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N Engl J Med. 2017 Mar 2;376(9):815-825. doi: 10.1056/NEJMoa1606205.

Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy.

Author information

1
From the University of Texas Southwestern Medical Center, Dallas (B.M.C.), the University of Texas Medical Branch, Galveston (G.S.), and the University of Texas Health Science Center at Houston, McGovern Medical School-Children's Memorial Hermann Hospital, Houston (B.S.) - all in Texas; George Washington University Biostatistics Center, Washington, DC (E.A.T.); Northwestern University, Chicago (A.M.P.); the University of Utah Health Sciences Center, Salt Lake City (M.W.V.); Wayne State University, Detroit (Y.S.); the National Institute of Neurological Disorders and Stroke (D.G.H.) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.M.R.), Bethesda, MD; Columbia University, New York (R.J.W.); the University of North Carolina at Chapel Hill, Chapel Hill (J.M.T.); the University of Alabama at Birmingham, Birmingham (A.T.N.T.); Brown University, Providence, RI (D.J.R.); Ohio State University, Columbus (J.D.I.), and MetroHealth Medical Center-Case Western Reserve University, Cleveland (B.M.M.) - both in Ohio; Oregon Health and Science University, Portland (J.T.); University of Pittsburgh, Pittsburgh (S.N.C.); and the Medical University of South Carolina, Charleston (J.P.V.).

Abstract

BACKGROUND:

Subclinical thyroid disease during pregnancy may be associated with adverse outcomes, including a lower-than-normal IQ in offspring. It is unknown whether levothyroxine treatment of women who are identified as having subclinical hypothyroidism or hypothyroxinemia during pregnancy improves cognitive function in their children.

METHODS:

We screened women with a singleton pregnancy before 20 weeks of gestation for subclinical hypothyroidism, defined as a thyrotropin level of 4.00 mU or more per liter and a normal free thyroxine (T4) level (0.86 to 1.90 ng per deciliter [11 to 24 pmol per liter]), and for hypothyroxinemia, defined as a normal thyrotropin level (0.08 to 3.99 mU per liter) and a low free T4 level (<0.86 ng per deciliter). In separate trials for the two conditions, women were randomly assigned to receive levothyroxine or placebo. Thyroid function was assessed monthly, and the levothyroxine dose was adjusted to attain a normal thyrotropin or free T4 level (depending on the trial), with sham adjustments for placebo. Children underwent annual developmental and behavioral testing for 5 years. The primary outcome was the IQ score at 5 years of age (or at 3 years of age if the 5-year examination was missing) or death at an age of less than 3 years.

RESULTS:

A total of 677 women with subclinical hypothyroidism underwent randomization at a mean of 16.7 weeks of gestation, and 526 with hypothyroxinemia at a mean of 17.8 weeks of gestation. In the subclinical hypothyroidism trial, the median IQ score of the children was 97 (95% confidence interval [CI], 94 to 99) in the levothyroxine group and 94 (95% CI, 92 to 96) in the placebo group (P=0.71). In the hypothyroxinemia trial, the median IQ score was 94 (95% CI, 91 to 95) in the levothyroxine group and 91 (95% CI, 89 to 93) in the placebo group (P=0.30). In each trial, IQ scores were missing for 4% of the children. There were no significant between-group differences in either trial in any other neurocognitive or pregnancy outcomes or in the incidence of adverse events, which was low in both groups.

CONCLUSIONS:

Treatment for subclinical hypothyroidism or hypothyroxinemia beginning between 8 and 20 weeks of gestation did not result in significantly better cognitive outcomes in children through 5 years of age than no treatment for those conditions. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00388297 .).

PMID:
28249134
PMCID:
PMC5605129
DOI:
10.1056/NEJMoa1606205
[Indexed for MEDLINE]
Free PMC Article

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