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

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. One hundred seventy-three mechanically ventilated very low birth weight infants were genotyped for the TNF-alpha -- 308 G/A SNP. 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). 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.