1. In pregnant women, treating subclinical hypothyroidism or hypothyroxinemia with levothyroxine did not significantly impact cognitive outcomes in children up to age 5 years of age when compared to placebo.
2. No significant adverse maternal or fetal/neonatal events were described as a result of treatment.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Adverse outcomes, such as lower intelligence quotient (IQ), have been associated with subclinical hypothyroidism during pregnancy. Treatment of subclinical hypothyroidism in pregnant women with levothyroxine remains an area of controversy. The primary objective of this study was to assess the effects of screening for hypothyroidism and levothyroxine replacement during pregnancy on cognitive outcomes of children at 5 years of age for women with either subclinical hypothyroidism or hypothyroxinemia. Women who completed the adherence run-in phase were randomized to receive placebo or levothyroxine. In summary, the study demonstrated no significant difference between the levothyroxine and placebo groups with regards to the childrens’ median IQ.
Relevant Reading: AOGS Practice Bulletin No. 148: Thyroid Disease in Pregnancy
In-Depth [randomized controlled trial]: This was a parallel, multicenter, randomized, placebo-controlled trial that included women diagnosed with subclinical hypothyroidism and hypothyroxinemia through screening tests. Subclinical hypothyroidism was defined as having a thyrotropin level >4.00 mU/liter and a normal free thyroxine (T4) level (0.86 to 1.90 ng/dL). Hypothyroxinemia was defined as having a normal thyrotropin level (0.08 to 3.99 mU/L) and a low free T4 level (<0.86 ng/dL).
A total of 677 women with subclinical hypothyroidism and 526 women with hypothyroxinemia were randomized to either placebo or levothyroxine treatment. The primary outcome was a child’s full-scale IQ assessed using multiple standardized scoring systems, such as the Wechsler Preschool and Primary Scale of Intelligence III (WPPSI-III) at 5 years of age. Alternatively, the Differential Ability Scales–II (DAS) at 3 years of age was also considered, if the WPPSI-III score was not available. Secondary outcomes included the cognitive, motor, and language scores on the Bayley Scales of Infant Development, Third Edition (Bayley-III), at 12 months and 24 months of corrected age for each child.
The median IQ score of the children in the subclinical hypothyroid group was 97 (95%CI 94 to 99) in the levothyroxine group and 94 (95%CI 92 to 96) in the placebo group (p = 0.71). 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 for the hypothyroxinemia group (p = 0.30). There were no significant differences between the groups in terms of adverse maternal or fetal/neonatal outcomes, including pre-term birth, placental abruption, gestational hypertension, stillbirth/miscarriage rates, and neonatal death.
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