Preterm infants are often exposed to both antenatal and postnatal glucocorticoids (GCs). We tested the hypothesis that combined antenatal and postnatal GCs have long-lasting adverse effects on fetal and neonatal growth, growth factors, and neurological outcomes. Pregnant rats were administered a single IM dose of betamethasone (0.2 mg/Kg, AB), dexamethasone (0.2 mg/Kg, AD), or equivalent volumes of saline (AS) at 17 & 18 days gestation. Following delivery, pups from each treatment group were sacrificed at P0, and the remainder was treated with a single IM dose of either betamethasone (0.25 mg/Kg, PB), dexamethasone (0.25 mg/Kg, PD), or equivalent volumes of saline (PS) on P5, P6, and P7. Somatic growth, neurological status, and growth factors were determined at P14, P21, and P45. At birth, AD resulted in decreased somatic growth. AB advanced the hopping reflex associated with spinal rhythmic mechanisms. At P21, all GC groups were growth suppressed, but only the AS/PD group had deficits in brain weight and delayed plantar reflex associated with brainstem function. By P45, sustained reductions in body and brain weight occurred all combined antenatal and postnatal GC groups, as well as elevated ACTH and corticosterone. Retardation in plantar reflex occurred in all AD groups. IGF-I, GH and insulin levels were elevated at all ages with dexamethasone. Combined antenatal and postnatal GCs has persistent detrimental lasting effects on growth, growth factors, neurological outcomes, and HPA axis activity. Whether these effects persist in adult life and are risk factors for insulin resistance, remains to be elucidated.

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.