Free thyroxine levels during the first weeks of life and neurodevelopmental outcome until the age of 5 years in very preterm infants

BACKGROUND: We have conducted a randomized trial with thyroxine (T4) in 200 infants <30 weeks' gestation. T4 treatment was associated with better 5-year outcome in infants <29 weeks' gestation, but with worse outcome in infants of 29 weeks. These effects could be related to low, respectively high free thyroxine (FT4) levels

METHODS: For each infant, the average FT4 of 5 scheduled measurements was calculated between day 3 and day 28. Infants of the placebo and the T4 group separately were divided in 2 groups. The placebo group consisted of a group of infants with average FT4 in the lowest quartile and a group in the upper 75%. The T4 group consisted of a group of infants with average FT4 in the upper quartile and a group in the lower 75%. Developmental outcome (mental/cognitive, motor, and neurologic) at 2 and 5.7 years was compared between high and low FT4 groups, and then compared separately for the T4 and placebo group.

RESULTS: In the placebo group, low FT4 was associated with worse outcome on all domains at both time points. After correction for confounding variables, mental and neurologic outcome remained significantly different at 2 years, and motor outcome at 5 years. In the T4 group, high FT4 was not associated with worse outcome, neither at 2 nor at 5 years.

CONCLUSIONS: In untreated infants, low FT4 values during the first 4 weeks after birth in infants born at <30 weeks' gestation are associated with worse neurodevelopmental outcome at 2 and 5 years. In T4-treated infants, high FT4 is not associated with worse outcome. Other factors than high FT4 concentrations must play a role in the worse outcome of the T4-treated group of 29 weeks' gestational age.