Antithyroid Drug Use in Pregnancy and Birth Defects: Why Some Studies Find Clear Associations, and Some Studies Report None.

  title={Antithyroid Drug Use in Pregnancy and Birth Defects: Why Some Studies Find Clear Associations, and Some Studies Report None.},
  author={Peter Laurberg and Stine Linding Andersen},
  journal={Thyroid : official journal of the American Thyroid Association},
  volume={25 11},
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 published studies did not find associations between the use… 

Figures from this paper

Birth defects after use of antithyroid drugs in early pregnancy: a Swedish nationwide study.

MMI and PTU were associated with subtypes of birth defects previously reported, but the frequency of ATD exposure in early pregnancy was low and severe malformations described in the MMI embryopathy were rarely observed.

Antithyroid drugs and birth defects

Current evidence corroborates a risk of birth defects associated with MMI while more evidence is needed to determine the teratogenic potential of PTU, and detailed assessment of type and timing of exposure in large cohorts are needed.

Effects of methimazole and propylthiouracil exposure during pregnancy on the risk of neonatal congenital malformations: A meta-analysis

For pregnant women with hyperthyroidism, exposure to MMI/CMZ significantly increased the incidence of neonatal congenital malformations compared to exposure to PTU and no antithyroid drug exposure; however, no differences were observed between PTU exposure and no anticancer drug exposure.

Maternal thyroid function, use of antithyroid drugs in early pregnancy and birth defects.

Results corroborate an increased risk of birth defects associated with the use of ATD in early pregnancy, and suggest that abnormal maternal thyroid function is not a major risk factor for birth defects.

Risk of embryopathies with use of antithyroidal medications

  • S. L. Andersen
  • Medicine
    Current opinion in endocrinology, diabetes, and obesity
  • 2017
Current guidelines highlight the need for clinical attention on the use of ATDs in early pregnancy, but if the risk of relapse or worsening of hyperthyroidism is considered low, it is suggested that ATD treatment can be withdrawn followed by frequent monitoring of thyroid function.

Treatment of Graves’ hyperthyroidism with thionamides: a position paper on indications and safety in pregnancy

Data available on the effect ofhyperthyroidism per se on the risk of fetal malformations, although scanty, are sufficient to recommend treatment with ATD of the hyperthyroid pregnant woman, and recommendations derived form the available data and published guidelines of International Scientific Societies are edited.

Hyperthyroidism in Pregnancy: The Delicate Balance between Too Much or Too Little Antithyroid Drug

In hyperthyroid women with long-term ATD treatment before conception, drugs could be withdrawn in T1 in 40% of them, the thyroid function control was better, and pregnancy and fetal complications were rarer, compared to women diagnosed during pregnancy.

Thyroid Medication Use and Birth Defects in the National Birth Defects Prevention Study.

BACKGROUND Thyroid disorders are common among reproductive-aged women, with hypothyroidism affecting 2 to 3% of pregnancies, and hyperthyroidism affecting an additional 0.1 to 1%. We examined

Graves’ disease: developments in first-line antithyroid drugs in the young

This review will focus on some of the key articles published in the field of thionamide ATD in children and highlight key issues that need to be discussed with families as well as addressing the approach and controversies in the treatment of GD.

Pregnancy and the incidence , diagnosing and therapy of Graves ’ disease

How pregnancy changes the risk of developing Graves’ disease (GD), how early pregnancy by several mechanisms leads to considerable changes in the results of the thyroid function tests used to diagnose hyperthyroidism, and how these changes may complicate the diagnosing of GD are described.



Birth defects after early pregnancy use of antithyroid drugs: a Danish nationwide study.

Both MMI/CMZ and PTU were associated with birth defects, but the spectrum of malformations differed, and new ATD with fewer side effects should be developed.

Therapy of endocrine disease: antithyroid drug use in early pregnancy and birth defects: time windows of relative safety and high risk?

The cases reported suggest that the risk of birth defects could be minimized if pregnant women terminate ATD intake before gestational week 6, which is the major period of organogenesis.

Treatment of graves' disease with antithyroid drugs in the first trimester of pregnancy and the prevalence of congenital malformation.

In utero exposure to MMI during the first trimester of pregnancy increased the rate of congenital malformations, and it significantly increased the rates of aplasia cutis congenita, omphalocele, and a symptomatic omphalomesenteric duct anomaly.

Severity of birth defects after propylthiouracil exposure in early pregnancy.

Details on possible PTU-associated birth defects tend to be less severe than the defects observed after MMI/CMZ exposure, and yet, the majority of affected children had to undergo surgery.

[Pregnancy outcomes of exposure to methimazole (POEM) study].

  • N. Arata
  • Medicine, Biology
    Nihon rinsho. Japanese journal of clinical medicine
  • 2012
To elucidate whether incidence of malformation related to 'methimazole (MMI) embryopathy' is increasing associated with exposure to MMI in the first 12 gestational weeks, Graves' women(MMI

Gestational thyrotoxicosis, antithyroid drug use and neonatal outcomes within an integrated healthcare delivery system.

Findings from a large, population-based cohort provide generalizable estimates of maternal and infant risks associated with maternal thyrotoxicosis and related pharmacotherapy in women with delivered pregnancies from 1996 to 2010.

Pregnancy outcome in women treated with methimazole or propylthiouracil during pregnancy

While a clear demonstration of a teratogenic effect of MMI is currently lacking, it seems reasonable to follow the current guidelines and advice for PTU treatment in hyperthyroid women during the first trimester of pregnancy.

Prevalence of thyrotoxicosis, antithyroid medication use, and complications among pregnant women in the United States.

There was some indication of an elevated risk of liver disease and congenital anomalies in women with TTX, but the risk did not appear to be related to the ATD use.

Antithyroid drugs and congenital heart defects: ventricular septal defect is part of the methimazole/carbimazole embryopathy.

A possible link between antithyroid drug (ATD) therapy and cardiac malformations is unclear and needs to be ascertained in larger databases, and the association between the use of ATD in pregnancy and birth defects has been considered.

Carbimazole embryopathy: An emerging phenotype

The phenotype associated with exposure to carbimazole appears to be rare but specific with distinctive facial features, and two new cases of carbimzole embryopathy with strikingly similar facial features are reported.