Congenital anomalies in children exposed to antithyroid drugs in-utero: a meta-analysis of cohort studies

PLoS One. 2015 May 14;10(5):e0126610. doi: 10.1371/journal.pone.0126610. eCollection 2015.

Abstract

Background: Hyperthyroidism affects about 0.2%-2.7% of all pregnancies, and is commonly managed with antithyroid drugs (ATDs). However, previous studies about the effects of ATDs on congenital anomalies are controversial. Therefore, the present meta-analysis was performed to explore the risk of congenital anomalies in children exposed to ATDs in-utero.

Methods: Embase, Pubmed, Web of Knowledge, and BIOSIS Citation Index were searched to find out studies about congenital anomalies in children exposed to ATDs in-utero reported up to May 2014. The references cited by the retrieved articles were also searched. The relative risks (RRs) and confidence intervals (CIs) for the individual studies were pooled by fixed effects models, and heterogeneity was analyzed by chi-square and I2 tests.

Results: Eight studies met the inclusion criteria. Exposure to propylthiouracil (PTU), methimazole/carbimazole (MMI/CMZ), and PTU & MMI/CMZ was investigated in 7, 7 and 2 studies, respectively. The pooled RR was 1.20 (95%CI: 1.02-1.42), 1.64 (95%CI: 1.39-1.92), and 1.83 (95%CI: 1.30-2.56) for congenital anomalies after exposure to PTU, MMI/CMZ, and PTU & MMI/CMZ, respectively.

Conclusions: The meta-analysis suggests that exposure to ATDs in-utero increases the risk of congenital anomalies. The use of ATDs in pregnancy should be limited when possible. Further research is needed to delineate the exact teratogenic risk for particular congenital anomaly.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Drug-Induced / etiology*
  • Antithyroid Agents / adverse effects*
  • Antithyroid Agents / therapeutic use
  • Carbimazole / adverse effects
  • Carbimazole / therapeutic use
  • Cohort Studies
  • Databases, Factual
  • Female
  • Humans
  • Hyperthyroidism / drug therapy
  • Infant, Newborn
  • Methimazole / adverse effects
  • Methimazole / therapeutic use
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Propylthiouracil / adverse effects
  • Propylthiouracil / therapeutic use
  • Risk

Substances

  • Antithyroid Agents
  • Methimazole
  • Propylthiouracil
  • Carbimazole

Grants and funding

This study was supported by the funding of National Natural Science Foundation of China (NO.81172680). JYL received the funding [http://www.nsfc.gov.cn/]. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.