Abstract
BackgroundNecrotizing enterocolitis (NEC) is a devastating disease of intestinal inflammation that primarily affects premature infants. A potential risk factor for necrotizing enterocolitis is exposure of the premature neonatal intestine to environmental bacteria and their proinflammatory products such as lipopolysaccharide. The metalloenzyme alkaline phosphatase (ALP) has been shown to reduce lipopolysaccharide-mediated inflammation. Additionally, premature rat pups have reduced alkaline phosphatase activity and expression as compared to full term pups. To explore the possibility that the human premature neonatal intestine has a paucity of alkaline phosphatase activity, we measured endogenously produced intestinal alkaline phosphatase activity in meconium as a function of gestational age. To test whether breast milk could serve as a source of exogenous alkaline phosphatase to the neonatal intestine through ingestion, we measured alkaline phosphatase activity in breast milk across a range of time points post-birth.MethodsAlkaline phosphatase activity was quantified in 122 meconium samples from infants of gestational ages ranging from 24 to 40 weeks and in 289 breast milk samples collected from 78 individual mothers between days 2–49 post-birth.ResultsWe observed a strong positive correlation between the meconium alkaline phosphatase activity and gestational age, with preterm infants having lower meconium alkaline phosphatase activities than early term or term infants. Breast milk alkaline phosphatase activity was highest in the first week post-birth, with peak alkaline phosphatase activity at day 2 post-birth, followed by relatively low alkaline phosphatase activity in weeks 2–7.ConclusionsOur results are consistent with the two major risk factors for necrotizing enterocolitis development, preterm birth and lack of breast milk feeding, both contributing to a paucity of alkaline phosphatase activity and impaired capacity to detoxify proinflammatory bacterial products such as lipopolysaccharide.
Highlights
Necrotizing enterocolitis (NEC) is a devastating disease of intestinal inflammation that primarily affects premature infants
Supplementation of the neonate rat pup intestine with alkaline phosphatase (ALP) was protective against both LPS induced inflammation and experimentally induced NEC [20, 21], These data, in conjunction with a recent report showed that prematurity in rat pups was associated with reduced intestinal ALP expression and activity [22], identify ALP deficiency as a risk factor for the development of NEC in premature infants, there are no studies to date reporting ALP activity of the developing human intestine as a function of gestational age
Meconium ALP activity is positively correlated with gestational age To investigate the amount of ALP in the infant intestine, we quantified ALP activity in meconium samples collected from infants at gestational ages 24–40 weeks
Summary
Necrotizing enterocolitis (NEC) is a devastating disease of intestinal inflammation that primarily affects premature infants. The metalloenzyme alkaline phosphatase (ALP) has been shown to reduce lipopolysaccharide-mediated inflammation. Supplementation of the neonate rat pup intestine with ALP was protective against both LPS induced inflammation and experimentally induced NEC [20, 21], These data, in conjunction with a recent report showed that prematurity in rat pups was associated with reduced intestinal ALP expression and activity [22], identify ALP deficiency as a risk factor for the development of NEC in premature infants, there are no studies to date reporting ALP activity of the developing human intestine as a function of gestational age
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