Antithyroid drug therapy in pregnant women poses modest risk of congenital anomalies

Exposure to thionamide antithyroid drugs (ATDs) during pregnancy contributes to a small increase in the risk of congenital anomalies, according to the results of a systematic review and meta-analysis.

Researchers searched multiple online databases for studies that examined the effect of ATD (eg, methimazole [MMI], its prodrug derivative, carbimazole [CMZ], and propylthiouracil [PTU]) use during pregnancy. The outcome was the risk of offspring congenital anomalies, such as aplasia cutis, choanal atresia, trachea-oesophageal fistula, and dysmorphic facial features.

Studies were included if they conducted comparisons between any two of the following groups: 1) a group exposed to either CMZ/MMI, PTU, or both drugs (exposure group); (2) a control group of women without hyperthyroidism or ATD exposure in pregnancy (control group); and (3) women with hyperthyroidism who did not receive ATD treatment in pregnancy (untreated disease group).

A total of 16 cohort studies were included in the meta-analysis. These studies involved 5,957 women exposed to CMZ/MMI during pregnancy, 15,785 of those who used PTU during pregnancy, and 15,666 pregnant women with untreated hyperthyroidism.

Pooled data revealed that relative to no-disease controls, the CMZ/MMI group did have a higher risk of giving birth to neonates with congenital anomalies (adjusted risk ratio [RR] 1.28, 95 percent confidence interval [CI], 1.06–1.54), as did the PTU group (RR, 1.16, 95 percent CI, 1.08–1.25). The risk increase was greater with CMZ/MMI relative to PTU (RR, 1.20, 95 percent CI, 1.01–1.43).

The risk of offspring congenital anomalies was also elevated among women who switched ATDs during pregnancy (RR, 1.51, 95 percent CI, 1.14–1.99). However, the timing of ATD switch was highly variable and included prepregnancy switches in some studies.

The excess number of anomalies per 1,000 live births was 17.2 for women with CMZ/MMI exposure, 9.8 for those with PTU exposure, and 31.4 for those with both CMZ/MMI and PTU exposures.

In subgroup analyses, there were more positive associations seen in studies with >500 exposures and up to 1-year follow-up.