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1.
Suitability and safety of L-5-methyltetrahydrofolate as a folate source in infant formula: A randomized-controlled trial.
Troesch, B, Demmelmair, J, Gimpfl, M, Hecht, C, Lakovic, G, Roehle, R, Sipka, L, Trisic, B, Vusurovic, M, Schoop, R, et al
PloS one. 2019;(8):e0216790
Abstract
L-5-methyltetrahydrofolate is the predominant folate form in human milk but is currently not approved as a folate source for infant and follow-on formula. We aimed to assess the suitability of L-5-methyltetrahydrofolate as a folate source for infants. Growth and tolerance in healthy term infants fed formulae containing equimolar doses of L-5-methyltetrahydrofolate (10.4 μg/ 100 ml, n = 120, intervention group) or folic acid (10.0 μg/ 100 ml, n = 120, control group) was assessed in a randomized, double-blind, parallel, controlled trial. A reference group of breastfed infants was followed. Both formulae were well accepted without differences in tolerance or occurrence of adverse events. The most common adverse events were common cold, poor weight gain or growth, rash, eczema, or dry skin and respiratory tract infection. Weight gain (the primary outcome) was equivalent in the two groups (95% CI -2.11; 1.68 g/d). In line with this, there was only a small difference in absolute body weight adjusted for birth weight and sex at visit 4 (95% CI -235; 135 g). Equivalence was also shown for gain in head circumference but not for recumbent length gain and increase in calorie intake. Given the nature of the test, this does not indicate an actual difference, and adjusted means at visit 4 were not significantly different for any of these parameters. Infants receiving formula containing L-5-methyltetrahydrofolate had lower mean plasma levels of unmetabolized folic acid (intervention: 0.73 nmol/L, control: 1.15 nmol/L, p<0.0001) and higher levels of red cell folate (intervention: 907.0 ±192.8 nmol/L, control: 839.4 ±142.4 nmol/L, p = 0.0095). We conclude that L-5-methyltetrahydrofolate is suitable for use in infant and follow-on formula, and there are no indications of untoward effects. Trial registration: This trial was registered at ClinicalTrials.gov (NCT02437721).
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2.
Palm Oil and Beta-palmitate in Infant Formula: A Position Paper by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) Committee on Nutrition.
Bronsky, J, Campoy, C, Embleton, N, Fewtrell, M, Mis, NF, Gerasimidis, K, Hojsak, I, Hulst, J, Indrio, F, Lapillonne, A, et al
Journal of pediatric gastroenterology and nutrition. 2019;(5):742-760
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Abstract
BACKGROUND Palm oil (PO) is used in infant formulas in order to achieve palmitic acid (PA) levels similar to those in human milk. PA in PO is esterified predominantly at the SN-1,3 position of triacylglycerol (TAG), and infant formulas are now available in which a greater proportion of PA is in the SN-2 position (typical configuration in human milk). As there are some concerns about the use of PO, we aimed to review literature on health effects of PO and SN-2-palmitate in infant formulas. METHODS PubMed and Cochrane Database of Systematic Reviews were systematically searched for relevant studies on possible beneficial effects or harms of either PO or SN-2-palmitate in infant formula on various health outcomes. RESULTS We identified 12 relevant studies using PO and 21 studies using SN-2-palmitate. Published studies have variable methodology, subject characteristics, and some are underpowered for the key outcomes. PO is associated with harder stools and SN-2-palmitate use may lead to softer stool consistency. Bone effects seem to be short-lasting. For some outcomes (infant colic, faecal microbiota, lipid metabolism), the number of studies is very limited and summary evidence inconclusive. Growth of infants is not influenced. There are no studies published on the effect on markers of later diseases. CONCLUSIONS There is insufficient evidence to suggest that PO should be avoided as a source of fat in infant formulas for health reasons. Inclusion of high SN-2-palmitate fat blend in infant formulas may have short-term effects on stool consistency but cannot be considered essential.
