The effect of thyroxine treatment started in the neonatal period on development and growth of two-year-old down syndrome children: A randomized clinical trial

A. S.Paul Van Trotsenburg*, Thomas Vulsma, Susanne L. Rutgers Van Rozenburg-Marres, Anneloes L. Van Baar, Jeannette C.D. Ridder, Hugo S.A. Heymans, Jan G.P. Tijssen, Jan J.M. De Vijlder

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Context: Young Down syndrome children appear to have a mild form of congenital hypothyroidism that is rarely detected by neonatal screening and usually left untreated. Objective: To investigate the effects of thyroxine treatment on development and growth of young Down syndrome children. Design, Setting, and Participants: Single-center, randomized, double-blind, 24-month trial (enrollment June 1999 to August 2001) with nationwide recruitment, comparing thyroxine administration with placebo in 196 Down syndrome neonates. Intervention: Neonates were randomly assigned to treatment for 2 yr with either thyroxine (n = 99; initial dose 8 μg/kg) or placebo (n = 97). Daily thyroxine doses were adjusted at regular intervals to maintain plasma TSH in its normal and free T4 concentrations in its high-normal range. Placebo dose adjustments mirrored those of thyroxine. Main Outcome Measures: The primary outcome was mental and motor development at age 24 months, assessed with the Bayley Scales of Infant Development II. Results: At age 24 months, the developmental testing results of 90 thyroxine-, and 91 placebo-treated children were available for analysis. The thyroxine-treated children had a 0.7-month smaller delay in motor developmental age (95% confidence interval, -1.4 to 0), corresponding to a difference of seven motor developmental index points. The mental developmental age delay was also 0.7 month smaller in the thyroxine group (95% confidence interval, -1.5 to 0.2), but lacked statistical significance. Thyroxine-treated children had greater gains in length (1.1 cm; 95% confidence interval, 0.2 to 2.0) and weight (378 g; 95% confidence interval 55 to 701). Conclusions: The data of our study provide evidence to support the hypothesis that thyroxine treatment may improve development and growth of young Down syndrome children. Thyroxine treatment should be considered in Down syndrome neonates to maximize their early development and growth.

Original languageEnglish
Pages (from-to)3304-3311
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Issue number6
Publication statusPublished - 1 Jun 2005

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