Do Antithyroid Drugs Increase the Risk of Congenital Anomalies?

Pavankumar Kamat

Disclosures

December 14, 2021

Takeaway

  • Antithyroid drug (ATD) therapy during pregnancy was associated with a small increase in the risk of congenital anomalies.

  • The magnitude of risk was slightly higher for carbimazole or methimazole (CMZ/MMI) than for propylthiouracil (PTU) and switching ATDs post-conception did not reduce the risk of congenital anomalies.

Why this matters

  • Findings warrant future studies to determine the risk associated with mild thyroid dysfunction and the optimal thyroid function threshold at which ATDs can be safely withdrawn during pregnancy.

Study design

  • UK reaserchers performed a meta-analysis of 16 cohort studies comprising 5957, 15,785 and 15,666 exposures to CMZ/MMI, PTU and untreated hyperthyroidism, respectively.

  • Funding: None disclosed.

Key results

  • The risk of congenital anomalies was higher in children of women exposed to CMZ/MMI (adjusted risk ratio [aRR], 1.28; 95% CI, 1.06-1.54; P=.01) and PTU (aRR, 1.16; 95% CI, 1.08-1.25; P<.0001) compared with children of women not exposed to ATDs.

  • Children of women who were exposed to CMZ/MMI had an increased risk of congenital anomalies compared with children of women exposed to PTU (aRR, 1.20; 95% CI, 1.01-1.43).

  • The risk of congenital anomalies was higher in children of women exposed to both CMZ/MMI and PTU (aRR, 1.51; 95% CI, 1.14-1.99; P=.004).

  • Switching from MMI to PTU was not associated with a lower risk of congenital anomalies compared with continuing with MMI alone (OR, 1.06; 95% CI, 0.79-1.42).

  • Switching from PTU to MMI was associated with an increased risk compared with continued treatment with PTU (OR, 1.79; 95% CI, 1.08-2.97).

  • The excess number of anomalies per 1000 live births was 17.2 for children of women exposed to CMZ/MMI, 9.8 for those exposed to PTU and 31.4 for those exposed to both CMZ/MMI and PTU.

Limitations

  • Study did not evaluate the severity and subtypes of birth defects.

Agrawal M, Lewis S, Premawardhana L, Dayan CM, Taylor PN, Okosieme OE. Antithyroid drug therapy in pregnancy and risk of congenital anomalies: Systematic review and meta-analysis. Clin Endocrinol (Oxf). 2021 Nov 29 [Epub ahead of print]. doi: 10.1111/cen.14646. PMID: 34845757 View abstract.

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