Necrotizing enterocolitis (NEC) is a severe multifactorial disease in preterm neonates associated with high morbidity and mortality. Better insight into prognostic values of the many reported factors associated with NEC is needed to enable identification of neonates at risk for NEC. The aim was to systematically review the literature to identify independent risk factors for NEC from the literature. Medline, Cochrane, Embase, Pubmed and Google Scholar were searched systematically for cohort studies reporting prognostic factors for NEC in neonates using multivariable analysis. Studies were scored with the Quality In Prognosis Studies tool (QUIPS). From 5154 initial hits, 14 prognostic studies were included, with various designs. Study quality was rated high in three studies, moderate or low in the 11 others. Significant prognostic factors for NEC reported in at least two studies were: low birth weight, small for gestational age, low gestational age, assisted ventilation, premature rupture of membranes, black ethnicity, sepsis, outborn, hypotension (all increased risk), surfactant therapy (conflicting results) and cesarean section (lower risk). Meta-analysis was considered not feasible. High quality studies on prognostic factors for NEC are rare. Several prognostic factors, that are not necessarily causal, are associated with NEC. High quality prognostic research is necessary to establish the predictive values of these factors.

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.

Background: Breastfeeding is considered the most optimal mode of feeding for neonates and mothers. Human milk changes over the course of lactation in order to perfectly suit the infant’s nutritional and immunological needs. Its composition also varies throughout the day. Circadian fluctuations in some bioactive components are suggested to transfer chronobiological information from mother to child to assist the development of the biological clock. This review aims to give a complete overview of studies examining human milk components found to exhibit circadian variation in their concentration. Methods: We included studies assessing the concentration of a specific human milk component more than once in 24 h. Study characteristics, including gestational age, lactational stage, sampling strategy, analytical method, and outcome were extracted. Methodological quality was graded using a modified Newcastle-Ottawa Scale (NOS). Results: A total of 83 reports assessing the circadian variation in the concentration of 71 human milk components were included. Heterogeneity among studies was high. The methodological quality varied widely. Significant circadian variation is found in tryptophan, fats, triacylglycerol, cholesterol, iron, melatonin, cortisol, and cortisone. This may play a role in the child’s growth and development in terms of the biological clock.

Research from JAMA Pediatrics — Effect of Donor Milk on Severe Infections and Mortality in Very Low-Birth-Weight Infants — The Early Nutrition Study Randomized Clinical Trial

In pregnancy, iron deficiency and iron overload increase the risk for adverse pregnancy outcomes, but the effects of maternal iron status on long-term child health are poorly understood. The aim of the study was to systematically review and analyze the literature on maternal iron status in pregnancy and long-term outcomes in the offspring after birth. We report a systematic review on maternal iron status during pregnancy in relation to child health outcomes after birth, from database inception until 21 January 2021, with methodological quality rating (Newcastle-Ottawa tool) and random-effect meta-analysis. (PROSPERO, CRD42020162202). The search identified 8139 studies, of which 44 were included, describing 12,7849 mother–child pairs. Heterogeneity amongst the studies was strong. Methodological quality was predominantly moderate to high. Iron status was measured usually late in pregnancy. The majority of studies compared categories based on maternal ferritin, however, definitions of iron deficiency differed across studies. The follow-up period was predominantly limited to infancy. Fifteen studies reported outcomes on child iron status or hemoglobin, 20 on neurodevelopmental outcomes, and the remainder on a variety of other outcomes. In half of the studies, low maternal iron status or iron deficiency was associated with adverse outcomes in children. Meta-analyses showed an association of maternal ferritin with child soluble transferrin receptor concentrations, though child ferritin, transferrin saturation, or hemoglobin values showed no consistent association. Studies on maternal iron status above normal, or iron excess, suggest deleterious effects on infant growth, cognition, and childhood Type 1 diabetes. Maternal iron status in pregnancy was not consistently associated with child iron status after birth. The very heterogeneous set of studies suggests detrimental effects of iron deficiency, and possibly also of overload, on other outcomes including child neurodevelopment. Studies are needed to determine clinically meaningful definitions of iron deficiency and overload in pregnancy.