sensitivity analyses produced comparable results.Opioid initiation may make only a small contribution to the elevated risk of suicidal behavior among young people receiving pharmacologic pain management. In weighing benefits and harms of opioid initiation, our results suggest that increased risk of suicidal behavior may not be a major concern.

  View details for DOI 10.1542/peds.2020-049750

  View details for Web of Science ID 000918191300002

  View details for PubMedID 35128560

  View details for PubMedCentralID PMC9624202

• A Nation-Wide Swedish Cohort Study on Early Maternal Age at First Childbirth and Risk for Offspring Deaths, Accidents, and Suicide Attempts BEHAVIOR GENETICS Sujan, A. C., O'Reilly, L. M., Rickert, M. E., Larsson, H., Lichtenstein, P., Oberg, A., D'Onofrio, B. M. 2022; 52 (1): 38-47

  Abstract

  In a sample of over one million Swedish first-born offspring, we examined associations between early maternal age at first childbirth (MAFC; i.e., < 20 and 20-24 vs 25-29 years) and offspring non-accidental deaths, accidental deaths, deaths by suicide, non-fatal accidents, and suicide attempts. We included year of birth and several maternal and paternal characteristics as covariates and conducted maternal cousin comparisons to adjust for unmeasured confounding. Early MAFC (e.g., teenage childbearing) was associated with all outcomes, with the most pronounced risk elevation for accidental deaths [Hazard Ratio (HR) < 20 2.50, 95% confidence interval (CI) 2.23, 2.80], suicides (HR < 20 2.08, 95% CI 1.79, 2.41), and suicide attempts (HR < 20 2.85, 95% CI 2.71, 3.00). Adjusting for covariates and comparing cousins greatly attenuated associations (e.g., accidental deaths HR < 20 1.61, 95% CI 1.22, 2.11; suicides HR < 20 1.01, 95% CI 0.69, 1.47; and suicide attempts HR < 20 1.35, 95% CI 1.19, 1.52). A similar pattern emerged for non-accidental deaths and non-fatal accidents. Therefore, results indicated maternal background factors may be largely responsible for observed associations.

  View details for DOI 10.1007/s10519-021-10091-7

  View details for Web of Science ID 000717444000001

  View details for PubMedID 34762227

  View details for PubMedCentralID 5662659

• A retrospective, observational study on medication for opioid use disorder during pregnancy and risk for neonatal abstinence syndrome FAMILY PRACTICE Sujan, A., Cleary, E., Douglas, E., Aujla, R., Boyars, L., Smith, C., Guille, C. 2022; 39 (2): 311-315

  Abstract

  The prevalence of opioid use disorder (OUD) among pregnant women is increasing. Research consistently demonstrates the efficacy of medications for OUD (MOUD); however, researchers have called for additional studies evaluating the safety of MOUD during pregnancy, particularly the relative safety of two commonly used MOUD medications-methadone and buprenorphine. This study aimed to evaluate the consequences of MOUD exposure during pregnancy on risk for neonatal abstinence syndrome (NAS).In a clinical sample of infants born to women with OUD, we evaluated the risk of NAS among those exposed to (i) methadone and (ii) buprenorphine compared with those unexposed to MOUD, as well as the risk of NAS among those exposed to (i) methadone compared with those exposed to (ii) buprenorphine.Compared with buprenorphine-exposed infants (n = 37), methadone-exposed infants (n = 27) were at increased risk for NAS (odds ratio [OR] = 4.67, 95% confidence interval [CI]: 1.03, 21.17). Compared with unexposed infants (n = 43), buprenorphine-exposed infants were at decreased risk for NAS (OR = 0.45, 95% CI: 0.14, 1.39) and methadone-exposed infants were at increased risk for NAS (OR = 2.64, 95% CI: 0.79, 8.76), though these associations were not statistically significant.Our study suggests that when methadone and buprenorphine are equally appropriate options for the treatment of OUD in pregnant women, buprenorphine may add the additional benefit of reduced risk of newborn NAS.

