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Thyroid hormone use reduces pregnancy loss risk in women with subclinical hypothyroidism

Stephen Padilla
27 Jan 2017

The use of thyroid hormone may lower the risk of pregnancy loss among women with subclinical hypothyroidism, particularly those with pretreatment thyroid stimulating hormone (TSH) concentrations of 4.1 to 10 mIU/L, a retrospective cohort study reveals.

“We found that use of thyroid hormone was associated with decreased risk of pregnancy loss, but it was also associated with increased risk of preterm delivery, gestational diabetes and pre-eclampsia,” researchers said.

A total of 5,405 pregnant women with subclinical hypothyroidism, defined as untreated thyroid stimulating hormone (TSH) concentration 2.5 to 10 mIU/L, were included in the study. Of these, 843 participants with a mean pretreatment TSH concentration of 4.8 mIU/L were treated with thyroid hormone and 4,562 with a mean baseline TSH concentration of 3.3 mIU/L were not treated (p<0.01).

Treated women (n=89; 10.6 percent) had significantly less pregnancy loss compared with untreated women (n=614; 13.5 percent; p<0.01). [BMJ 2017;doi:10.1136/bmj.i6865]

Treated women also had lower adjusted odds of pregnancy loss (odds ratio [OR], 0.62; 95 percent CI, 0.48 to 0.82) but higher odds of preterm delivery (OR, 1.60; 1.14 to 2.24), gestational diabetes (OR, 1.37; 1.05 to 1.79) and pre-eclampsia (OR, 1.61; 1.10 to 2.37) than untreated women. Other pregnancy-related adverse outcomes between the two groups were similar.

Furthermore, treated women had lower adjusted odds of pregnancy loss than untreated women if their pretreatment TSH concentration was 4.1 to 10 mIU/L (OR, 0.45; 0.30 to 0.65) but not if it was 2.5 to 4.0 mIU/L (OR, 0.91; 0.65 to 1.23; p<0.01).

“Thyroid hormone treatment had no apparent effect on other important adverse outcomes,” researchers said. “Moreover, the benefit of thyroid hormone use on pregnancy loss was observed only among women with pre-treatment TSH concentrations of 4.1 to 10.0 mIU/L … raising questions about the current guideline recommended threshold of 2.5 mIU/L for treating subclinical hypothyroidism when population reference ranges are unavailable.”

Based on these findings, it is reasonable to continue to offer thyroid hormone treatment in pregnant women with TSH concentrations of 4.1 to 10 mIU/L to reduce their risk of pregnancy loss, according to researchers.

They added, however, that such treatment may need to be withheld and revised in women with TSH concentrations of 2.5 to 4.0 mIU/L due to the smaller magnitude of effect in the said group and in light of the possible increased risk of other adverse events.

“In fact, in the 2016 draft Guidelines for Subclinical Hypothyroidism in Pregnancy presented at the 2016 Endocrine Society meeting, levothyroxine treatment is recommended for women positive for thyroid peroxidase antibody if TSH is above 4.0 mIU/L (strong recommendation; moderate quality evidence) and may be considered if TSH is above 2.5 mIU/L (weak recommendation; low quality evidence) or for thyroid peroxidase antibody negative women (weak recommendation; low quality evidence),” they said.

The study was limited by its retrospective observational design and use of administrative claims data, particularly the potential for misclassification of treatment and confounders, lack of clinical detail and selection biases related to health plan enrolment, diagnostic testing and treatment choice.

According to researchers, the elevated risk of other pregnancy-related adverse outcomes calls for randomized trials assessing the safety of thyroid hormones treatment in pregnant women with subclinical hypothyroidism.

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