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Thyroid function in very preterm newborns: possible implications
A G Van Wassenaer1, J H Kok, J M Briët
1Emma Children's Hospital AMC, Department of Neonatology and Experimental Pediatric Endocrinology, Amsterdam, The Netherlands.
Insights
Thyroid hormone (T4) supplementation in very preterm infants showed a trend toward improved outcomes. Further trials are needed to confirm benefits, especially for infants under 27 weeks gestation.
Area of Science:
- Neonatalogy
- Endocrinology
- Neuroscience
Background:
- Thyroid hormones are crucial for infant brain development.
- Very preterm infants often exhibit low thyroxine (T4) and free thyroxine (FT4) levels.
- Transient hypothyroxinemia may contribute to neurodevelopmental disabilities in preterm infants.
Purpose of the Study:
- To investigate the effects of T4 supplementation on neurodevelopmental outcomes in very preterm infants.
- To assess the impact of T4 on hormone levels, mortality, and morbidity in this population.
Main Methods:
- A randomized, double-blind, placebo-controlled trial involving 200 infants under 30 weeks gestation.
- T4 (or placebo) was administered at 8 microg/kg/day for the first 6 weeks of life.
- Hormone levels (T4, FT4, rT3, TSH, T3), mortality, morbidity, heart rate, and neurodevelopmental outcomes at 2 years were assessed.
Main Results:
- T4 supplementation significantly increased T4, FT4, and rT3 levels, while suppressing TSH and decreasing T3.
- Mortality rates were 14% in the T4 group versus 21% in the placebo group (not significant).
- A trend toward improved adverse outcomes (death or abnormal development) was observed; mental outcomes were significantly better in T4-treated infants <27 weeks gestation.
Conclusions:
- Current trial results are not conclusive regarding T4 supplementation benefits in very preterm infants.
- Further research is warranted to determine if T4 supplementation is necessary for infants <27-28 weeks gestation.
- Consideration should be given to including T3 in future treatment protocols.
Abstract:
Thyroid hormones are essential for brain maturation. Very preterm infants, who are at risk of neurodevelopmental disabilities also have low thyroxine (T4) and free thyroxine (FT4) values in the first weeks after birth. This transient hypothyroxinemia may in part be causal to the neurodevelopmental problems. We have carried out a randomized, double-blind, placebo-controlled trial with T4 in 200 infants less than 30 weeks gestation. T4 (or placebo) was given in fixed dose of 8 microg/kg birth weight per day during the first 6 weeks after birth. It resulted in a significant increase of T4, FT4, and reverse triiodothyronine (rT3). Thyrotropin (TSH) secretion was suppressed, and, probably as a result of TSH suppression, triodothyronine (T3) levels were decreased in the T4 group. Mortality was 14% in the T4 group and 21% in the placebo group (NS). No effect was found on morbidity. Heart rate was significantly higher in T4-treated infants less than 28 weeks gestation, but not in T4-treated infants 28 weeks or more, who had the highest FT4 levels. In the study groups as a whole, no clear effect of T4 administration was found on neurodevelopmental outcome. However, there was a strong trend toward improvement of adverse outcome, defined as death or abnormal developmental outcome at 2 years of age. In addition, mental outcome in a subgroup of T4-treated infants less than 27 weeks' gestation was significantly better than in placebo infants of the same age group. In conclusion, this trial does not clearly have conclusive results. New trials of thyroid hormone treatment should be carried out in preterm infants, in order to investigate whether indeed T4 supplementation is required in preterm infants less than 27 or 28 weeks gestation. Addition of T3 to the treatment schedule needs to be considered.