To examine the risk for congenital defects associated with first-trimester exposure to different antipsychotics, Krista Huybrechts, M.S., Ph.D., of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues analyzed a nationwide sample of over 1.3 million pregnant women enrolled in Medicaid. Exposure to antipsychotics was defined as filling at least one prescription during the first 90 days of pregnancy, and congenital malformations overall and cardiac malformations were assessed during the first 90 days after delivery.
Among the 1,341,715 pregnancies included in the study cohort, 9,258 women (0.69%) filled a prescription for an atypical antipsychotic during the first trimester, and 733 women (0.05%) filled a prescription for a typical antipsychotic. The most frequently used atypical antipsychotic was quetiapine, followed by aripiprazole, risperidone, olanzapine, and ziprasidone.
The authors found that overall, 32.7 per 1,000 infants not exposed to antipsychotics were diagnosed with congenital malformations compared with 44.5 per 1,000 infants exposed to atypical antipsychotics and 38.2 per 1,000 infants exposed to typical antipsychotics.
While unadjusted analyses suggested an increased risk of birth defects with atypical antipsychotics (relative risk [RR], 1.36) but not for typical antipsychotics (RR, 1.17), after controlling for potential confounding by mental and physical comorbid conditions and their associated behaviors, these relative risks fell to 1.05 and 0.90 for atypical antipsychotic and typical antipsychotic exposure, respectively. Additional analysis revealed that women taking risperidone were 26% more likely than women not taking antipsychotics to give birth to an infant with a birth defect.
“The small increase in absolute risk and RR for malformations observed with risperidone should be interpreted with caution because no apparent biological mechanism can readily explain this outcome, and the possibility of a chance finding cannot be ruled out,” the authors wrote. “This finding should therefore be interpreted as a potential safety signal that will require follow-up in other studies.
Reflecting on the findings in a related editorial, Katherine Wisner, M.D., M.S., and colleagues wrote, “The sophisticated pharmacoepidemiologic methodology comprehensively tackles the major challenge in observational studies, that is, confounding by underlying disease factors that are (like the APs [antipsychotics]) potentially associated with pregnancy outcomes. The task is to separate the effect of two exposures (APs and psychiatric disease) on the reproductive outcomes. The finding that “associations between AP exposure and birth defects were attenuated after adjustment for confounding ... implies that these variables, rather than AP exposure, account for much of the effect on congenital malformations.”
For related information on weighing the risks and benefits of medications when treating pregnant women, see the Psychiatric News article “Yes or No: Prescribing Antidepressants to Pregnant Patients” by Jennifer L. Payne, M.D.