Reproductive Safety of Second-Generation Antipsychotics: Current Data From the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics

Am J Psychiatry. 2016 Mar 1;173(3):263-70. doi: 10.1176/appi.ajp.2015.15040506. Epub 2015 Oct 6.


Objective: Second-generation antipsychotics are used to treat a spectrum of psychiatric illnesses in reproductive-age women. The National Pregnancy Registry for Atypical Antipsychotics was established to determine the risk of major malformations among infants exposed to second-generation antipsychotics during pregnancy relative to a comparison group of unexposed infants of mothers with histories of psychiatric morbidity.

Method: Women were prospectively followed during pregnancy and the postpartum period; obstetric, labor, delivery, and pediatric medical records were obtained. Eligible enrollees were pregnant women ages 18-45. The Registry is based at the Center for Women's Mental Health at Massachusetts General Hospital. Women were recruited through provider referral, self-referral, and the Center's web site.

Results: As of December 2014, 487 women were enrolled: 353 who used second-generation antipsychotics and 134 comparison women. Medical records were obtained for 82% of participants. A total of 303 women had completed the study and were eligible for inclusion in the analysis. Of 214 live births with first-trimester exposure to second-generation antipsychotics, three major malformations were confirmed. In the control group (N=89), one major malformation was confirmed. The absolute risk of major malformations was 1.4% for exposed infants and 1.1% for unexposed infants. The odds ratio for major malformations comparing exposed infants with unexposed infants was 1.25 (95% CI=0.13-12.19).

Conclusions: The results suggest that it would be unlikely for second-generation antipsychotics to raise the risk of major malformations more than 10-fold beyond that observed in the general population or among control groups using other psychotropic medications. If the estimate stabilizes around the null with ongoing data collection, findings may be reassuring for both clinicians and women trying to make risk-benefit treatment decisions about using atypical antipsychotics during pregnancy. These findings are timely given the renewed focus of regulatory agencies on reproductive safety.

Trial registration: NCT01246765.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Drug-Induced* / diagnosis
  • Abnormalities, Drug-Induced* / epidemiology
  • Abnormalities, Drug-Induced* / etiology
  • Adult
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / classification
  • Female
  • Humans
  • Massachusetts / epidemiology
  • Mental Disorders* / drug therapy
  • Mental Disorders* / epidemiology
  • Outcome Assessment, Health Care
  • Pregnancy
  • Pregnancy Outcome
  • Pregnancy Trimesters / drug effects
  • Prenatal Exposure Delayed Effects* / epidemiology
  • Prenatal Exposure Delayed Effects* / etiology
  • Registries / statistics & numerical data


  • Antipsychotic Agents

Associated data