Pregnancy with Graves’ Disease – risk of birth defects for mothers taking anti-thyroid drugs

On the never-ending thread about long-term use of methimazole (MMI), several people have asked about the risks of anti-thyroid drugs during pregnancy.  Because MMI is thought to cause more birth defects than propylthiouracil (PTU) in the first trimester, women are often encouraged to switch to PTU when they become pregnant or plan to become pregnant.  But, is this necessary?

A recent (2011) paper by Yoshihara et al. attempts to provide more information about this topic by reviewing the cases of over 5,000 women who gave birth after taking PTU or MMI and to see whether one group had more birth defects than the other.

High thyroid levels from untreated Graves’ Disease during pregnancy can be extremely harmful to the baby and the mother.  They raise the risk of delivering a baby that is too small, too early, or has birth defects, and the risks to the mother of thyrotoxicosis and thyroid storm are serious as well.  Therefore, getting thyroid levels normal is very important part of ensuring a healthy pregnancy.

Women who plan to become pregnant often choose surgery or radioactive iodine treatments to kill the thyroid gland.  However, these treatments carry their own risks and costs, and many women may choose or need to stay with the less invasive anti-thyroid drugs, typically methimazole/carbimazole (MMI) or propylthiouracil (PTU) instead.

This study tested whether MMI, PTU, or no treatment produced the most birth defects.

5,069 women with Graves’ Disease were interviewed after giving birth.  Of these mothers, during the first trimester:

  • 1,426 took MMI
  • 1,578 took PTU
  • 2,065 took no anti-thyroid medications (control group)

Overall, 2.5% of the babies had a birth defect.  The babies from the MMI group had a rate of 4.1%, the PTU group was 1.9%, and the control group was 2.1%.  This means that MMI in the first trimester very likely increases the risk of birth defects and confirms recommendations that women who are pregnant should switch to PTU.

The amount (dosage) of MMI or PTU that the mothers took had no effect on the rate of birth defects.  Also, the thyroid status of the women did not affect the rate of birth defects in the PTU or control groups.  But, being hyperthyroid and on MMI increased the rate of birth defects to 4.5% (from 4.1%).  However, women who took MMI but had normal thyroid levels had a slightly lower rate: 3.8%.  Interestingly, women who were hypOthyroid (thyroid hormone was too low) was much higher than in any of the other groups – 9.3%, although there were so few hypothyroid patients that this may not be a meaningful number.

The birth defects that occurred were the following (with links to wikipedia):

With one exception in an infant who had several defects and did not survive, the mothers reported that surgery was able to cure all of these defects.

This study’s findings support the idea that women who are or may soon become pregnant and will use antithyroid drugs during pregnancy should take PTU rather than MMI.

The authors conclude,

“In summary, exposure to MMI during the first trimester of pregnancy increased the risk of congenital anomalies, including the risk of the rare anomalies aplasia cutis con- genita, omphalocele, and a symptomatic omphalomesen- teric duct anomaly. It seems preferable to treat Graves’ disease with PTU because it appears to be safer to use in the fertile period; however, the reported risk of hepatotoxicity in both the mother and the child is a concern. “

Download File (PDF)

Yoshihara A, Noh J, Yamaguchi T, Ohye H, Sato S, Sekiya K, Kosuga Y, Suzuki M, Matsumoto M, Kunii Y, Watanabe N, Mukasa K, Ito K, & Ito K (2012). Treatment of graves’ disease with antithyroid drugs in the first trimester of pregnancy and the prevalence of congenital malformation. The Journal of clinical endocrinology and metabolism, 97 (7), 2396-403 PMID: 22547422

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