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

Adele C. Viguera, MD, MPH; Marlene P. Freeman, MD; Lina Góez-Mogollón, MD, MSc; Alexandra Z. Sosinsky, MS; Sara A. McElheny, BA; Taylor R. Church, BS; Amanda V. Young, BA; Phoebe S. Caplin, BA; David Chitayat, MD; Sonia Hernández-Díaz, MPH, DrPH; Lee S. Cohen, MD

J Clin Psychiatry 2021;82(4):20m13745

ABSTRACT

Objective: Second-generation antipsychotics (SGAs) are prescribed for a wide range of indications in women of reproductive age. The National Pregnancy Registry for Atypical Antipsychotics (NPRAA) was established to determine the risk of major malformations among infants exposed to these medications during the first trimester relative to a comparison group of unexposed infants of mothers with histories of psychiatric morbidity.

Methods: Women, aged 18–45 years, with histories of psychiatric illness were prospectively followed through pregnancy and during the postpartum period. Pediatric and maternal medical records were obtained and screened for evidence of major malformations. Potential cases were adjudicated by a dysmorphologist who was blinded to drug exposure. Recruitment to the Registry, which is based at the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH), includes nationwide provider referral, self-referral, and advertisement through the MGH Center for Women’s Mental Health website.

Results: As of April 9, 2020, 1,906 women had enrolled, including 889 in the exposure group and 1,017 controls. A total of 1,311 women completed the study and were eligible for inclusion in the analysis. Medical records were obtained for 81.3% of participants. Among 640 live births in the exposure group, 16 (2.50%) had confirmed major malformations reported, and among 704 live births in the control group, 14 (1.99%) had confirmed major malformations reported. The estimated odds ratio for major malformations comparing exposed and unexposed infants was 1.48 (95% CI, 0.625–3.517).

Conclusions: Data from the Registry assessing SGAs as a class indicate that they are unlikely to have a major teratogenic effect. These findings provide pertinent information for women and their health care providers regarding decisions about atypical antipsychotic use during pregnancy.

Trial Registration: ClinicalTrials.gov identifier: NCT01246765

Continue Reading...

Did you know members enjoy unlimited free PDF downloads as part of their subscription? Subscribe today for instant access to this article and our entire library in your preferred format. Alternatively, you can purchase the PDF of this article individually.

Subscribe Now

Already a member? Login

Download Free PDF

View Related Activity

Go to Activity

References (29)

