Mayo Clinic Proceedings Home
MCP Digital Health Home

Antipsychotic Use in Early Pregnancy and the Risk of Maternal and Neonatal Complications

  • Hsuan-Yu Lin
    School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei City, Taiwan
    Search for articles by this author
  • Fang-Ju Lin
    Department of Obstetrics and Gynecology, Taipei Medical University, Taipei City, Taiwan

    Graduate Institute of Clinical Pharmacy and School of Pharmacy, College of Medicine, National Taiwan University

    Department of Pharmacy, National Taiwan University Hospital
    Search for articles by this author
  • Aaron J. Katz
    Departments of Population Health and Radiation Oncology, University of Kansas School of Medicine, Kansas City, KS, USA

    Department of Radiation Oncology, University of Kansas School of Medicine, Kansas City, KS, USA
    Search for articles by this author
  • I-Te Wang
    Department of Obstetrics and Gynecology, Taipei Medical University, Taipei City, Taiwan

    Department of Obstetrics and Gynecology, Taipei Medical University Hospital
    Search for articles by this author
  • Chung-Hsuen Wu
    Correspondence: Address to Chung-Hsuen Wu, PhD, School of Pharmacy, College of Pharmacy, Taipei Medical University, No 250, Wu-hsing St, Xinyi District, Taipei 11031, Taiwan.
    School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei City, Taiwan
    Search for articles by this author
Published:October 07, 2022DOI:



      To assess the association between antipsychotic use in early pregnancy and the risk of maternal and neonatal metabolic complications.


      We conducted a population-based retrospective cohort study (January 1, 2010, to December 31, 2016) using the Health and Welfare Database in Taiwan. Pregnant women (18 to 49 years of age) were grouped as antipsychotic users (ie, received oral antipsychotic monotherapy during the first 20 weeks of pregnancy) and nonusers. Antipsychotic users were further categorized into first-generation antipsychotic and second-generation antipsychotic users. Propensity score methods, including matching and inverse probability of treatment weighting, were used to balance covariates. Conditional logistic regression and Cox proportional hazards models were used to compare risks of maternal (gestational diabetes mellitus, preterm birth) and neonatal (low birth weight [LBW], macrosomia) outcomes.


      Antipsychotic users had a notably higher risk of preterm birth compared with nonusers (adjusted HR, 1.29; 95% CI, 1.04 to 1.60), but the risk of gestational diabetes mellitus (HR, 1.21; 95% CI, 0.94 to 1.56), LBW (odds ratio [OR], 1.07; 95% CI, 0.84 to 1.37), and macrosomia (OR, 1.36; 95% CI, 0.63 to 2.92) did not differ between the two groups. Among women who received antipsychotics, the odds of LBW were significantly higher in second-generation antipsychotic users compared with first-generation antipsychotic users (adjusted OR, 1.32; 95% CI, 1.04 to 1.68).


      This study found that using antipsychotics in early pregnancy did not result in a greater risk of metabolic complications both for mothers and newborns. For women requiring treatment with antipsychotics during pregnancy, they should be monitored for the risk of preterm birth and low infant birth weight.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Mayo Clinic Proceedings
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • National Collaborating Centre for Mental H. National Institute for Health and Clinical Excellence: Guidance
        Antenatal and Postnatal Mental Health: Clinical Management and Service Guidance.
        Updated Edition. British Psychological Society, Leicester, UK2014
        • Toh S.
        • Li Q.
        • Cheetham T.C.
        • 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 Womens Ment Health. 2013; 16: 149-157
        • Leong C.
        • Raymond C.
        • Chateau D.
        • et al.
        Psychotropic drug use before, during, and after pregnancy: a population-based study in a Canadian cohort (2001–2013).
        Can J Psychiatry. 2017; 62: 543-550
        • Reutfors J.
        • Cesta C.E.
        • Cohen J.M.
        • et al.
        Antipsychotic drug use in pregnancy: a multinational study from ten countries.
        Schizophr Res. 2020; 220: 106-115
      1. Federation ID. IDF DIABETES ATLAS Eighth edition.

