title: Early postnatal blood concentrations of inflammation-related proteins and microcephaly two years later in infants born before the 28th post-menstrual week.
abstract: BACKGROUND
  To evaluate if concentrations of inflammation-related proteins were elevated in early postnatal blood specimens of preterm newborns who two years later had a small head.
  
  
  METHODS
  We measured 25 proteins in blood collected on days 1, 7, and 14 from 839 infants born before the 28th week of gestation and whose head circumference was measured at birth and near 24-months post-term equivalent. We excluded children whose birth head circumference was at or below the third centile. A protein concentration was considered elevated if it was in the highest quartile for gestational age and the day the specimen was obtained.
  
  
  RESULTS
  When proteins were evaluated individually, elevated concentrations of SAA on day 1 and five proteins on day 14, IL-6, TNF-R2, IL-8, MCP-1, and ICAM-1 were associated with significantly increased risk of microcephaly (head circumference Z-score <-2). The ten proteins whose elevated concentrations on two separate days a week apart predicted microcephaly, but did not do so when elevated on only one of these days were CRP, SAA, IL-1β, IL-6, TNF-α, IL-8, MCP-1, ICAM-1, E-SEL, IGFBP-1. Elevated protein concentrations weakly predicted a less severe reduction in head circumference (Z-score ≥ -2, < -1).
  
  
  CONCLUSIONS
  Concentrations of inflammation-related proteins in the circulation shortly after preterm birth provide information about the risk of a reduced head circumference more than two years later.
  
  
  BACKGROUND
  The ELGAN Study was supported by a cooperative agreement with the National Institute of Neurological Disorders and Stroke of the United States.
authors.affiliation: Children's Hospital Boston, Boston MA 02115-5724, United States. alan.leviton@childrens.harvard.edu
authors.forename: Alan
authors.initials: A
authors.lastname: Leviton
authors.forename: Karl C K
authors.initials: KC
authors.lastname: Kuban
authors.forename: Elizabeth N
authors.initials: EN
authors.lastname: Allred
authors.forename: Raina N
authors.initials: RN
authors.lastname: Fichorova
authors.forename: T Michael
authors.initials: TM
authors.lastname: O'Shea
authors.forename: Nigel
authors.initials: N
authors.lastname: Paneth
mesh_terms: D001798:Blood Proteins / Q000032:analysis* / Q000276:immunology; D002657:Child Development; D002675:Child, Preschool; D006257:Head / Q000033:anatomy & histology / Q000000981:diagnostic imaging; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood* / Q000276:immunology; D016015:Logistic Models; D008831:Microcephaly / Q000097:blood* / Q000276:immunology; D014463:Ultrasonography
chemical_list: D001798:Blood Proteins