Increased levels of tumor necrosis factor-alpha and decreased levels of interleukin-12 p 70 in tracheal aspirates, within 2 hrs after birth, are associated with mortality among ventilated preterm infants.
OBJECTIVE
To determine the association of antibacterial interleukin (IL)-12 p 70 levels as well as the pathogen-induced proinflammatory cytokine response in tracheal aspirate (TA) to respiratory failure and mortality among ventilated preterm infants.


METHODS
A prospective observational clinical cohort study with measurements of cytokine levels and microbial cultures of TA from ventilated preterm neonates. Interleukin (IL)-1 beta, IL-8, IL-6, IL-10, IL-12 p 70, and tumor necrosis factor (TNF)-alpha were measured in TA within 2 hrs of birth, and comorbidity characteristics were recorded prospectively. The association between cytokine levels in TA and neonatal mortality was determined, with correction for comorbidity factors by means of multivariate stepwise logistic regression.


METHODS
A single tertiary neonatal intensive care unit at the University Hospital of Antwerp, Belgium.


METHODS
One hundred forty-one neonates born before a gestational age of 31 wks and who required ventilation were enrolled in the study; 31 (22%) died and 37 (26%) had airway colonization.


RESULTS
The airway colonization rate was significantly greater among deceased neonates (45% vs. 21%; chi-square, 7.4; p=.007). Neonates who died had a significantly lower IL-12 p 70 cytokine level (6 pg/mL vs. 11 pg/mL; p<.05) in their TA. Neonates with a low IL-12 p 70 cytokine level had more pronounced respiratory failure (significantly higher oxygenation index, higher degree of radiologic respiratory distress syndrome, higher critical index for babies score, and more surfactant use). Multivariate analysis revealed that, after correction for severity of disease by critical index for babies score, the degree of intraventricular hemorrhage (odds ratio, 5.0 [95% confidence interval, 2.6-9.7]), low IL-12 p 70 levels (odds ratio, 4.9 [95% confidence interval, 2.1-11.7]), and high TNF-alpha levels in TA (odds ratio, 3.5 [95% confidence interval, 1.6-7.5]) were significantly associated with neonatal mortality.


CONCLUSIONS
Pathogen-induced excessive production of the proinflammatory cytokine TNF-alpha and lack of antibacterial IL-12 p 70 response in the TA are associated with increased neonatal mortality among ventilated preterm infants.
Mahieu
Ludo M
LM
Department of Pediatrics, Division of Neonatology, Faculty of Medicine, University of Antwerp, Antwerp, Belgium.
De Dooy
Jozef J
JJ
Ieven
Margareta M
MM
Bridts
Chris H
CH
Stevens
Wim J
WJ
D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007363:Intensive Care Units, Neonatal; D018664:Interleukin-12 / Q000096:biosynthesis*; D008297:Male; D011446:Prospective Studies; D021122:Protein Subunits / Q000096:biosynthesis*; D012121:Respiration, Artificial / Q000009:adverse effects; D012131:Respiratory Insufficiency / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality*; D014132:Trachea / Q000276:immunology* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D021122:Protein Subunits; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12