Most of the major morbidities in the preterm newborn are caused by or are associated with oxygen-induced injuries and are aptly called oxygen radical diseases in neonatology or ORDIN. These include bronchopulmonary dysplasia, retinopathy of prematurity, periventricular leukomalacia, intraventricular hemorrhage, necrotizing enterocolitis and others. Relative hyperoxia immediately after birth, immature antioxidant systems, biomolecular events favoring oxidative stress such as iron availability and the role of hydrogen peroxide as a key molecular mediator of these events are reviewed. Potential therapeutic strategies such as caffeine, antioxidants, non-steroidal anti-inflammatory drugs, and others targeted to these critical sites may help prevent oxidative radical diseases in the newborn resulting in improved neonatal outcomes.

Background

Oxidative stress and inflammation are associated with the development of inflammatory bowel diseases such as necrotizing enterocolitis. We tested the hypothesis that probiotics, prebiotics or synbiotics (a combination of pre- and probiotics) is effective for prevention of inflammatory responses to formula-feeding in the terminal ileum of neonatal rats.

Methods

Neonatal rats were exposed to hyperoxia/hypoxia during which they were either maternally-fed or hand-fed with formula supplemented with probiotics, prebiotics or synbiotics. A non-supplemented formula group served as controls. Cytokines and genes associated with oxidative stress and toll-like receptor signaling were determined in the terminal ileum. Data were compared to room air littermates.

Results

Exposure to hyperoxia/ hypoxia reduced growth accretion in maternally-fed pups. NEC-like symptoms and intestinal inflammatory markers were induced with formula feeding. Supplementation with probiotics, prebiotics or synbiotics decreased proinflammatory cytokines and downregulated genes involved in oxidative stress and toll-like receptor pathways, however, the effect was attenuated in hyperoxia/hypoxia.

Conclusions

The combination of suboptimal nutrition due to removal of breast milk and formula feeding with hyperoxia/hypoxia may increase susceptibility to oxidative stress, inflammation, and NEC. Probiotics, prebiotics and synbiotics are protective against oxidative stress and inflammation, but their efficacy may be reduced when administered during hyperoxia/hypoxia insults.