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1.
Intestinal microbiota in infants at high risk for allergy: Effects of prebiotics and role in eczema development.
Wopereis, H, Sim, K, Shaw, A, Warner, JO, Knol, J, Kroll, JS
The Journal of allergy and clinical immunology. 2018;(4):1334-1342.e5
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Abstract
BACKGROUND Development of the gut microbiota in infancy is important in maturation of the immune system. Deviations in colonization patterns have been associated with allergic manifestations such as eczema, but exact microbiome dysfunctions underlying allergies remain unclear. We studied the gut microbiota of 138 infants at increased risk of allergy, participating in a clinical trial investigating the effectiveness of a partially hydrolyzed protein formula supplemented with nondigestible oligosaccharides on the prevention of eczema. OBJECTIVE The effects of interventions and breast-feeding on fecal microbiota were investigated. Additionally, we aimed to identify microbial patterns associated with the onset of eczema. METHODS Bacterial taxonomic compositions in the first 26 weeks of life were analyzed by using 16S rRNA gene sequencing. Additionally, fecal pH and microbial metabolite levels were measured. RESULTS Fecal microbial composition, metabolites, and pH of infants receiving partially hydrolyzed protein formula supplemented with nondigestible oligosaccharides was closer to that of breast-fed infants than that of infants receiving standard cow's milk formula. Infants with eczema by 18 months showed discordant development of bacterial genera of Enterobacteriaceae and Parabacteroides species in the first 26 weeks, as well as decreased acquisition of lactate-utilizing bacteria producing butyrate, namely Eubacterium and Anaerostipes species, supported by increased lactate and decreased butyrate levels. CONCLUSIONS We showed that a partially hydrolyzed protein infant formula with specific prebiotics modulated the gut microbiota closer to that of breast-fed infants. Additionally, we identified a potential link between microbial activity and onset of eczema, which might reflect a suboptimal implementation of gut microbiota at specific developmental stages in infants at high risk for allergy.
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DHA and ARA addition to infant formula: Current status and future research directions.
Lien, EL, Richard, C, Hoffman, DR
Prostaglandins, leukotrienes, and essential fatty acids. 2018;:26-40
Abstract
Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are present in breast milk and play important roles in early infant development. A supply of these fatty acids in infant formula (typically following breast milk as a model with ARA > DHA) is thought to be important since endogenous synthesis is insufficient to maintain tissue levels equivalent to breast-fed infants. Intervention studies assessing the impact of DHA- and ARA-supplemented formulas have resulted in numerous positive developmental outcomes (closer to breast-fed infants) including measures of specific cognition functions, visual acuity, and immune responses. A critical analysis of outcome assessment tools reveals the essentiality of selecting appropriate, focused techniques in order to provide accurate evaluation of DHA- and ARA-supplemented formulas. Future research directions should encompass in-depth assessment of specific cognitive outcomes, immune function, and disease incidence, as well as sources of experimental variability such as the status of fatty acid desaturase polymorphisms.
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Early nutrition and signs of metabolic syndrome at 6 y of age in children born very preterm.
Toftlund, LH, Halken, S, Agertoft, L, Zachariassen, G
The American journal of clinical nutrition. 2018;(5):717-724
Abstract
BACKGROUND In term-born infants, the risk of developing metabolic syndrome (MetS) has been shown to be associated with formula feeding and early rapid growth. Breastfeeding, however, seems to be associated with a lower risk of MetS among term-born infants. OBJECTIVE The possible association between type of early nutrition, early growth, and possible influence on different metabolic outcomes at 6 y of age was investigated in very-preterm-born children. DESIGN This study is a 6-y follow-up of 281 very-preterm-born infants with a gestational age of ≤32 wk. Infants breastfed at discharge from the hospital were randomly assigned to receive unfortified or fortified mother's milk, whereas those who were not breastfed received a preterm formula. The intervention lasted until 4 mo of corrected age. At 6 y of age, height, weight, and body mass index were measured and a dual-energy X-ray absorptiometry scan and blood sampling were performed. RESULTS In total, 239 children participated in the follow-up. No differences were found between the 2 breastfed groups. Formula-fed children were more often predisposed to obesity and from families with a lower social status than were children who were breastfed only. Early rapid growth (crossing of weight percentiles with >1 SD in either direction) was seen in 53% of the children from 34 wk of postmenstrual age and until 2 mo of corrected age and was significantly correlated with several metabolic outcomes at 6 y of age. CONCLUSIONS Children fed a preterm formula postdischarge more often showed early rapid growth than did breastfed children, and early rapid growth was correlated with early signs of MetS at 6 y of age. However, all of the values were within normal ranges. This trial was registered at as NCT02078687.
