A Randomized Trial of Thyroxine Therapy for Subclinical Hypothroidism or Hypothroxinemia Diagnosed During Pregnancy

The purpose of this study was to determine whether levothyroxine treatment of women who are identified as having subclinical hypothyroidism or hypothyroxinemia during pregnancy improves cognitive function in their children. Women with a singleton pregnancy before 20 weeks’ gestation were screened for subclinical hypothyroidism, defined as a thyrotropin level of 4.0 mU/L or more and normal free T4 (0.86-1.9 ng/dL), and for hypothyroxinemia, defined by normal thyrotropin level (0.08–3.99 mU/L) but low free T4 (<0.86dL). In separate trials for the two conditions, women were randomly assigned to levothyroxine or placebo. Thyroid function was assessed monthly and levothyroxine dose adjusted to attain a normal thyrotropin or free T4, respectively, with sham adjustments for placebo. Children underwent annual developmental and behavioral testing for five years. The primary outcome was death or IQ score at age 5 (3 if the 5-year examination was missing).