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Differences in energy expenditure in human donor milk versus formula milk in preterm newborns: A crossover study.
Soares, FVM, Abranches, AD, Méio, MDBB, Gomes, SC, Villela, LD, Moreira, MEL
Nutrition (Burbank, Los Angeles County, Calif.). 2019;:1-4
Abstract
OBJECTIVE The aim of this study was to compare the ratio between energy expenditure and caloric density in human donor milk versus formula milk in preterm newborn infants. METHODS This was a crossover, randomized clinical trial with 29 preterm newborn infants receiving full diet. The infants were randomly assigned to receive either human milk or formula milk alternating, after a 24-h period. Energy expenditure was evaluated by indirect calorimetry. Total calorie and macronutrient values in the human milk were calculated individually with infrared technique; energy expenditure/caloric density ratio was calculated. RESULTS Human donor milk energy expenditure/caloric density ratio was significantly greater than in formula milk at all time points. The total mean was 1.04 ± 0.27 for the human milk and 0.81 ± 0.11 for the formula. However, when we analyzed a subgroup of newborns that received human donor milk with >60 kcal/100 mL, there was no statistical difference (P = 0.36). The mean calorie values were 58.9 kcal/100 mL (human donor milk) and 81.4 kcal/100 mL (formula milk). CONCLUSION Formula milk produced a better metabolic response than human donor milk. Human donor milk with higher caloric content showed no difference from formula, so the use of human donor milk with more caloric density should be reinforced.
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Improved lung function at age 6 in children born very preterm and fed extra protein post-discharge.
Toftlund, LH, Agertoft, L, Halken, S, Zachariassen, G
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2019;(1):47-54
Abstract
BACKGROUND In very preterm-born children, alveolar maturation is challenged and lung function is often compromised during childhood. So far, very few studies have focused on type of early nutrition and lung function in children born preterm. METHODS This study is a 6 years follow-up of 281 very preterm-born infants (VPI) with a gestational age (GA) <32 + 0 weeks. Infants breastfed at discharge from hospital were randomized to unfortified (UHM) or fortified (FHM) mother's (human) milk, whereas those not breastfed received a preterm formula (PF). The intervention lasted until 4 months corrected age. At 6 years of age fractional exhaled nitric oxide (FeNO), airway resistance and occlusion measurements with reversibility were performed. Data on predisposition to asthma and allergy as well as possible allergic symptoms of the child were obtained with questionnaires. RESULTS Outcome data was fully or partially available on 160 (66.9%) of 239 children. This included 49 (30.6%) children fed UHM, 58 (36.3%) fed FHM and 53 (33.1%) fed PF. Successful FeNO measurements were obtained in 119 (74.4%) children and airway resistance measurements in 160. FeNO results were not significantly different between feeding groups. Children fed a protein-enriched diet (FMH/PF) had the lowest, for example, best, airway resistance; FHM-fed had lower values than UHM-fed (P = 0.042) before, and PF-fed had significantly lower values than UHM-fed after beta-2-agonist inhalation (P = 0.050). The tendency of lower airway resistance when protein enriched were the same in gender-specific analyses. In SGA children, the same tendency was found between PF- and UHM-fed (P = 0.007 before and P = 0.046 after beta-2-agonist inhalation). All values were within reference limits. CONCLUSIONS Lung function in very preterm-born children may improve when fed a protein-enriched nutrition post-discharge.
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Partially Hydrolysed Whey-Based Formulae with Reduced Protein Content Support Adequate Infant Growth and Are Well Tolerated: Results of a Randomised Controlled Trial in Healthy Term Infants.
