Risk of Major Congenital Malformations Associated With the First‐Trimester Exposure to Antipsychotics: A Large Claims Database Study

This study aimed to evaluate the risk of major congenital malformations (MCMs) associated with first-trimester exposure to antipsychotics, using a large claims database in Japan. This retrospective cohort study was based on data from a large claims database in Japan. We used a large claims database from 2010 to 2019. Dates of pregnancy onset and delivery were estimated using the developed algorithms. Overall MCMs were defined according to the International Classification of Diseases, 10th revision codes. To address confounding by indication, the risk of MCM in relation to first-trimester antipsychotic use was evaluated among pregnant women with psychiatric disorders diagnosed before the end of the first-trimester. We compared the prevalence of MCMs among infants born to pregnant women with or without first-trimester exposure to antipsychotics and estimated the weighted odds ratios (wORs) using propensity-score overlap weights. The prevalence of psychiatric diagnoses before the end of the first-trimester was 6291 women among the 91 390 who delivered between 2010 and 2019. Among the 6291 diagnosed with psychiatric disorders, 317 were exposed to any antipsychotics during the first-trimester of pregnancy. The prevalence of overall MCMs among live births was 411 (6.9%) among women unexposed to any antipsychotics and 24 (7.6%) among those exposed. The first-trimester exposure to any antipsychotics was not significantly associated with overall MCMs when wORs were calculated using propensity-score overlap weights (wOR 1.144, 95% confidence intervals 0.727-1.799). Exposure to any antipsychotics during the first-trimester of pregnancy was not associated with an increased risk of overall MCMs in infants.