title: Elevated blood levels of inflammation-related proteins are associated with an attention problem at age 24 mo in extremely preterm infants.
abstract: BACKGROUND
  Extremely preterm birth is associated with subsequent behavioral problems. We hypothesized that perinatal systemic inflammation, a risk factor for cerebral white matter injury and cognitive impairment, is associated with behavior problems observed at 2 y.
  
  
  METHODS
  In a cohort of 600 children born before 28 wk gestation, we measured 25 inflammation-related proteins in blood collected on postnatal days 1, 7, and 14, and identified behavior problems using parent responses to the Child Behavior Checklist for Ages 1.5-5 (CBCL/1.5-5) at 2 y of age. A persistent or recurrent protein elevation was defined as a concentration in the highest quartile (for gestational age and postnatal age) on at least 2 d ~1 wk apart. Behavior problems were defined by CBCL/1.5-5 subscale scores at or above the 93 rd percentile.
  
  
  RESULTS
  A single-day elevation of intercellular adhesion molecule-3 was associated with an increased risk of an attention problem, as were persistent or recurrent elevations of myeloperoxidase, interleukin-6, tumor necrosis factor-RI, interleukin-8, intercellular adhesion molecule-3, vascular endothelial growth factor-R1, and vascular endothelial growth factor-R2. These associations persisted among infants without white matter injury and cognitive impairment.
  
  
  CONCLUSIONS
  Among children born extremely prematurely, recurrent, or persistent elevations of inflammation-related proteins in blood during in the first two postnatal weeks are associated with an attention problem at age 2 y.
authors.affiliation: Department of Pediatrics, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: T Michael
authors.initials: TM
authors.lastname: O'Shea
authors.affiliation: Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Joseph
authors.affiliation: Department of Pediatrics, Boston Medical Center, Boston, Massachusetts.
authors.forename: Karl C K
authors.initials: KC
authors.lastname: Kuban
authors.affiliation: Department of Neurology, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts.
authors.forename: Elizabeth N
authors.initials: EN
authors.lastname: Allred
authors.affiliation: Department of Medicine, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Janice
authors.initials: J
authors.lastname: Ware
authors.affiliation: Department of Medicine, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Taryn
authors.initials: T
authors.lastname: Coster
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
authors.forename: Raina N
authors.initials: RN
authors.lastname: Fichorova
authors.affiliation: 1] Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts [2] Perinatal Neuroepidemiology Unit, Hannover Medical School, Hannover, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Dammann
authors.affiliation: Department of Neurology, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts.
authors.forename: Alan
authors.initials: A
authors.lastname: Leviton
mesh_terms: D015703:Antigens, CD / Q000097:blood; D001289:Attention Deficit Disorder with Hyperactivity / Q000209:etiology*; D001724:Birth Weight; D001798:Blood Proteins / Q000032:analysis*; D015815:Cell Adhesion Molecules / Q000097:blood; D002652:Child Behavior / Q000502:physiology*; D002675:Child, Preschool; D015331:Cohort Studies; D005865:Gestational Age; D006801:Humans; D062071:Infant, Extremely Premature / Q000097:blood*; D007231:Infant, Newborn; D007249:Inflammation / Q000097:blood* / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008163:Luminescent Measurements; D016017:Odds Ratio; D009195:Peroxidase / Q000097:blood; D048069:Tumor Necrosis Factors / Q000097:blood; D014481:United States; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood
chemical_list: D015703:Antigens, CD; D001798:Blood Proteins; D015815:Cell Adhesion Molecules; C483616:ICAM3 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D048069:Tumor Necrosis Factors; D009195:Peroxidase; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2