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Partially Hydrolyzed Whey Infant Formula: Literature Review on Effects on Growth and the Risk of Developing Atopic Dermatitis in Infants from the General Population.
Sauser, J, Nutten, S, de Groot, N, Pecquet, S, Simon, D, Simon, HU, Spergel, JM, Koletzko, S, Blanchard, C
International archives of allergy and immunology. 2018;(2):123-134
Abstract
Limited evidence is available regarding the effect of partially hydrolyzed whey-based formula (pHF-W) on growth and atopic dermatitis (AD) risk reduction in infants within the general infant population, and without a familial history of allergy as an inclusion or exclusion criterion. We reviewed the current evidence available from studies using pHF-W in the general population and summarized the data on safety (growth) and efficacy outcomes (reduction of AD), comparing the studies side by side. A total of 8 clinical trials were identified from the literature search, 7 of which used the same pHF-W. Six out of 8 studies indicated a reduction of atopic manifestations using a specific pHF-W versus cow's milk formula (CMF) in the first years of life. Data were summarized and compared side by side for growth (3 studies) and efficacy (5 studies). In these diverse general populations, the results on growth and AD were consistent with the previous findings reported on infants with a family history of allergy, but numerous limitations to these studies were identified. This literature review confirms that pHF-W supports normal growth in infants, and suggests that the risk of AD may be reduced in not-fully breastfed infants from the general population when supplemented with a specific pHF-W when compared to CMF during the first 4-6 months of life. Further studies are warranted to confirm these results.
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Infant formula feeding practices associated with rapid weight gain: A systematic review.
Appleton, J, Russell, CG, Laws, R, Fowler, C, Campbell, K, Denney-Wilson, E
Maternal & child nutrition. 2018;(3):e12602
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Abstract
Excess or rapid weight gain during the first 2 years of life is associated with an increased risk of later childhood and adult overweight and obesity. When compared with breastfed infants, formula fed infants are more likely to experience excess or rapid weight gain, and this increased risk in formula fed infant populations may be due to a number of different mechanisms. These mechanisms include the nutrient composition of the formula and the way formula is prepared and provided to infants. This systematic literature review examines the association between formula feeding practice and excess or rapid weight gain. This review explores these different mechanisms and provides practical recommendations for best practice formula feeding to reduce rapid weight gain. Eighteen studies are included in this review. The findings are complicated by the challenges in study design and accuracy of measurements. Nevertheless, there are some potential recommendations for best practice formula feeding that may reduce excess or rapid weight gain, such as providing formula with lower protein content, not adding cereals into bottles, not putting a baby to bed with a bottle, and not overfeeding formula. Although further well designed studies are required before more firm recommendations can be made.
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Hydrolyzed Formula With Reduced Protein Content Supports Adequate Growth: A Randomized Controlled Noninferiority Trial.
