Abstract
Prior to birth, the neonate has limited exposure to pathogens. The transition from the intra-uterine to the postnatal environment initiates a series of complex interactions between the newborn host and a variety of potential pathogens that persist over the first few weeks of life. This transition is particularly complex in the case of the premature and very low birth weight infant, who may be susceptible to many disorders as a result of an immature and underdeveloped immune system. Chief amongst these disorders is necrotizing enterocolitis (NEC), an acute inflammatory disorder that leads to necrosis of the intestine, and which can affect multiple systems and have the potential to result in long term effects if the infant is to survive. Here, we examine what is known about the interplay of the immune system with the maternal uterine environment, microbes, nutritional and other factors in the pathogenesis of neonatal pathologies such as NEC, while also taking into consideration the effects on the long-term health of affected children.
Highlights
The characteristic underdevelopment of the neonatal immune system predisposes infants to inflammatory disorders, including necrotizing enterocolitis (NEC), an acute inflammatory disease that develops in up to 10% of premature infants [1]
Unique characteristics of the neonatal immune system that confer a susceptibility to the development of diseases like NEC include the potential exposure of priming antigens within the maternal uterine environment [4], changes in cytokine, growth factor and hormone signaling pathways [5, 6], nutritional effects related to exposure to probiotics and breastmilk [7], as well as patterns of microbial colonization in the gut and other mucosa that are specific to the neonatal period [8]
These direct effects of TLR4 activation cumulatively promote bacterial translocation [76], which leads to further TLR4 activation on the endothelium, leading to loss of endothelial nitric oxide synthase and associated vasoconstriction [77], which in turn contributes to the development of ischemic necrosis in NEC
Summary
The characteristic underdevelopment of the neonatal immune system predisposes infants to inflammatory disorders, including necrotizing enterocolitis (NEC), an acute inflammatory disease that develops in up to 10% of premature infants [1]. Unique characteristics of the neonatal immune system that confer a susceptibility to the development of diseases like NEC include the potential exposure of priming antigens within the maternal uterine environment [4], changes in cytokine, growth factor and hormone signaling pathways [5, 6], nutritional effects related to exposure to probiotics and breastmilk [7], as well as patterns of microbial colonization in the gut and other mucosa that are specific to the neonatal period [8]. In infants who are fortunate to survive NEC, lifelong problems may develop, including short bowel syndrome [13], nutritional deficiencies impact growth [14], and persistent white matter injury associated with cognitive impairment [10, 15,16,17] among others
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