Treating Pregnant Women for Subclinical Thyroid Disease Is Unlikely to Improve Cognition in Their Progeny

March 1, 2017

Treating Pregnant Women for Subclinical Thyroid Disease Is Unlikely to Improve Cognition in Their Progeny

  1. Robert W. Rebar, MD

Maternal levothyroxine administration beginning before 20 weeks' gestation did not raise IQ scores in offspring at age 5 years.

  1. Robert W. Rebar, MD

The possibility that subclinical thyroid disease during pregnancy can impair the offspring's cognitive development has long been postulated (N Engl J Med 1999; 341:549). To explore this issue further, investigators screened >97,000 women with singleton pregnancies before 20 weeks' gestation to identify those with subclinical hypothyroidism (defined by thyrotropin levels ≥4.00 mU/L and normal levels of free thyroxine [T4]) or hypothyroxinemia (normal thyrotropin levels and free T4 levels <0.86 ng/dL). In two parallel trials, 677 women with subclinical hypothyroidism and 526 with hypothyroxinemia were randomized to receive levothyroxine or placebo beginning at a mean 17 or 18 weeks' gestation. Their progeny underwent yearly neurodevelopmental and behavioral testing.

In the subclinical hypothyroidism trial, median IQ score of the children at age 5 years was 97 in the levothyroxine group and 94 in the placebo group (P=0.71). In the hypothyroxinemia trial, median IQ scores were 94 and 91 in the levothyroxine and placebo groups, respectively (P=0.30). Neurodevelopmental and behavioral outcomes did not differ significantly between groups in either trial, and incidence of adverse events during pregnancy was similarly low in all groups.

Comment

Neither the editorialists nor I find these results surprising, given that the fetal thyroid axis becomes functional between 12 and 16 weeks' gestation; moreover, basing the management of subclinical disorders solely on the results of imprecise clinical testing is itself problematic. Treating women with subclinical hypothyroidism early in pregnancy seems reasonable to consider, however, because levothyroxine can reduce the likelihood of pregnancy loss (NEJM JW Womens Health Feb 2017 and BMJ 2017; 356:i6865). As the editorialists properly conclude, we still don't have the answers regarding how best to manage subclinical hypothyroidism and hypothyroxinemia during pregnancy.

Editor Disclosures at Time of Publication

  • Disclosures for Robert W. Rebar, MD at time of publication Grant / Research support Religious, Ethical and Cultural Impacts on the Delivery of Reproductive Healthcare: A Program for InterProfessional Education (RECIPE; Co-Principal Investigator) from the Association of Professors of Gynecology (APGO) Education Foundation Editorial boards Contraception (Deputy Editor); EndoText (Section Editor); Clinical OB/GYN Alert (Associate Editor) Leadership positions in professional societies American Society for Reproductive Medicine (Member Practice Committee)

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