Antithyroid drugs in early pregnancy up risk of birth defects

Use of antithyroid drug (ATD) therapy in early pregnancy appears to increase the risk of birth defects, suggesting that abnormal maternal thyroid function is not a major risk factor for birth defects, a recent study has shown.

The investigators sought to assess the risk of birth defects associated with the use of ATD in an extended nationwide cohort and the role of abnormal maternal thyroid function in birth cohorts including stored maternal blood samples from early pregnancy.

The study population involved Danish pregnant women and their live-born children, including 1,243,353 children from a Nationwide Register-Based Cohort (NRBC; 1997–2016), 8,830 children from the Danish National Birth Cohort (DNBC; 1997–2003), and 14,483 children from the North Denmark Region Pregnancy Cohort (NDRPC; 2011–2015). Primary outcome was birth defects diagnosed before 2 years of age.

A total of 2,718 (0.2 percent) children in the NRBC had been exposed to ATD in early pregnancy. Birth defects had an overall frequency of 6.7 percent (95 percent confidence interval [CI], 6.7–6.8 percent) in nonexposed children. This rose following exposure to methimazole/carbimazole (9.6 percent; 95 percent CI, 8.2–11.2 percent) and propylthiouracil (8.3 percent, 95 percent CI, 6.7–10.3 percent).

Conversely, the frequency of maternal thyroid dysfunction in early pregnancy was similar in the random cohort and in cases of birth defect in the DNBC (12.4 percent vs 12.6 percent; p=0.8) and the NDRPC (15.1 percent vs 15.4 percent; p=0.8).

“ATD therapy in early pregnancy is associated with birth defects, but more data are needed to substantiate the risk associated with different types of ATD,” the investigators noted.