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Updated: May 1, 2026

Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale
Published on: August 25, 2014
Thyroid hormone supplementation in preterm infants born before 28 weeks gestational age and neurodevelopmental
Aleid van Wassenaer-Leemhuis1, Susana Ares, Sergio Golombek
11 Emma Children's Hospital-Academic Medical Center , Amsterdam, Netherlands .
Insights
Thyroid hormone (thyroxine, T4) supplementation in extremely preterm infants did not improve neurodevelopmental outcomes by age three. Further research is needed to confirm these findings in larger populations.
Area of Science:
- Neonatalogy
- Developmental Pediatrics
- Endocrinology
Background:
- Thyroid hormones are crucial for normal brain development.
- Infants born before 28 weeks gestation have low neonatal thyroid hormone levels.
- The impact of thyroid hormone treatment on neurodevelopment in these infants is unknown.
Purpose of the Study:
- To assess the neurodevelopmental outcomes at three years corrected age in infants born at less than 28 weeks gestation who received thyroid hormone treatment.
- To evaluate the effect of different doses and administration methods of thyroxine (T4) on neurodevelopment.
Main Methods:
- A phase 1 trial involving infants born at less than 28 weeks gestational age.
- Eight study arms included T4 treatment (various doses/modes), iodine only, and placebo.
- Neurodevelopmental assessments included mental, motor, neurological development, cerebral palsy (CP) rates, and adverse outcomes at three years corrected age.
Main Results:
- Of 166 randomized infants, 32 (19%) died neonatally.
- Follow-up data were available for 89 of 134 survivors (66%).
- No significant differences in mental/motor development or cerebral palsy rates were observed between treatment groups or compared to placebo.
Conclusions:
- Thyroid hormone treatment in this cohort did not demonstrate improved neurodevelopmental outcomes at three years.
- The study was underpowered to detect smaller differences in neurodevelopment.
- Further investigation with larger sample sizes is warranted.
Background:
Thyroid hormones are required for normal brain maturation, and neonatal plasma thyroid hormone concentrations are low in infants less than 28 weeks gestation. It is not known whether treatment of such infants with thyroid hormone improves neurodevelopmental outcome.
Methods:
At three years corrected age, mental, motor, and neurological development was assessed in infants born at less than 28 weeks gestational age who had participated in a phase 1 trial of differing doses and modes of administration of thyroid hormone. The trial's endpoints were thyroid hormone (thyroxine, T4) and thyotropin plasma concentrations in eight study arms: six treated with T4 [4, 8, and 16 μg/(kg · day)], bolus or continuous], one treated with iodine only, and one treated with placebo. Follow-up at three years was not part of the original study goals. Developmental index scores, rates of cerebral palsy (CP), and rates of adverse outcome (death or moderate to severe delay in development and/or disabling CP) were compared between the eight study groups and between groups combined by dosage level, and between infants with and without T4 supplementation.
Results:
Of 166 randomized infants, 32 (19%) died in the neonatal period. Of the 134 survivors, follow-up results were available for 89 children (66%). Mental and motor development and rates of cerebral palsy did not differ in any of the comparisons made.
Conclusion:
In this study, no differences in neurodevelopment were found in relation to thyroid hormone treatment, but power was insufficient to detect any but very large differences.
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