Objective: To investigate the risk of major congenital malformations associated with exposure to second-generation antipsychotics (SGAs) in the first trimester.
Methods: Pregnant women who received consultation on drug exposure from the Japan Drug Information Institute in Pregnancy from October 2005 to December 2016 were asked to complete a questionnaire at 1 month after the expected delivery date. The questionnaire included items on pregnancy outcome, date of delivery, gestational age at delivery, malformations in the infant that were confirmed by the pediatrician’s report, and the following parameters at birth: height, weight, head circumference, and chest circumference. Odds ratios (ORs) for major congenital malformations among live-born children of pregnant women with SGA exposure during the first trimester (SGA group) relative to children of women not exposed to SGAs and medications known to be teratogenic (comparison group) were estimated using an inverse probability of treatment weighting approach.
Results: Of 404 women with SGA exposure during the first trimester, there were 351 live births, 3 stillbirths, 34 spontaneous abortions, and 16 elective abortions. The rate of major congenital malformations among live-born children was 0.9% (3/351) in the SGA group and 1.8% (70/3,899) in the comparison group. No statistically significant differences were observed in the adjusted OR for major congenital malformations (adjusted OR = 0.44; 95% CI, 0.12–1.48; P = .179).
Conclusions: SGA exposure during the first trimester is not associated with an increased risk of major congenital malformations. These findings might be reassuring for pregnant women who require SGAs.
Continue Reading...
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.
Kendig S, Keats JP, Hoffman MC, et al. Consensus bundle on maternal mental health: perinatal depression and anxiety. Obstet Gynecol. 2017;129(3):422–430. PubMedCrossRef
Jones I, Chandra PS, Dazzan P, et al. Bipolar disorder, affective psychosis, and schizophrenia in pregnancy and the post-partum period. Lancet. 2014;384(9956):1789–1799. PubMedCrossRef
Orsolini L, Valchera A, Vecchiotti R, et al. Suicide during perinatal period: epidemiology, risk factors, and clinical correlates. Front Psychiatry. 2016;7:138. PubMedCrossRef
Takeda S, Takeda J, Murakami K, et al. Annual Report of the Perinatology Committee, Japan Society of Obstetrics and Gynecology, 2015: proposal of urgent measures to reduce maternal deaths. J Obstet Gynaecol Res. 2017;43(1):5–7. PubMedCrossRef
Damkier P, Christensen LS, Broe A. Patterns and predictors for prescription of psychotropics and mood-stabilizing antiepileptics during pregnancy in Denmark 2000-2016. Br J Clin Pharmacol. 2018;84(11):2651–2662. PubMedCrossRef
Reutfors J, Cesta CE, Cohen JM, et al. Antipsychotic drug use in pregnancy: a multinational study from ten countries. Schizophr Res. 2020;220:106–115. PubMedCrossRef
Park Y, Huybrechts KF, Cohen JM, et al. Antipsychotic medication use among publicly insured pregnant women in the United States. Psychiatr Serv. 2017;68(11):1112–1119. PubMedCrossRef
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. PubMedCrossRef
Viguera AC, Freeman MP, Góez-Mogollón L, et al. Reproductive safety of second-generation antipsychotics: updated data from the Massachusetts General Hospital National Pregnancy Registry for atypical antipsychotics. J Clin Psychiatry. 2021;82(4):20m13745. PubMedCrossRef
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. PubMedCrossRef
Freeman MP, Viguera AC, Góez-Mogollón L, et al. Reproductive safety of aripiprazole: data from the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics. Arch Women Ment Health. 2021;24(4):659–667. PubMedCrossRef
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. PubMedCrossRef
Ellfolk M, Leinonen MK, Gissler M, et al. Second-generation antipsychotic use during pregnancy and risk of congenital malformations. Eur J Clin Pharmacol. 2021;77(11):1737–1745. PubMedCrossRef
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. PubMedCrossRef
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. PubMedCrossRef
Kulkarni J, Worsley R, Gilbert H, et al. A prospective cohort study of antipsychotic medications in pregnancy: the first 147 pregnancies and 100 one year old babies. PLoS One. 2014;9(5):e94788. PubMedCrossRef
Raffi ER, Nonacs R, Cohen LS. Safety of psychotropic medications during pregnancy. Clin Perinatol. 2019;46(2):215–234. PubMedCrossRef
Murashima A, Yakuwa N, Koinuma S, et al. The advances in dealing with the safety of medicated drugs in pregnancy. Glob Health Med. 2021;3(3):175–179. PubMedCrossRef
Carandang RR, Sakamoto JL, Kunieda MK, et al. Roles of the Maternal and Child Health Handbook and other home-based records on newborn and child health: a systematic review. Int J Environ Res Public Health. 2021;18(14):7463. PubMedCrossRef
Coding and classification. In: EUROCAT Guide1.4: and Reference Documents: Instructions for the Registration and Surveillance of Congenital Anomalies. Ulster, United Kingdom: EUROCAT; 2016.
Almaghlouth I, Pullenayegum E, Gladman DD, et al. Propensity score methods in rare disease: a demonstration using observational data in systemic lupus erythematosus. J Rheumatol. 2021;48(3):321–325. PubMed
Allan V, Ramagopalan SV, Mardekian J, et al. Propensity score matching and inverse probability of treatment weighting to address confounding by indication in comparative effectiveness research of oral anticoagulants. J Comp Eff Res. 2020;9(9):603–614. PubMedCrossRef
Jentink J, Loane MA, Dolk H, et al; EUROCAT Antiepileptic Study Working Group. Valproic acid monotherapy in pregnancy and major congenital malformations. N Engl J Med. 2010;362(23):2185–2193. PubMedCrossRef
Tomson T, Battino D, Bonizzoni E, et al; EURAP study group. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry. Lancet Neurol. 2011;10(7):609–617. PubMedCrossRef
Yamane R, Hayashi M, Tanaka M, et al. Survey regarding pregnant women receiving novel antipsychotic agents. (in Japanese) Jpn J Drug Inform. 2008;11(1):35–38.
International Clearinghouse for Birth Defects Surveillance and Research JAPAN. https://icbdsr-j.jp/2018data.html. Accessed June 18, 2021.
Martínez-Frías ML, Rodríguez-Pinilla E. Problems of using data from Teratology Information Services (TIS) to identify putative teratogens. Teratology. 1999;60(2):54–55. PubMedCrossRef
Ornoy A, Mastroiacovo P. More on data from teratogen information systems (TIS). Teratology. 2000;61(5):327–328. PubMedCrossRef
Yakuwa N, Nakajima K, Koinuma S, et al. Perception of pregnant Japanese women regarding the teratogenic risk of medication exposure during pregnancy and the effect of counseling through the Japan drug information institute in pregnancy. Reprod Toxicol. 2018;79:66–71. PubMedCrossRef