Psychiatric problems are quite common and have been related to detrimental effects on maternal functioning, conception, and healthy infant development. Despite the fact that the use of antipsychotic medications is expanding, there are still many questions about their safety when used during pregnancy. Therefore, concentrate on specific medications and subtypes of congenital malformations to evaluate the risk of first-trimester antipsychotic exposure for congenital malformations.

This cohort analysis included the years 1996 to 2018 and used information from national health registers in the US, the five Nordic nations, and the UK. The US cohort consists of publicly insured mothers connected to their live-born infants nested in the national Medicaid Analytic eXtract, while the Nordic cohort included all pregnancies resulting in singleton live-born infants. From November 2020 to April 2022, data were examined.

Any combination of atypical, typical, and/or individual antipsychotic medications given during the first trimester. Anorectal atresia/stenosis, gastroschisis, hydrocephalus, other specific brain anomalies, oral clefts, neural tube defects, hip dysplasia, limb reduction defects, cardiovascular malformations, oral clefts, hydrocephalus, esophageal disorders, and major congenital malformations have all been linked to prenatal antipsychotic exposure. Potential confounders were eliminated using propensity score stratification. Indirect standardisation was used to get the pooled adjusted estimates.

The study cohort consisted of 6,455,324 mothers who were not exposed to antipsychotic drugs (mean maternal age range across countries: 24-31 years), 21 751 mothers who were exposed to these drugs (mean age range: 26-31 years), and 6,371 mothers who were exposed to these drugs (mean age range: 27-32 years). The prevalence of any significant abnormality was 2.7% (95% CI, 2.7%-2.8%) in newborns who were not exposed to antipsychotic drugs, 4.3% (95% CI, 4.1%-4.6%) in infants who were, and 3.1% (95% CI, 2.7%-3.5%) in infants who were treated to typical antipsychotic drugs in utero. Adjusted relative risks (aRR) for the most common exposure-outcome combinations were typically very close to zero. The only exception was the association between oral cleft and olanzapine exposure (aRR, 2.1 [95% CI, 1.1-4.3]), but estimations varied across sensitivity analyses.

Increased risks were seen for cardiac malformations after exposure to chlorprothixene (aRR, 1.6 [95% CI, 1.0-2.7]) and for gastroschisis and other specific brain defects after exposure to atypical antipsychotics (aRR, 1.5 [95% CI, 0.8-2.6] and 1.9 [95% CI, 1.1-3.0]). Although the direction of the association was constant across sensitivity studies, the broad confidence intervals prohibited solid conclusions.In this research, the data from the primary and sensitivity analyses, as well as the inevitable statistical noise for very unusual exposure-outcome combinations, showed that in utero antipsychotic exposure was not significantly related with an elevated risk of abnormalities. The identified elevated risks of gastroschisis, other particular brain defects, and mouth clefts related with olanzapine, atypical antipsychotics, and chlorprothixene, as well as cardiac malformations connected with the latter, need to be confirmed as more and more evidence mounts.