Antithyroid Drug Use During Pregnancy and Risk of Birth Defects in Offspring

Sarfaroj Khan 


April 08, 2021


  • Previously conducted meta-analyses have overestimated the risk of birth defects in offspring associated with antithyroid drug use during pregnancy because of bias.

  • Propylthiouracil (PTU) use during pregnancy is associated with a smaller risk of birth defects vs methimazole/carbimazole (MMI/CMZ) and may be similar in size as that observed with untreated hyperthyroidism.

Why this matters

  • Antithyroid drug use during pregnancy has been associated with an increased risk of birth defects in offspring.

  • However, uncertainty remains on the size of this risk and how it compares to untreated hyperthyroidism because of methodological limitations of previous studies.

Study design

  • 7 cohort studies and 1 case-control study involving 6,212,322 pregnancies and 388,976 birth defects met eligibility criteria after a search on MEDLINE and EMBASE.

  • Funding: None.

Key results

  • Maternal antithyroid drug use during pregnancy was associated with an increased risk of birth defects in offspring compared with unexposed women:

    • PTU (adjusted risk ratio [aRR], 1.16; 95% CI, 1.08-1.25);

    • MMI/CMZ (aRR, 1.28; 95% CI, 1.06-1.54); and

    • exposure to both MMI/CMZ and PTU (aRR, 1.51; 95% CI, 1.16-1.97).

  • The risk of birth defects was significantly higher in unexposed women with hyperthyroidism vs unexposed women without hyperthyroidism (aRR, 1.15; 95% CI, 1.02-1.29).    

  • The risk of any birth defect per 1000 was:

    • 9.6 for unexposed hyperthyroidism;

    • 10.2 for PTU;

    • 17.8 for MMI/CMZ; and

    • 32.5 for both MMI/CMZ and PTU.

  • Corresponding numbers for major birth defects per 1000 live births were 1.2, 1.3, 2.3, and 4.1.


  • Risk of residual confounding.


Morales DR, Fonkwen L, Nordeng HME. Antithyroid drug use during pregnancy and the risk of birth defects in offspring: systematic review and meta-analysis of observational studies with methodological considerations. Br J Clin Pharmacol. 2021 Mar 30 [Epub ahead of print]. doi: 10.1111/bcp.14805. PMID: 33783857.  View full text 

This clinical summary originally appeared on Univadis, part of the Medscape Professional Network.


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