Neonatal gut and immune maturation is determined more by postnatal age than by postconceptional age in moderately preterm pigs

Abstract

Preterm infants have immature organ functions that predispose them to gut and immune disorders. Developmental delays at preterm birth may affect various organs differently at term-corrected age. We hypothesized that gut and immune maturation in moderately preterm neonates depends more on birth and postnatal factors than on advancing post-conceptional age (PCA). Using preterm pigs as models, we investigated how gut and immune parameters develop until term-corrected age, and how these differ from those in term counterparts. Preterm (n=43, 106 d of gestation) and term pigs (n=41, 116 d of gestation) were delivered by caesarean section, and euthanized at birth (d 1) or postnatal d 11 (term-corrected age for preterm pigs), using identical rearing conditions. Relative to term pigs, preterm pigs had lower blood oxygenation, glucose, and cortisol levels, lower gut lactase activity, villus height and goblet cell density, and lower blood neutrophil, helper-T and cytotoxic-T cell numbers at birth. Despite slower growth in preterm pigs, most intestinal and immune parameters increased markedly after birth in both groups. However, some parameters remained negatively affected by preterm birth until postnatal d 11 (goblet cells, gut permeability, cytotoxic-T cells). The colon microbiota showed limited differences between preterm and term pigs at this time. At the same PCA, preterm 11 d-old pigs had higher blood leukocyte numbers and gut enzyme activities but lower villus height and blood cytotoxic-T cell numbers, relative to newborn term pigs. Birth and postnatal factors, not advancing PCA, are key determinants of gut and immune maturation in moderately preterm neonates.

Gut and immune effects of bioactive milk factors in preterm pigs exposed to prenatal inflammation

“…In addition to gut effects, some systemic immune parameters were also modulated by colostrum feeding, including the increased percentage of blood T-helper cells, as well as decreased blood neutrophil phagocytosis function, relative to formula feeding. Increased percentage of blood T-helper cells were associated with the immune maturation over the first two weeks of life in preterm pigs (40), suggesting systemic immune maturational effects of bovine colostrum in the current study. In contrast, decreased neutrophil phagocytic capacity may relate to the numerical increase in blood neutrophil counts in COL vs.…”

Bovine Colostrum Before or After Formula Feeding Improves Systemic Immune Protection and Gut Function in Newborn Preterm Pigs

“…Plasma inflammatory mediators, such as C-reactive protein, interleukin (IL)-1β, and IL-6 at euthanasia were analyzed by commercial porcine DuoSet ELISA kits according to the manufacturer's protocols (R&D Systems Denmark, Abingdon, United Kingdom). On days 5 and 9, arterial blood from the umbilical catheter was collected before euthanasia for the characterization of immune cell subsets and functions, including blood cell count by an automatic cell counter (Advia 2120i Hematology System, Siemens, Germany), T-cell profiling, and ex vivo neutrophil phagocytosis function by flow cytometry, as previously described (24,25). Neutrophil phagocytosis function was measured as the proportion of phagocytic neutrophils using pHrodo Red Escherichia coli bioparticles phagocytosis kit for flow cytometry (Thermofisher).…”

Impaired Neonatal Immunity and Infection Resistance Following Fetal Growth Restriction in Preterm Pigs

“…Collectively, our results suggest that preterm pigs born moderately growth restricted were immune suppressed or experienced some delay in immune maturation, which may be further exacerbated by neonatal antibiotic use. Such effects may be most pronounced in the immediate neonatal period (e.g., the first 1-2 weeks), as supported by the limited effects of moderate FGR and prematurity on blood immune parameters (10,53) and gut and brain development beyond the first 2 weeks of life (53,54). Correspondingly, a dysfunctional immune system and an increased risk of infections in preterm infants with fetal growth restriction suggest special care and medical attention in this population to avoid damaging infections in the critical neonatal period.…”