Johannes B. van Goudoever

Breast-feeding: A Commentary by the ESPGHAN Committee on Nutrition

This medical position article by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition summarises the current status of breast-feeding practice, the present knowledge on the composition of human milk, advisable duration of exclusive and partial breast-feeding, growth of the breast-fed infant, health benefits associated with breast-feeding, nutritional supplementation for breast-fed infants, and contraindications to breast-feeding. This article emphasises the important role of paediatricians in the implementation of health policies devised to promote breast-feeding. The European Society for Paediatric Gastroenterology, Hepatology, and Nutrition Committee on Nutrition recognises breast-feeding as the natural and advisable way of supporting the healthy growth and development of young children. This article delineates the health benefits of breast-feeding, reduced risk of infectious diarrhoea and acute otitis media being the best documented. Exclusive breast-feeding for around 6 months is a desirable goal, but partial breast-feeding as well as breast-feeding for shorter periods of time are also valuable. Continuation of breast-feeding after the introduction of complementary feeding is encouraged as long as mutually desired by mother and child. The role of health care workers, including paediatricians, is to protect, promote, and support breast-feeding. Health care workers should be trained in breast-feeding issues and counselling, and they should encourage practices that do not undermine breast-feeding. Societal standards and legal regulations that facilitate breast-feeding should be promoted, such as providing maternity leave for at least 6 months and protecting working mothers.

Supplementation of infant formula with probiotics and/or prebiotics: A systematic review and comment by the ESPGHAN committee on nutrition

Infant formulae are increasingly supplemented with probiotics, prebiotics, or synbiotics despite uncertainties regarding their efficacy. The present article, developed by the Committee on Nutrition of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition, systematically reviews published evidence related to the safety and health effects of the administration of formulae supplemented with probiotics and/or prebiotics compared with unsupplemented formulae. Studies in which probiotics/prebiotics were not administered during the manufacturing process, but thereafter, for example in capsules, the contents of which were supplemented to infant formula or feeds, were excluded. On the basis of this review, available scientific data suggest that the administration of currently evaluated probiotic- and/or prebiotic-supplemented formula to healthy infants does not raise safety concerns with regard to growth and adverse effects. The safety and clinical effects of 1 product should not be extrapolated to other products. At present, there is insufficient data to recommend the routine use of probiotic- and/or prebiotic-supplemented formulae. The Committee considers that the supplementation of formula with probiotics and/or prebiotics is an important field of research. There is a need in this field for well-designed and carefully conducted randomised controlled trials, with relevant inclusion/exclusion criteria and adequate sample sizes. These studies should use validated clinical outcome measures to assess the effects of probiotic and/or prebiotic supplementation of formulae. Such trials should also define the optimal doses and intake durations, as well as provide more information about the long-term safety of probiotics and/or prebiotics. Because most of the trials were company funded, independent trials, preferentially financed jointly by national/governmental/European Union bodies and other international organisations, would be desirable.

Structural position and amount of palmitic acid in infant formulas: Effects on fat, fatty acid, and mineral balance

The structure of the triglycerides (TG) in human milk (HM) differs from those of vegetable oils used in infant formulas. In HM, palmitic acid is predominantly esterified to the center or beta-position of the TG, in vegetable oil, it is mainly at the external or alpha-positions. These differences in configuration affect intestinal fat absorption. Fat and mineral balances were investigated in three groups of 9 healthy term infants aged 5 weeks. Infants were randomly assigned to receive one of the three study formulas from birth: (a) formula beta, resembling the structure of HM fat most closely (24% palmitic acid, 66% esterified to beta-position), (b) formula intermediate (24% palmitic acid, 39% esterified to the beta-position), and (c) regular formula (20% palmitic acid; 13% esterified to the beta-position). Fat absorption was highest in infants fed the beta formula (97.6 +/- 0.9%), intermediate in those fed with the intermediate formula (93.0 +/- 1.8%), and lowest in infants receiving the regular formula (90.4 +/- 4.6%). Fecal calcium excretion was significantly lower in the beta group than in the other two groups (43.3 +/- 18.1 vs. 59.9 +/- 15.1 vs. 68.4 +/- 22.3 mg.kg-1.day-1 for beta, intermediate, and regular respectively). Dietary TG containing palmitic acid predominantly at the beta-position, as in HM, have significant beneficial effects on the intestinal absorption of fat and calcium in healthy term infants.

