CNSPulse
T101

THE NATIONAL PREGNANCY REGISTRY FOR PSYCHIATRIC MEDICATIONS: RISK OF MAJOR MALFORMATIONS FOLLOWING FETAL EXPOSURE TO SECOND GENERATION ANTIPSYCHOTICS

Lee Cohen — Marlene Freeman1, Ana Manuelian1, Bridget Murphy1, Emma Grassi1, Peri Barest1, Skye Scoggins1, Ella Slaby1, Lily Cork1, Hannah Dineen1, David Chitayat2, Sonia Hernandez-Diaz3, Adele Viguera4 1Massachusetts General Hospital, Ammon-Pinizzotto Center for Women’s Mental Health, 2University of Toronto, 3Harvard T.H. Chan School of Public Health, 4Massachusetts General Hospital, Center for Women's Mental Health; Cleveland Clinic, Cleveland Clinic Neurological Institute

2026 ASCP Annual Meeting

Background

The Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications (NPRPM) is a longitudinal prospective research study which systematically gathers reproductive safety data on psychotropic use during pregnancy. Second generation antipsychotics (SGAs) are commonly used in reproductive-aged women to treat psychiatric disorders, such as bipolar disorder and major depressive disorder. The NPRPM’s primary outcome of interest is major malformations following first trimester SGAexposure, with data informing the care of reproductive-aged women with psychiatric histories.

Methods

The NPRPM prospectively collects data from pregnant women, aged 18-45 years, with histories of psychiatric disorders. Three phone interviews are conducted to ascertain information on the mothers and babies, two of which occur during pregnancy and the final interview occurs three months postpartum. Enrollment and longitudinal follow-up of participants are ongoing. In this analysis, exposure is defined as SGA-use during the first trimester of pregnancy as reported by the participant. The control group consists of women who did not use an SGA at any point during pregnancy. Participants exposed to SGAs in the second and/or third trimester but not the first trimester were excluded from analysis. Prenatal exposure to psychotropics other than SGAs does not exclude participants from either the exposure or control groups. Major malformations are identified through a multi-step process: pertinent information is abstracted from medical records, and potential malformation cases are then adjudicated by a dysmorphologist blinded to psychiatric diagnoses and drug exposure.

Results

As of April 4th, 2025, 3940 women were enrolled in the NPRPM, including 1375 in the exposure group and 2456 in the comparison group. Medical records were obtained for 75% of participants. A total of 3014 participants (1049 exposed to an SGA in the first trimester, 1965 unexposed to an SGA during pregnancy) completed the postpartum interview and were eligible for analysis. Of 1080 infants in the exposure group, 28 confirmed major malformations were identified. In the control group of 1997 infants, 32 malformations were identified. The absolute risk of major malformations was 2.59% in the exposure group and 1.60% in the comparison group. No specific patterns of major malformations were observed in either group.

Conclusion

According to CDC national data, the prevalence of major malformations is approximately 3% among all live births in the United States. In this analysis, the absolute risk of neonatal major malformations was similar at 2.59% in the exposed group, while it was lower at 1.60% in the unexposed group compared to this external reference. The low absolute risk in our unexposed group could be attributed to random error or increased rates of healthy behaviors compared to the general population of reproductive-aged women. This highlights the need for a larger sample size. Ongoing data collection through the Registry is critical in defining the risk estimate more precisely and reducing uncertainty.