Conference Coverage

ITC: Levothyroxine may improve obstetric outcomes in women with low thyroid function


AT ITC 2015


LAKE BUENA VISTA, FLA. – Normalizing maternal thyroid function early in pregnancy may improve obstetric outcomes for women with subclinical hypothyroidism.

A high level of thyroid-stimulating hormone (TSH) was associated with increased stillbirth in women who didn’t receive prenatal levothyroxine, Peter N. Taylor, Ph.D., reported at the International Thyroid Congress.

Dr. Peter N. Taylor

Dr. Peter N. Taylor

And women who were untreated for low free thyroxine (T4) were significantly more likely to need an early cesarean section than treated women, suggesting that levothyroxine could be reducing conditions leading to maternal-fetal distress.

“The good thing is that many physicians are already treating with levothyroxine anyway,” said Dr. Taylor of Cardiff (Wales) University. “There are no obvious adverse obstetric events associated with it. It seems relatively benign, and the accepted dose of 150 mcg per day seems adequate.”

He reported data from a subgroup analysis of the large Controlled Antenatal Thyroid Screening Study (N Eng J Med. 2012;366:493-501). That trial enrolled more than 21,000 mother-child pairs, and examined the effect of maternal levothyroxine treatment on the child’s IQ at 3 years. Among the children of women with hypothyroidism, the mean IQ scores were 99.2 and 100 in the treated and control groups – not significantly different. The proportions of children with an IQ of less than 85 were 12% in the treated group and 14% in the control group, also not significantly different.

Dr. Taylor’s cohort involved about 14,000 mother-child pairs from this study, all of whom were from Wales. Using national health care databases as well as study data, he was able to examine obstetric outcomes in women with low thyroid function (664) who received or did not receive levothyroxine early between 11 and 16 weeks’ gestation.

About half of the hypothyroid women (351) had TSH levels above 3.5 mU/L. The remainder had free T4 levels below 10.9 pmol/L. Each of these groups was randomized to levothyroxine treatment or placebo. The rest of the cohort had normal thyroid status.

The study’s primary endpoint was the rate of stillbirth. Secondary endpoints were cesarean section rate (both overall and early); gestational age at birth; and macrosomia.

Among the euthyroid group, the rate of stillbirth was 0.34%, similar to the national background rate. There were no stillbirths among women with high TSH who were treated. Three (1.68%) occurred in the untreated group. The TSH levels in those women before treatment were 3.63 mU/L, 3.66 mU/L, and 4.58 mU/L – not dramatically high, Dr. Taylor noted. “But they could have risen later in pregnancy as stress on the thyroid increased.”

After adjusting for maternal age, weight, parity, birth year, and smoking, stillbirths were five times more likely among the untreated women than the treated women. However, Dr. Taylor cautioned, “This is a very small number of events. But it is quite seductive to think that stillbirths could be prevented by levothyroxine.”

There were no significant associations of high TSH with macrosomia or gestational age.

Untreated low free T4 was not associated with stillbirth. However, Dr. Taylor said, it was very strongly associated with early C-section.

The overall C-section rate was similar between untreated and treated women (28%). But 5.6% of the untreated women had an early C-section, compared with none of the treated women. This hints strongly at a protective effect of levothyroxine, Dr. Taylor said. Early C-sections – between 26 and 32 weeks – are medically driven rather than driven by patient choice. This finding of fewer early interventions among treated women suggests that levothyroxine is exerting some protective effect, especially given the finding that infants of untreated mothers actually tended to be about 133 g lighter at birth.

“We would speculate this is probably due to a decrease in preeclampsia and gestational hypertension, which are more common among women with hypothyroidism.”

Infants of untreated mothers also were born slightly earlier – about half a week, he said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.

Dr. Taylor had no financial disclosures.

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