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

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 postconceptional 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 days of gestation) and term pigs ( n = 41, 116 days of gestation) were delivered by caesarean section and euthanized at birth ( day 1) or postnatal day 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 day 11 (goblet cells, gut permeability, and cytotoxic T cells). The colon microbiota showed limited differences between preterm and term pigs at this time. At the same PCA, preterm 11-day-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. NEW & NOTEWORTHY Postnatally, preterm infants are often considered to reach a physiological maturation similar to that in term infants when they reach term-corrected postconceptional age (PCA). Using preterm pigs as models, we show that PCA may be a poor measure of gut and immune maturation because environmental triggers (regardless of PCA at birth) are critical. Possibly, PCA is only relevant to evaluate physiological maturation of organs that develop relatively independent of the external environment (e.g., the brain).