        • Mirghani Dirar A.
        • Doupis J.
        Gestational diabetes from A to Z.
        World J Diabetes. 2017; 8: 489-511
        • Buchanan T.A.
        • Xiang A.H.
        • Page K.A.
        Gestational diabetes mellitus: risks and management during and after pregnancy.
        Nat Rev Endocrinol. 2012; 8: 639-649
        • Bianco M.E.
        • Josefson J.L.
        Hyperglycemia during pregnancy and long-term offspring outcomes.
        Curr Diab Rep. 2019; 19: 143
        • Nankervis A.
        • McIntyre H.
        • Moses R.
        • et al.
        ADIPS consensus guidelines for the testing and diagnosis of hyperglycaemia in pregnancy in Australia and New Zealand.
        Australasian Diabetes in Pregnancy Society. 2014; : 1-8
        • Fisher J.E.
        • Smith R.S.
        • Lagrandeur R.
        • Lorenz R.P.
        Gestational diabetes mellitus in women receiving beta-adrenergics and corticosteroids for threatened preterm delivery.
        Obstet Gynecol. 1997; 90: 880-883
        • Deng C.
        Effects of antipsychotic medications on appetite, weight, and insulin resistance.
        Endocrinol Metab Clin North Am. 2013; 42: 545-563
        • Ballon J.S.
        • Pajvani U.
        • Freyberg Z.
        • Leibel R.L.
        • Lieberman J.A.
        Molecular pathophysiology of metabolic effects of antipsychotic medications.
        Trends Endocrinol Metab. 2014; 25: 593-600
        • Reis M.
        • Kallen B.
        Maternal use of antipsychotics in early pregnancy and delivery outcome.
        J Clin Psychopharmacol. 2008; 28: 279-288
        • Boden R.
        • Lundgren M.
        • Brandt L.
        • Reutfors J.
        • Kieler H.
        Antipsychotics during pregnancy: relation to fetal and maternal metabolic effects.
        Arch Gen Psychiatry. 2012; 69: 715-721
        • Vigod S.N.
        • Gomes T.
        • Wilton A.S.
        • Taylor V.H.
        • Ray J.G.
        Antipsychotic drug use in pregnancy: high dimensional, propensity matched, population based cohort study.
        BMJ. 2015; 350: h2298
        • Sadowski A.
        • Todorow M.
        • Yazdani Brojeni P.
        • Koren G.
        • Nulman I.
        Pregnancy outcomes following maternal exposure to second-generation antipsychotics given with other psychotropic drugs: a cohort study.
        BMJ Open. 2013; 3e003062
        • Park Y.
        • Hernandez-Diaz S.
        • Bateman B.T.
        • et al.
        Continuation of atypical antipsychotic medication during early pregnancy and the risk of gestational diabetes.
        Am J Psychiatry. 2018; 175: 564-574
        • 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 (quiz 546): 444-449
        • Panchaud A.
        • Hernandez-Diaz S.
        • Freeman M.P.
        • et al.
        Use of atypical antipsychotics in pregnancy and maternal gestational diabetes.
        J Psychiatr Res. 2017; 95: 84-90
        • Petersen I.
        • McCrea R.L.
        • Sammon C.J.
        • et al.
        Risks and benefits of psychotropic medication in pregnancy: cohort studies based on UK electronic primary care health records.
        Health Technol Assess. 2016; 20: 1-176
        • Lee K.W.
        • Ching S.M.
        • Ramachandran V.
        • et al.
        Prevalence and risk factors of gestational diabetes mellitus in Asia: a systematic review and meta-analysis.
        BMC Pregnancy Childbirth. 2018; 18: 494
        • Health and Welfare Data Science Center Asia
        Database User Manual.
        (Accessed August 1, 2020)
        • National Health Insurance Administration, Ministry of Health and Welfare, Executive Yuan
        National Health Insurance Annual Statistical Report.
        2019 (Accessed November 9, 2020.
        • Correll C.U.
        • Citrome L.
        • Haddad P.M.
        • et al.
        The Use of Long-Acting Injectable Antipsychotics in Schizophrenia: Evaluating the Evidence.
        J Clin Psychiatry. 2016; 77: 1-24
        • Correll C.U.
        • Gallego J.A.
        Antipsychotic polypharmacy: a comprehensive evaluation of relevant correlates of a long-standing clinical practice.
        Psychiatr Clin North Am. 2012; 35: 661-681
        • ACOG Practice Bulletin no
        189 summary: nausea and vomiting of pregnancy.
        Obstet Gynecol. 2018; 131: 190-193
        • Andrade S.E.
        • Moore Simas T.A.
        • Boudreau D.
        • et al.
        Validation of algorithms to ascertain clinical conditions and medical procedures used during pregnancy.
        Pharmacoepidemiol Drug Saf. 2011; 20: 1168-1176
        • Austin P.C.
        Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies.
        Pharm Stat. 2011; 10: 150-161
        • Austin P.C.
        The performance of different propensity score methods for estimating marginal hazard ratios.
        Stat Med. 2013; 32: 2837-2849
        • Austin P.C.
        Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples.
        Stat Med. 2009; 28: 3083-3107
        • Austin P.C.
        Comparing paired vs non-paired statistical methods of analyses when making inferences about absolute risk reductions in propensity-score matched samples.
        Stat Med. 2011; 30: 1292-1301
        • Schneeweiss S.
        Sensitivity analysis and external adjustment for unmeasured confounders in epidemiologic database studies of therapeutics.
        Pharmacoepidemiol Drug Saf. 2006; 15: 291-303
        • Lin H.C.
        • Chen I.J.
        • Chen Y.H.
        • Lee H.C.
        • Wu F.J.
        Maternal schizophrenia and pregnancy outcome: does the use of antipsychotics make a difference?.
        Schizophr Res. 2010; 116: 55-60
        • Zhang C.
        • Tobias D.K.
        • Chavarro J.E.
        • et al.
        Adherence to healthy lifestyle and risk of gestational diabetes mellitus: prospective cohort study.
        BMJ. 2014; 349: g5450