Comparative effects of probiotics and pentoxifylline on intestinal injury biomarkers (HMGB-1,I-FABP) in preterm neonates with necrotizing enterocolitis: A randomized controlled trial

Abstract

Background

This study aimed to evaluate whether pentoxifylline and probiotics are effective adjunctive therapies in necrotizing enterocolitis (NEC) by assessing their effects on serum high-mobility group box protein 1 (HMGB-1), intestinal fatty acid-binding protein (I-FABP), and total antioxidant capacity (TAC).

Methods

This prospective randomized controlled trial included 85 preterm neonates with Bell’s stage IIA NEC who were randomized into 3 groups, but only 75 completed the study and were included in the per-protocol analysis. Group I received standard antibiotic therapy alone. Group II received antibiotics plus intravenous pentoxifylline (30 mg/kg/day infused over 6 h). Group III received antibiotics plus probiotic supplementation (1 × 10⁹ CFU daily via feeding tube). Serum HMGB-1, I-FABP, and TAC levels were measured at diagnosis (before adjunctive therapy) and at discharge.

Results

After treatment, all groups showed significant decreases in HMGB-1 and I-FABP and significant increases in TAC (p < 0.05). Both pentoxifylline and probiotics showed greater biomarker improvement. The probiotic group had the largest reduction in I-FABP (p < 0.05). Hospital stay was significantly shorter in the pentoxifylline and probiotic groups, with the shortest duration observed in the probiotic group (p < 0.05). Mortality and progression to stage III NEC occurred only in the antibiotic group; however, the study was not powered to detect differences in major clinical outcomes. Higher HMGB-1 and I-FABP levels were associated with longer hospitalization.

Conclusion

Pentoxifylline and probiotics may serve as beneficial adjunctive therapies in the treatment of stage IIA NEC, with probiotics showing greater improvements in biomarkers. Further large-scale studies are needed to confirm clinical benefit.