Ahrens, B, Hellmuth, C, Haiden, N, Olbertz, D, Hamelmann, E, Vusurovic, M, Fleddermann, M, Roehle, R, Knoll, A, Koletzko, B, et al
Journal of pediatric gastroenterology and nutrition. 2018;(5):822-830
Abstract
OBJECTIVE A high protein content of nonhydrolyzed infant formula exceeding metabolic requirements can induce rapid weight gain and obesity. Hydrolyzed formula with too low protein (LP) content may result in inadequate growth. The aim of this study was to investigate noninferiority of partial and extensively hydrolyzed formulas (pHF, eHF) with lower hydrolyzed protein content than conventionally, regularly used formulas, with or without synbiotics for normal growth of healthy term infants. METHODS In an European multi-center, parallel, prospective, controlled, double-blind trial, 402 formula-fed infants were randomly assigned to four groups: LP-formulas (1.9 g protein/100 kcal) as pHF with or without synbiotics, LP-eHF formula with synbiotics, or regular protein eHF (2.3 g protein/100 kcal). One hundred and one breast-fed infants served as observational reference group. As primary endpoint, noninferiority of daily weight gain during the first 4 months of life was investigated comparing the LP-group to a regular protein eHF group. RESULTS A comparison of daily weight gain in infants receiving LPpHF (2.15 g/day CI -0.18 to inf.) with infants receiving regular protein eHF showed noninferior weight gain (-3.5 g/day margin; per protocol [PP] population). Noninferiority was also confirmed for the other tested LP formulas. Likewise, analysis of metabolic parameters and plasma amino acid concentrations demonstrated a safe and balanced nutritional composition. Energetic efficiency for growth (weight) was slightly higher in LPeHF and synbiotics compared with LPpHF and synbiotics. CONCLUSIONS All tested hydrolyzed LP formulas allowed normal weight gain without being inferior to regular protein eHF in the first 4 months of life. This trial was registered at clinicaltrials.gov, NCT01143233.
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Thickened infant formula: What to know.
Salvatore, S, Savino, F, Singendonk, M, Tabbers, M, Benninga, MA, Staiano, A, Vandenplas, Y
Nutrition (Burbank, Los Angeles County, Calif.). 2018;:51-56
Abstract
OBJECTIVES This study aimed to provide an overview of the characteristics of thickened formulas to aid health care providers manage infants with regurgitations. METHODS The indications, properties, and efficacy of different thickening agents and thickened formulas on regurgitation and gastroesophageal reflux in infants were reviewed. PubMed and the Cochrane database were searched up to December 2016. RESULTS Based on the literature review, thickened formulas reduce regurgitation, may improve reflux-associated symptoms, and increase weight gain. However, clinical efficacy is related to the characteristics of the formula and of the infant. Commercial thickened formulas are preferred over the supplementation of standard formulas with thickener because of the better viscosity, digestibility, and nutritional balance. Rice and corn starch, carob bean gum, and soy bean polysaccharides are available as thickening agents. Hydrolyzed formulas have recently shown promising additional benefit. CONCLUSIONS Thickened formulas reduce the frequency and severity of regurgitation and are indicated in formula-fed infants with persisting symptoms despite reassurance and appropriate feeding volume intake.
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Effects on Fatty Acid Metabolism of a New Powdered Human Milk Fortifier Containing Medium-Chain Triacylglycerols and Docosahexaenoic Acid in Preterm Infants.
Billeaud, C, Boué-Vaysse, C, Couëdelo, L, Steenhout, P, Jaeger, J, Cruz-Hernandez, C, Ameye, L, Rigo, J, Picaud, JC, Saliba, E, et al
Nutrients. 2018;(6)
Abstract
Preterm infants require fortification of human milk (HM) with essential fatty acids (FA) to ensure adequate post-natal development. As part of a larger randomized controlled study, we investigated FA metabolism in a subset of 47 clinically stable preterm infants (birth weight ≤1500 g or gestational age ≤32 weeks). Infants were randomized to receive HM supplemented with either a new HM fortifier (nHMF; n = 26) containing 12.5 g medium-chain FA (MCFA), 958 mg linoleic acid (LA), 417 mg α-linolenic acid (ALA), and 157 mg docosahexaenoic acid (DHA) per 100 g of powder (in compliance with the latest guidelines) or a fat-free HMF (cHMF; n = 21). Plasma phospholipid (PL) and triacylglycerol (TAG), and red blood cell phosphatidylcholine (RBC-PC) and phosphatidylethanolamine (RBC-PE) FA profiles were assessed before and after 21 days of feeding. In the nHMF group, significantly increased levels of n-9 monounsaturated fatty acids were observed, formed most likely by elongation and desaturation of dietary saturated fatty acids present in HM. ALA fortification increased ALA assimilation into plasma TAG. Similarly, DHA fortification enriched the DHA content in RBC-PE, which, in this compartment, was not associated with lower arachidonic acid levels as observed in plasma TAG and phospholipids. RBC-PE, a reliable indicator of FA metabolism and accretion, was the most sensitive compartment in this study.
