Takeaway
- 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.
Limitations
- Risk of residual confounding.
This clinical summary originally appeared on Univadis, part of the Medscape Professional Network.
