Abstract

Pre-term infants have an immature digestive system predisposing to short- and long-term complications including feeding intolerance, maldigestion and necrotizing enterocolitis (NEC). Optimal feeding strategies are required to promote maturation of the gut including the exocrine pancreas. Little is known about age- and diet-related development of pancreatic exocrine enzymes following pre-term birth. Currently, bovine colostrum supplementation is investigated in clinical trials on pre-term infants. Using pigs as models for infants, we hypothesized that pancreatic enzyme content is (1) immature following pre-term birth, (2) stimulated by early colostrum supplementation, and (3) stimulated by later colostrum fortification. Thus, using piglets as models for infants, we measured trypsin, amylase, lipase and total protein in pancreatic tissue collected from piglets delivered by cesarean section either pre-term (90% gestation) or close to term. Experiment 1:Pre-term and term pigs were compared at birth and 11 days. Experiment 2: Pre-term and term pigs were either enterally supplemented with bovine colostrum or fed total parenteral nutrition for 5 days, followed by exclusive milk feeding until day 26. Experiment 3: Pre-term pigs were fed bovine's milk with or without colostrum fortification until 19 days. The results showed that pancreatic trypsin, amylase and total protein contents were reduced in pre-term vs. term pigs. Trypsin mainly increased with advancing post-conceptional age (2-fold), while amylase was affected predominantly by advancing post-natal age, and mostly in pre-term pigs from birth to 11 or 26 days. Colostrum feeding in both term and pre-term piglets decreased trypsin and increased amylase contents. Lipase activity decreased with advancing gestational age at birth and post-natal age, with no consistent responses to colostrum feeding, with lipase activities decreasing relative to total pancreatic protein content. In summary, key pancreatic enzymes, amylase and trypsin, are immature following pre-term birth, potentially contributing to reduced digestive capacity in pre-term neonates. Rapid post-natal increases occurs within few weeks of pre-term birth, partly stimulated by enteral colostrum intake, reflecting a marked adaptation capacity. Alternatively, lipase is less affected by pre-/post-natal age and feeding. Thus, there is a highly enzyme-specific and asymmetric perinatal development of the exocrine pancreas.

Highlights

  • Pre-maturity, which accounts for ∼10% of all live births, is associated with developmental complications and increased morbidity and mortality among pre-term infants born before the 32nd week of gestation [1]

  • We investigated the influence of post-conceptional age and postnatal age on the development of the exocrine pancreatic function, by comparing piglets born 11 days pre-term to piglets born term, and as both groups were evaluated at post-natal day 11, it allows us to compare pigs of identical post-conceptional age (i.e., PRE-TERM-d11 vs. TERM-d1) age, and identical post-natal age (i.e., PRE-TERM-d11 vs. TERM-d11) (Figure 2)

  • While pancreatic trypsin activity was lower in pre-term piglets at birth (p < 0.05) compared to all other groups, we found the opposite for lipase activity, which was higher in pre-term piglets at birth (p < 0.05) compared to all other groups

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Summary

Introduction

Pre-maturity, which accounts for ∼10% of all live births, is associated with developmental complications and increased morbidity and mortality among pre-term infants born before the 32nd week of gestation [1]. A rapid adaptation of the digestive system is needed to facilitate nutrient uptake and growth, which is of particular importance after pre-term birth where feeding intolerance and maldigestion are common problems [2]. The newborn piglet, both pre-term and term, is a clinically relevant animal model for translational studies of newborn human infants [3,4,5]. Noteworthy for humans, amylase, lipase and esterase enzyme activities are natural components of human breast milk that may play an important role for luminal digestion of dietary lipids in the human neonate in the immediate post-natal period [16, 17]

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