In pregnant women, exposure to antithyroid drug therapy exhibits a small risk of congenital anomalies that is greater for carbimazole/methimazole when compared to propylthiouracil. Switching antithyroid drugs in pregnancy does not seem to minimize this risk.

A systematic review and meta-analysis were carried out to investigate the congenital anomaly risk in females exposed to carbimazole or methimazole, propylthiouracil, or untreated hyperthyroidism in pregnancy.

Using a combination of keywords, databases such as Embase, Medline, and Cochrane databases were explored to find out the relevant articles on women treated with antithyroid drug therapy in pregnancy. Pooling of separate crude and adjusted risk estimates was done utilizing random-effects models and subgroup assessment for addressing heterogeneity.

In total, 16 cohort studies were found that comprised of 5957, 15,785, and 15,666 exposures to carbimazole/methimazole, propylthiouracil, and untreated hyperthyroidism, respectively. The adjusted risk ratio (RR) and 95% confidence intervals for congenital anomalies was elevated for propylthiouracil (RR, 1.16) and carbimazole/methimazole (RR, 1.28) in comparison with the nondisease controls.

The magnitude of risk was more for carbimazole/methimazole when compared to propylthiouracil exposure (RR, 1.20). The highest level of risk was witnessed for exposure to both carbimazole/methimazole and propylthiouracil, that is, females who switched antithyroid drugs in pregnancy (RR, 1.51). But, the timing of the antithyroid drug switch was extremely variable and incorporated prepregnancy switches in a few studies.

Notably, the excess number of anomalies per 1000 live births for people exposed to carbimazole/methimazole, propylthiouracil, and both carbimazole/methimazole and propylthiouracil is shown in Table 1:

The risk in the untreated group did not differ from the control or antithyroid drug groups. In terms of thyroid status, the untreated group was found to be extremely heterogeneous. The subgroup assessment demonstrated a greater number of positive links in studies with >500 exposures and up to one-year follow-up.

In comparison with the general pregnant population, females exposed to carbimazole/methimazole, propylthiouracil, and both carbimazole/methimazole and propylthiouracil showed an elevated risk of congenital anomalies. However, additional research is warranted.