Treating Hypothyroidism May Improve Some Neonatal Outcomes

Nancy A Melville

October 28, 2015

ORLANDO, Florida — Women treated for subclinical hypothyroidism in pregnancy with levothyroxine (LT4) were less likely to have infants with low birth weight or low Apgar scores compared with untreated peers, according to a large retrospective study.

"Our study represents the largest cohort reporting pregnancy outcomes of women with subclinical hypothyroidism who were treated with LT4 therapy compared with those who were not treated," said first author Spyridoula Maraka, MD, of the Mayo Clinic, in Rochester, Minnesota.

Subclinical hypothyroidism in pregnancy has been linked to an array of adverse pregnancy outcomes, including pregnancy loss, gestational diabetes, and preeclampsia, as well as to numerous neonatal outcomes, including low Apgar score, intrauterine growth restriction, low birth weight, and even neonatal death.

In an effort to determine the effectiveness of LT4 therapy during pregnancy in preventing adverse outcomes, Dr Maraka and her colleagues retrospectively evaluated women treated at the Mayo Clinic between 2011 and 2013 who had subclinical hypothyroidism during pregnancy. Hypothyroidism was defined as having a thyroid-stimulating hormone (TSH) level of greater than 2.5 mIU/L in the first trimester or greater than 3 mIU/L in the second or third trimesters but less than or equal to 10 mIU/L, along with normal levels of free thyroxine (free T4).

The researchers divided the women into two groups, those who had been started on LT4 (n=79) and those who did not receive treatment (n=285).

In following the women until pregnancy loss or the first postpartum visit, the researchers found no statistically significant differences in terms of pregnancy loss between the treatment group (5.1%) and the nontreatment group (8.8%).

Those receiving treatment, however, showed significantly lower rates of infants who had low birth weight (less than 2500 g; 1.3%), compared with the nontreatment group (10%; P = .02); and none of the women in the treatment group had infants with an Apgar score of 7 or lower (0%), compared with 6.9% in the nontreatment group (P = .02).

While preterm delivery (less than 37 weeks) rates were numerically lower in the treatment group, at 5.1% vs 10.5% in the nontreatment group, the difference did not reach statistical significance (P = .14).

No other significant differences were observed between the two groups in terms of other pregnancy or neonatal outcomes, including preeclampsia, NICU admission, and neonatal death.

The findings were presented here at the 2015 International Thyroid Congress and Annual Meeting of the American Thyroid Association (ITC/ATA).

Dr Maraka noted that differences in the size of the treatment vs nontreatment groups reflect the fact that more women go untreated.

"It surprised us that so many women with subclinical hypothyroidism were not treated, despite the guidelines," she said.

Previous studies looking at LT4 therapy in pregnancy have shown inconclusive or no benefits associated with the therapy for hypothyroidism, including a 2012 randomized controlled trial of LT4 therapy that enrolled nearly 800 pregnant women (N Engl J Med. 2012;366:493-501).

The study found that at 3 years of age, offspring of the women showed no difference in IQ between those who were and were not treated.

John Lazarus, MD, an emeritus professor of clinical endocrinology at Cardiff University School of Medicine, in Wales, and first author on that study, noted that one important limitation was that women were possibly started on LT4 too late — at approximately 13 weeks.

He said the current study supports previous findings, with some notable exceptions.

"For one thing, the study excluded women with low free T4, which I think are an important group," he told Medscape Medical News.

"The question of whether to treat subclinical hypothyroidism, in the absence of thyroid antibodies, is controversial," he added.

"Some but not all studies have shown deleterious effects on neurocognitive function. In children from mothers with low free T4 and normal TSH, I think there is better evidence that this is deleterious."

Even with the existing evidence on subclinical hypothyroidism, uncertainties remain on the appropriate management of hypothyroidism in pregnancy, he noted.

"Clinicians should be aware that there is still much controversy, especially with regard to routine screening of thyroid function in early pregnancy."

The authors and Dr Lazarus had no relevant financial relationships.

2015 International Thyroid Congress and Annual Meeting of the American Thyroid Association; Orlando, Florida. Abstract 70, presented October 20, 2015.

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