Levothyroxine for Subclinical Hypothyroidism in Pregnancy

Becky McCall

August 09, 2016

Levothyroxine therapy given to pregnant women with subclinical hypothyroidism is associated with a decreased risk of having low-birth-weight babies and of having infants with low Apgar scores.

However, no differences in pregnancy loss or other maternal and neonatal outcomes were found in the new retrospective study, which represents the largest cohort to date reporting pregnancy outcomes of women with subclinical hypothyroidism.

The findings were published in the July issue of Thyroid.

Prevalence figures from the United States suggest that up to 15% of pregnant women have subclinical hypothyroidism. However, evidence on the effects of levothyroxine therapy in this population is mixed. Some observational studies show an association with increased risk of adverse pregnancy outcomes in pregnant women with untreated subclinical hypothyroidism, while other studies show no such association. Of note, a Cochrane review published in 2013 concluded that there were insufficient data to make recommendations for clinical practice with respect to levothyroxine in this population (Cochrane Database Syst Rev. 2013;5:CD007752).

Yet despite this uncertainty and the lack of randomized or interventional trial evidence, the American Thyroid Association (ATA) 2011 guidelines recommended levothyroxine therapy for pregnant women with subclinical hypothyroidism, and in 2012, the US Endocrine Society made a similar recommendation, note the authors of this latest study, led by Spyridoula Maraka, MD, from Mayo Clinic, Rochester, Minnesota.

In order to help address this uncertainty, Dr Maraka and colleagues performed their large single-center study to evaluate the potential benefits of levothyroxine therapy in this population.

Recommendations on Levothyroxine Not Universally Implemented

The study used electronic medical records (EMRs) from 366 pregnant women aged between 18 and 45 years evaluated at the Mayo Clinic. Subclinical hypothyroidism during pregnancy was defined as serum thyroid-stimulating hormone (TSH) of greater than 2.5 mIU/L during the first trimester or greater than 3 mIU/L during the second and third trimesters, but less than 10 mIU/L. Pregnant women were divided into two groups depending on whether they received levothyroxine (n = 82) or not (n = 284).

The outcomes assessed included placental abruption, gestational diabetes, gestational hypertension, preeclampsia, eclampsia, premature rupture of membranes (PROM), preterm delivery, and intrauterine growth restriction (IUGR). Low birth weight and 5-minute Apgar score were also recorded among the infants. Data were evaluated from a time period prior to and after the guideline changes.

The study is the "largest to date reporting on pregnancy outcomes of women with subclinical hypothyroidism who were treated with levothyroxine compared with those who were not," the investigators stress.

This enabled more adverse events to be identified, showing differences between groups in certain outcomes, they write. In addition, the use of EMRs captured detailed clinical data, and complete follow-up of the subjects allowed for a comprehensive outcome assessment.

The authors found an association between levothyroxine therapy and decreased risk of low birth weight (with therapy 1.3% of babies were of low birth weight vs 10% without therapy; P < .001) and of low Apgar score (0% with therapy vs 7% without therapy; P < .001).

However, no statistically significant differences in pregnancy loss (6.1% with therapy vs 8.8% without therapy; P = .12) or other maternal and neonatal outcomes were found.

Despite a twofold increase in the number of pregnant women who received levothyroxine replacement therapy for subclinical hypothyroidism after the release of the updated guidelines (ATA and Endocrine Society), these recommendations have not been universally implemented, the authors note.

"It is believed that this is related in part to the paucity of strong supportive data of such recommendations, as well as the limited penetration guidelines have in various specialty groups," they observe.

Use of Levothyroxine Should Be Discussed With Pregnant Women

Finally, they add that until further evidence becomes available, the results currently support levothyroxine therapy without identifying any evidence of harm. However, they add that the possibility of overtreatment in pregnancy still cannot be excluded.

"Clinicians and pregnant women with subclinical hypothyroidism need to have a frank discussion regarding the potential benefits of levothyroxine therapy while taking into consideration the burden of treatment (ie, daily pills, frequent tests, healthcare visits) and each woman's values and preferences."

They stress, however, that the association found in this study requires confirmation in randomized trials before consideration of widespread use of levothyroxine therapy in pregnant women with subclinical hypothyroidism.

The study authors declare no relevant financial relationships.

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Thyroid 2016;7:980-986. Article


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