Effect of thyroxine on brain microstructure in extremely premature babies: magnetic resonance imaging findings in the TIPIT study

TY - JOUR

T1 - Effect of thyroxine on brain microstructure in extremely premature babies

T2 - magnetic resonance imaging findings in the TIPIT study

AU - Ng, Sze May

AU - Turner, Mark A

AU - Gamble, Carrol

AU - Didi, Mohammed

AU - Victor, Suresh

AU - Atkinson, Jessica

AU - Sluming, Vanessa

AU - Parkes, Laura M

AU - Tietze, Anna

AU - Abernethy, Laurence J

AU - Weindling, Alan Michael

PY - 2014/8

Y1 - 2014/8

N2 - 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.

AB - 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.

KW - Anisotropy

KW - Brain

KW - Brain Mapping

KW - Dietary Supplements

KW - Diffusion Tensor Imaging

KW - Double-Blind Method

KW - Female

KW - Humans

KW - Infant, Extremely Premature

KW - Infant, Newborn

KW - Magnetic Resonance Imaging

KW - Male

KW - Thyroxine

U2 - 10.1007/s00247-014-2911-6

DO - 10.1007/s00247-014-2911-6

M3 - Article

C2 - 24671720

SN - 0301-0449

VL - 44

SP - 987

EP - 996

JO - Pediatric Radiology

JF - Pediatric Radiology

IS - 8

ER -