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Necrotizing enterocolitis (NEC) has been recognized for well over 5 decades yet remains the most common life-threatening surgical emergency in the newborn. The incidence of NEC has decreased steadily in preterm and very-low-birthweight infants over several decades and is typically uncommon in term newborns and infants with a birthweight greater than 2,500 g. Evidence accumulating during the past decade, however, suggests that practitioners should consider NEC in this broader subset of term infants with chromosomal and congenital anomalies complicated by heart or gastrointestinal defects when signs and symptoms of feeding intolerance, abdominal illness, or sepsis are present. The short- and long-term consequences of NEC are devastating in all infants, and although early disease recognition and treatment are essential, promoting human milk feeding as a primary modality in prevention is critical. This article highlights our current understanding of the pathophysiology, the clinical presentation, the risk factors for NEC in term infants compared with premature infants, and the treatment of NEC and discusses strategies in the prevention of NEC. Finally, we review the long-term consequences of NEC and the importance of primary care practitioners in the long-term care of infants after hospitalization for NEC.

ClinicalTrials.gov: NCT00854633.

Objective To evaluate safety and explore efficacy of recombinant human lactoferrin (talactoferrin, TLf) to reduce infection. Study design We conducted a randomized, double blind, placebo-controlled trial in 6 0 infants with birth weights of 750 to 1500 grams. Each infant received enteral TLf or placebo on day 1 through 28 days of life; TLf dose was 150 mg/kg/12 hour. Primary outcomes were bacteremia, pneumonia, urinary tract infection, meningitis and necrotizing enterocolitis. Secondary outcomes were sepsis syndrome and suspected NEC. We recorded clinical, laboratory and radiologic findings, diseases, and adverse events in a database used for statistical analyses. Results Infants in the two groups had similar demographics. We attributed no enteral or organ-specific adverse events to TLf. There were two deaths in the group with TLf (posterior fossa hemorrhage and post-discharge sudden infant death), and one infant given placebo died of necrotizing enterocolitis. Hospital-acquired infections in the group with Tlf were 50% of that observed in infants fed placebo (p<0.04), including fewer blood or line infections, urinary tract infections, and pneumonia. Fourteen infants treated with TLf-weighing <1 kg at birth weight had no Gram-negative infections versus three of 14 infants given placebo. Non-infectious outcomes did not differ statistically in the two arms. No differences in growth or neurodevelopment occurred among infants treated with TLf and placebo during a one-year, post-hospitalization period. Conclusion We found no clinical or laboratory toxicity and a trend towards less infectious morbidity in infants treated with TLf. Trial registration ClinicalTrials.gov: NCT00854633.

Objective: Articles previously published by Sullivan et al. and Cristofalo et al. were reanalyzed using the proportion of cow milk-based nutrition received to determine whether that affected clinical outcomes during hospitalization for infants birth weight 500–1250 g. Abrams et al. showed in the same cohort incidences of necrotizing enterocolitis (NEC), NEC requiring surgery and sepsis increased proportionally to the amount of dietary cow milk.Methods: The data from the two studies conducted under essentially the same protocol were combined yielding a cohort of 260 infants receiving a diet ranging from 0% to 100% cow milk. Data analysis utilized negative binomial regression which mitigates differences between subjects in terms of their time on study by incorporating that number into the statistical model. The percent of cow milk-based nutrition was the only predictor investigated.Results: For all outcomes the larger the amount of cow's milk in the diet the greater the number of days of that intervention required. A trend toward statistical significance was seen for ventilator days; however, only parenteral nutrition (PN) days and days to full feeds achieved statistical significance.Conclusions: Incorporation of any cow milk-based nutrition into the diet of extremely premature infants correlates with more days on PN and a longer time to achieve full feeds. There was a nonstatistically significant trend toward increased ventilator days. These represent additional clinical consequences of the use of any cow milk-based protein in feeding EP infants.

and Niklas have disclosed no financial relationships relevant to this article. This commentary does contain a discussion of an unapproved/ investigative use of a commercial product/ device. Educational Gaps1. In clinical trials, lactoferrin (LF) shows promise for reducing mortality and preventing neonatal infections, particularly late-onset sepsis and necrotizing enterocolitis. 2. Until the U.S. Food and Drug Administration approves of LF-containing preparations to ward off neonatal infection, colostrum feeding should be encouraged for preterm infants as soon as possible after birth because of its high LF concentrations. AbstractHuman milk is the ideal nutrient for neonates. Breastfeeding exposes neonates to maternal microflora, provides host protection, and has proteins that mediate immune system development. Lactoferrin (LF) is the major whey protein in mammalian milk, and its multifunctional characteristics have shown importance in preventing infections. Ferric iron binding and natural peptide antibiotic properties of LF likely promote a healthy intestinal microbiome that prevents bacterial translocation and mediates optimal epithelial growth and differentiation. An established asset of LF is stimulation of naïve dendritic cells; this initiates the emergence of neonatal Th1 helper cells, thereby reversing the Th2 bias associated with pregnancy. Moreover, LF promotes development of Peyer patches, which leads to enhanced IgA secretion into the intestinal lumen. The anti-inflammatory properties of LF involve its binding of endotoxin and other proinflammatory molecules released by intestinal pathogens. LF also blocks receptors that microbes use for epithelial invasion, and thus LF mitigates a proinflammatory response by the host during infection. These properties of LF are known from basic science research and preclinical investigations, and they have resulted in the enteral use of bovine and recombinant human LF to prevent neonatal late onset sepsis. Bovine LF has been shown to reduce the incidence of late onset sepsis in extremely preterm infants, but Food and Drug Administration approval of LF for use in the NICU has not taken place. Because LF is currently available only for scientific investigations, the feeding of a mother's milk is encouraged shortly after birth because the concentration of LF is highest in colostrum.

Extremely preterm infants should receive colostrum, a natural lactoferrin concentrate, immediately after birth and, ideally, continue on breast milk throughout the hospital stay. This practice appears well tolerated, but additional experience will tell us whether this practice reduces the prevalence of necrotizing enterocolitis.

Congenital hypothyroidism (CH) is the most common endocrine disorder affecting the newborn. Universal newborn screening (NBS) has virtually eliminated the static encephalopathy and devastating neurodevelopmental syndrome known as cretinism. This report describes the presentation of an infant referred by the primary pediatrician to our hospital at 12 days of age for confirmatory testing after the NBS was consistent with CH. The infant had hypoglycemia secondary to lethargy and poor feeding and required transfer to the neonatal intensive care unit for worsening abdominal distension despite normalization of serum thyroid function tests following hormone replacement. In particular, the recalcitrant ileus and secondary bowel obstruction resulted in an additional diagnostic workup and lengthened hospital day. Our report highlights the acute gastrointestinal consequences of hypothyroidism despite evidence of effective treatment. We believe that the preclinical detection and immediate therapy for CH have lessened the prevalence of this presentation in general practice, and hence practitioners are less likely to be familiar with its natural history and management.