Platelet-Activating Factor Concentration in the Stool of Human Newborns: Effects of Enteral Feeding and Neonatal Necrotizing Enterocolitis

Abstract

Epidemiologic studies have identified enteral feedings as a risk factor for necrotizing enterocolitis (NEC). Enteral feedings provide the substrate for colonization of the newborn gut with gram-negative bacteria with endotoxin production, which may trigger the production of endogenous inflammatory mediators, including platelet-activating factor (PAF). In this prospective study, we examined the effect of enteral feeding on PAF concentration in the stool of preterm and full-term human newborns. The concentration of PAF levels in stool was measured at the following times: at passage of first meconium, within 24 h prior to the onset of feedings, at the 3rd and 14th day of feeding and at any time confirmed NEC developed. Stool samples also were analyzed for levels of acetylhydrolase, the PAF breakdown enzyme. Stool PAF concentration rose significantly following the start of enteral feedings. The mean PAF concentration for day 14 samples was significantly higher than the mean concentration of meconium samples (4.90 ± 1.03 vs. 1.81 ± 0.38 ng/g, p < 0.05) and day 0 samples (4.90 ± 1.03 vs. 1.79 ± 0.39 ng/g, p < 0.05). For the 7 patients diagnosed with definite NEC, the mean stool PAF concentration was 12.42 ± 0.77 ng/g, significantly elevated compared to the mean PAF levels in stool from healthy infants at all sampling times (p < 0.01). There was no significant change in acetylhydrolase activity at any of the sampling times. Stool PAF concentration increases with the provision of enteral feedings and rises further with the development of NEC. Since stool acetylhydrolase activity remained unchanged, we speculate the increase of PAF in stool likely represents increased PAF production at the local level following the provision of enteral feedings or the development of neonatal necrotizing enterocolitis.

Comparison of the efficacy of serum amyloid A, C-reactive protein, and procalcitonin in the diagnosis and follow-up of necrotizing enterocolitis in premature infants

“…Therefore, the absence of a consistent, reliable, and early marker of intestinal inflammation in the peripheral blood has been one of the great challenges for the diagnosis and management of NEC [7,26]. Although some serum markers such as CRP, interleukin-6, and platelet-activating factor have been studied, all of them showed a lack of specificity [9,27,28]. There are also conflicting data about the use of these inflammatory mediators in the diagnosis and follow-up of NEC [8][9][10][11][12].…”

Feeding strategies and necrotizing enterocolitis

“…Seven of the infants subsequently developed NEC. The mean stool PAF level in the infants with NEC was approximately 3 to 4 times higher than levels seen in the stools from healthy infants at similar ages [28]. Ewer et al [29] have shown in a neonatal pig model that the administration of the PAF antagonist WEB2170 ameliorates vascular responses after hypoxiaendotoxin challenge, suggesting that this animal model may be useful in evaluating preventative or therapeutic interventions for infants.…”

“…The initiation of enteral feeding results in a surge of plasma PAF in preterm infants [27]. Amer et al [28] measured PAF content in stools of 68 preterm infants before and after the initiation of feeding. Seven of the infants subsequently developed NEC.…”

Pathogenesis of neonatal necrotizing enterocolitis

“…Elevated stool PAF concentrations were detected (1) when enteral nutrition was initiated in preterm neonates, and (2) in patients with NEC [108,109].…”