title: An explanatory randomised placebo controlled trial of levothyroxine supplementation for babies born <28 weeks' gestation: results of the TIPIT trial.
abstract: BACKGROUND
  Babies born before 28 weeks' gestation have lower plasma thyroid hormone concentrations than more mature infants. This may contribute to their risk of poor developmental outcome. Previous studies have suggested that thyroxine supplementation for extremely preterm neonates may be beneficial. The aim of this study was to investigate the effect of administration of supplemental thyroxine to very premature babies on brain size and somatic growth at 36 weeks' corrected gestational age (CGA).
  
  
  METHODS
  In this explanatory multicentre double blind randomised placebo controlled trial, 153 infants born below 28 weeks' gestation were randomised to levothyroxine (LT4) supplementation or placebo until 32 weeks' CGA. The primary outcome was brain size assessed by the width of the subarachnoid space measured by cranial ultrasound at 36 weeks' CGA. Lower leg length was measured by knemometry.
  
  
  RESULTS
  Babies in the LT4-supplemented and placebo groups had similar baseline characteristics. There were no significant differences between infants given LT4 (n=78) or placebo (n=75) for width of the subarachnoid space, head circumference at 36 weeks' CGA, body weight at 36 weeks' CGA or mortality. Infants who received LT4 had significantly shorter leg lengths at 36 weeks' CGA although adjusted analysis for baseline length did not find a statistical difference. There was a significant correlation between low FT4 and wider subarachnoid space. No unexpected serious adverse events were noted and incidence of adverse events did not differ between the two groups.
  
  
  CONCLUSIONS
  This is the only randomised controlled trial of thyroxine supplementation targeting extremely premature infants. Supplementing all babies below 28 weeks' gestation with LT4 had no apparent effect on brain size. These results do not support routine supplementation with LT4 for all babies born below 28 weeks' gestation.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN89493983EUDRACT number: 2005-003-09939.
authors.affiliation: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. may.ng@nhs.net
authors.forename: Sze M
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: Donal
authors.initials: D
authors.lastname: Manning
authors.forename: Paul
authors.initials: P
authors.lastname: Settle
authors.forename: Richa
authors.initials: R
authors.lastname: Gupta
authors.forename: Paul
authors.initials: P
authors.lastname: Newland
authors.forename: Alan Michael
authors.initials: AM
authors.lastname: Weindling
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D002508:Cephalometry; D004311:Double-Blind Method; D004453:Echoencephalography; D004739:England; D005260:Female; D005865:Gestational Age; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D007226:Infant Mortality; D062071:Infant, Extremely Premature / Q000097:blood*; D007231:Infant, Newborn; D035002:Lower Extremity / Q000254:growth & development; D008297:Male; D009929:Organ Size; D013346:Subarachnoid Space / Q000000981:diagnostic imaging; D013974:Thyroxine / Q000009:adverse effects / Q000097:blood / Q000172:deficiency / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D013974:Thyroxine