  View details for DOI 10.1093/fampra/cmab121

  View details for Web of Science ID 000773012700014

  View details for PubMedID 34537839

  View details for PubMedCentralID PMC8956128

• A Clinical Trial of a Program for Pain Management and Opioid Reduction During Pregnancy REPRODUCTIVE SCIENCES Shapiro, M., Sujan, A. C., Guille, C. 2022; 29 (2): 606-613

  Abstract

  A substantial proportion of pregnant women use prescription opioids. However, the lack of efficacy of chronic prescription opioid use for pain, combined with an increased risk of these medications in general and during pregnancy, suggests that the risks of these medications may outweigh the benefits of continued use. Though research has not evaluated non-pharmacological approaches to treat chronic pain during pregnancy, research conducted with the general population outside of pregnancy suggests that cognitive behavioral therapy (CBT) is an effective, non-pharmacological treatment. Therefore, the purpose of this study was to evaluate the effectiveness of CBT for chronic pain paired with shared decision-making for prescription opioid dose reduction among pregnant women with prescription opioid misuse. The study was an open-label, 8-week clinical trial of CBT for chronic pain and shared decision-making for prescription opioid dose reduction. Participants included a clinical sample of 20 pregnant women between the ages of 18 and 45 years who were misusing opioids but did not meet DSM-IV criteria for an opioid use disorder or other substance use disorder. Compared to baseline, at 8 weeks, participants had significant reductions in average prescription opioid morphine equivalent dose, prescription opioid misuse, worst pain ratings, and pain interference in general activity and at work. They did not report improvement in other pain ratings or areas of functioning. This study provides valuable information regarding the preliminary efficacy of CBT for chronic pain paired with shared decision-making among pregnant women misusing prescription opioids. ClinicalTrials.gov: NCT02804152.

  View details for DOI 10.1007/s43032-021-00701-4

  View details for Web of Science ID 000685717800001

  View details for PubMedID 34403125

  View details for PubMedCentralID 4020039

• A nation-wide Swedish study of opioid analgesic prescribing patterns during pregnancy and associated preexisting mental health conditions JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE Sujan, A. C., Quinn, P. D., Rickert, M. E., Wiggs, K. K., Larsson, H., Lichtenstein, P., Oberg, A., D'Onofrio, B. M. 2022; 35 (25): 5161-5167

  Abstract

  Research has consistently shown individuals with mental health conditions are more likely to be prescribed opioid analgesic medications and to engage in heavier utilization. However, it is unclear whether these findings apply to pregnant women.We explored opioid analgesic prescription in 689,400 pregnancies occurring in Sweden between 2007 and 2013. We investigated prescription patterns across time and type of source clinic for any opioid analgesic and for strong and weak opioid analgesics. We further evaluated the extent to which receipt of opioid analgesic medications was associated with previous mental health diagnoses and prescriptions of other psychoactive medications.The prevalence of pregnant women who filled prescriptions for opioid analgesics (4.5%) was relatively stable across the assessed years. However, among pregnant women who filled opioid analgesic prescriptions, there was a large increase in strong opioid analgesic prescriptions-from 6.1% in 2007 to 17.1% in 2013. The main source of opioid analgesic prescriptions were primary care and obstetrics and gynecology clinics-38.7% of all filled prescriptions originated from primary care providers and 25.3% from obstetrics and gynecology practitioners. Compared to pregnant women who did not fill any opioid analgesic prescriptions, those who did were more likely to have a wide range of preexisting mental health diagnoses (e.g. anxiety disorder odds ratio [OR] = 3.13, 95% confidence interval [CI]:2.98,3.29) and to utilize a wide range of other psychoactive medications (e.g. benzodiazepines OR = 4.26, 95% CI:4.10,4.43). Similarly, those who received strong opioids were more likely to have a wide range of mental health diagnoses and be prescribed a wide range of psychoactive medications compared to those who received weak opioids.These results highlight the need for physicians treating pregnant women and women of childbearing age for painful conditions to obtain detailed histories of mental health problems, screen for symptoms of mental health problems, and facilitate integrated care and evidence-based mental health interventions if needed.

  View details for DOI 10.1080/14767058.2021.1875436

  View details for Web of Science ID 000627618700001

  View details for PubMedID 33441038

• A population-based study of concurrent prescriptions of opioid analgesic and selective serotonin reuptake inhibitor medications during pregnancy and risk for adverse birth outcomes PAEDIATRIC AND PERINATAL EPIDEMIOLOGY Sujan, A. C., Rickert, M. E., Quinn, P. D., Ludema, C., Wiggs, K. K., Larsson, H., Lichtenstein, P., Almqvist, C., Oberg, A., D'Onofrio, B. M. 2021; 35 (2): 184-193

