Abstract
BackgroundMorbidities of impaired immunity and dysregulated inflammation are common in preterm infants. Postnatal Intestinal development plays a critical role in the maturation of the immune system and is, in part, driven by exposure to an enteral diet.ObjectiveThe aim of this study was to evaluate the influence of the timing of the first enteral feeding on intestinal inflammation and risk of disease.Methods130 infants <33 weeks’ gestation were studied. Maternal and infant data were abstracted from the medical record. Single and multiplex ELISA assays quantified cytokines from fecal and serum samples at two weeks postnatal age.ResultsA delay in enteral feedings after the third postnatal day is associated with a 4.5 (95% CI 1.8-11.5, p=0.002) fold increase in chronic lung disease, 2.9 (1.1-7.8, p=0.03) fold increase in retinopathy of prematurity, and 3.4 (1.2-9.8, p=0.02) fold increase in multiple comorbidities compared to infants fed on or before the third day. Additionally, a delay in the initiation of feedings is associated with increased fecal IL-8 levels and a decreased IL-10:IL-8 ratio.ConclusionsA delay in enteral feeding is associated with intestinal inflammation and increased risks of morbidities. To improve neonatal outcomes, early nutritional practices need to be reevaluated.
Highlights
The intestine is the largest immune organ in the human body
A delay in enteral feedings after the third postnatal day is associated with a 4.5 fold increase in chronic lung disease, 2.9 (1.1-7.8, p=0.03) fold increase in retinopathy of prematurity, and 3.4 (1.2-9.8, p=0.02) fold increase in multiple comorbidities compared to infants fed on or before the third day
A delay in the initiation of feedings is associated with increased fecal IL-8 levels and a decreased IL-10:IL-8 ratio
Summary
Recent human and animal data suggest that postnatal gastrointestinal development as well as microbial colonization are critical for proper host immune function [1], [2]. This is supported by data in mice reared in germ free conditions where prevention of normal microbial colonization leads to underdeveloped gut associated lymphoid organs, decreased expression of MHC-II on antigen presenting cells and reduced IgA production [3], [4], [5]. Inflammation and infections early in life have been linked to chronic lung disease (CLD), retinopathy of prematurity (ROP) [8], necrotizing enterocolitis (NEC), periventricular leukomalacia (PVL) [9,10] and impaired neurodevelopment [11]. Postnatal Intestinal development plays a critical role in the maturation of the immune system and is, in part, driven by exposure to an enteral diet.
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