Antithyroid drug use during pregnancy and the risk of birth defects in offspring: systematic review and meta-analysis of observational studies with methodological considerations

Daniel R. Morales*, Lionel Fonkwen, Hedvig M.E. Nordeng

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Aims: Maternal antithyroid drug (ATD) use during pregnancy has been associated with an increased risk of birth defects in offspring. Uncertainty remains on the size of this risk and how it compares to untreated hyperthyroidism due to methodological limitations of previous studies. Methods: Systematic review of MEDLINE and EMBASE identifying observational studies examining ATD use during pregnancy and risk of birth defects by 28 August 2020. Data were extracted on study characteristics, effect estimates and comparator groups. Adjusted effect estimates were pooled using a random-effects generic inverse variance method and absolute risk calculated. Results: Seven cohort studies and 1 case–control study involving 6 212 322 pregnancies and 388 976 birth defects were identified reporting regression effect estimates. Compared to an unexposed population comparison, the association between ATD use during pregnancy and birth defects in offspring was: adjusted risk ratio (aRR) 1.16 95% confidence interval (CI) 1.08–1.25 for propylthiouracil (PTU); aRR 1.28 95%CI 1.06–1.54 for methimazole/carbimazole (MMI/CMZ); aRR 1.51, 95%CI 1.16–1.97 for both MMI/CMZ and PTU; and aRR 1.15 95%CI 1.02–1.29 for untreated hyperthyroidism. The excess risk of any and major birth defects per 1000, respectively, was: 10.2 and 1.3 for PTU; 17.8 and 2.3 for MMI/CMZ; 32.5 and 4.1 for both MMI/CMZ and PTU; and 9.6 and 1.2 for untreated hyperthyroidism. Conclusions: When appropriately analysed the risk of birth defects associated with ATD use in pregnancy is attenuated. Although still elevated, the risk of birth defects is smallest with PTU compared to MMI/CMZ and may be similar to that of untreated hyperthyroidism.

Original languageEnglish
JournalBritish Journal of Clinical Pharmacology
ISSN0306-5251
DOIs
Publication statusE-pub ahead of print - 30. Mar 2021

Bibliographical note

Publisher Copyright:
© 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Keywords

  • carbimazole
  • congenital abnormalities
  • hyperthyroidism
  • pregnancy
  • propylthiouracil

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