  Abstract

  Pregnant women with painful conditions often have mental health problems, including depression and anxiety. Co-morbid conditions may cause pregnant women to use multiple medications, although safety of such practice is poorly understood.We investigated the influence of combined prescriptions of opioid analgesics and selective serotonin reuptake inhibitors (SSRIs) during pregnancy on two adverse birth outcomes.We analysed Swedish population-based births (n = 688 914) between 2007 and 2013. Using national registers, we obtained data on filled medication prescriptions, birth outcomes, and a wide range of parental characteristics. We estimated preterm birth and small-for-gestational-age risk following independent or combined prescriptions of the two medications compared with no filled prescriptions for either medication. We adjusted for confounders using inverse probability of treatment weights.After adjusting for confounders, preterm birth risk was higher among women with opioid analgesic prescriptions only (5.9%; risk ratio [RR] 1.27, 95% confidence interval [CI] 1.22, 1.33), SSRIs only (6.2%; RR 1.34, 95% CI 1.27, 1.42), and both medications (7.8%; RR 1.70, 95% CI 1.47, 1.96) compared with unexposed women (4.6%). The interaction between the medications on preterm birth was small (risk difference [RD] 0.4%, 95% CI -0.8%, 1.6%); relative excess risk due to interaction [RERI] 0.09, 95% CI -0.17, 0.34; RR 1.00, 95% CI 0.85, 1.17). For small for gestational age, risk was approximately 2% across all groups, and there was no interaction between the medications (RD 0.3%, 95% CI -0.4%, 1.1%); RERI 0.15, 95% CI -0.16, 0.47; RR 1.15, 95% CI 0.87, 1.52).Compared with unexposed pregnancies, those with either medication alone had a small increased risk for preterm birth but no increased risk for small for gestational age. The magnitude of associations with combined exposure to both medications were not greater than the sum of the associations with each medication considered individually.

  View details for DOI 10.1111/ppe.12721

  View details for Web of Science ID 000600684400001

  View details for PubMedID 33350491

  View details for PubMedCentralID PMC7878346

• Antiseizure medication use during pregnancy and risk of ASD and ADHD in children NEUROLOGY Wiggs, K. K., Rickert, M. E., Sujan, A. C., Quinn, P. D., Larsson, H., Lichtenstein, P., Oberg, A., D'Onofrio, B. M. 2020; 95 (24): E3232-E3240

  Abstract

  To determine whether children born to women who use antiseizure medications (ASMs) during pregnancy have higher risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) independent of confounding factors.We used Swedish register data (n = 14,614 children born 1996-2011 and followed up through 2013) to examine associations in children of women with epilepsy, using the largest sample to date and adjusting for a range of measured confounders. We examined maternal-reported first-trimester use of any ASM (22.7%) and the 3 most commonly reported individual drugs (valproic acid 4.8%, lamotrigine 6.8%, and carbamazepine 9.7%). We identified ASD with ICD-10 diagnoses and ADHD with ICD-10 diagnoses or filled prescriptions of ADHD medication.Examination of individual drugs revealed that after adjustment for confounding, use of valproic acid was associated with ASD (hazard ratio [HR] 2.30, 95% confidence interval [CI] 1.53-3.47) and ADHD (HR 1.74, 95% CI 1.28-2.38). Whereas a small, nonstatistically significant association with ASD (HR 1.25, 95% CI = 0.88-1.79) and ADHD (HR 1.18, 95% CI 0.91-1.52) remained for reported use of carbamazepine, confounding explained all of the associations with lamotrigine (HRASD 0.86, 95% CI 0.67-1.53; HRADHD 1.01, 95% CI 0.67-1.53).We found no evidence of risk related to exposure to lamotrigine, whereas we observed elevated risk of ASD and ADHD related to maternal use of valproic acid. Associations with carbamazepine were weak and not statistically significant. Our findings add to a growing body of evidence that suggests that certain ASMs may be safer than others in pregnancy.

  View details for DOI 10.1212/WNL.0000000000010993

  View details for Web of Science ID 000607315800019

  View details for PubMedID 33115775

  View details for PubMedCentralID PMC7836668

• Association of Opioid Prescription Initiation During Adolescence and Young Adulthood With Subsequent Substance-Related Morbidity JAMA PEDIATRICS Quinn, P. D., Fine, K. L., Rickert, M. E., Sujan, A. C., Boersma, K., Chang, Z., Franck, J., Lichtenstein, P., Larsson, H., D'Onofrio, B. M. 2020; 174 (11): 1048-1055

