BACKGROUND
Graves’ disease is a common cause of hyperthyroidism. It is an autoimmune disease in which the person makes antibodies (TSI or TRAb) that attack the thyroid gland, turning it on and causing an overactive thyroid. It is generally recommended that women with Graves’ disease have normal thyroid function prior to becoming pregnant and be monitored closely during and after pregnancy. If they have active Graves’ disease and hyperthyroidism during pregnancy, they are often treated with antithyroid medications such as methimazole or PTU to normalize their thyroid hormone levels. Women with active Graves’ disease who become pregnant can pass both the antibodies and the antithyroid medications to the baby during pregnancy.

In general, the baby’s thyroid hormone levels are often lower than those in the mother levels, so mothers are treated with the lowest dose of antithyroid drug to keep the free T4 level in the upper normal or just above the normal range for pregnancy. Overtreatment with antithyroid medications in the mother can lead to hypothyroidism in the baby. This is called neonatal hypothyroidism, as it resolves after the antithyroid medications get out of the baby’s system after birth. The aim of this study was to determine how common neonatal hypothyroidism is in babies born to mothers with Graves’ disease treated with antithyroid medications during pregnancy.

THE FULL ARTICLE TITLE
Yoshihara A et al 2023 Incidence of and risk factors for neonatal hypothyroidism among women with Graves’ disease treated with antithyroid drugs until delivery. Thyroid. Epub 2023 Feb 21. PMID: 36680759

SUMMARY OF THE STUDY
This study is a study examining the pregnancy outcomes of women with Graves’ diseases followed at a single hospital in Japan. They measured thyroid hormone (free T4) and TRAb levels and recorded antithyroid drug doses every 4-8 weeks during pregnancy and at the time of delivery.

They assessed umbilical cord thyroid hormone levels at delivery to categorize neonatal thyroid status. They determined the incidence and predictors of neonatal hypothyroidism. A total of 305 mothers with Graves’ disease that had been treated throughout pregnancy with antithyroid drugs and their babies were included in the study (63 treated with methimazole and 242 treated with PTU).

There were no significant differences in rates of neonatal hypothyroidism, defined as a low FreeT4 and high TSH in the umbilical cord blood sample, in babies born to mothers treated with methimazole (19%) compared to PTU (12.8%). Mothers of hypothyroid babies were more likely to have had higher thyroid hormone and TRAb levels than mothers of babies without hypothyroidism at birth, suggesting they had more active Graves’ disease. Neonatal hypothyroidism is more commonly seen in babies born to women on higher doses of antithyroid drugs. Specifically, doses greater than 10 mg per day for methimazole and 150 mg per day for PTU were predictors of neonatal hypothyroidism. The authors recommended that mothers with active Graves’ disease on antithyroid medications be followed closely during pregnancy with careful monitoring to optimize fetal health.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
Managing Graves’ disease in women during pregnancy is complex and requires close monitoring of the mother and baby before and after delivery to reduce the risk of either hyper or hypothyroidism. Neonatal hypothyroidism was more common in babies born to mothers on higher antithyroid medication doses with more active Graves disease. Mothers and their babies should be closely monitored during pregnancy and after delivery to ensure normal thyroid function in both.

— Whitney Woodmansee, MD

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