Mental illnesses complicate over 15% of all pregnancies. Many of these conditions require treatment with psychotropic drugs. However, multiple studies have suggested an association between prenatal exposure to psychotropic drugs and an increased risk of major malformations, growth restriction, neonatal withdrawal syndrome and respiratory problems in the newborn, as well as gestational diabetes, preeclampsia and cesarean section in the mother. On the other hand, pregnant women with mental and/or neurological conditions who discontinue therapy may experience relapse of symptoms that can be dangerous for them and their offspring. Because many of these conditions require pharmacologic treatment and many pregnancies are unplanned, the clinically relevant questions are 1) which specific medication to recommend for women of childbearing age and 2) whether and when to discontinue treatment during pregnancy. Despite the difficult decisions faced by patients and physicians, sufficient information to guide therapeutic recommendations for the use of psychotropic drugs during pregnancy is lacking. Even when these medications may be safe, the lack of knowledge may instill unnecessary anxiety in pregnant women. Our primary objective is to provide direct evidence on the comparative safety of specific strategies used to manage mood disorders, psychosis, and attention deficit hyperactivity disorders (ADHD) in a population of pregnant women, which includes vulnerable indigent young women. We hypothesize that not all drugs are equal and that the risk-benefit trade- off of continuing treatment during pregnancy will differ by drug. We propose to quantify the risk of maternal and fetal adverse events associated with continuing and discontinuing specific psychotropic drugs during pregnancy. Within both the Medicaid Analytic eXtract (MAX) and the UnitedHealth Research database, two large population-based claims databases linkable to additional obstetrical, birth, and psychiatric records, we will identify cohorts of over 18,500 women on mood stabilizers (antiepileptics), 6,500 on antipsychotics, and 3,000 on psychostimulants at conception who delivered between 2000 and 2012. Relative risks and 95% confidence intervals will be calculated using regression models that account for the possible correlation induced by multiple gestations. We will apply an innovative combination of high dimensional propensity score techniques, instrumental variables and external adjustment to minimize the potential for confounding, and Bayesian approaches to account for prior information and support patient subgroup analyses. We will obtain information from medical records to validate specific outcomes and from the National Health and Nutrition Examination Survey to obtain information on potential confounders such as smoking, alcohol and obesity. The current proposal is an interdisciplinary collaboration between the Brigham and Women's Hospital and the Department of Epidemiology at Harvard School of Public Health.

Public Health Relevance

Given the high prevalence of mental disorders in pregnant women, the potential toxicity of medications for the fetus and the mother, and the risk of relapse of symptoms if drugs are discontinued, it is critical to quantify the risks and benefits of alternative approaches used to manage mental disorders during pregnancy. We propose to compare the safety and effectiveness of 1) specific anticonvulsants/mood stabilizers, antipsychotics, and stimulants;and 2) continuing versus discontinuing these drugs during pregnancy.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Behavioral Genetics and Epidemiology Study Section (BGES)
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Rupp, Agnes
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Harvard University
Public Health & Prev Medicine
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United States
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MacDonald, Sarah C; Hernán, Miguel A; McElrath, Thomas F et al. (2018) Assessment of recording bias in pregnancy studies using health care databases: An application to neurologic conditions. Paediatr Perinat Epidemiol 32:281-286
Park, Yoonyoung; Hernandez-Diaz, Sonia; Bateman, Brian T et al. (2018) Continuation of Atypical Antipsychotic Medication During Early Pregnancy and the Risk of Gestational Diabetes. Am J Psychiatry 175:564-574
Desai, Rishi J; Rothman, Kenneth J; Bateman, Brian T et al. (2017) A Propensity-score-based Fine Stratification Approach for Confounding Adjustment When Exposure Is Infrequent. Epidemiology 28:249-257
Cohen, Jacqueline M; Hernández-Díaz, Sonia; Bateman, Brian T et al. (2017) Placental Complications Associated With Psychostimulant Use in Pregnancy. Obstet Gynecol 130:1192-1201
Desai, Rishi J; Bateman, Brian T; Huybrechts, Krista F et al. (2017) Risk of serious infections associated with use of immunosuppressive agents in pregnant women with autoimmune inflammatory conditions: cohort study. BMJ 356:j895
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Bateman, Brian T; Patorno, Elisabetta; Desai, Rishi J et al. (2017) Angiotensin-Converting Enzyme Inhibitors and the Risk of Congenital Malformations. Obstet Gynecol 129:174-184
Patorno, Elisabetta; Huybrechts, Krista F; Bateman, Brian T et al. (2017) Lithium Use in Pregnancy and the Risk of Cardiac Malformations. N Engl J Med 376:2245-2254
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Patorno, Elisabetta; Bateman, Brian T; Huybrechts, Krista F et al. (2017) Pregabalin use early in pregnancy and the risk of major congenital malformations. Neurology 88:2020-2025

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