BACKGROUND: Existing data may underestimate the potential teratogenic effects of prenatal antipsychotic exposure because of lacking data on miscarriages and induced abortions.

OBJECTIVE: To present comprehensive analyses 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 among pregnancies exposed to antipsychotics in the first trimester with unexposed pregnancies. In secondary analyses, the comparison was made with pregnancies of women who used antipsychotics before but not during pregnancy (discontinuers). We used weighted log-binomial regression to estimate adjusted prevalence ratios (PRs) and propensity score fine stratifications for confounding control. We performed four sensitivity analyses, including a sibling-controlled analysis.

RESULTS: Of the 503,158 pregnancies, 1,252 (0.2%) were to women who filled an antipsychotic prescription in the first trimester. Major malformations were present in 7.3% of antipsychotic-exposed pregnancies, 5.1% of unexposed pregnancies, and 6.0% of discontinuers' pregnancies. The adjusted PR was 1.23 (95% CI: 1.01-1.50) among exposed pregnancies compared with unexposed pregnancies. The PR was attenuated to 1.14 (0.88-1.48) compared with discontinuers and 1.08 (0.47-2.49) in the sibling analysis. Similar findings were observed with cardiac malformations. Results were consistent for classes and individual antipsychotics, and remained robust across four sensitivity analyses.

CONCLUSIONS: Our findings suggest limited or no overall teratogenic effect of first-trimester antipsychotic exposure. For individual antipsychotics, with estimations based on very few cases, further studies with sufficient sample size are warranted.