title: Elevated plasma and cerebrospinal fluid interleukin-1 beta and tumor necrosis factor-alpha concentration and combined outcome of death or abnormal neuroimaging in preterm neonates with early-onset clinical sepsis.
abstract: OBJECTIVE
  Prematurity and sepsis are the major contributors of neonatal mortality and neurodevelopmental sequelae. The present study was conducted to measure the plasma and cerebrospinal fluid (CSF) concentration of interleukin (IL)-1β and tumor necrotic factor (TNF)-α in preterm neonates with early-onset clinical sepsis (EOCS), and to find out their association with combined outcome of death or abnormal neuroimaging.
  
  
  METHODS
  Thirty-two preterm (⩽34 weeks) neonates with EOCS and 32 gestational age-matched, healthy neonates served as cases and controls, respectively. Samples were collected soon after birth. Neonates were followed up clinically and by serial cranial ultrasonography (CUS) until discharge and subsequently by magnetic resonance imaging (MRI) of brain until 1 year. Developmental screening was done by Denver Developmental Screening test-II.
  
  
  RESULTS
  In EOCS group, no neonate had any clinical/microbiological evidence of meningitis. Blood culture was positive in 17 (53%). CUS was abnormal in 12 (37%) (intracranial hemorrhage-11, periventricular leukomalacia-1). Ten (31%) neonates expired. Significant elevation of plasma and CSF IL-1β and TNF-α was observed in the EOCS group. On follow-up, seven (22%) neonates showed evidence of white matter damage in MRI, two of them had developmental delay and microcephaly. Plasma and CSF IL-1β and TNF-α concentration were significantly elevated in deceased neonates and those with abnormal neuroimaging. Both biomarkers demonstrated high predictive accuracy for poor outcome in receiver-operating curve analysis.
  
  
  CONCLUSIONS
  Elevation of plasma and CSF IL-1β and TNF-α is associated with an increase in the combined outcome of death or abnormal neuroimaging in preterm neonates with EOCS in the absence of clinical/microbiological evidence of meningitis with high predictive accuracy.
authors.affiliation: Division of Neonatology, Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
authors.forename: S
authors.identifier: http://orcid.org/0000-0001-5048-4849
authors.initials: S
authors.lastname: Basu
authors.affiliation: Division of Neonatology, Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
authors.forename: P
authors.initials: P
authors.lastname: Agarwal
authors.affiliation: Department of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
authors.forename: S
authors.initials: S
authors.lastname: Anupurba
authors.affiliation: Department of Radiodiagnosis, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
authors.forename: R
authors.initials: R
authors.lastname: Shukla
authors.affiliation: Division of Neonatology, Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
authors.forename: A
authors.initials: A
authors.lastname: Kumar
mesh_terms: D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D004453:Echoencephalography; D005260:Female; D005865:Gestational Age; D006784:Hospitals, Teaching; D006801:Humans; D007194:India; D007231:Infant, Newborn; D007234:Infant, Premature; D053583:Interleukin-1beta / Q000097:blood* / Q000134:cerebrospinal fluid*; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging; D011446:Prospective Studies; D012372:ROC Curve; D018805:Sepsis / Q000401:mortality*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha