Abstract
Objectives: Maternal milk is often absent or in limited supply just after preterm birth. Many preterm infants are therefore fed infant formula as their first enteral feed despite an increased risk of feeding intolerance, necrotizing enterocolitis (NEC), and infection. Using preterm pigs as a model for preterm infants, we hypothesized that bovine colostrum given before or after formula feeding would alleviate formula-induced detrimental effects during the first days after preterm birth.Methods: A total of 74 preterm pigs received gradually increasing volumes of formula (F) or bovine colostrum (C) until day 5, when they were euthanized or transitioned to either C or F for another 4 days, resulting in six groups: C or F until day 5 (C5, F5, n = 11 each), C or F until day 9 (CC, FF n = 12–13 each), C followed by F (CF, n = 14), and F followed by C (FC, n = 13).Results: Systemically, colostrum feeding stimulated circulating neutrophil recruitment on day 5 (C5 vs. F5, P < 0.05). Relative to initial formula feeding, initial colostrum feeding promoted the development of systemic immune protection as indicated by a decreased T-helper cell population and an increased regulatory T-cell population (CC + CF vs. FC + FF, P < 0.01). In the gut, colostrum feeding improved intestinal parameters such as villus heights, enzymes, hexose absorption, colonic goblet cell density, and decreased the incidence of severe NEC (27 vs. 64%), diarrhea (16 vs. 49%), and gut permeability on day 5, coupled with lowered expression of LBP, MYD88, IL8, HIF1A, and CASP3 (C5 vs. F5, all P < 0.05). On day 9, the incidence of severe NEC was similarly low across groups (15–21%), but diarrhea resistance and intestinal parameters were further improved by colostrum feeding, relative to exclusive formula feeding (CC, CF, or FC vs. FF, respectively, all P < 0.05). The expression of MYD88 and CASP3 remained downregulated by exclusive colostrum feeding (CC vs. FF, P < 0.01) and colostrum before or after formula feeding down regulated HIF1A and CASP3 expression marginally.Conclusion: Colostrum feeding ameliorated detrimental effects of formula feeding on systemic immunity and gut health in preterm newborns, especially when given immediately after birth.
Highlights
Optimal nutrition supply is an essential aspect of clinical care for very preterm infants
For pigs euthanized on day 9, there were four feeding groups: colostrum feeding until day 9 (CC, n = 12), colostrum feeding for 4 days followed by formula until day 9 (CF, n = 14), formula feeding for 4 days followed by colostrum until day 9 (FC, n = 13), and formula feeding until day 9 (FF, n = 13)
A sample size of 10–15 piglets per group is often used in this model to detect a ∼50% reduction in necrotizing enterocolitis (NEC) incidence (α = 0.05, β = 80%), and this reduction is expected when comparing bovine colostrum and infant formula feeding according to our previous studies [21]
Summary
Optimal nutrition supply is an essential aspect of clinical care for very preterm infants (gestational age < 32 weeks). Clinical nutrition guidelines recommend initiation of enteral feeding within a few hours, and the goal is to minimize time to full enteral feeding (TFF) without inducing feeding intolerance and other intestinal complications, such as necrotizing enterocolitis (NEC) [1,2,3,4] This goal is better achieved when maternal milk (MM) is available. Formula remains associated with longer TFF, increased risk of feeding intolerance and NEC [5], and impaired systemic immunity (e.g., more sepsis) [6, 7]. This may be due to the fact that formula lacks many bioactive components that are present in MM and beneficial to immune defense (e.g., alpha-lactalbumin, lactoferrin, osteopontin) [8]. Milk fat is replaced by vegetable oil during formula processing, and formula lacks milk fat globule membrane, which consists of numerous lipids and proteins that have functions on immunerelated pathways [10, 11]
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