REVIEW OF: Bruno C et al, eClinical Medicine 2024;70:102531; Straub L et al, JAMA Intern Med 2022;182(5):522–533; Swetlik C et al, J Clin Psychiatry 2024;85(1):23m14965

STUDY TYPE: Three cohort studies—one multinational registry study, one national birth registry, and one prospective clinical registry

Antipsychotics are widely used in reproductive-age women, and families want to know the long-term risks for kids. These three complementary cohorts point in the same direction.

Straub followed 3.4 million births from US claims (Medicaid + commercial) up to 14 years. After adjusting for maternal illness and other confounders, late-pregnancy antipsychotic exposure was not meaningfully linked to neurodevelopmental disorders (adjusted HR ≈ 1.08). A small statistical signal (meaning a possible association) surfaced for aripiprazole (HR ≈ 1.36) but needs replication.

Swetlik’s prospective registry compared 178 children exposed to second-generation antipsychotics (mostly quetiapine, aripiprazole, and lurasidone) with 174 unexposed peers at preschool age. On validated parent-rated tools, global development and behavior were similar. An initial increase in abnormal communication scores disappeared after adjusting for maternal diagnosis and breastfeeding.

Bruno pooled Nordic registry data (Denmark, Finland, Iceland, Norway, and Sweden) on 213,302 children of mothers with psychiatric diagnoses; 11,626 (5.5%) were exposed in utero, most often to quetiapine or olanzapine, with a median 6.7-year follow-up. They examined timing by trimester and found similar results whether exposure occurred early, late, or throughout pregnancy. Prenatal exposure didn’t raise the already low risk of intellectual, speech/language, or learning disorders (composite aHR ≈ 1.06), and school performance was similar (math aRR 1.04; language aRR 1.00). Results were consistent regardless of the specific drug or timing of exposure. A small, uncertain chlorpromazine signal for speech/language disorders appeared but was based on few cases.

CARLAT TAKE
Across large national databases, a prospective registry, and a multinational Nordic cohort, prenatal antipsychotic exposure wasn’t linked to later developmental, behavioral, or learning problems. Small possible increases in risk with aripiprazole and chlorpromazine are worth keeping an eye on, but for now the main message stands: Once maternal diagnosis and other confounders are accounted for, antipsychotic exposure itself does not show a meaningful independent association with adverse neurodevelopmental outcomes. Keep monitoring exposed children as a precaution, but you can reassure parents that long-term neurodevelopmental outcomes look good.