Gerard E, Pack AM. Pregnancy registries: what do they mean to clinical practice? Curr Neurol Neurosci Rep. 2008;8(4):325–332. PubMed CrossRef
Gliklich RE, Dreyer NA, Leavy MB. Registries for Evaluating Patient Outcomes: A User’s Guide. Rockville, MD: Agency for Healthcare Research and Quality (US); 2014.
Tomson T, Battino D, Craig J, et al; ILAE Commission on Therapeutic Strategies. Pregnancy registries: differences, similarities, and possible harmonization. Epilepsia. 2010;51(5):909–915. PubMed CrossRef
Holmes LB, Wyszynski DF, Lieberman E. The AED (antiepileptic drug) pregnancy registry: a 6-year experience. Arch Neurol. 2004;61(5):673–678. PubMed CrossRef
Toh S, Li Q, Cheetham TC, et al. Prevalence and trends in the use of antipsychotic medications during pregnancy in the US, 2001–2007: a population-based study of 585,615 deliveries. Arch Women Ment Health. 2013;16(2):149–157. PubMed CrossRef
Çamsarı U, Viguera AC, Ralston L, et al. Prevalence of atypical antipsychotic use in psychiatric outpatients: comparison of women of childbearing age with men. Arch Women Ment Health. 2014;17(6):583–586. PubMed CrossRef
Alexander GC, Gallagher SA, Mascola A, et al. Increasing off-label use of antipsychotic medications in the United States, 1995–2008. Pharmacoepidemiol Drug Saf. 2011;20(2):177–184. PubMed CrossRef
Freeman MP, Farchione T, Yao L, et al. Psychiatric medications and reproductive safety: scientific and clinical perspectives pertaining to the US FDA Pregnancy and Lactation Labeling Rule. J Clin Psychiatry. 2018;79(4):18ah38120. PubMed CrossRef
Cohen LS, Viguera AC, McInerney KA, et al. Establishment of the National Pregnancy Registry for Atypical Antipsychotics. J Clin Psychiatry. 2015;76(7):986–989. PubMed CrossRef
Cohen LS, Viguera AC, McInerney KA, et al. Reproductive safety of second-generation antipsychotics: current data from the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics. Am J Psychiatry. 2016;173(3):263–270. PubMed CrossRef
Holmes LB. Need for inclusion and exclusion criteria for the structural abnormalities recorded in children born from exposed pregnancies. Teratology. 1999;59(1):1–2. PubMed CrossRef
Cohen LS, Góez-Mogollón L, Sosinsky AZ, et al. Risk of major malformations in infants following first-trimester exposure to quetiapine. Am J Psychiatry. 2018;175(12):1225–1231. PubMed CrossRef
Update on Overall Prevalence of Major Birth Defects—Atlanta, Georgia, 1978–2005. CDC. 2008. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5701a2.htm ED: changed tags to eref and added URL; please review/verify. /rhb
Holmes LB, Nasri H, Westgate MN, et al. The Active Malformations Surveillance Program, Boston in 1972–2012: methodology and demographic characteristics. Birth Defects Res. 2018;110(2):148–156. PubMed CrossRef
McBride WG. Thalidomide and Congenital Abnormalities. Lancet. 1961;278(7216):1358. CrossRef
Wyszynski DF, Nambisan M, Surve T, et al; Antiepileptic Drug Pregnancy Registry. Increased rate of major malformations in offspring exposed to valproate during pregnancy. Neurology. 2005;64(6):961–965. PubMed CrossRef
McKenna K, Koren G, Tetelbaum M, et al. Pregnancy outcome of women using atypical antipsychotic drugs: a prospective comparative study. J Clin Psychiatry. 2005;66(4):444–449, quiz 546. PubMed CrossRef
Huybrechts KF, Hernández-Díaz S, Patorno E, et al. Antipsychotic use in pregnancy and the risk for congenital malformations. JAMA Psychiatry. 2016;73(9):938–946. PubMed CrossRef
Habermann F, Fritzsche J, Fuhlbrück F, et al. Atypical antipsychotic drugs and pregnancy outcome: a prospective, cohort study. J Clin Psychopharmacol. 2013;33(4):453–462. PubMed CrossRef
Reis M, Källén B. Maternal use of antipsychotics in early pregnancy and delivery outcome. J Clin Psychopharmacol. 2008;28(3):279–288. PubMed CrossRef
Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002;39(12):1890–1900. PubMed CrossRef
Bar-Oz B, Einarson T, Einarson A, et al. Paroxetine and congenital malformations: meta-analysis and consideration of potential confounding factors. Clin Ther. 2007;29(5):918–926. PubMed CrossRef
Clarren SK, Smith DW. The fetal alcohol syndrome. N Engl J Med. 1978;298(19):1063–1067. PubMed CrossRef
Shiono PH, Klebanoff MA, Berendes HW. Congenital malformations and maternal smoking during pregnancy. Teratology. 1986;34(1):65–71. PubMed CrossRef
Naeye RL. Maternal age, obstetric complications, and the outcome of pregnancy. Obstet Gynecol. 1983;61(2):210–216. PubMed
Werler MM, Shapiro S, Mitchell AA. Periconceptional folic acid exposure and risk of occurrent neural tube defects. JAMA. 1993;269(10):1257–1261. PubMed CrossRef
Werler MM, Louik C, Shapiro S, et al. Prepregnant weight in relation to risk of neural tube defects. JAMA. 1996;275(14):1089–1092. PubMed CrossRef
Toufaily MH, Westgate MN, Lin AE, et al. Causes of congenital malformations. Birth Defects Res. 2018;110(2):87–91. PubMed CrossRef
Harden CL, Meador KJ, Pennell PB, et al; American Academy of Neurology; American Epilepsy Society. Practice parameter update: management issues for women with epilepsy—focus on pregnancy (an evidence-based review): teratogenesis and perinatal outcomes: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology. 2009;73(2):133–141. PubMed CrossRef