  Abstract

  Concerns about adverse outcomes associated with opioid analgesic prescription have led to major guideline and policy changes. Substantial uncertainty remains, however, regarding the association between opioid prescription initiation and increased risk of subsequent substance-related morbidity.To examine the association of opioid initiation among adolescents and young adults with subsequent broadly defined substance-related morbidity.This cohort study analyzed population-register data from January 1, 2007, to December 31, 2013, on Swedish individuals aged 13 to 29 years by January 1, 2013, who were naive to opioid prescription. To account for confounding, the analysis compared opioid prescription recipients with recipients of nonsteroidal anti-inflammatory drugs as an active comparator, compared opioid-recipient twins and other multiple birth individuals with their nonrecipient co-multiple birth offspring (co-twin control), examined dental prescription as a specific indication, and included individual, parental, and socioeconomic covariates. Data were analyzed from March 30, 2019, to January 22, 2020.Opioid prescription initiation, defined as first dispensed opioid analgesic prescription.Substance-related morbidity, assessed as clinically diagnosed substance use disorder or overdose identified from inpatient or outpatient specialist records, substance use disorder or overdose cause of death, dispensed pharmacotherapy for alcohol use disorder, or conviction for substance-related crime.Among the included cohort (n = 1 541 862; 793 933 male [51.5%]), 193 922 individuals initiated opioid therapy by December 31, 2013 (median age at initiation, 20.9 years [interquartile range, 18.2-23.6 years]). The active comparator design included 77 143 opioid recipients without preexisting substance-related morbidity and 229 461 nonsteroidal anti-inflammatory drug recipients. The adjusted cumulative incidence of substance-related morbidity within 5 years was 6.2% (95% CI, 5.9%-6.5%) for opioid recipients and 4.9% (95% CI, 4.8%-5.1%) for nonsteroidal anti-inflammatory drug recipients (hazard ratio, 1.29; 95% CI, 1.23-1.35). The co-twin control design produced comparable results (3013 opioid recipients and 3107 nonrecipients; adjusted hazard ratio, 1.43; 95% CI, 1.02-2.01), as did restriction to analgesics prescribed for dental indications and additional sensitivity analyses.Among adolescents and young adults analyzed in this study, initial opioid prescription receipt was associated with an approximately 30% to 40% relative increase in risk of subsequent substance-related morbidity in multiple designs that adjusted for confounding. These findings suggest that this increase may be smaller than previously estimated in some other studies.

  View details for DOI 10.1001/jamapediatrics.2020.2539

  View details for Web of Science ID 000604983700013

  View details for PubMedID 32797146

  View details for PubMedCentralID PMC7418042

• Associations of Prescribed ADHD Medication in Pregnancy with Pregnancy-Related and Offspring Outcomes: A Systematic Review CNS DRUGS Li, L., Sujan, A. C., Butwicka, A., Chang, Z., Cortese, S., Quinn, P., Viktorin, A., Oberg, A., D'Onofrio, B. M., Larsson, H. 2020; 34 (7): 731-747

  Abstract

  Increasing numbers of reproductive-aged women are using attention-deficit/hyperactivity disorder (ADHD) medications. Findings from studies exploring the safety of these medications during pregnancy are mixed, and it is unclear whether associations reflect causal effects or could be partially or fully explained by other factors that differ between exposed and unexposed offspring.The aim of this systematic review was to evaluate the adverse pregnancy-related and offspring outcomes associated with exposure to prescribed ADHD medication during pregnancy with a focus on how studies to date have handled the influence of confounding.We searched PubMed, Embase, PsycINFO, and Web of Science up to 1 July 2019 without any restrictions on language or date of publication. We included all observational studies (e.g., cohort studies, case-control studies, case-crossover studies, cross-sectional studies, and registry-based studies) with pregnant women of any age or from any setting who were prescribed ADHD medications and evaluated any outcome, including both short- and long-term maternal and offspring outcomes. Two independent authors then used the Newcastle-Ottawa Scale to rate the quality of the included studies.Eight cohort studies that estimated adverse pregnancy-related and offspring outcomes associated with exposure to ADHD medication during pregnancy were included in the qualitative review. The included studies had substantial methodological differences in data sources, type of medications examined, definitions of studied pregnancy-related and offspring outcomes, types of control groups, and confounding adjustment. There was no convincing evidence for teratogenic effects according to the relative risk of pregnancy-related and offspring outcomes, and the observed differences in absolute risks were overall small in magnitude. Adjustment for confounding was inadequate in most studies, and none of the included studies adjusted for ADHD severity in the mothers.The current evidence does not suggest that the use of ADHD medication during pregnancy results in significant adverse consequences for mother or offspring. However, the data are too limited to make an unequivocal recommendation. Therefore, physicians should consider whether the advantages of using ADHD medication outweigh the potential risks for the developing fetus according to each woman's specific circumstances. Future research should attempt to triangulate research findings based on a combination of different designs that differ in their underlying strengths and limitations and should investigate specific confounding factors, the potential impact of timing of exposure, and potential long-term outcomes in the offspring.