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Daily Intake of Milk Powder and Risk of Celiac Disease in Early Childhood: A Nested Case-Control Study.
Hård Af Segerstad, EM, Lee, HS, Andrén Aronsson, C, Yang, J, Uusitalo, U, Sjöholm, I, Rayner, M, Kurppa, K, Virtanen, SM, Norris, JM, et al
Nutrients. 2018;(5)
Abstract
Milk powder and gluten are common components in Swedish infants' diets. Whereas large intakes of gluten early in life increases the risk of celiac disease in genetically at-risk Swedish children, no study has yet evaluated if intake of milk powder by 2 years of age is associated with celiac disease. A 1-to-3 nested case-control study, comprised of 207 celiac disease children and 621 controls matched for sex, birth year, and HLA genotype, was performed on a birth cohort of HLA-DR3-DQ2 and/or DR4-DQ8-positive children. Subjects were screened annually for celiac disease using tissue transglutaminase autoantibodies (tTGA). Three-day food records estimated the mean intake of milk powder at ages 6 months, 9 months, 12 months, 18 months, and 24 months. Conditional logistic regression calculated odds ratios (OR) at last intake prior to seroconversion of tTGA positivity, and for each time-point respectively and adjusted for having a first-degree relative with celiac disease and gluten intake. Intake of milk powder prior to seroconversion of tTGA positivity was not associated with celiac disease (OR = 1.00; 95% CI = 0.99, 1.03; p = 0.763). In conclusion, intake of milk powder in early childhood is not associated with celiac disease in genetically susceptible children.
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Cost-Effectiveness of Supplemental Donor Milk Versus Formula for Very Low Birth Weight Infants.
Trang, S, Zupancic, JAF, Unger, S, Kiss, A, Bando, N, Wong, S, Gibbins, S, O'Connor, DL, ,
Pediatrics. 2018;(3)
Abstract
OBJECTIVES To determine the cost-effectiveness of supplemental donor human milk (DHM) versus preterm formula (PTF) for very low birth weight (VLBW, <1500 g) infants from a societal perspective to 18 months' corrected age. METHODS This prospective cost-effectiveness analysis of 363 VLBW infants was conducted for a randomized control trial. Infants recruited from October 2010 to December 2012 were fed DHM or PTF whenever mother's milk was unavailable. Formal health care costs for initial hospitalization and readmissions were obtained from standardized cost-accounting systems and physician fees. Informal and nonhealth care sector costs (eg, caregiver transportation, labor market earnings) were calculated from parent reports. RESULTS Mean infant birth weight was 996 (SD, 272) grams. Incidence of necrotizing enterocolitis (NEC) differed between groups (all stages 3.9% DHM, 11.0% PTF; P = .01). Costs to 18 months did not differ with a mean (95% confidence interval) of 217 624 (197 697-237 551) and 217 245 (196 494-237 995) 2015 Canadian dollars in the DHM and PTF groups. Postdischarge costs were lower in the DHM (46 440 [40 648-52 233]) than PTF group (55 102 [48 269-61 934]) (P = .04), driven by parent lost wages. DHM cost an additional $5328 per case of averted NEC. CONCLUSIONS In a high mother's milk use setting, total costs from a societal perspective to 18 months of providing supplemental DHM versus PTF to VLBW infants did not differ, although postdischarge costs were lower in the DHM group. Although supplemental DHM was not cost-saving, it reduced NEC supporting its use over PTF.