title: Effect of thyroxine on brain microstructure in extremely premature babies: magnetic resonance imaging findings in the TIPIT study.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Crown Street, L8 7SS, Liverpool, UK, may.ng@nhs.net.
authors.forename: Sze May
authors.initials: SM
authors.lastname: Ng
authors.forename: Mark A
authors.initials: MA
authors.lastname: Turner
authors.forename: Carrol
authors.initials: C
authors.lastname: Gamble
authors.forename: Mohammed
authors.initials: M
authors.lastname: Didi
authors.forename: Suresh
authors.initials: S
authors.lastname: Victor
authors.forename: Jessica
authors.initials: J
authors.lastname: Atkinson
authors.forename: Vanessa
authors.initials: V
authors.lastname: Sluming
authors.forename: Laura M
authors.initials: LM
authors.lastname: Parkes
authors.forename: Anna
authors.initials: A
authors.lastname: Tietze
authors.forename: Laurence J
authors.initials: LJ
authors.lastname: Abernethy
authors.forename: Alan Michael
authors.initials: AM
authors.lastname: Weindling
mesh_terms: D016880:Anisotropy; D001921:Brain / Q000187:drug effects* / Q000254:growth & development*; D001931:Brain Mapping / Q000379:methods; D019587:Dietary Supplements; D056324:Diffusion Tensor Imaging / Q000379:methods; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D013974:Thyroxine / Q000097:blood* / Q000627:therapeutic use*
chemical_list: D013974:Thyroxine