  View details for DOI 10.1007/s40263-020-00728-2

  View details for Web of Science ID 000528411400001

  View details for PubMedID 32333292

  View details for PubMedCentralID PMC7338246

• Risk factors and child outcomes associated with short and long interpregnancy intervals EARLY CHILD DEVELOPMENT AND CARE Sujan, A. C., Class, Q. A., Rickert, M. E., Van Hulle, C., D'Onofrio, B. M. 2021; 191 (14): 2281-2292

  Abstract

  Previous research assessing consequences of interpregnancy intervals (IPIs) on child development is mixed. Utilizing a population-based US sample (n=5,339), we first estimated the associations between background characteristics (e.g., sociodemographic and maternal characteristics) and short (≤ 1 year) and long (> 3 years) IPI. Then, we estimated associations between IPI and birth outcomes, infant temperament, cognitive ability, and externalizing symptoms. Several background characteristics, such as maternal age at childbearing and previous pregnancy loss, were associated with IPI, indicating research on the putative effects of IPI must account for background characteristics. After covariate adjustment, short IPI was associated with poorer fetal growth and long IPI was associated with lower infant activity level; however, associations between short and long IPI and the other outcomes were neither large nor statistically significant. These findings indicate that rather than intervening to modify IPI, at-risk families may benefit from interventions aimed at other modifiable risk factors.

  View details for DOI 10.1080/03004430.2019.1703111

  View details for Web of Science ID 000502500500001

  View details for PubMedID 34924676

  View details for PubMedCentralID PMC8673594

• Maternal prescribed opioid analgesic use during pregnancy and associations with adverse birth outcomes: A population-based study PLOS MEDICINE Sujan, A. C., Quinn, P. D., Rickert, M. E., Wiggs, K. K., Lichtenstein, P., Larsson, H., Almqvist, C., Oberg, A., D'Onofrio, B. M. 2019; 16 (12): e1002980

  Abstract

  Published research on prescribed opioid analgesic (POA) use during pregnancy and birth outcomes is limited in scope and has not adequately adjusted for potential confounding factors. To help address these gaps, we estimated associations between maternal POAs during pregnancy and two adverse birth outcomes using a large population-based dataset, multiple definitions of POA exposure, and several methods to evaluate the influence of both measured and unmeasured confounding factors.We obtained data by linking information from several Swedish registers and conducted a retrospective cohort study on a population-based sample of 620,458 Swedish births occurring between 2007 and 2013 (48.6% female; 44.4% firstborn). We evaluated associations between prenatal POA exposure and risk for preterm birth (PTB; <37 gestational weeks) and small for gestational age (SGA; birth weight 2 standard deviations below the expected weight for gestational age or lower). We evaluated the influence of confounding by adjusting for a wide range of measured covariates while comparing exposed and unexposed infants. Additionally, we adjusted for unmeasured confounding factors by using several advanced epidemiological designs. Infants exposed to POAs anytime during pregnancy were at increased risk for PTB compared with unexposed infants (6.4% exposed versus 4.4% unexposed; adjusted odds ratio [OR] = 1.38, 95% confidence interval [CI] 1.31-1.45, p < 0.001). This association was attenuated when we compared POA-exposed infants with acetaminophen-exposed infants (OR = 1.18, 95% CI 1.07-1.30, p < 0.001), infants born to women who used POAs before pregnancy only (OR = 1.05, 95% CI 0.96-1.14, p = 0.27), and unexposed siblings (OR = 0.99, 95% CI 0.85-1.14, p = 0.92). We also evaluated associations with short-term versus persistent POA use during pregnancy and observed a similar pattern of results, although the magnitudes of associations with persistent exposure were larger than associations with any use or short-term use. Although short-term use was not associated with SGA (adjusted ORsingle-trimester = 0.95, 95% CI 0.87-1.04, p = 0.29), persistent use was associated with increased risk for SGA (adjusted ORmultiple-trimester = 1.40, 95% CI 1.17-1.67, p < 0.001) compared with unexposed infants. The association with persistent exposure was attenuated when we used alternative comparison groups (e.g., sibling comparison OR = 1.22, 95% CI 0.60-2.48, p = 0.58). Of note, our study had limitations, including potential bias from exposure misclassification, an inability to adjust for all sources of confounding, and uncertainty regarding generalizability to countries outside of Sweden.Our results suggested that observed associations between POA use during pregnancy and risk of PTB and SGA were largely due to unmeasured confounding factors, although we could not rule out small independent associations, particularly for persistent POA use during pregnancy.