Malnutrition in critically ill children: from admission to 6 months after discharge☆

BACKGROUND & AIMS Little is known about the nutritional status of critically ill children during hospitalisation in and after discharge from an intensive care unit. We set up a prospective, observational study to evaluate the nutritional status of children in an intensive care unit from admission up to 6 months after discharge. A secondary aim was identifying patient characteristics that influence the course of the various anthropometric parameters. METHODS The nutritional status of 293 children--104 preterm neonates, 96 term neonates and 93 older children--admitted to our multidisciplinary tertiary pediatric and neonatal intensive care unit was evaluated by anthropometry upon and during admission, at discharge and 6 weeks and 6 months following discharge. RESULTS Upon admission, 24% of all children appeared to be undernourished. Preterm and term neonates, but not older children, showed a decline in nutritional status during admission. At 6 months after discharge almost all children showed complete recovery of nutritional status. Length of stay and history of disease were the parameters that most adversely affected the nutritional status of preterm and term neonates at discharge and during follow-up. CONCLUSION While malnutrition is a major problem in pediatric intensive care units, most children have good long-term outcome in terms of nutritional status after discharge.

The regulation of intestinal mucin MUC2 expression by short-chain fatty acids: implications for epithelial protection.

SCFAs (short-chain fatty acids), fermentation products of bacteria, influence epithelial-specific gene expression. We hypothesize that SCFAs affect goblet-cell-specific mucin MUC2 expression and thereby alter epithelial protection. In the present study, our aim was to investigate the mechanisms that regulate butyrate-mediated effects on MUC2 synthesis. Human goblet cell-like LS174T cells were treated with SCFAs, after which MUC2 mRNA levels and stability, and MUC2 protein expression were analysed. SCFA-responsive regions and cis-elements within the MUC2 promoter were identified by transfection and gel-shift assays. The effects of butyrate on histone H3/H4 status at the MUC2 promoter were established by chromatin immunoprecipitation. Butyrate (at 1 mM), as well as propionate, induced an increase in MUC2 mRNA levels. MUC2 mRNA levels returned to basal levels after incubation with 5-15 mM butyrate. Interestingly, this decrease was not due to loss of RNA stability. In contrast, at concentrations of 5-15 mM propionate, MUC2 mRNA levels remained increased. Promoter-regulation studies revealed an active butyrate-responsive region at -947/-371 within the MUC2 promoter. In this region we identified an active AP1 (c-Fos/c-Jun) cis-element at -818/-808 that mediates butyrate-induced activation of the promoter. Finally, MUC2 regulation by butyrate at 10-15 mM was associated with increased acetylation of histone H3 and H4 and methylation of H3 at the MUC2 promoter. In conclusion, 1 mM butyrate and 1-15 mM propionate increase MUC2 expression. The effects of butyrate on MUC2 mRNA are mediated via AP-1 and acetylation/methylation of histones at the MUC2 promoter.

Donor Human Milk for Preterm Infants : Current Evidence and Research Directions

ABSTRACT The Committee on Nutrition of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition aims to document the existing evidence of the benefits and common concerns deriving from the use of donor human milk (DHM) in preterm infants. The comment also outlines gaps in knowledge and gives recommendations for practice and suggestions for future research directions. Protection against necrotizing enterocolitis is the major clinical benefit deriving from the use of DHM when compared with formula. Limited data also suggest unfortified DHM to be associated with improved feeding tolerance and with reduced cardiovascular risk factors during adolescence. Presence of a human milk bank (HMB) does not decrease breast-feeding rates at discharge, but decreases the use of formula during the first weeks of life. This commentary emphasizes that fresh own mothers milk (OMM) is the first choice in preterm infant feeding and strong efforts should be made to promote lactation. When OMM is not available, DHM is the recommended alternative. When neither OMM nor DHM is available, preterm formula should be used. DHM should be provided from an established HMB, which follows specific safety guidelines. Storage and processing of human milk reduces some biological components, which may diminish its health benefits. From a nutritional point of view, DHM, like HM, does not meet the requirements of preterm infants, necessitating a specific fortification regimen to optimize growth. Future research should focus on the improvement of milk processing in HMB, particularly of heat treatment; on the optimization of HM fortification; and on further evaluation of the potential clinical benefits of processed and fortified DHM.

