Effects of early thyroxine treatment on development and growth at age 10.7 years: follow-up of a randomized placebo-controlled trial in children with Down's syndrome.

Context: In 2-year-old children with Down's syndrome (DS), early T4 treatment was found to result in slightly better motor development and growth.

Objectives: This study sought to determine long-term effects of early T4 treatment on development and growth in children with DS with either an elevated or normal neonatal TSH concentration.

Design: Patients received a single follow-up visit 8.7 years after a randomized placebo-controlled trial (RCT) comparing T4 and placebo treatment during the first 2 years of life.

Setting: Dutch Academic Hospital.

Participants: All children who completed the RCT (N = 181, of 196 randomly assigned children) were invited for the follow-up study. A total of 123 participants enrolled, at a mean age of 10.7 years.

Interventions: T4 or placebo treatment from the neonatal period until 2 years.

Main Outcome Measures: Primary: mental and motor development. Secondary: communication skills, fine-motor coordination, height, weight, and head circumference (HC). Outcomes were compared between T4- and placebo-treated children, and between treatment groups with either a normal (<5 mIU/L), or elevated (≥ 5 mIU/L) TSH concentration at original trial entry.

Results: Mental or motor development, communication skills, or fine-motor coordination did not differ between T4- (N = 64) and placebo-treated children (N = 59). T4-treated children had a larger HC (50.4 vs 49.8 cm, P = .04) and tended to be taller (133.2 vs 131.1 cm, P = .06). These differences were somewhat greater in children with TSH ≥ 5 mIU/L (HC: T4, 50.5 vs placebo, 49.7 cm; P = .01; height: T4, 133.8 vs placebo, 130.8 cm; P = .02), but were not found in children with TSH <5 mIU/L (HC: T4, 50.1 vs placebo, 50.0 cm; P = .75; height: T4, 132.1 vs placebo, 131.6 cm; P = .22).

Conclusions: Early T4 treatment of children with DS does not seem to benefit mental or motor development later in life. However, the positive effect on growth is still measurable, especially in children with an elevated plasma TSH concentration in the neonatal period.