
Given the variety of young women using atypical or second-generation antipsychotic medications, there may be an urgent need for more accurate data regarding the reproductive safety of those medications. So far, studies haven’t documented an increased risk of malformations amongst women using newer antipsychotic medications while pregnant; nevertheless, the data on the reproductive safety of this class of medicines is restricted.
In a recent population-based cohort study from Denmark of singleton pregnancies, researchers compared the chance of major malformations in pregnancies exposed to antipsychotics in the primary trimester and unexposed pregnancies. Rates of major congenital malformations within the antipsychotic medication-exposed group were in comparison with rates in unexposed pregnancies and in unexposed pregnancies of ladies who used antipsychotics before but not while pregnant (discontinuers).
Of the 503,158 pregnancies ending in miscarriage, termination, stillbirth, and live birth were included on this study, with a complete of 1,252 (0.2%) women who filled an antipsychotic prescription in the primary trimester. Major malformations were present in 7.3% of antipsychotic-exposed pregnancies, 5.1% of unexposed pregnancies, and 6.0% of discontinuers’ pregnancies. After adjusting for potential confounding variables, the researchers calculated an adjusted prevalence ratio of 1.14 (95% CI , 0.88-1.48) comparing exposed pregnancies with discontinuers.
In a sibling evaluation, where they compared siblings born to the identical mother (one exposed and one unexposed), the adjusted prevalence ratio was 1.08 (95% CI, 0.47-2.49). On this study, the vast majority of the ladies (n=868, with 594 on quetiapine) were taking newer atypical or second-generation antipsychotic medications. While the study was not adequately powered to discover differences between exposures to individual antipsychotics, the researchers observed similar rates of malformations when comparing first vs. second-generation antipsychotics.
Little or No Risk of Malformations
On this register-based cohort study from Denmark of 503,158 clinically recognized pregnancies, including miscarriages, terminations, and stillbirth, the present study observed little or no risk of teratogenesis related to first trimester exposure to antipsychotic medications. Given the sample size, it will not be possible to rule out a small increase in the general risk of malformations or increased risk of specific but rare malformations. Nonetheless, the info are reassuring and don’t suggest a significant teratogenic risk.
While most studies analyzing risk of major malformations depend on the evaluation of liveborn children, the present study looks in danger in all identified singleton pregnancies, including miscarriages, terminations, and stillbirth. (This is the reason the general rate of malformations is so high on this study: 5.1% in unexposed pregnancies.) It is feasible that studies examining only liveborn children may potentially miss more serious malformations that lead either to termination or pregnancy loss; thus, it’s reassuring that the findings of the present study are consistent with previous studies assessing the chance for malformations in antipsychotic-exposed liveborn children.
For individual antipsychotic medications, with estimations based on only a few cases, further studies with sufficient sample size and power are warranted. Because the info available regarding using atypical or second generation antipsychotic medications in pregnancy is sparse, there may be an ideal need to check these medications and their use in pregnancy. The National Pregnancy Registry for Atypical Antipsychotics is currently enrolling pregnant patients taking atypical antipsychotic medications to learn more about reproductive safety of those medications. Those taken with the study may call TOLL-FREE: 1-866-961-2388.
Ruta Nonacs, MD PhD
References
Liu X, Kolding L, Momen N, Gasse C, Pedersen LH. Maternal antipsychotic use while pregnant and congenital malformations. Am J Obstet Gynecol MFM. 2023 Jun;5(6):100950.