Rigo, J, Schoen, S, Verghote, M, van Overmeire, B, Marion, W, Abrahamse-Berkeveld, M, Alliet, P
Nutrients. 2019;(7)
Abstract
The current study aimed to investigate growth, safety and tolerance of partially hydrolysed infant formulae in healthy full-term infants. Fully formula-fed infants were randomised ≤14 days of age to receive a partially hydrolysed whey formula with 2.27 g protein/100 kcal (pHF2.27) or the same formula with 1.8 g or 2.0 g protein/100 kcal (pHF1.8 and pHF2.0) until 4 months of age. The primary outcome was equivalence in daily weight gain within margins of ± 3 g/day; comparison with WHO Child Growth Standards; gastrointestinal tolerance parameters and number of (serious) adverse events were secondary outcomes. A total of 207 infants were randomised, and 61 (pHF1.8), 46 (pHF2.0) and 48 (pHF2.27) infants completed the study per protocol. Equivalence in daily weight gain was demonstrated for the comparison of pHF1.8 and pHF2.27, i.e., the estimated difference was -1.12 g/day (90% CI: [-2.72; 0.47]) but was inconclusive for the comparisons of pHF2.0 and pHF2.27 with a difference of -2.52 g/day (90% CI: [-4.23; -0.81]). All groups showed adequate infant growth in comparison with the World Health Organization (WHO) Child Growth Standards. To conclude, the evaluated partially hydrolysed formulae varying in protein content support adequate growth and are safe and well tolerated in healthy infants.
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NICU Diet, Physical Growth and Nutrient Accretion, and Preterm Infant Brain Development.
Belfort, MB, Ramel, SE
NeoReviews. 2019;(7):e385-e396
Abstract
Half of very preterm infants experience neurodevelopmental impairments after NICU discharge. These adverse outcomes result in part from abnormal brain development and injury that occur during the NICU hospitalization. Although many factors influence infant brain development, nutritional determinants are of particular interest because they are highly modifiable within clinical care. Physical growth of preterm infants in the NICU continues to lag behind the reference fetus, suggesting reduced nutrient accretion during a critical period for brain development. Nutrient accretion is driven by intake of specific nutrients such as macro- and micronutrients as well as non-nutritional factors such as systemic inflammation. Most often, anthropometric indicators, such as weight, length, and head circumference, are used as proxies for nutrient accretion. A limitation of weight is that it does not differentiate the healthy growth of specific organs and tissues from excess fat accumulation. Body length provides information about skeletal growth, and linear growth stunting predicts neurodevelopmental impairment. Head circumference is only a crude proxy for brain size. More recently, application of new technologies such as air displacement plethysmography and magnetic resonance imaging has allowed the direct estimation of lean tissue accretion and brain growth in the NICU. These newer techniques can facilitate research to improve our understanding of the links among the NICU diet, inflammation, physical growth, and brain development. These new measures may also be relevant within clinical care to identify infants who may benefit from specific interventions to enhance nutrient accretion and brain development.
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Comparing patterns of volatile organic compounds exhaled in breath after consumption of two infant formulae with a different lipid structure: a randomized trial.
Smolinska, A, Baranska, A, Dallinga, JW, Mensink, RP, Baumgartner, S, van de Heijning, BJM, van Schooten, FJ
Scientific reports. 2019;(1):554
Abstract
Infant formulae have been used since decades as an alternative to or a complement to human milk. Human milk, the "gold standard" of infant nutrition, has been studied for its properties in order to create infant formulae that bring similar benefits to the infant. One of the characteristics of milk is the size of the lipid droplets which is known to affect the digestion, gastric emptying and triglyceride metabolism. In the current study a concept infant milk formula with large, phospholipid coating of lipid droplets (mode diameter 3-5 μm; NUTURIS, further described as "active"), was compared to a commercially available formula milk characterised by smaller lipid droplets, further described as "control" (both products derived from Nutricia). We investigated whether we could find an effect of lipid droplet size on volatile compounds in exhaled air upon ingestion of either product. For that purpose, exhaled breath was collected from a group of 29 healthy, non-smoking adult males before ingestion of a study product (baseline measurements, T0) and at the following time points after the test meal: 30, 60, 120, 180 and 240 min. Volatile organic compounds (VOCs) in breath were detected by gas chromatography-time-of-flight-mass spectrometry. Any differences in the time course of VOCs patterns upon intake of active and control products were investigated by regularised multivariate analysis of variance (rMANOVA). The rMANOVA analysis revealed statistically significant differences in the exhaled breath composition 240 min after ingestion of the active formula compared to control product (p-value < 0.0001), but did not show significant changes between active and control product at any earlier time points. A set of eight VOCs in exhaled breath had the highest contribution to the difference found at 240 minutes between the two formulas. A set of ten VOCs was different between baseline and the two formulae at T240 with p-value < 0.0001. To our knowledge this is the first study that shows the ability of VOCs in exhaled breath to monitor metabolic effects after ingestion of infant formulae with different lipid structure. The statistically significant differences in compound abundance found between active and control formula milk may be related to: (i) specific differences in the digestion, (ii) absorption of lipids and proteins and (iii) assimilation of the products in the gut.
