Research from the CWMH: Prenatal Exposure to Second Generation Antipsychotics and Neurodevelopmental Outcomes in Preschool-Aged Children

The newer “atypical” or second-generation antipsychotic agents are used to treat a spectrum of psychiatric disorders, including schizophrenia, bipolar disorder, major depression, PTSD and anxiety disorders. The National Pregnancy Registry for Atypical Antipsychotics and other studies have yielded important information on the reproductive safety of this class of medications; however, we have more data on the risk of congenital malformations and considerably less information on long-term neurodevelopmental outcomes in children with prenatal exposure to these newer medications. A recent study from the MGH Center for Women’s Mental Health reports on neurodevelopmental outcomes in preschool-aged children prenatally exposed to second-generation antipsychotics (SGAs). 

Between January 2, 2018, to February 2, 2021, the registry included 520 children eligible to participate in this study. Responses were collected from 520 participants (67.7%), including 178 children in the SGA-exposed group (mean age?=?2.6 years) and 174 children in the unexposed comparison group (mean age?=?2.1 years). Developmental and behavioral outcomes were assessed using validated, parent-reported assessments: the Ages and Stages Questionnaire, Third Edition (ASQ-3) and the Preschool Child Behavior Checklist for Ages 1½–5 (CBCL).

Outcomes of children exposed in utero to SGAs were compared to outcomes in children unexposed to SGAs in a cohort of mothers with a history of psychiatric illness. Exposure to other psychotropic medications during pregnancy was not an exclusion criterion for either group.

No significant differences between groups were detected with respect to neurodevelopmental outcomes assessed using the ASQ-3 (OR?=?1.24, 95% CI, 0.74–2.09). Similarly, for behavioral outcomes, the researchers observed no significant differences between exposed and unexposed children on scores measured using the CBCL composite scales.

Clinical Implications

The current study is the first to examine neurobehavioral outcomes of preschool-aged children exposed prenatally to SGAs. While this is a relatively small study, one important strength of the study is that it relied on standardized assessments of developmental and behavioral outcomes. The current study observed no significant differences in overall developmental outcomes or behavior in exposed versus unexposed children.

These findings are consistent with a previous study analyzing data from two large databases: the Medicaid Analytic eXtract (MAX, 2000-2014) and the IBM Health MarketScan Research Database (MarketScan, 2003-2015). In this study, ICD-10 codes were used to identify neurodevelopmental disorders, including autism spectrum disorder and ADHD, in a total of 10,772 children with prenatal exposure to an antipsychotic medication (about 90% were exposed to SGAs). In this study, the most commonly prescribed antipsychotic medications did not appear to meaningfully increase risk for neurodevelopmental disorders in offspring (although there was a potential signal identified for aripiprazole).

These studies provide important information to patients and their providers who may be considering the use of the newer, second generation antipsychotic agents during pregnancy. We have a growing body of literature indicating that SGAs may be a reasonable option during pregnancy. While further study is warranted, this study complements previous studies and does not show an increased risk of neurodevelopmental disorders or behavioral problems in preschool-aged children prenatally exposed to SGAs. 

Ruta Nonacs, MD PhD

References
Swetlik, C., Cohen, L. S., Kobylski, L. A., Sojka, E. T., Killenberg, P. C., Freeman, M. P., & Viguera, A. C. (2024). Effects of Prenatal Exposure to Second-Generation Antipsychotics on Development and Behavior Among Preschool-Aged Children: Preliminary Results From the National Pregnancy Registry for Psychiatric Medications. The Journal of Clinical Psychiatry, 85(1).