  View details for DOI 10.1371/journal.pmed.1002980.r004

  View details for Web of Science ID 000507280500016

  View details for PubMedID 31790390

  View details for PubMedCentralID PMC6886755

• Annual Research Review: Maternal antidepressant use during pregnancy and offspring neurodevelopmental problems - a critical review and recommendations for future research JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY Sujan, A. C., Oberg, A., Quinn, P. D., D'Onofrio, B. M. 2019; 60 (4): 356-376

  Abstract

  Children of women treated with antidepressants during pregnancy are more likely to develop neurodevelopmental problems than are unexposed children. Associations between prenatal antidepressant exposure and neurodevelopmental problems could reflect a causal effect or could be partially or fully explained by other factors that differ between exposed and unexposed offspring, including having mothers with conditions requiring antidepressant treatment (e.g. depression), environmental risk factors, and/or genetic risk factors shared across disorders. This translational review aims to provide a brief overview of findings from rodent experiments and critically evaluate observational studies in humans to assess the extent to which associations between prenatal antidepressant exposure and neurodevelopmental problems are due to causal mechanisms versus other influences. We focus our review on two important neurodevelopmental outcomes - autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). In general, rodent studies have reported adverse effects of perinatal antidepressant exposure on neurodevelopment. Between-species differences raise questions about the generalizability of these findings to humans. Indeed, converging evidence from studies using multiple designs and approaches suggest that observed associations between prenatal antidepressant exposure and neurodevelopmental problems in humans are largely due to confounding factors. We also provide specific recommendations for future research. Animal research should explicitly evaluate the impact of timing of exposure and dosage of medications, as well as better map outcome measures in rodents to human neurodevelopmental problems. Observational studies should investigate specific confounding factors, specific antidepressant drugs and classes, the potential impact of timing of exposure, and a wider range of other potential offspring outcomes. The findings summarized in this review may help women and their doctors make informed decisions about antidepressant use during pregnancy by providing reassurance that use of these medications during pregnancy is unlikely to substantially increase the risk of ASD and ADHD.

  View details for DOI 10.1111/jcpp.13004

  View details for Web of Science ID 000463970500004

  View details for PubMedID 30515808

  View details for PubMedCentralID PMC6438736

• Outcome-dependent associations between short interpregnancy interval and offspring psychological and educational problems: a population-based quasi-experimental study INTERNATIONAL JOURNAL OF EPIDEMIOLOGY Class, Q. A., Rickert, M. E., Larsson, H., Oberg, A., Sujan, A. C., Almqvist, C., Lichtenstein, P., D'Onofrio, B. M. 2018; 47 (4): 1159-1168

  Abstract

  Causal interpretation of associations between short interpregnancy interval (the duration from the preceeding birth to the conception of the next-born index child) and the offspring's psychological and educational problems may be influenced by a failure to account for unmeasured confounding.Using population-based Swedish data from 1973-2009, we estimated the association between interpregnancy interval and outcomes [autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), severe mental illness, suicide attempt, criminality, substance-use problem and failing grades] while controlling for measured covariates. We then used cousin comparisons, post-birth intervals (the interval between the second- and third-born siblings to predict second-born outcomes) and sibling comparisons to assess the influence of unmeasured confounding. We included an exploratory analysis of long interpregnancy interval.Interpregnancy intervals of 0-5 and 6-11 months were associated with higher odds of outcomes in cohort analyses. Magnitudes of association were attenuated following adjustment for measured covariates. Associations were eliminated for ADHD, severe mental illness and failing grades, but maintained magnitude for ASD, suicide attempt, criminality and substance-use problem in cousin comparisons. Post-birth interpregnancy interval and sibling comparisons suggested some familial confounding. Associations did not persist across models of long interpregnancy interval.Attenuation of the association in cousin comparisons and comparable post-birth interval associations suggests that familial genetic or environmental confounding accounts for a majority of the association for ADHD, severe mental illness and failing grades. Modest associations appear independently of covariates for ASD, suicide attempt, criminality and substance-use problem. Post-birth analyses and sibling comparisons, however, show some confounding in these associations.

  View details for DOI 10.1093/ije/dyy042

  View details for Web of Science ID 000444559900026

  View details for PubMedID 29566153

  View details for PubMedCentralID PMC6124608

• Within-Family Analysis of Interpregnancy Interval and Adverse Birth Outcomes OBSTETRICS AND GYNECOLOGY Class, Q. A., Rickert, M. E., Oberg, A. S., Sujan, A. C., Almqvist, C., Larsson, H., Lichtenstein, P., D'Onofrio, B. M. 2017; 130 (6): 1304-1311

