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High serum thyroid hormone concentrations in pregnant women are associated with increased fetal loss and low birth weight

(November 2004)

The background of the study. The extent to which maternal hyperthyroidism affects pregnancy is uncertain. This study evaluated the effects of the high serum thyroxine (T4) and triiodothyronine (T3) concentrations in women and men with the syndrome of resistance to thyroid hormone on the course of pregnancy and on the development and thyroid function of their offspring.

How the study was done. The study subjects were 167 members of a large family with resistance to thyroid hormone caused by a mutation in the T3 nuclear receptor. Among them, 44 carried the mutation, and 123 did not. The subjects were identified by biochemical findings, and the diagnosis was confirmed by mutation analysis. The subjects with the mutation had high serum free T4 index and free T3 index values and normal serum thyrotropin (TSH) concentrations; the respective values were normal in all the other subjects.

The results of the study. There were 18 couples in which one subject carried the mutation and 18 couples of unaffected first-degree relatives. The frequency of miscarriage was considerably higher (24 percent) in the couples in which the woman carried the mutation, as compared with the couples in which the man carried the mutation (7 percent), the couples of unaffected first-degree relatives (9 percent), and couples of unrelated subjects (8 percent).

The affected mothers delivered 20 affected infants and 11 unaffected infants, and the spouses of the affected men delivered 15 affected infants and 12 unaffected infants. The birth weight of the unaffected infants of affected mothers was significantly lower than that of the affected infants of affected mothers. Newborn screening blood-spot thyrotropin (TSH) values were undetectable in 3 unaffected infants of affected mothers, but similar (approximately 5 mU/L) in 8 affected infants of affected mothers, 13 affected or unaffected infants of affected fathers, and 19 infants of the unaffected first-degree relatives.

The conclusions of the study. The miscarriage rate is high among women with high serum thyroid hormone concentrations caused by generalized thyroid hormone resistance. Their affected infants have normal birth weight and normal serum TSH values, but their unaffected infants have low birth weight and low serum TSH values.

The original article. Anselmo J, Cao D, Karrison T, Weiss RE, Refetoff S. Fetal loss associated with excess thyroid hormone exposure. JAMA 2004;292:691-5.

Thyroid Research Archive
Pregnancy