Anti-thyroid drug use in pregnancy and birth defects: Why some studies find clear associations, and some studies report none

BACKGROUND: Rare cases of birth defects after the use of methimazole (MMI) or carbimazole to treat hyperthyroidism in early pregnancy have been reported since 1972, whereas propylthiouracil (PTU) has not been considered teratogenic. Recently two studies reported birth defects after the use of MMI in early pregnancy to affect 2-4 % of exposed children, and one study also found birth defects after the use of PTU. On the other hand, some studies finding no associations have been published.

SUMMARY: We review in detail the methods used in the two positive and the four negative reports. The two positive studies included a sufficient number of children exposed to MMI (n=1,231 and 1,097) to evaluate the outcomes studied, whereas the four negative studies icluded a much lower number of exposed children (n= 73, 108, 30 and 124). Considering PTU, the birth defects observed in one study were in general milder and tended to be diagnosed and registered only when they gave complica-tions and led to surgery after the age of one year. None of the negative studies had investigated outcomes after the age of one year.

CONCLUSION: Studies finding no associations between early pregnancy exposure to antithyroid drugs and birth defects were either not sufficiently powered or did not study outcomes at optimal ages.