Neonatal Exposure to Antipsychotic Medications Does Not Substantially Increase Risk for NDD

Risk for neurodevelopmental disorders (NDD) among children born to women who took antipsychotic medications late in pregnancy seems to be unrelated with exposure to medication. These findings were published in JAMA Internal Medicine.

Investigators with Brigham and Women’s Hospital sourced data for this study from the Medicaid Analytic eXtract (MAX) and IBM Health MarketScan Research Database. Mother-child dyads were evaluated for exposure to antipsychotic medications during pregnancy and the impact on the development of an NDD among their children. NDD risk was evaluated using a propensity matching approach to account for baseline cohort differences.

The MAX dataset was collected between 2000 and 2014 and there were 9551 exposed and 2,034,883 unexposed pregnancies. The pregnant women were aged mean 26.8 (SD, 6.1) and 24.4 (SD, 5.8) years, they had 3.2 (SD, 3.1) and 0.3 (SD, 0.9) distinct mental health-related diagnoses, and 28.2% and 10.7% had an obstetric comorbid index of ≥3, respectively.

The MarketScan dataset was collected between 2000 and 2015 and there were 1214 exposed and 1,306,408 unexposed pregnancies. The pregnant women were aged mean 33.1 (SD, 5.0) and 32.0 (SD, 4.6) years, they had 2.6 (SD, 2.6) and 0.1 (SD, 0.6) distinct mental health-related diagnoses, and 27.5% and 14.5% had an obstetric comorbid index of ≥3, respectively.

Among the women using antipsychotics, most received atypical antipsychotic drugs, specifically quetiapine and aripiprazole. The most common indications for the medications were bipolar disorder, depression, and anxiety.

After propensity matching in the MAX dataset, by 8 years of age, 37.3% of children born from an exposed pregnancy and 23.7% from an unexposed pregnancy were diagnosed with an NDD. The incidence rates of attention-deficit/hyperactivity disorder (ADHD) were 24.5% and 14.3%, and autism spectrum disorder (ASD) were 3.5% and 1.6% among the exposed and unexposed cohorts, respectively. For the MarketScan dataset, the rates of NDD (24.5% vs 11.0%), ADHD (17.5% vs 5.8%), and ASD (3.8% vs 1.3%) were higher among the exposed children.

In the fully adjusted model, any exposure did not substantially increase risk for NDDs compared with the unexposed cohort (pooled adjusted hazard ratio[paHR], 1.08; 95% CI, 1.01-1.17). However, the children of women who took aripiprazole during the second half of their pregnancy were associated with increased risk for any NDD (paHR, 1.36; 95% CI, 1.14-1.63), a speech or language disorder (paHR, 1.61; 95% CI, 1.28-2.02), and a behavioral disorder (paHR, 1.63; 95% CI, 1.18-2.26).

In a sensitivity analysis, risk for 2 or more NDDs was associated with aripiprazole exposure during the second half of pregnancy (paHR, 1.48; 95% CI, 1.11-1.99) and the first half of pregnancy (paHR, 1.45; 95% CI, 1.20-1.74).

This study may have been limited by using pharmacy dispensations as a proxy for drug exposure.

The study authors concluded, “This birth cohort study found that the most commonly prescribed antipsychotic medications do not appear to meaningfully increase NDD risk in offspring after accounting for confounding. The potential signal identified for aripiprazole requires replication in other data sources before causality can be assumed.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Straub L, Hernández-Díaz S, Bateman BT, et al. Association of antipsychotic drug exposure in pregnancy with risk of neurodevelopmental disorders: a national birth cohort study. JAMA Intern Med. Published online March 28, 2022. doi:10.1001/jamainternmed.2022.0375