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Effects of dietary nucleotide supplementation on growth in infants: a meta-analysis of randomized controlled trials.
Wang, L, Mu, S, Xu, X, Shi, Z, Shen, L
European journal of nutrition. 2019;(3):1213-1221
Abstract
PURPOSE Dietary nucleotides are thought to be conditionally essential nutrients in infancy. However, studies have reported inconsistent findings regarding the association between nucleotide supplementation and infant physical growth. We conducted this meta-analysis to examine the efficacy of nucleotide supplementation of infant formula in promoting early infant growth. METHODS Randomized controlled trials that evaluated the association between nucleotide supplementation and infant growth through June 2017 were included. Study quality was assessed using the Cochrane Collaboration's Risk of Bias tool. Standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed using Q and I2 tests. RESULTS Nucleotide supplementation significantly increased the rate of weight gain (SMD 0.26; 95% CI 0.06-0.47), but had no effect on weight (SMD - 0.16; 95% CI - 0.55-0.23), weight Z score (SMD, - 0.42; 95% CI - 1.64-0.81), length (SMD 0.01; 95% CI - 0.18-0.21) and length Z score (SMD 0.15; 95% CI - 0.10-0.40). Occipitofrontal head circumference (OFC) at 7-8 weeks (SMD 0.30; 95% CI 0.10-0.50) and the rate of OFC gain (SMD 0.34; 95% CI 0.09-0.58) were significantly improved with nucleotide supplementation, whereas, 16- and 20-week OFC values did not differ. CONCLUSIONS Our meta-analysis indicated that nucleotide supplementation can increase the rate of weight gain, OFC and rate of OFC gain; however, we cannot conclude that it affects weight, weight Z score, length or length Z score. Large-scale randomized controlled trials of long-term nucleotide supplementation are needed to reach definitive conclusions.
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Unexplained case of hypophosphataemic rickets.
Godden, B, Hilditch, C, Agrawal, R
Journal of paediatrics and child health. 2019;(7):851-853
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10.
Dietary Fatty Acids and Host-Microbial Crosstalk in Neonatal Enteric Infection.
Quin, C, Gibson, DL
Nutrients. 2019;(9)
Abstract
Human milk is the best nutritional choice for infants. However, in instances where breastfeeding is not possible, infant formulas are used as alternatives. While formula manufacturers attempt to mimic the performance of human breast milk, formula-fed babies consistently have higher incidences of infection from diarrheal diseases than those breastfed. Differences in disease susceptibility, progression and severity can be attributed, in part, to nutritional fatty acid differences between breast milk and formula. Despite advances in our understanding of breast milk properties, formulas still present major differences in their fatty acid composition when compared to human breast milk. In this review, we highlight the role of distinct types of dietary fatty acids in modulating host inflammation, both directly and through the microbiome-immune nexus. We present evidence that dietary fatty acids influence enteric disease susceptibility and therefore, altering the fatty acid composition in formula may be a potential strategy to improve infectious outcomes in formula-fed infants.