Tumor necrosis factor α -308 polymorphism associated with increased sepsis mortality in ventilated very low birth weight infants

Background: Sepsis commonly complicates the clinical course of critically ill very low birth weight infants, with as many as 30% developing hospital-acquired bacteremia. The tumor necrosis factor alpha (TNF-alpha) -308 G/A single nucleotide polymorphism (SNP) is associated with adverse outcome in septic adult patients. Methods: One hundred seventy-three mechanically ventilated very low birth weight infants were genotyped for the TNF-alpha -308 G/A SNP. Results: One hundred twenty (69%) infants were homozygous GG, 45 (26%) were heterozygous AG and 8 (5%) were homozygous AA; 2 of 120 (2%) infants developed early bacteremia in the GG group, and 1 of 53 (2%) developed early bacteremia in the AA/AG group (P = 0.919). One or more episodes of late bacteremia/fungemia developed in 59 of 120 (49%) infants with the GG genotype and 23 of 53 (43%) infants with the AG/AA genotype (P = 0.484). Endotracheal tube colonization rates were 65 of 120 (54%) for infants with the GG genotypes and 28 of 53 (53%) for infants with the AG/AA genotypes (P = 0.871). Nosocomial pneumonia developed in a similar number of infants in both genotype groups (9 of 120 infants vs. 3 of 53 infants; P = 0.461). Mortality from sepsis was 3 times greater in infants with the AA/AG genotypes than in those with the GG genotype (10% vs. 3%; P = 0.038). This difference in sepsis mortality was even greater when only bacteremic/fungemic infants are considered (4 of 59 infants vs. 6 of 23 infants; P = 0.026). Conclusions: These data suggest that the TNF-alpha -308 A allele does not affect the development of sepsis in ventilated premature infants but may increase mortality once sepsis develops.