Levothyroxine During Pregnancy May Improve Fetal Outcomes

Marcia Frellick

November 21, 2016

Giving levothyroxine to more pregnant women with mild hypothyroidism could prevent more stillbirths, low-birth-weight babies, and early cesarean sections, results from a new study indicate.

The findings were presented November 9 by Peter Taylor, MBChB, from the departments of diabetology and epidemiology at University of Cardiff in Wales, at the UK Society for Endocrinology Annual Conference in Brighton.

"If you screen for [thyroid-hormone deficiency] during pregnancy and treat those who are borderline, you do get substantial benefit," Dr Taylor told Medscape Medical News.

Levothyroxine in Subclinical Hypothyroidism in Pregnancy

Thyroid hormones are critical for fetal brain development, but fetuses can't make their own until the second trimester so they depend on maternal supplies.

Suboptimal thyroid function in pregnancy is associated with adverse obstetric outcomes, but it is unclear whether levothyroxine treatment, initiated during pregnancy, is beneficial, say Dr Taylor and colleagues.

And the issue of screening for subclinical hypothyroidism in pregnancy is the subject of debate due to conflicting data on the benefits.

New American Thyroid Association guidelines addressing the issue are expected to be published in coming months.

In this new analysis, Dr Taylor and colleagues retrospectively examined a cohort from the Controlled Antenatal Thyroid Screening (CATS) study and linked that data with routinely collected obstetric outcomes in the Secure Anonymised Information Linkage (SAIL) databank.

The cohort included 13,224 women who were 12 to 16 weeks pregnant. Of those, 340 had subclinical hypothyroidism (SCH) and 305 had isolated hypothyroxinemia (IH).

Of the women with abnormal thyroid function, 518 were randomized to either receive levothyroxine at the end of the first trimester (n = 263) or to receive no treatment (n = 255).

The researchers looked primarily at a composite of stillbirths and neonatal deaths; preterm delivery (less than 34 weeks); length of hospital stay (more than 5 days); and APGAR score at 5 minutes (less than 7).

As secondary events, they looked at whether babies were born at less than 37 weeks or whether mothers had a cesarean section before 37 weeks.

For the primary composite outcome, there was no significant difference between the women with abnormal thyroid function who got levothyroxine and those who didn't — there were 22 total events in the treated group compared with 29 in the untreated group (odds ratio 0.75).

But for individual outcomes, there were some notable differences.

Untreated women with SCH had more than a fourfold increased risk of stillbirth (odds ratio [OR], 4.37) compared with women with normal thyroid function. And no stillbirths occurred in women taking levothyroxine.

Untreated women with IH also had higher odds (1.58) of delivering before 37 weeks' gestation than women with normal thyroid function.

And women with IH randomized to receive treatment with levothyroxine had reduced odds of early gestational age at delivery (OR, 0.37) compared with those who got no treatment, and none had early cesarean sections compared with 4% of untreated women (P = .04).

Dr Taylor said his team plans to submit the results for publication in a peer-reviewed journal early next year.

And although they say that larger studies are required to confirm the benefits of screening and treatment in pregnancy, he believes these results have "really opened up the thought that there should be universal thyroid screening in pregnancy because [hypothyroidism] is so common, and you can treat it with a straight-forward, safe, and cheap drug."

Some countries are already taking the lead in universal screening, he noted.

"China has just announced it is doing universal thyroid screening and Spain is starting it as well. They've both broken ranks," he said.

Is Levothyroxine Overprescribed? Not in Pregnancy...

At the same time, there has been discussion in the literature recently about potential overuse of levothyroxine.

In a comment published in the Lancet Diabetes and Endocrinology, reported last week in Medscape Medical News, two clinicians concerned about overuse of levothyroxine to treat subclinical hypothyroidism said the drug should be considered only after at least two thyroid-stimulating-hormone (TSH) tests show an abnormal result.

The authors note that prescriptions for levothyroxine have sharply increased in the United Kingdom and United States in recent years and say they are driven by guidelines recommending the treatment of subclinical increases in TSH levels even in the absence of symptoms.

Dr Taylor, whose work is referenced in the comment, said he agrees the drug is often overprescribed.

"I'm a big fan of this drug, and I think we're overusing it in the normal population, but we're underusing it in the pregnant population. Pregnancy increases your thyroid stress and you need about 150% more thyroid hormone," he said.

Dr Taylor reports no relevant financial relationships.

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Society for Endocrinology Annual Conference. Brighton, United Kingdom. November 7–9, 2016. Abstract OC6.3

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