Pilot study assessing TNF gene polymorphism as a prognostic marker for disease progression in neonates with sepsis

In adult postoperative intensive care patients, the biallelic NcoI polymorp hism within the tumor necrosis factor (TNF) locus has been shown to be a ge nomic marker for individuals with increased TNF-alpha response and poor pro gnosis in severe sepsis. We characterized the genomic distribution and alle le frequency of the NcoI polymorphism in 23 preterm and term neonatal inten sive care unit (NICU) patients with culture-proven sepsis and compared it w ith clinical and laboratory characteristics to assess its prognostic value for disease progression. Genotype analysis demonstrated the following absol ute (relative) frequencies: 7 (0.31) infants were homozygous for the allele TNFB2 (Group A). 12 (0.52) infants were heterozygous (TNFB1/TNFB2) and fou r (0.17) infants homozygous for the allele TNFB1 (Group B). There was no si gnificant difference compared to adult intensive care patients with severe sepsis (p = 0.31). The median gestational age of all infants (13 female and ten male) as well as for either group was 28 weeks (range 23-37) with a me dian birth weight of 845 g (range 560-2,720). The study population included a total of 16 very low birth weight (VLBW) infants, four in Group A and 12 in Group B. However, there was no significant difference for gestational a ge and birth weight in both groups (p = 0.82 and 0.71, respectively). Labor atory parameters as maximum and minimum leukocyte and thrombocyte counts, m aximum immature to total neutrophil ratios (ITR), maximum C-reactive protei n (CRP) levels, days of CRP levels > 5 mg/l and total days of antibiotic tr eatment, were not statistically different in both groups. In total, three i nfants (13%) died in consequence of their underlying disease. Two infants b elonged to Group A and one to Group B. The statistical analysis of outcome variables (mortality, neurological impairment, failure to thrive) was not p ossible, because the study population was small and the reasons for poor ou tcome and death in these high-risk patients had to be considered multifacto rial. In conclusion, in this pilot study the biallelic NcoI polymorphism wi thin the TNF locus was not a prognostic marker for disease progression in h igh-risk NICU-admitted term and preterm infants with culture-proven sepsis. In order to detect differences in outcome similar to adult postsurgical pa tients with severe sepsis, an unfeasibly high number of NICU patients with culture-proven sepsis would need to be included for a similar study.