title: Systemic inflammation on postnatal days 21 and 28 and indicators of brain dysfunction 2years later among children born before the 28th week of gestation.
abstract: BACKGROUND
  Systemic inflammation during the first two postnatal weeks in extremely preterm newborns (<28weeks gestation) has been associated with an increased risk of neurodevelopmental dysfunctions. Little is known, however, about the relationship between systemic inflammation during the third and fourth postnatal weeks and subsequent development.
  
  
  METHODS
  We measured the concentrations of 16 inflammation-related proteins in blood spots collected on postnatal days 21 (N=749) and 28 (N=697) from infants born before the 28th week of gestation and assessed at age 2years. We then sought the developmental correlates of top quartile concentrations for gestational age and day the specimen was collected. Odds ratios and 95% confidence intervals were calculated from regular or multinomial logistic regression models (as appropriate).
  
  
  RESULTS
  Top quartile concentrations of CRP, IL-1β, IL-6, IL-6R, TNF-R2, IL-8, ICAM-1, and TSH on both days 21 and 28 were associated with ventriculomegaly (when in the NICU) and microcephaly at age 2years. Top quartile concentrations of CRP, SAA, IL-6, TNF-R2, IL-8, and ICAM-1 were associated with mental development index (MDI) of the Bayley-II<55, while top quartile concentrations of CRP, TNF-α (inversely), IL-8, and ICAM-1 were associated with psychomotor development index (PDI)<55 CONCLUSION: Extremely preterm newborns who had systemic inflammation during the third and fourth postnatal weeks were at increased risk of ventriculomegaly during the months after birth, and of microcephaly, and low Bayley Scale scores at 2years old.
authors.affiliation: Neuroepidemiology Unit, Department of Neurology, Boston Children's Hospital, Harvard University, Boston, MA 02115, United States. Electronic address: alan.leviton@childrens.harvard.edu.
authors.forename: Alan
authors.initials: A
authors.lastname: Leviton
authors.affiliation: Neuroepidemiology Unit, Department of Neurology, Boston Children's Hospital, Harvard University, Boston, MA 02115, United States.
authors.forename: Elizabeth N
authors.initials: EN
authors.lastname: Allred
authors.affiliation: Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Boston, MA 02115, United States.
authors.forename: Raina N
authors.initials: RN
authors.lastname: Fichorova
authors.affiliation: Division of Neurology, Department of Pediatrics, Boston Medical Center and Boston University, Boston, MA 02118, United States.
authors.forename: Karl C K
authors.initials: KC
authors.lastname: Kuban
authors.affiliation: Department of Pediatrics, Wake Forest University, Winston-Salem, NC 27157, United States.
authors.forename: T
authors.initials: T
authors.lastname: Michael O'Shea
authors.affiliation: Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA 02111, United States; Perinatal Neuropidemiology Unit, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Dammann
mesh_terms: D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002657:Child Development; D016207:Cytokines / Q000097:blood; D006801:Humans; D006849:Hydrocephalus / Q000097:blood* / Q000453:epidemiology; D062071:Infant, Extremely Premature / Q000097:blood* / Q000254:growth & development; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight / Q000097:blood* / Q000254:growth & development; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008831:Microcephaly / Q000097:blood* / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein
keywords: Brain; Developmental disabilities; Infant; Inflammation; Premature