title: Are preterm newborns who have relative hyperthyrotropinemia at increased risk of brain damage?
abstract: BACKGROUND
  We sought to disentangle the contributions of hyperthyrotropinemia (an indicator of thyroid dysfunction) (HTT) and intermittent or sustained systemic inflammation (ISSI) to structural and functional indicators of brain damage.
  
  
  METHODS
  We measured the concentrations of thyroid-stimulating hormone (TSH) on day 14 and of 25 inflammation-related proteins in blood collected during the first 2 postnatal weeks from 786 infants born before the 28th week of gestation who were not considered to have hypothyroidism. We defined hyperthyrotropinemia (HTT) as a TSH concentration in the highest quartile for gestational age on postnatal day 14 and ISSI was defined as a concentration in the top quartile for gestational age of a specific inflammation-related protein on 2 separate days a week apart during the first 2 postnatal weeks. We first assessed the risk of brain damage indicators by comparing 1) neonates who had HTT to those without (regardless of ISSI) and 2) neonates with HTT only, ISSI only, or HTT+ISSI to those who were exposed to neither HTT nor ISSI.
  
  
  RESULTS
  In univariable models that compared those with HTT to those without, HTT was not significantly associated with any indicator of brain damage. In models that compared HTT only, ISSI only, and HTT+ISSI to those with neither, children with ISSI only or with HTT+ISSI were at significantly higher risk of ventriculomegaly [odds ratios (ORs) 2-6], whereas those with HTT only were at significantly reduced risk of a hypoechoic lesion (ORs 0.2-0.4). Children with HTT only had a higher risk of quadriparesis and those with ISSI alone had a higher risk of hemiparesis (ORs 1.6-2.4). Elevated risk of a very low mental development score was associated with both ISSI only and HTT+ISSI, whereas a very low motor development score and microcephaly were associated with HTT+ISSI.
  
  
  CONCLUSIONS
  The association of HTT with increased or decreased risk of indicators of brain damage depends on the presence or absence of ISSI.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Korzeniewski
authors.forename: Carmen L
authors.initials: CL
authors.lastname: Soto-Rivera
authors.forename: Raina N
authors.initials: RN
authors.lastname: Fichorova
authors.forename: Elizabeth N
authors.initials: EN
authors.lastname: Allred
authors.forename: Karl C K
authors.initials: KC
authors.lastname: Kuban
authors.forename: T Michael
authors.initials: TM
authors.lastname: O'Shea
authors.forename: Nigel
authors.initials: N
authors.lastname: Paneth
authors.forename: Michael
authors.initials: M
authors.lastname: Agus
authors.forename: Olaf
authors.initials: O
authors.lastname: Dammann
authors.forename: Alan
authors.initials: A
authors.lastname: Leviton
mesh_terms: D001927:Brain Diseases / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D002657:Child Development; D005260:Female; D005500:Follow-Up Studies; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000097:blood / Q000175:diagnosis*; D007236:Infant, Small for Gestational Age / Q000097:blood / Q000254:growth & development*; D007249:Inflammation / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D008297:Male; D008831:Microcephaly / Q000097:blood / Q000150:complications / Q000175:diagnosis; D011247:Pregnancy; D011379:Prognosis; D013959:Thyroid Diseases / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D013972:Thyrotropin / Q000097:blood*
chemical_list: D013972:Thyrotropin