Oxidative Stress and Necrotizing Enterocolitis in Preterm Newborns: The Role of GSTM1 and GSTT1 Null Genotypes

Necrotizing enterocolitis (NEC) is a multifactorial disease associated with prematurity, intestinal hypoperfusion, dysbiosis, and oxidative stress. Interindividual variability in disease occurrence suggests a role for genetic susceptibility. Null genotypes of the GSTM1 and GSTT1 genes result in absent glutathione S-transferase activity and may impair antioxidant defenses. This study investigated whether GSTM1 and GSTT1 null genotypes are associated with NEC development and severity in preterm newborns. This single-center case-control pilot study included 100 preterm newborns (50 NEC and 50 controls). Genotyping was performed by multiplex polymerase chain reaction. Baseline characteristics were comparable between groups (p > 0.05). Stages II-A and II-B accounted for 82% of NEC cases. A significant inverse correlation was observed between gestational age and postnatal age at NEC diagnosis (r = -0.5994; p < 0.0001). The GSTM1-null genotype was more frequent in the NEC group (60% vs. 36%) and was associated with increased disease risk in both unadjusted (OR = 2.667; 95%CI: 1.188-5.986; p = 0.027) and adjusted analyses (aOR = 3.09; 95%CI: 1.29-7.40; p = 0.011). No significant associations were observed for GSTT1, combined genotypes, or disease severity. These findings provide preliminary evidence of an association between the GSTM1-null genotype and NEC susceptibility. Given the exploratory pilot design, these results should be considered hypothesis-generating and require confirmation in larger prospective studies.