title: Inflammation-initiating illnesses, inflammation-related proteins, and cognitive impairment in extremely preterm infants.
abstract: Neonatal inflammation is associated with perinatal brain damage. We evaluated to what extent elevated blood levels of inflammation-related proteins supplement information about the risk of impaired early cognitive function provided by inflammation-related illnesses. From 800 infants born before the 28th week of gestation, we collected blood spots on days 1, 7 and 14, for analysis of 25 inflammation-related proteins, and data about culture-positive bacteremia, necrotizing enterocolitis (Bell stage IIIb), and isolated perforation of the intestine, during the first two weeks, and whether they were ventilated on postnatal day 14. We considered a protein to be persistently or recurrently elevated if its concentration was in the top quartile (for gestational age and day blood was collected) on two separate days one week apart. We assessed the children at 2 years of age with the Bayley Mental Development Index (MDI). The combinations of NEC and ventilation on day 14, and of bacteremia and ventilation on day 14 consistently provided information about elevated risk of MDI <55, regardless of whether or not a variable for an elevated protein concentration was included in the model. A variable for a persistently or recurrently elevated concentration of each of the following proteins provided additional information about an increased risk of MDI <55: CRP, SAA, IL-6, TNF-alpha, IL-8, MIP-1beta, ICAM-1, E-SEL, and IGFBP-1. We conclude that elevated blood concentrations of inflammation-related proteins provide information about the risk of impaired cognitive function at age 2 years that supplements information provided by inflammation-associated illnesses.
authors.affiliation: Division of Neonatology, Department of Pediatrics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. Electronic address: moshea@wakehealth.edu.
authors.forename: T Michael
authors.initials: TM
authors.lastname: O'Shea
authors.affiliation: Department of Pediatrics, Baystate Children's Hospital, Springfield, MA 01199, USA.
authors.forename: Bhavesh
authors.initials: B
authors.lastname: Shah
authors.affiliation: Department of Neurology, Children's Hospital Boston, and Harvard Medical School, Boston, MA 02115, USA.
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 and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Raina N
authors.initials: RN
authors.lastname: Fichorova
authors.affiliation: Division of Pediatric Neurology, Department of Pediatrics, Boston University, Boston, MA 02118, USA.
authors.forename: Karl C K
authors.initials: KCK
authors.lastname: Kuban
authors.affiliation: Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA 02111, USA; Perinatal Epidemiology Unit, Hannover Medical School, 30623 Hannover, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Dammann
authors.affiliation: Department of Neurology, Children's Hospital Boston, and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Leviton
mesh_terms: D000328:Adult; D016470:Bacteremia / Q000150:complications; D002657:Child Development; D002659:Child Development Disorders, Pervasive / Q000378:metabolism / Q000523:psychology; D002675:Child, Preschool; D003072:Cognition Disorders / Q000209:etiology* / Q000523:psychology*; D015331:Cohort Studies; D003142:Communication; D020345:Enterocolitis, Necrotizing / Q000150:complications; D056344:Executive Function; D005260:Female; D005865:Gestational Age; D006801:Humans; D062071:Infant, Extremely Premature / Q000378:metabolism* / Q000523:psychology*; D007231:Infant, Newborn; D007249:Inflammation / Q000378:metabolism / Q000523:psychology*; D007361:Intelligence Tests; D007804:Language Development; D009483:Neuropsychological Tests; D016017:Odds Ratio; D011247:Pregnancy; D014176:Protein Biosynthesis / Q000502:physiology*; D018805:Sepsis / Q000150:complications