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Effect of thyroxine on brain microstructure in extremely premature babies: magnetic resonance imaging findings in the
Sze May Ng1, Mark A Turner, Carrol Gamble
1Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Crown Street, L8 7SS, Liverpool, UK, may.ng@nhs.net.
Insights
Low thyroid hormone levels in preterm infants are linked to poorer brain microstructure development. Further research is needed to explore levothyroxine (LT4) supplementation benefits for these vulnerable infants.
Area of Science:
- Neonatal Neurology
- Neuroimaging
- Endocrinology
Background:
- Thyroid hormone status is crucial for brain development.
- Very preterm infants (born before 28 weeks' gestation) are at risk for thyroid dysfunction.
- The Thyroxine supplementation In Preterm InfanTs (TIPIT) study investigated levothyroxine (LT4) supplementation in this population.
Purpose of the Study:
- To assess the relationship between thyroid hormone levels and brain magnetic resonance imaging (MRI) findings in very preterm infants.
- To evaluate the impact of LT4 supplementation on white matter development.
Main Methods:
- Brain MRI with diffusion tensor imaging (DTI) was performed on 45 TIPIT participants at term-equivalence.
- DTI metrics including apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were analyzed.
- Comparisons were made between infants with the lowest and highest plasma free thyroxine (FT4) concentrations.
Main Results:
- No significant differences in DTI metrics were observed between LT4-supplemented and placebo groups.
- In placebo recipients, lowest FT4 levels correlated with higher ADC in the posterior corpus callosum and reduced streamline metrics in the right internal capsule.
- In LT4 recipients, highest FT4 levels were associated with lower ADC in the left occipital lobe and enhanced FA and streamline metrics in the anterior corpus callosum.
Conclusions:
- Low plasma FT4 concentrations post-birth are associated with markers of poorly organized brain microstructure in very immature infants.
- Plasma FT4 levels appear to influence brain development in this vulnerable population.
- The potential benefits of LT4 supplementation for preterm infants with low FT4 warrant further investigation.
Background:
In order to assess relationships between thyroid hormone status and findings on brain MRI, a subset of babies was recruited to a multi-centre randomised, placebo-controlled trial of levothyroxine (LT4) supplementation for babies born before 28 weeks' gestation (known as the TIPIT study, for Thyroxine supplementation In Preterm InfanTs). These infants were imaged at term-equivalence.
Materials And Methods:
Forty-five TIPIT participants had brain MRI using diffusion tensor imaging (DTI) to estimate white matter development by apparent diffusion coefficient (ADC), fractional anisotropy (FA) and tractography metrics of number and length of streamlines. We made comparisons between babies with the lowest and highest plasma FT4 concentrations during the initial 4 weeks after birth.
Results:
There were no differences in DTI metrics between babies who had received LT4 supplementation and those who had received a placebo. Among recipients of a placebo, babies in the lowest quartile of plasma-free thyroxine (FT4) concentrations had significantly higher apparent diffusion coefficient measurements in the posterior corpus callosum and streamlines that were shorter and less numerous in the right internal capsule. Among LT4-supplemented babies, those who had plasma FT4 concentrations in the highest quartile had significantly lower apparent diffusion coefficient values in the left occipital lobe, higher fractional anisotropy in the anterior corpus callosum and longer and more numerous streamlines in the anterior corpus callosum.
Conclusion:
DTI variables were not associated with allocation of placebo or thyroid supplementation. Markers of poorly organised brain microstructure were associated with low plasma FT4 concentrations after birth. The findings suggest that plasma FT4 concentrations affect brain development in very immature infants and that the effect of LT4 supplementation for immature babies with low FT4 plasma concentrations warrants further study.
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