Predicting disease severity of necrotizing enterocolitis: How to identify infants for future novel therapies

Abstract

Necrotizing enterocolitis (NEC) remains a very devastating problem within the very low birth weight neonatal population. Several experimental therapies are being tested in animal models and soon may be ready for human trials. Despite this progress, we currently have no way to identify infants who would be optimal targets for therapy. Specifically, we are unable to predict which infants will progress to the more severe Bell's stage of disease that may necessitate surgery. Ideally, an algorithm could be constructed that would encompass multiple neonatal and maternal risk factors as well as potential biologic markers of disease so that these infants could be identified in a more timely fashion. This review summarizes the known risk factors and biomarkers of disease in hopes of stimulating clinical research to identify such an “early warning” NEC algorithm.

Current Knowledge of Necrotizing Enterocolitis in Preterm Infants and the Impact of Different Types of Enteral Nutrition Products

“…Three major risk factors for NEC are <32 wk gestational age, <1500 g at birth, and cardiac complications (10). NEC is more prevalent in preterm infants (19), with ;85% of cases occurring in infants born <35 wk gestation, whereas only 7-15% of cases occur in late-preterm (35-36 wk gestation) or term infants (37-42 wk gestation) (20)(21)(22). The incidence of NEC also drastically increases from 0.7% to 6.6% for infants with a birth weight <1500 g (10).…”

“…Bovine milk-based and HM-based HM fortifiers (HMFs) contain additional energy, protein, fat, vitamins, and minerals (56) to ensure adequate growth, neurodevelopment, and bone mineralization (53). HMFs are typically added once enteral intake reaches 100 mL $ kg 21 $ d 21 to ensure the gut can tolerate more concentrated feeds. Some clinicians prefer to start the fortifier at 80 mL $ kg 21 $ d 21 or earlier to meet protein and energy goals sooner.…”

“…A tool used to monitor and evaluate health and nutritional status for preterm infants is the Fenton preterm growth charts for boys and girls (57). Expected postnatal growth velocities of preterm infants are based on an intrauterine growth of ;15 g $ kg 21 $ d 21 (8,54). Although this approach may not be precise given the differences between intra-and extrauterine environments, to our knowledge there are currently no alternative standards (57).…”

“…Piglets on the elemental diet were fed intragastrically at a continuous rate, whereas piglets on the polymeric formula were fed orally 3 times/d. The elemental diet provided less calories and protein than the polymeric diet (165 kcal $ kg 21 body weight or intestinal cell morphology (crypt depth, villus height, and muscle thickness) at the end of the 6-d trial. In contrast to the aforementioned piglet study (86), Stoll et al (88) found that cell proliferation and protein synthesis, measured by the percentage of labeled crypt cells in the S-phase and ornithine decarboxylase activity, were considerably higher in the proximal jejunum and ileum of the piglets fed an elemental diet.…”

Necrotising Enterocolitis - epidemiology and imaging

“…83 Luig and Lui 99 Long term complications include strictures of the bowel in 20--57% of survivors, 24,113 adhesions, enteric fistulas, intestinal insufficiency, and neurodevelopmental impairment, as well as secondary complications due to parenteral nutrition and prolonged intensive care. 2,10,207,211 Data from Canada and Sweden show that 73-83% of survivors after extremely preterm birth have no severe neurodevelopmental impairment. 212,213 NEC, however, significantly increases the risk.…”