Abstract

Background: Preterm infants are born with an immature immune system, limited passive immunity, and are at risk of developing bacteremia and sepsis in the postnatal period. We hypothesized that enteral feeding, with or without added immunoglobulins, improves the clinical response to systemic infection by coagulase negative staphylococci.Methods: Using preterm cesarean delivered pigs as models for preterm infants, we infused live Staphylococcus epidermidis (SE, 5 × 109 colony forming units per kg) systemically 0–3 days after birth across five different experiments. SE infection responses were assessed following different gestational age at birth (preterm vs. term), enteral milk diets (bovine colostrum, infant formula with or without added porcine plasma) and with/without systemic immunoglobulins. Pigs infected with SE were assessed 12–48 h for clinical variables, blood bacteriology, chemistry, hematology, and gut dysfunction (intestinal permeability, necrotizing enterocolitis lesions).Results: Adverse clinical responses and increased mortality were observed in preterm vs. term pigs, when infected with SE just after birth. Feeding bovine colostrum just after birth improved blood SE clearance and clinical status (improved physical activity and intestinal structure, fewer bone marrow bacteria), relative to pigs fed infant formula. A few days later, clinical responses to SE bacteremia (hematology, neutrophil phagocytic capacity, T cell subsets) were less severe, and less affected by different milk diets, with or without added immunoglobulins.Conclusion: Prematurity increases the sensitivity of newborn pigs to SE bacteremia, potentially causing sepsis. Sensitivity to systemic SE infection decreases rapidly in the days after preterm birth. Both age and diet (parenteral nutrition, colostrum, milk, formula) may influence gut inflammation, bacterial translocation and systemic immune development in the days after birth in preterm newborns.

Highlights

  • Preterm infants have an increased risk of infection in the neonatal period

  • To investigate the influence of gestational age on the response to Staphylococcus epidermidis (SE) inoculation, we tested the effects of SE or saline infusion (SE or CON) shortly after term or preterm birth (TERM or PRE)

  • Considering the high clinical affection from the SE infusion, remaining preterm pigs were euthanized after 24 h

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Summary

Introduction

Preterm infants have an increased risk of infection in the neonatal period. Use of infant formula, or prolonged use of parenteral nutrition, and associated use of catheters, increases the risk of LOS [3]. Severe inflammation of the gut is associated with sepsis in preterm neonates, but it is unknown if this effect is due mainly to increased bacterial translocation, or if local gut inflammatory conditions adversely affect systemic immunity. The type of nutrition after birth (parenteral, or enteral feeding with formula, milk or colostrum) rapidly affects gut maturation in immunocompromised preterm infants and pigs [6]. Whether the first enteral feeding influences systemic immunity in such infants is less clear, clinical outcomes may be improved after early feeding with milk or colostrum of either human or animal origin [7,8,9]. We hypothesized that enteral feeding, with or without added immunoglobulins, improves the clinical response to systemic infection by coagulase negative staphylococci

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