Antipsychotic Use in Pregnancy and the Risk for Congenital Malformations

Abstract

IMPORTANCE The frequency of antipsychotic (AP) use during pregnancy has approximately doubled during the last decade. However, little is known about their safety for the developing fetus, and concerns have been raised about a potential association with congenital malformations. OBJECTIVE To examine the risk for congenital malformations overall and cardiac malformations associated with first-trimester exposure to APs. DESIGN, SETTING, AND PARTICIPANTS This nationwide sample of 1 360 101 pregnant women enrolled in Medicaid with a live-born infant constituted the pregnancy cohort nested in the Medicaid Analytic Extract database, which included data from January 1, 2000, to December 31, 2010. Participants were enrolled in Medicaid from 3 months before their last menstrual period through at least 1 month after delivery. Relative risks (RRs) were estimated using generalized linear models with fine stratification on the propensity score to control for the underlying psychiatric disorders and other potential confounders. Data were analyzed during 2015. EXPOSURES Use of APs during the first trimester, the etiologically relevant period for organogenesis. MAIN OUTCOMES AND MEASURES Major congenital malformations overall and cardiac malformations identified during the first 90 days after delivery. RESULTS Of the 1 341 715 pregnancies that met inclusion criteria (mean [SD] age of women, 24.02 [5.77] years), 9258 (0.69%) filled at least 1 prescription for an atypical AP and 733 (0.05%) filled at least 1 prescription for a typical AP during the first trimester. Overall, 32.7 (95% CI, 32.4–33.0) per 1000 births not exposed to APs were diagnosed with congenital malformations compared with 44.5 (95% CI, 40.5–48.9) per 1000 births exposed to atypical and 38.2 (95% CI, 26.6–54.7) per 1000 births exposed to typical APs. Unadjusted analyses suggested an increased risk for malformations overall for atypical APs (RR, 1.36; 95% CI, 1.24–1.50) but not for typical APs (RR, 1.17; 95% CI, 0.81–1.68). After confounding adjustment, the RR was reduced to 1.05 (95% CI, 0.96–1.16) for atypical APs and 0.90 (95% CI, 0.62–1.31) for typical APs. The findings for cardiac malformations were similar. For the individual agents examined, a small increased risk in overall malformations (RR, 1.26; 95% CI, 1.02–1.56) and cardiac malformations (RR, 1.26; 95% CI, 0.88–1.81) was found for risperidone that was independent of measured confounders. CONCLUSIONS AND RELEVANCE Evidence from this large study suggests that use of APs early in pregnancy generally does not meaningfully increase the risk for congenital malformations overall or cardiac malformations in particular. The small increase in the risk for malformations observed with risperidone requires additional study.

Bipolar Disorder in Pregnancy: A Review of Pregnancy Outcomes

“…Coughlin et al's meta‐analysis found that the most common organ affected was the heart, but there was no specific pattern of malformations found in Terrana et al's meta‐analysis (Table ). One study that assessed the effects of individual antipsychotics based on prescriptions written for a nationwide sample of pregnant women enrolled in Medicaid (N = 1,360,101) found that risperidone was associated with a small increased risk of malformations overall (RR, 1.26; 95% CI, 1.02–1.56) and cardiac malformations more specifically (RR, 1.26; 95% CI, 0.88–1.81) but found no increased risk associated with other typical or atypical antipsychotics . The systematic review by Ennis and Kamkier did not find that olanzapine, quetiapine, risperidone, or aripiprazole was associated with an increased incidence of congenital malformations.…”

“…Articles scoring below 6 were excluded. Following the rating process, 20 articles met the inclusion criteria, including 5 systematic reviews, 12 cohort studies, 2 case‐control studies, and one meta‐analysis …”

Antipsychotic Medication Use Among Publicly Insured Pregnant Women in the United States

“…There are few large, well-controlled studies examining the teratogenicity of atypical antipsychotics (10, 11), but the results from a recent large study with 9,258 women exposed to atypical antipsychotics did not find increased risk of congenital malformation. (12). Atypical antipsychotics are known to cause weight gain and increase the risk of Type 2 diabetes mellitus in the general population (13), which may translate into higher risks for diabetes associated adverse pregnancy outcomes like fetal macrosomia or increased risk of gestational diabetes and its attendant effects.…”

Treatment With Antipsychotics in Pregnancy: Changes in Drug Disposition

“…Weighing these options against each other, the recommendation has often been to discontinue treatment, especially during the first trimester 1. However, during the past decade more safety data have accumulated suggesting that antipsychotics are relatively safe to use in pregnancy 1, 2, 3. It has also been demonstrated that discontinuing ongoing maintenance treatment for severe mood and psychotic disorders during pregnancy carries a high risk of disease recurrence 2.…”