  Abstract

  To examine associations among interpregnancy interval, the duration from the preceding birth to the conception of the next-born index child, and adverse birth outcomes using designs that adjust for measured and unmeasured factors.In this prospective cohort study, we used population-based Swedish registries from 1973 to 2009 to estimate the associations between interpregnancy interval (referent 18-23 months) and adverse birth outcomes (ie, preterm birth [less than 37 weeks of gestation], low birth weight [LBW; less than 2,500 g], small for gestational age [SGA; greater than 2 SDs below average weight for gestational age]). Analyses included cousin and sibling comparisons and postbirth intervals (ie, the interval between secondborn and thirdborn offspring predicting secondborn outcomes) to address unmeasured familial confounding.Traditional cohort-wide analyses showed higher odds of preterm birth (adjusted odds ratio [OR] 1.51, 99% CI 1.39-1.63, 5.99% preterm births]) and LBW (adjusted OR 1.25, 99% CI 1.13-1.39, 3.32% LBW) after a short interpregnancy interval (0-5 months) compared with offspring born after an interpregnancy interval of 18-23 months (3.21% preterm births, 1.92% LBW). Except for preterm birth (adjusted OR 1.72, 99% CI 1.26-2.35), associations were attenuated in cousin comparisons. A small association between a short interpregnancy interval and preterm birth remained in sibling comparisons (adjusted OR 1.22, 99% CI 1.11-1.35), but associations with LBW (adjusted OR 0.83, 99% CI 0.74-0.94) and SGA (adjusted OR 0.74, 99% CI 0.64-0.85) reversed direction. For pregnancy intervals of 60 months or more, odds of preterm birth (adjusted OR 1.51, 99% CI 1.43-1.60, 5.07% preterm births), LBW (adjusted OR 1.61, 99% CI 1.50-1.73, 3.43% low-birth-weight births), and SGA (adjusted OR 1.54, 99% CI 1.42-1.66, 2.49% SGA births) were also higher when compared with the reference interval (1.53% SGA). Associations between long interpregnancy interval and adverse birth outcomes remained through cousin and sibling comparisons. Postbirth interval analyses showed familial confounding is present for short interpregnancy intervals, but supported independent associations for long interpregnancy intervals.Familial confounding explains most of the association between a short interpregnancy interval and adverse birth outcomes, whereas associations with long interpregnancy intervals were independent of measured and unmeasured factors.

  View details for DOI 10.1097/AOG.0000000000002358

  View details for Web of Science ID 000419132400019

  View details for PubMedID 29112654

  View details for PubMedCentralID PMC5783305

• Maternal Antidepressant Use and Pregnancy Outcomes Reply JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION D'Onofrio, B. M., Sujan, A. C. 2017; 318 (7): 666-667

  View details for DOI 10.1001/jama.2017.9194

  View details for Web of Science ID 000407616000026

  View details for PubMedID 28810020

  View details for PubMedCentralID PMC8180292

• An illustration of how program implementers can use population-specific analyses to facilitate the selection of evidence-based home visiting programs PSYCHOSOCIAL INTERVENTION Sujan, A. C., Eckenrode, J. 2017; 26 (2): 117-124

  View details for DOI 10.1016/j.psi.2017.01.001

  View details for Web of Science ID 000416619700006

• Associations of Maternal Antidepressant Use During the First Trimester of Pregnancy With Preterm Birth, Small for Gestational Age, Autism Spectrum Disorder, and Attention-Deficit/Hyperactivity Disorder in Offspring JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Sujan, A. C., Rickert, M. E., Oberg, S., Quinn, P. D., Hernandez-Diaz, S., Almqvist, C., Lichtenstein, P., Larsson, H., D'Onofrio, B. M. 2017; 317 (15): 1553-1562

