Physical activity level is impaired and diet dependent in preterm newborn pigs

Abstract

Background: Preterm infants show delayed development of motor function after birth. This may relate to functional immaturity of many organs, including the gut and brain. Using pigs as model for preterm infants, we hypothesized that early initiation of enteral feeding stimulates both gut growth and neonatal physical activity. Methods:In experiment 1, preterm and term pigs were fed parenteral nutrition (PN) or PN plus bovine colostrum (BC, 16-64 ml/kg/d enterally) for 5 d. In experiment 2, preterm pigs were fed PN+BC or PN+formula for 5 d. In experiment 3, preterm pigs were fed BC, formula, or human milk (HM) for 10 d. Incubator home cage activity (HCA) was quantified by continuous camera recordings. results: Preterm birth was associated with reduced intestinal weight and HCA (experiment 1), and BC or formula supplementation increased intestinal weights and HCA (experiments 1+2). Enteral BC and HM feeding increased HCA, intestinal weights, and necrotizing enteritis resistance, relative to formula (experiment 3). conclusion: Preterm pigs show decreased physical activity, and the first enteral feeds diet dependently stimulate both gut growth and physical activity. The effects may arise from maturation of digestive, metabolic, and neurological functions, including gut serotonin production, by the first enteral feeds and milk bioactive factors.P reterm infants are a high-risk patient population with a variety of developmental complications, including delayed neurodevelopment and a high incidence of brain insults. Even when newborn preterm infants show no clinically observable brain defects, it is common to observe that such infants exhibit slower postnatal development of motor skills, compared with term infants. Even at term-corrected age, the brains in preterm infants may show compromised gray matter volume and altered developmental trajectory (1), probably explaining delayed neonatal arousal (2,3) and immature neuromuscular function and brain electroencephalography (4). In more longterm studies, preterm infants have shown reduced postural complexity (5) and lowered motor function (6), potentially persisting until school age (7), or even into adulthood (8). Thus, early impairment of physical locomotion in preterm infants may have long-term consequences.There is rapidly increasing evidence of functional links among the gastrointestinal tract (GIT), the diet, and the brain, especially in early life (9). Growth rate and nutrient intakes in early life may affect later neuromuscular and cognitive outcomes, but the mechanisms are largely unknown (10). Much focus has been devoted to the possible role of the lipid fraction of milk, but firm evidence for diet effects are lacking, not only in infants (11) but also in various animal models (12). In addition to the direct effects of nutrients and dietary factors on neurodevelopmental endpoints, indirect effects may arise from links between the early diet on gut growth, enteric nervous system, signaling molecules like serotonin (5-HT), and/ or gut microbiota. Studies in mice show...

Early gradual feeding with bovine colostrum improves gut function and NEC resistance relative to infant formula in preterm pigs

“…We suspect that this subclinical NEC phenotype observed in IF pigs would have eventually developed into more severe intestinal inflammation if feeding volumes had been advanced further, leading to the typical more severe clinical NEC symptoms such as apnea, discoloration, abdominal distension, and bloody stools. Whereas severe NEC will inevitably decrease physical activity in both pigs and infants, the initial feeding-related increase in physical activity, with small feeding volumes, was similar for formula-and colostrum-fed pigs (11). Although these results have to be confirmed in clinical practice, and should be related to different clinical complications and gestational ages at birth, they demonstrate that the preterm pig is an effective preclinical model to evaluate when and how best to advance enteral feeding for preterm infants (60).…”

“…After feeding preterm pigs for 5 days, NEC lesions and a series of gut structural, functional, immunological, and microbiological parameters were measured. Some of the preterm pigs in this study were previously used to show how the first enteral feeding increases physical activity (11) and a series of intestinal inflammatory and pattern recognition receptor genes with corresponding changes in chromatin structures (69).…”

Physical Activity and Gastric Residuals as Biomarkers for Region-Specific NEC Lesions in Preterm Neonates

“…Until euthanasia on day 5, each pig received its predefined, fixed PN and enteral formula volume intakes. The physical activity of each pig was recorded and quantified by infrared camera surveillance, as described in detail previously [11]. Further details of the animal procedures are found in the online supplementary material (for all online suppl.…”

“…Consequently, preterm pigs may be used as a sensitive model to understand the early clinical and physiological signs of NEC that enable timely preventive interventions in both piglets and infants. Based on our recent observations that physical activity is reduced and is diet dependent in preterm pigs [11], we investigated if physical activity during the first days after birth relates to clinical well-being, food intolerance and NEC lesions on day 5. We hypothesized that early postnatal onset of NEC is preceded by decreased physical activity and increased gastric residuals.…”

Animal Models of Fetal Medicine and Obstetrics

“…They have the same gestation length of around 115 days. Piglets are wellestablished models in fetal and neonatal research [21] and have been used, in particular, to study neonatal physiology in response to physical activity and nutrition [22].…”