Closing critical gaps in antiseizure medication safety for pregnancy and offspring health

The National Institute of Child Health and Human Development awarded Brigham & Women's Hospital Inc. $846,324 on August 19, 2026, under the Child Health and Human Development Extramural Research program (CFDA 93.865) to conduct epidemiologic research on antiseizure medication (ASM) safety during pregnancy and paternal exposure.

The project applies advanced causal inference methods to two large U.S. healthcare databases—Medicaid and MarketScan, comprising over 50 million pregnancies—to evaluate the safety of maternal use of newer ASMs (cenobamate, lacosamide, pregabalin, oxcarbazepine, zonisamide), maternal ASM polytherapy involving lamotrigine and levetiracetam, and paternal ASM use during spermatogenesis. For each aim, the research evaluates risk of major congenital malformations, neonatal complications, non-livebirths, and neurodevelopmental disorders using validated diagnostic and procedure code algorithms. The study incorporates methodological innovations including target trial emulation, latent class regression to detect malformation patterns, and AI-enhanced confounding control.

Performance occurs at Mission Hill, Massachusetts. The project period runs through June 30, 2031. Brigham & Women's Hospital operates as a subsidiary of Partners Healthcare System Incorporated and serves as prime recipient on this award.

Abstract

Antiseizure medications (asms) are widely used among individuals of childbearing age, not only for epilepsy but also for conditions such as mood disorders, neuropathic pain, and migraine. While treatment during pregnancy is often essential to avoid serious maternal and fetal complications, asms cross the placenta and some have been linked to major congenital malformations (mcms), adverse birth outcomes, and neurodevelopmental disorders (ndds). Substantial evidence exists for older asms, but major knowledge gaps remain regarding the safety of maternal exposure to newer asms and to polytherapy strategies. There is also growing concern that paternal ASM exposure during spermatogenesis may affect offspring outcomes, yet data on this remain sparse, leaving many important questions unanswered. These uncertainties leave patients and clinicians without adequate evidence to guide treatment decisions. This proposal will leverage two large U.S. Healthcare databases-medicaid and marketscan-comprising over 50 million pregnancies, with detailed information on outpatient prescription fills, comorbidity, and longitudinal child outcome data. We will apply advanced causal inference methods to generate robust evidence on the safety of: (aim 1) maternal use of newer asms (e.g., cenobamate, lacosamide, pregabalin, oxcarbazepine, zonisamide); (aim 2) maternal ASM polytherapy involving lamotrigine and levetiracetam; and (aim 3) paternal ASM use during spermatogenesis. For all aims, we will evaluate the risk of mcms, neonatal complications, non- livebirths, and ndds, using previously validated algorithms based on diagnostic and procedure codes, which yielded high positive predictive values. Methodological innovations include target trial emulation, latent class regression to detect malformation patterns, and AI-enhanced confounding control. The influence of ASM dose and treatment indication will be assessed. By providing the first comprehensive evaluation of these maternal and paternal ASM treatment strategies, the proposed study will generate critical evidence to guide clinical counseling, regulatory decision-making, and practice guidelines. The findings will advance maternal-child health and reproductive safety by reducing uncertainty around maternal medication use during pregnancy and paternal medication use during spermatogenesis-an area of growing public health importance that has remained largely understudied.