Background: The incidence of necrotizing enterocolitis (NEC) and possibly also of sepsis is lower in preterm infants fed their own mother’s milk (hereafter ‘mother’s milk’) compared with formula-fed infants. It is unclear whether this is caused by the protective properties of breast milk or by the absence of cow’s milk. Especially in early life, mother’s milk is often unavailable to preterm infants, while minimal enteral nutrition is initiated immediately. Objectives: To determine whether there is an association between intake of mother’s milk during the first days of life and the combined outcome of sepsis, NEC and death over a prolonged period. Methods: Retrospective study in infants with a birth weight <1,500 g. Intake of mother’s milk and formula during the first 10 days of life was recorded. The occurrence of sepsis, NEC and death was registered during the first 60 days. Data were analysed using Cox regression analysis, taking confounders into account. Results: In total, 349 infants were included. Intake of mother’s milk during the first 5 days of life was associated with a lower incidence of NEC, sepsis and/or death during the first 60 days of life (hazard ratio (HR) in the category 0.01–50% intake of mother’s milk: 0.49, 95% confidence interval (CI) 0.28, 0.87; HR in the category 50.01–100% intake of mother’s milk: 0.50, 95% CI 0.31, 0.83, both compared to no mother’s milk). During days 6–10, the protective effect was only present if >50% of the total intake was mother’s milk (HR = 0.37, 95% CI 0.22, 0.65). Conclusion: The type of enteral nutrition during the first 10 days of life is associated with the risk of NEC, sepsis and/or death during the first 60 days of life.

Infections and necrotizing enterocolitis, major causes of mortality and morbidity in preterm infants, are reduced in infants fed their own mother's milk when compared with formula. When own mother's milk is not available, human donor milk is considered a good alternative, albeit an expensive one. However, most infants at modern neonatal intensive care units are predominantly fed with own mother's milk. The benefits of add-on donor milk over formula are not clear. OBJECTIVE To determine whether providing donor milk instead of formula as supplemental feeding whenever own mother's milk is insufficiently available during the first 10 days of life reduces the incidence of serious infection, necrotizing enterocolitis, and mortality. DESIGN, SETTINGS, AND PARTICIPANTS The Early Nutrition Study was a multicenter, double-blind randomized clinical trial in very low-birth-weight infants (birth weight <1500 g) admitted to 1 of 6 neonatal intensive care units in the Netherlands from March 30, 2012, through August 17, 2014. Intent-to-treat analysis was performed. INTERVENTIONS Infants received pasteurized donor milk or preterm formula during the first 10 days of life if own mother's milk was not (sufficiently) available. MAIN OUTCOMES AND MEASURES The primary end point was cumulative occurrence of serious infection (sepsis or meningitis), necrotizing enterocolitis, or mortality during the first 60 days of life. RESULTS A total of 930 infants were screened for inclusion; 557 were excluded, resulting in 373 infants (183 receiving donor milk and 190 receiving formula) who were evaluated by intent-to-treat analysis (median birth weight, 1066 g; mean gestational age, 28.4 weeks). Own mother's milk comprised 89.1% and 84.5% of total mean intake during the intervention period for the donor milk and formula groups, respectively. The incidence of the combined outcome was not different (85 [44.7%] [formula] vs 77 [42.1%] [donor milk]; mean difference, 2.6%; 95% CI, −12.7% to 7.4%). The adjusted hazard ratio was 0.87 (95% CI, 0.63-1.19; P = .37). CONCLUSIONS AND RELEVANCE In the current study, pasteurized donor milk and preterm formula as supplemental feeding during the first 10 days of life yielded similar short-term outcomes in very low-birth-weight infants regarding safety and efficacy when own mother's milk availability was insufficient. Future studies investigating longer duration of use of human donor milk on short-term and long-term outcomes are necessary. TRIAL REGISTRATION trialregister.nl Identifier: NTR3225

Summary This study, performed as part of the international EarlyNutrition research project (http://www.project-earlynutrition.eu), provides a systematic review of systematic reviews on the effects of nutritional interventions or exposures in children (up to 3 years of age) on the subsequent risk of obesity, overweight and adiposity. Electronic databases (including MEDLINE, Embase and Cochrane Library) were searched up until September 2015. Forty systematic reviews were included. A consistent association of breastfeeding with a modest reduction in the risk of later overweight and obesity in childhood and adulthood was found (the odds decreased by 13% based on high‐quality studies), but residual confounding cannot be excluded. Lowering the protein content of infant formula is a promising intervention to reduce the risk of later overweight and obesity in children. There is no consistent evidence of an association of the age of introducing complementary foods, sugar‐sweetened beverage or energy intake in early childhood with later overweight/obesity, but there are some indications of an association of protein intake during the complementary feeding period with later overweight/obesity. There was inadequate evidence to determine the effects of other nutritional interventions or exposures, including modifications of infant formula composition, fat intake or consumption of different food groups.

The current evidence is insufficient for assessing the effects of reducing the protein concentration in infant formulas on long-term outcomes, but, if confirmed, this could be a promising intervention for reducing the risk of overweight and obesity in children. In view of the limited available evidence, more studies replicating effects on long-term health outcomes are needed.

The cause of growth restriction in preterm infants is multifactorial, but it has been estimated that about 50% of the variance in early postnatal growth can be attributed to nutrition. Very low birth weight (VLBW) infants who were born small-for-gestational age (SGA) seem to have the highest risk to become growth restricted. Possibly, the intrauterine growth-retarded preterm infant is metabolically different from its appropriately grown counterpart and therefore has different nutritional needs. Neonatal nutrition and the resulting postnatal growth are major determinants in the short- and long-term outcomes of preterm neonates. Although having favorable effects on neurodevelopmental outcome, rapid postnatal weight gain after a period of nutritional restriction is associated with the development of insulin resistance and metabolic syndrome in later life. It seems likely that minimization of postnatal growth failure will decrease the need for catch-up growth and thereby decrease the risk of developing cardiovascular risk factors. Monitoring postnatal growth with current growth charts is complicated. Most growth charts that are currently being used are a reflection of current (nutritional) practices and are not a prescription of how VLBW should grow under optimal conditions. In addition to body weight, other aspects of growth such as lean body mass and length gain should also be taken into account when assessing the quality of postnatal growth. Noninvasive measurements of infant body composition are useful tools in evaluating the success of different nutritional interventions. However, all currently available methods have substantial drawbacks. A relatively new and promising method is air displacement plethysmography. This method still needs to be validated in preterm neonates. In conclusion, neonatal nutrition is a major determinant in the short- and long-term outcomes of preterm neonates. Monitoring postnatal growth is complicated by the lack of prescriptive growth charts and noninvasive measurements to assess the quality of growth.