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A randomized controlled trial of different young child formulas on upper respiratory and gastrointestinal tract infections in Chinese toddlers.
Leung, TF, Ulfman, LH, Chong, MKC, Hon, KL, Khouw, IMSL, Chan, PKS, Delsing, DJ, Kortman, GAM, Bovee-Oudenhoven, IMJ
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2020;(7):745-754
Abstract
BACKGROUND Bioactive proteins and human milk oligosaccharides (HMOs), important ingredients in breast milk, that protect against infections are lacking in young child formula (YCF). This study investigated the effects of new YCFs on respiratory and gastrointestinal infections in toddlers. METHODS Four hundred and sixty one healthy Chinese children aged 1-2.5 years were recruited in this randomized, controlled, double-blind, parallel-group clinical trial of different YCFs. They were randomly assigned to either standard milk formula (YCF-Ref) or one of three new YCFs containing bioactive proteins and/or the HMO 2'-fucosyllactose (2'-FL) and/or milk fat for six months. Primary outcomes were incidence of upper respiratory tract infection (URTI) and duration of gastrointestinal tract infections (GITI). RESULTS There were no significant between-group differences in primary outcomes. For secondary outcomes, subjects receiving 2'-FL-supplemented YCF had longer URTI. Subjects receiving YCF supplemented with milk fat and intact bioactive proteins, and 2'-FL at levels found in breast milk, had more GITI episodes and shorter time to first GITI but similar effects on URTI duration than YCF-Ref recipients. No effects on URTI and GITI were observed in toddlers receiving YCF with bioactive proteins at lower levels than breast milk. Occurrence of adverse events and anthropometry were similar in all groups. CONCLUSIONS All three YCFs supplemented with different combinations of intact bioactive proteins, 2'-FL, and milk fat are safe in toddlers. No difference is detected among YCFs on URTI incidence and GITI duration. Further studies are needed to verify these findings especially in infants who may benefit most from the immune-boosting effects of bioactive proteins and HMOs.
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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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Reduction of Arachidonate Is Associated With Increase in B-Cell Activation Marker in Infants: A Randomized Trial.
Miklavcic, JJ, Larsen, BM, Mazurak, VC, Scalabrin, DM, MacDonald, IM, Shoemaker, GK, Casey, L, Van Aerde, JE, Clandinin, MT
Journal of pediatric gastroenterology and nutrition. 2017;(3):446-453
Abstract
BACKGROUND Infants who are not breast-fed benefit from formula with both docosahexaenoic acid (C22:6n3) and arachidonic acid (ARA; C20:4n6). The amount of ARA needed to support immune function is unknown. Infants who carry specific fatty acid desaturase (FADS) polymorphisms may require more dietary ARA to maintain adequate ARA status. OBJECTIVE The aim of the study was to determine whether ARA intake or FADS polymorphisms alter ARA levels of lymphocytes, plasma, and red blood cells in term infants fed infant formula. METHODS Infants (N = 89) were enrolled in this prospective, double-blind controlled study. Infants were randomized to consume formula containing 17 mg docosahexaenoic acid and 0, 25, or 34 mg ARA/100 kcal for 10 weeks. Fatty acid composition of plasma phosphatidylcholine and phosphatidylethanolamine, total fatty acids of lymphocytes and red blood cells, activation markers of lymphocytes, and polymorphisms in FADS1 and FADS2 were determined. RESULTS Lymphocyte ARA was higher in the 25-ARA formula group than in the 0- or 34-ARA groups. In plasma, 16:0/20:4 and 18:0/20:4 species of phosphatidylcholine and phosphatidylethanolamine were highest and 16:0/18:2 and 18:0/18:2 were lowest in the 34-ARA formula group. In minor allele carriers of FADS1 and FADS2, plasma ARA content was elevated only at the highest level of ARA consumed. B-cell activation marker CD54 was elevated in infants who consumed formula containing no ARA. CONCLUSIONS ARA level in plasma is reduced by low ARA consumption and by minor alleles in FADS. Dietary ARA may exert an immunoregulatory role on B-cell activation by decreasing 16:0/18:2 and 18:0/18:2 species of phospholipids. ARA intake from 25 to 34 mg/100 kcal is sufficient to maintain cell ARA level in infants across genotypes.
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Effects of osteopontin-enriched formula on lymphocyte subsets in the first 6 months of life: a randomized controlled trial.
West, CE, Kvistgaard, AS, Peerson, JM, Donovan, SM, Peng, YM, Lönnerdal, B
Pediatric research. 2017;(1):63-71
Abstract
BackgroundHuman milk is rich in osteopontin (OPN), which has immunomodulatory functions.MethodsIn a randomized controlled trial, standard formula (SF) and the same formula with 65 mg of OPN/L (F65) or 130 mg of OPN/L (F130), representing ~50 and 100% of the OPN concentration in human milk, were compared. We examined frequencies and composition of peripheral blood immune cells by four-color immunoflow cytometry of formula-fed infants at ages 1, 4, and 6 months, and compared them with a breastfed (BF) reference group.ResultsThe F130 group had increased T-cell proportions compared with the SF (P=0.036, average effect size 0.51) and F65 groups (P=0.008, average effect size 0.65). Compared with the BF group, the monocyte proportions were increased in the F65 (P=0.001, average effect size 0.59) and F130 (P=0.006, average effect size 0.50) groups, but were comparable among the formula groups.ConclusionOPN in an infant formula at a concentration close to that of human milk increased the proportion of circulating T cells compared with both SF and formula with added OPN at ~50% of the concentration in human milk. This suggests that OPN may favorably influence immune ontogeny in infancy and that the effects appear to be dose-dependent.