Maternal antipsychotic use during pregnancy and congenital malformations

BACKGROUND: Existing data may underestimate the potential terato-genic effects of prenatal antipsychotic exposure because of lacking data on miscarriages and induced abortions. OBJECTIVE: This study aimed to present a comprehensive analysis based on information on pregnancies ending in termination, miscarriage, stillbirth, and live birth. STUDY DESIGN: We conducted a population-based cohort study in Denmark of clinically recognized singleton pregnancies with the first-trimester scan performed from 2008 to 2017. We compared the risk of major malformations between pregnancies exposed to antipsychotics in the first trimester and unexposed pregnancies. In secondary analy-ses, the comparison was made with pregnancies of women who used antipsychotics before but not during pregnancy (discontinuers). We used weighted log-binomi al regression to estimate adjusted prevalence ratios and propensity score fine stratifications for confounding control. We performed 4 sensitivity analyses, including a sibling-controlled analysis. RESULTS: Of the 503,158 pregnancies, 1252 (0.2%) were of women who filled an antipsychotic prescription in the first trimester. Major malfor-mations were present in 7.3% of antipsychotic-exposed pregnancies, 5.1% of unexposed pregnancies, and 6.0% of discontinuers' pregnancies. The adjusted prevalence ratio was 1.23 (95% confidence interval, 1.01-1.50) among exposed pregnancies compared with unexposed pregnancies. The prevalence ratio was attenuated to 1.14 (95% confidence interval, 0.88 -1.48) compared with discontinuers and 1.08 (95% confidence interval, 0.47-2.49) in the sibling analysis. Similar findings were observed with car-diac malformations. Results were consistent for classes and individual anti-psychotics, and remained robust across the 4 sensitivity analyses. CONCLUSION: Our findings suggest limited or no overall teratogenic effect of first-trimester antipsychotic exposure. For individual antipsy-chotics, with estimations based on very few cases, further studies with sufficient sample sizes are warranted.