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.

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.

There is an intense interest among neonatal caregivers as to whether lactoferrin given enterally may reduce the incidence of necrotizing enterocolitis in preterm infants. This review presents scientific and clinical evidence that lactoferrin alleviates or prevents this life-threatening disease. Preclinical studies in neonatal rats showed that lactoferrin given orally before enteral infection with pathogenic Escherichia coli reduced bacteremia and mortality. A multicentered clinical trial found that very low-birth weight preterm infants given bovine lactoferrin had a significant reduction in late-onset sepsis; there was also a trend towards a diminished incidence of necrotizing enterocolitis. Although multicentered trials of lactoferrin use in preterm infants are near completion, regulatory burdens required to bring lactoferrin to the bedside may limit its availability. 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.

Introduction: Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity, characterised by impaired alveolarisation and pulmonary vascular development. BPD has been associated with an increased risk of respiratory morbidity, neurodevelopmental impairment and death, intensifying a lifelong health and economic burden. The current standard of neonatal care is primarily supportive, with no approved therapies to restore lung development, promote maturation and lung growth or prevent long-term sequelae. Therefore, there is a critical unmet need for novel interventions, particularly in high-risk, extremely premature (EP) infants. In EP infants, serum insulin-like growth factor-1 (IGF-1) levels decrease rapidly and remain low for the first weeks after birth relative to the corresponding foetal levels in utero. Methods and analysis: OHB-607, a recombinant human IGF-1 combined with its binding protein-3, may replenish IGF-1 during this period of deficiency and support lung and vascular maturation. OHB-607 is being investigated as a first-line therapy to prevent severe BPD in EP infants in a Phase 2b, multicentre, open-label, randomised trial. Here, we present the Phase 2b study protocol. Target enrolment is 338 EP infants. To mimic physiological IGF-1 levels in utero, OHB-607 will be administered starting within 24 hours of birth until 29 ⁺⁶ weeks postmenstrual age (PMA) via continuous intravenous infusion. The primary endpoint is the incidence of severe BPD, based on the modified National Institute of Child Health and Human Development criteria, or death by 36 weeks PMA. Key secondary endpoints include weaning from respiratory support at 12 months corrected age and BPD severity (Grade 2/3) by the 2019 Neonatal Research Network definition. Other secondary endpoints include other complications of prematurity, neurodevelopmental outcomes and family and infant well-being and social functioning through 24 months’ corrected age, and pharmacokinetic and dynamic impact of OHB-607 on the multisystem consequences of prematurity, and overall safety in modifying the natural history of BPD and its consequences. Ethics and dissemination: Findings will be disseminated via local and international congresses and publications. Trial registration number: ClinicalTrials.gov ( NCT03253263 ), Clinicaltrialsregister.eu (EudraCT: 2018-001393-16), Euclinicaltrials.eu (EUCT: 2024-515914-41-00) and Pmda.go.jp (PMDA: jRCT2031240339).

Extremely preterm (EP) infants have high rates of respiratory morbidity and correspondingly high healthcare resource utilization.Data from the PHARMO Perinatal Research Network were analyzed to qua...