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Subclinical hypothyroidism in pregnancy, is it a real risk?

In the ‘largest analysis to date’, researchers have determined that subclinical hypothyroidism is associated with preterm birth but have stopped short of recommending screening.

It is well-known that overt thyroid disease in pregnancy is linked with preterm birth, as defined as delivery before 37 weeks. But whether milder forms of thyroid disease make a difference has been controversial.

Consequently, research published in JAMA looked at 19 prospective cohort studies that had investigated this issue. Over 47,000 pregnant women were included. What the reviewers found was that three types of mild thyroid abnormality were linked with prematurity. These were isolated elevated TSH (which increased the risk of 29% compared with euthyroid women), isolated decreased thyroxine levels (which increased the risk by 46%),  and women who were euthyroid but had thyroid antibodies (TPO positive) who were 33% more likely to have a preterm birth.

The authors of this meta-analysis were quite definitive.

“These findings provide evidence that subclinical hypothyroidism, isolated hypothyroxinemia, and thyroid peroxidase antibody positivity in pregnant women are risk factors for preterm birth,” they said.

But, as an accompanying editorial points out, the real question is whether this finding is going to change clinical practice. And to answer this, there are two major factors to consider.

Firstly do any of these scenarios pose a risk to mother or child or both? This review fails to show any link of these thyroid abnormalities with a risk to the mother but there is an inherent risk to the infant associated with preterm.

The second, very important issue is whether we can ameliorate this risk by treating the mother with levothyroxine during pregnancy.

And this is where it gets complicated. According to both the authors of the meta-analysis and the editorial author, there is no evidence anywhere that treating these pregnant women with levothyroxine makes any difference to the risk of prematurity.

“Several recent large, well-done clinical trials that assessed the effect of routine pregnancy screening for and thyroid hormone treatment of subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity have failed to show benefit,” the US endocrinologist who authored the editorial wrote.

Consequently, what needs to be considered is the possibility that there might be factors at play that result in these thyroid abnormalities, and these same factors might be responsible for the risk of preterm birth, rather than the thyroid hormones being the causative factor.

“It seems plausible that these thyroid testing abnormalities may reflect other nonthyroidal processes rather than thyroid dysfunction” the editorial concluded.

Bottom line? While the meta-analysis is of interest, in itself it doesn’t justify routinely ordering free T4 or TPO antibody measurement in women with a normal TSH. At least not until further randomised trials are done.

Reference

The Consortium on Thyroid and Pregnancy—Study Group on Preterm Birth. Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis. JAMA. 2019 Aug 20; 322(7): 632–41. DOI:10.1001/jama.2019.10931