title: Association between high cytokine levels with white matter injury in preterm infants with sepsis.
abstract: OBJECTIVE
  To examine the association among interleukin-6, interleukin-8, tumor necrosis factor-α, interleukin-10, and interleukin-1β and white matter injury in very-low-birth-weight infants with clinical sepsis and to help predict infants at risk for development of white matter injury.
  
  
  METHODS
  A prospective cohort study was carried out.
  
  
  METHODS
  Neonatal intensive care unit.
  
  
  METHODS
  Very low birth weight infants with clinical early-onset sepsis. Exclusion criteria were death before 14 days, major malformations, and congenital infections.
  
  
  METHODS
  Ultrasound brain scans were carried out on the third day and weekly until the sixth week of life or discharge and confirmed by a magnetic resonance image performed in the first year. Plasma was assayed for interleukin-6, interleukin-8, tumor necrosis factor-α, interleukin-10, and interleukin-1β in the same sample collected for sepsis work-up. Mann-Whitney, chi-square, t tests, multiple regression, and receiver operating characteristic analysis were applied.
  
  
  RESULTS
  From July 2005 to October 2007 we studied 84 very-low-birth-weight infants, 27 (32%) with white matter injury, and 57 (68%) control subjects (with no white matter injury). Proven early-onset sepsis and necrotizing enterocolitis were high risk for white matter injury after adjustment for gestational age and birth weight (relative risk, 3.04; 1.93-4.80 and relative risk, 2.2; 1.31-3.74, respectively). Interleukin-6, interleukin-8, and tumor necrosis factor-α levels were higher in infants with white matter injury than in control subjects (p < .0001). Interleukin-1β and interleukin-10 were similar. The areas under the curve for interleukin-6, interleukin-8, and tumor necrosis factor-α were 0.96 (0.92-0.99), 0.97 (0.94-1.0), and 0.93 (0.86-0.99), respectively. Interleukin-8 ≥100 pg/mL was the best predictor of white matter injury; the sensitivity and specificity were 96% and 83%, respectively, and negative predictive value was 98%.
  
  
  CONCLUSIONS
  Very-low-birth-weight infants with proven early-onset sepsis, necrotizing enterocolitis, and high plasma levels of interleukin-6, interleukin-8, and tumor necrosis factor-α are at high risk for white matter injury.
authors.affiliation: Department of Pediatrics, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Rrenatosp@terra.com.br
authors.forename: Renato S
authors.initials: RS
authors.lastname: Procianoy
authors.forename: Rita C
authors.initials: RC
authors.lastname: Silveira
mesh_terms: D001930:Brain Injuries / Q000000981:diagnostic imaging / Q000453:epidemiology*; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000097:blood*; D019102:Infant, Very Low Birth Weight; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D056784:Leukoencephalopathies / Q000000981:diagnostic imaging / Q000453:epidemiology*; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D018805:Sepsis / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014463:Ultrasonography
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10