Vitamin D in the Healthy European Paediatric Population

ABSTRACT In recent years, reports suggesting a resurgence of vitamin D deficiency in the Western world, combined with various proposed health benefits for vitamin D supplementation, have resulted in increased interest from health care professionals, the media, and the public. The aim of this position paper is to summarise the published data on vitamin D intake and prevalence of vitamin D deficiency in the healthy European paediatric population, to discuss the health benefits of vitamin D and to provide recommendations for the prevention of vitamin D deficiency in this population. Vitamin D plays a key role in calcium and phosphate metabolism and is essential for bone health. There is insufficient evidence from interventional studies to support vitamin D supplementation for other health benefits in infants, children, and adolescents. The pragmatic use of a serum concentration >50 nmol/L to indicate sufficiency and a serum concentration <25 nmol/L to indicate severe deficiency is recommended. Vitamin D deficiency occurs commonly among healthy European infants, children, and adolescents, especially in certain risk groups, including breast-fed infants, not adhering to the present recommendation for vitamin D supplementation, children and adolescents with dark skin living in northern countries, children and adolescents without adequate sun exposure, and obese children. Infants should receive an oral supplementation of 400 IU/day of vitamin D. The implementation should be promoted and supervised by paediatricians and other health care professionals. Healthy children and adolescents should be encouraged to follow a healthy lifestyle associated with a normal body mass index, including a varied diet with vitamin D–containing foods (fish, eggs, dairy products) and adequate outdoor activities with associated sun exposure. For children in risk groups identified above, an oral supplementation of vitamin D must be considered beyond 1 year of age. National authorities should adopt policies aimed at improving vitamin D status using measures such as dietary recommendations, food fortification, vitamin D supplementation, and judicious sun exposure, depending on local circumstances.

Critical systematic review of the level of evidence for routine use of probiotics for reduction of mortality and prevention of necrotizing enterocolitis and sepsis in preterm infants

BACKGROUND & AIMS Probiotics have been suggested to prevent severe necrotizing enterocolitis (NEC) and decrease mortality in preterm infants. The aim of this paper was to systematically analyze the level of evidence (LoE) of published controlled randomized trials (RCTs) on probiotics in preterm infants. METHODS Literature searches were made up to November 2010. LoE of recommendations based on single trials or meta-analyses were scored following the Oxford Center for Evidence based Medicine approach (1a - meta-analyses of 1b LoE studies; 1b - well designed RCT; 2a - meta-analyses which include 2b LoE studies; 2b - lesser quality RCT). RESULTS Fifteen trials were included (Two 1b LoE trials and thirteen 2b LoE trials). Methodological assessment revealed considerable heterogeneity. Some probiotics may be beneficial in relation to reduction of severe NEC (2b LoE) and reduction of mortality (2b LoE). Probiotics do not accelerate feeding advancement (1b and 2b LoE). There was no convincing benefit with regard to prevention of sepsis (1b and 2b LoE). CONCLUSION There is insufficient evidence to recommend routine probiotics. However, there is encouraging data (2b LoE) which justifies the further investigation regarding the efficacy and safety of specific probiotics in circumstances of high local incidence of severe NEC.

Iron requirements of infants and toddlers

ABSTRACT Iron deficiency (ID) is the most common micronutrient deficiency worldwide and young children are a special risk group because their rapid growth leads to high iron requirements. Risk factors associated with a higher prevalence of ID anemia (IDA) include low birth weight, high cows-milk intake, low intake of iron-rich complementary foods, low socioeconomic status, and immigrant status. The aim of this position paper was to review the field and provide recommendations regarding iron requirements in infants and toddlers, including those of moderately or marginally low birth weight. There is no evidence that iron supplementation of pregnant women improves iron status in their offspring in a European setting. Delayed cord clamping reduces the risk of ID. There is insufficient evidence to support general iron supplementation of healthy European infants and toddlers of normal birth weight. Formula-fed infants up to 6 months of age should receive iron-fortified infant formula, with an iron content of 4 to 8 mg/L (0.6–1.2 mg · kg−1 · day−1). Marginally low-birth-weight infants (2000–2500 g) should receive iron supplements of 1–2 mg · kg−1 · day−1. Follow-on formulas should be iron-fortified; however, there is not enough evidence to determine the optimal iron concentration in follow-on formula. From the age of 6 months, all infants and toddlers should receive iron-rich (complementary) foods, including meat products and/or iron-fortified foods. Unmodified cows milk should not be fed as the main milk drink to infants before the age of 12 months and intake should be limited to <500 mL/day in toddlers. It is important to ensure that this dietary advice reaches high-risk groups such as socioeconomically disadvantaged families and immigrant families.

Perinatal programming of adult hippocampal structure and function; emerging roles of stress, nutrition and epigenetics

Early-life stress lastingly affects adult cognition and increases vulnerability to psychopathology, but the underlying mechanisms remain elusive. In this Opinion article, we propose that early nutritional input together with stress hormones and sensory stimuli from the mother during the perinatal period act synergistically to program the adult brain, possibly via epigenetic mechanisms. We hypothesize that stress during gestation or lactation affects the intake of macro- and micronutrients, including dietary methyl donors, and/or impairs the dams metabolism, thereby altering nutrient composition and intake by the offspring. In turn, this may persistently modulate gene expression via epigenetic programming, thus altering hippocampal structure and cognition. Understanding how the combination of stress, nutrition, and epigenetics shapes the adult brain is essential for effective therapies.