Abstract
BackgroundNecrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of neonates, especially premature neonates. To date, there is no prophylactic treatment against NEC, except breast milk and slow increase in enteral feeding, and there is no antenatal prophylaxis.AimsTo assess possible protective effects of antenatal N-Acetyl Cysteine (NAC) against the intestinal pathophysiological changes associated with NEC in a rat model of NEC and against its associated mortality.MethodsNewborn Sprague-Dawley rats were divided into 5 groups: control (n = 33); NEC (n = 32)-subjected to hypoxia and formula feeding for 4 days to induce NEC; NEC-NAC (n = 34)-with induced NEC and concomitant postnatal NAC administration; NAC-NEC (n = 33)-born to dams treated with NAC for the last 3 days of pregnancy starting at gestational age of 18 days, and then subjected to induced NEC after birth; NAC-NEC-NAC (n = 36)—subjected to induced NEC with both prenatal and postnatal NAC treatment. At day of life 5, weight and survival of pups in the different groups were examined, and pups were euthanized. Ileal TNF-α, IL-6, IL-1β, IL-10, NFkB p65, iNOS and cleaved caspase 3 protein levels (western blot) and mRNA expression (RT-PCR) were compared between groups.ResultsPup mortality was significantly reduced in the NAC-NEC-NAC group compared to NEC (11% vs. 34%, P<0.05). Ileal protein levels and mRNA expression of all injury markers tested except IL-10 were significantly increased in NEC compared to control. These markers were significantly reduced in all NAC treatment groups (NEC-NAC, NAC-NEC, and NAC-NEC-NAC) compared to NEC. The most pronounced decrease was observed in the NAC-NEC NAC group.ConclusionsAntenatal NAC decreases injury markers and mortality associated with NEC in a rat model. Antenatal administration of NAC may present a novel approach for NEC prophylaxis in pregnancies with risk for preterm birth.
Highlights
Necrotizing enterocolitis (NEC) is the leading gastrointestinal disease of the neonate affecting 3,000–5000 neonates in the US each year [1]
Newborn Sprague-Dawley rats were divided into 5 groups: control (n = 33); NEC (n = 32)subjected to hypoxia and formula feeding for 4 days to induce NEC; NEC-N-Acetyl Cysteine (NAC) (n = 34)-with induced NEC and concomitant postnatal NAC administration; NAC-NEC (n = 33)-born to dams treated with NAC for the last 3 days of pregnancy starting at gestational age of 18 days, and subjected to induced NEC after birth; NAC-NEC-NAC (n = 36)—subjected to induced NEC with both prenatal and postnatal NAC treatment
Pup mortality was significantly reduced in the NAC-NEC-NAC group compared to NEC (11% vs. 34%, P
Summary
Necrotizing enterocolitis (NEC) is the leading gastrointestinal disease of the neonate affecting 3,000–5000 neonates in the US each year [1] It affects mainly premature infants [2], with mortality rate as high as 30% [3,4]. Clinical data support the addition of probiotics for prevention [21,22], this method has not gained popular use due to fears of increase in sepsis incidents [23], and currently, there is only a conditional recommendation to provide specific strains in order to reduce NEC rate [24].So far, there are no published studies investigating prophylactic treatment to mothers at risk for preterm labor for the prevention of NEC. There is no prophylactic treatment against NEC, except breast milk and slow increase in enteral feeding, and there is no antenatal prophylaxis.
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