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Antipsychotic use in pregnancy and congenital malformations

Abstract

Overview of: Wang Z, Brauer R, Man KKC, et al. Prenatal exposure to antipsychotic agents and the risk of congenital malformations in children: a systematic review and meta-analysis. Br J Clin Pharmacol 2021;87:4101–23.

  • Drug-Related Side Effects and Adverse Reactions
  • Health Care Quality, Access, and Evaluation

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Key points

  • Prescribing for women who are pregnant requires careful assessment of the potential impact of medication during pregnancy.

  • A systematic review has evaluated the association between antipsychotic use in pregnancy and risk of congenital malformation.

  • Limited evidence showed no statistically significant association between use of antipsychotic agents during pregnancy and overall congenital malformations in children.

A systematic review and meta-analysis found no strong evidence of an association between antipsychotic exposure during pregnancy and congenital malformations in children.1

Overview

A systematic review and meta-analysis assessed the association between use of antipsychotic medication during pregnancy and risk of congenital malformations.1 The authors included 13 studies (2 612 385 pregnancy episodes), of which 8 were prospective cohort studies, 4 were retrospective cohort studies and 1 was a case–control study. Four studies evaluated any antipsychotic, three studies focused only on first-generation antipsychotics and six studies assessed second-generation antipsychotics. Six studies reported the daily dose, but only one study looked at dose–response. Six studies that were deemed to be of good quality were included in a meta-analysis.

The meta-analysis (6 studies, 2 515 032 pregnancy episodes, 13 805 exposed infants) found no statistically significant association between the risk of congenital malformations and prenatal exposure to any antipsychotic (adjusted risk ratio [aRR] 1.23, 95% CI 0.96 to 1.58; p=0.173).1 There was also no link between prenatal exposure to second-generation antipsychotics and congenital malformations (aRR 1.35, 95% CI 0.73 to 2.47; p=0.056). In four studies that limited exposure to first or second trimester, the aRR was 1.05 (95% CI 0.96 to 1.15). One study found no evidence of a dose–response association for individual antipsychotics except for risperidone, for which a dose of >2mg/day was associated with an increased risk of cardiac malformation (risk ratio 2.08, 95% CI 1.32 to 3.28), although this may have been a chance finding.2

Context

A previous systematic review (13 studies, 6057 antipsychotic-exposed infants) included a meta-analysis (7 studies, 3346 antipsychotic-exposed infants) that concluded there was an increased risk of major congenital malformations with antipsychotic exposure (OR 2.12, 95% CI 1.25 to 3.57), but the results were based on crude data with no adjustment for confounders.1 3 New research has been published since and has been included in this latest review and meta-analysis to provide an updated estimate of risk.1 However, there are still limitations to the analysis, including no detail on individual malformations and concomitant medicines. In addition, it was not possible to evaluate risk of first-generation antipsychotics because of the small number of studies. Moreover, the analysis included studies that used registry and database data, which cannot confirm actual antipsychotic exposure.

Prescribers and pregnant women must carefully consider the potential risks of antipsychotic treatment in pregnancy. A recent Drug and Therapeutics Bulletin review outlined principles for safe prescribing in pregnant women with a mental health diagnosis.4 These include optimising and stabilising medication and the mental health condition prior to conception, prescribing the lowest effective dose and using monotherapy, if possible, and advising women not to stop their medication without discussing it with an experienced practitioner. Collaborative working across specialities with the woman and her family at the centre of decision-making is key to optimising outcomes for the mother and child. Information on the risks associated with individual antipsychotic drugs is available from the UK Teratology Information Service.5

References

Footnotes

  • Contributors DTB Team.

  • Provenance and peer review Commissioned; internally peer reviewed.