  Abstract

  Prenatal antidepressant exposure has been associated with adverse outcomes. Previous studies, however, may not have adequately accounted for confounding.To evaluate alternative hypotheses for associations between first-trimester antidepressant exposure and birth and neurodevelopmental problems.This retrospective cohort study included Swedish offspring born between 1996 and 2012 and followed up through 2013 or censored by death or emigration. Analyses controlling for pregnancy, maternal and paternal covariates, as well as sibling comparisons, timing of exposure comparisons, and paternal comparisons, were used to examine the associations.Maternal self-reported first-trimester antidepressant use and first-trimester antidepressant dispensations.Preterm birth (<37 gestational weeks), small for gestational age (birth weight <2 SDs below the mean for gestational age), and first inpatient or outpatient clinical diagnosis of autism spectrum disorder and attention-deficit/hyperactivity disorder in offspring.Among 1 580 629 offspring (mean gestational age, 279 days; 48.6% female; 1.4% [n = 22 544] with maternal first-trimester self-reported antidepressant use) born to 943 776 mothers (mean age at childbirth, 30 years), 6.98% of exposed vs 4.78% of unexposed offspring were preterm, 2.54% of exposed vs 2.19% of unexposed were small for gestational age, 5.28% of exposed vs 2.14% of unexposed were diagnosed with autism spectrum disorder by age 15 years, and 12.63% of exposed vs 5.46% of unexposed were diagnosed with attention-deficit/hyperactivity disorder by age 15 years. At the population level, first-trimester exposure was associated with all outcomes compared with unexposed offspring (preterm birth odds ratio [OR], 1.47 [95% CI, 1.40-1.55]; small for gestational age OR, 1.15 [95% CI, 1.06-1.25]; autism spectrum disorder hazard ratio [HR], 2.02 [95% CI, 1.80-2.26]; attention-deficit/hyperactivity disorder HR, 2.21 [95% CI, 2.04-2.39]). However, in models that compared siblings while adjusting for pregnancy, maternal, and paternal traits, first-trimester antidepressant exposure was associated with preterm birth (OR, 1.34 [95% CI, 1.18-1.52]) but not with small for gestational age (OR, 1.01 [95% CI, 0.81-1.25]), autism spectrum disorder (HR, 0.83 [95% CI, 0.62-1.13]), or attention-deficit/hyperactivity disorder (HR, 0.99 [95% CI, 0.79-1.25]). Results from analyses assessing associations with maternal dispensations before pregnancy and with paternal first-trimester dispensations were consistent with findings from the sibling comparisons.Among offspring born in Sweden, after accounting for confounding factors, first-trimester exposure to antidepressants, compared with no exposure, was associated with a small increased risk of preterm birth but no increased risk of small for gestational age, autism spectrum disorder, or attention-deficit/hyperactivity disorder.

  View details for DOI 10.1001/jama.2017.3413

  View details for Web of Science ID 000399393900015

  View details for PubMedID 28418479

  View details for PubMedCentralID PMC5875187

• Translational Epidemiologic Approaches to Understanding the Consequences of Early-Life Exposures BEHAVIOR GENETICS D'Onofrio, B. M., Class, Q. A., Rickert, M. E., Sujan, A. C., Larsson, H., Kuja-Halkola, R., Sjolander, A., Almqvist, C., Lichtenstein, P., Oberg, A. 2016; 46 (3): 315-328

  Abstract

  Prominent developmental theories posit a causal link between early-life exposures and later functioning. Yet, observed associations with early exposures may not reflect causal effects because of genetic and environmental confounding. The current manuscript describes how a systematic series of epidemiologic analyses that combine several genetically-informative designs and statistical approaches can help distinguish between competing theories. In particular, the manuscript details how combining the use of measured covariates with sibling-comparisons, cousin-comparisons, and additional designs can help elucidate the sources of covariation between early-life exposures and later outcomes, including the roles of (a) factors that are not shared in families, including a potential causal effect of the exposure; (b) carryover effects from the exposure of one child to the next; and (c) familial confounding. We also describe key assumptions and how they can be critically evaluated. Furthermore, we outline how subsequent analyses, including effect decomposition with respect to measured, plausible mediators, and quantitative genetic models can help further specify the underlying processes that account for the associations between early-life exposures and offspring outcomes.

  View details for DOI 10.1007/s10519-015-9769-8

  View details for Web of Science ID 000375616400004

  View details for PubMedID 26590988

  View details for PubMedCentralID PMC4860044

• A Genetically Informed Study of the Associations Between Maternal Age at Childbearing and Adverse Perinatal Outcomes BEHAVIOR GENETICS Sujan, A. C., Rickert, M. E., Class, Q. A., Coyne, C. A., Lichtenstein, P., Almqvist, C., Larsson, H., Sjolander, A., Lahey, B. B., van Hulle, C., Waldman, I., Oberg, A., D'Onofrio, B. M. 2016; 46 (3): 431-456

  Abstract

  We examined associations of maternal age at childbearing (MAC) with gestational age and fetal growth (i.e., birth weight adjusting for gestational age), using two genetically informed designs (cousin and sibling comparisons) and data from two cohorts, a population-based Swedish sample and a nationally representative United States sample. We also conducted sensitivity analyses to test limitations of the designs. The findings were consistent across samples and suggested that, associations observed in the population between younger MAC and shorter gestational age were confounded by shared familial factors; however, associations of advanced MAC with shorter gestational age remained robust after accounting for shared familial factors. In contrast to the gestational age findings, neither early nor advanced MAC was associated with lower fetal growth after accounting for shared familial factors. Given certain assumptions, these findings provide support for a causal association between advanced MAC and shorter gestational age. The results also suggest that there are not causal associations between early MAC and shorter gestational age, between early MAC and lower fetal growth, and between advanced MAC and lower fetal growth.

  View details for DOI 10.1007/s10519-015-9748-0

  View details for Web of Science ID 000375616400013

  View details for PubMedID 26404627

  View details for PubMedCentralID PMC4808498