Effect of feeding mode on infant growth and cognitive function: study protocol of the Chilean infant Nutrition randomized controlled Trial (ChiNuT).
ABSTRACT: BACKGROUND:A central aim for pediatric nutrition is to develop infant formula compositionally closer to human milk. Milk fat globule membranes (MFGM) have shown to have functional components that are found in human milk, suggesting that addition of bovine sources of MFGM (bMFGM) to infant formula may promote beneficial outcomes potentially helping to narrow the gap between infants who receive human breast milk or infant formula. The objective of the current study is to determine how the addition of bMFGM in infant formula and consumption in early infancy affects physical growth and brain development when compared to infants fed with a standard formula and a reference group of infants fed with mother's own milk. METHODS:Single center, double-blind, and parallel randomized controlled trial. Planned participant enrollment includes: infants exclusively receiving breast milk (n?=?200; human milk reference group; HM) and infants whose mothers chose to initiate exclusive infant formula feeding before 4?months of age (n?=?340). The latter were randomized to receive one of two study formulas until 12?months of age: 1) cow's milk based infant formula that had docosahexaenoic (DHA) (17?mg/100?kcal) and arachidonic acid (ARA) (25?mg/100?kcal); 1.9?g protein/100?kcal; 1.2?mg Fe/100?kcal (Standard formula; SF) or 2) a similar infant formula with an added source of bovine MFGM (whey protein-lipid concentrate (Experimental formula; EF). Primary outcomes will be: 1) Physical growth (Body weight, length, and head circumference) at 730?days of age; and 2) Cognitive development (Auditory Event-Related Potential) at 730?days of age. Data will be analyzed for all participants allocated to each study feeding group. DISCUSSION:The results of this study will complement the knowledge regarding addition of bMFGM in infant formula including support of healthy growth and improvement of neurodevelopmental outcomes. TRIAL REGISTRATION:NCT02626143, registered on December 10th 2015.
Project description:OBJECTIVE:This multicenter non-inferiority study evaluated the safety of infant formulas enriched with bovine milk fat globule membrane (MFGM) fractions. METHODS:Healthy, full-term infants (n = 119) age ?14 days were randomized to standard infant formula (control), standard formula enriched with a lipid-rich MFGM fraction (MFGM-L), or standard formula enriched with a protein-rich MFGM fraction (MFGM-P). Primary outcome was mean weight gain per day from enrollment to age 4 months (non-inferiority margin: -3.0 g/day). Secondary (length, head circumference, tolerability, morbidity, adverse events) and exploratory (phospholipids, metabolic markers, immune markers) outcomes were also evaluated. RESULTS:Weight gain was non-inferior in the MFGM-L and MFGM-P groups compared with the control group. Among secondary and exploratory outcomes, few between-group differences were observed. Formula tolerance rates were high (>94%) in all groups. Adverse event and morbidity rates were similar across groups except for a higher rate of eczema in the MFGM-P group (13.9% vs control [3.5%], MFGM-L [1.4%]). CONCLUSION:Both MFGM-enriched formulas met the primary safety endpoint of non-inferiority in weight gain and were generally well tolerated, although a higher rate of eczema was observed in the MFGM-P group.
Project description:Human milk delivers an array of bioactive components that safeguard infant growth and development and maintain healthy gut microbiota. Milk fat globule membrane (MFGM) is a biologically functional fraction of milk increasingly linked to beneficial outcomes in infants through protection from pathogens, modulation of the immune system and improved neurodevelopment. In the present study, we characterized the fecal microbiome and metabolome of infants fed a bovine MFGM supplemented experimental formula (EF) and compared to infants fed standard formula (SF) and a breast-fed reference group. The impact of MFGM on the fecal microbiome was moderate; however, the fecal metabolome of EF-fed infants showed a significant reduction of several metabolites including lactate, succinate, amino acids and their derivatives from that of infants fed SF. Introduction of weaning food with either human milk or infant formula reduces the distinct characteristics of breast-fed- or formula-fed- like infant fecal microbiome and metabolome profiles. Our findings support the hypothesis that higher levels of protein in infant formula and the lack of human milk oligosaccharides promote a shift toward amino acid fermentation in the gut. MFGM may play a role in shaping gut microbial activity and function.
Project description:Formula-fed (FF) infants exhibit a different metabolic profile than breast-fed (BF) infants. Two potential mechanisms are the higher protein level in formula compared with breast milk and the removal of the milk fat and associated milk fat globule membranes (MFGM) during production of infant formula. To determine whether MFGM may impact metabolism, formula-fed infants were randomly assigned to receive either an MFGM isolate-supplemented experimental formula (EF) or a standard formula (SF) from 2 until 6 months and compared with a BF reference group. Infants consuming EF had higher levels of fatty acid oxidation products compared to infants consuming SF. Although the protein level in the study formula was approximately 12?g/L (lower than most commercial formulas), a metabolic difference between FF and BF remained such that FF infants had higher levels of amino acid catabolism by-products and a low efficiency of amino acid clearance (preference for protein metabolism). BF infants had higher levels of fatty acid oxidation products (preference for fat metabolism). These unique, energy substrate-driven metabolic outcomes did not persist after diet was shifted to weaning foods and appeared to be disrupted by complementary feeding. Our results suggest that MFGM may have a role in directing infant metabolism.
Project description:In a recent study, supplementation of infant formula with milk fat globule membranes (MFGM) decreased the incidence of otitis media in infants <6 months of age.The aim of the present study was to characterize the oral microbiota in infants fed MFGM-supplemented formula and compare it to that of infants fed standard formula or breast milk.In a prospective double-blinded randomized controlled trial, exclusively formula-fed infants <2 months of age were randomized to be fed experimental formula (EF, n = 80) with reduced energy and protein and supplemented with a bovine MFGM concentrate, or standard formula (SF, n = 80) until 6 months of age. A breast-fed reference (BFR, n = 80) group was also recruited. The oral microbiota was analyzed at 4 (n = 124) and 12 (n = 166) months of age using Illumina MiSeq multiplex sequencing and taxonomic resolution against the HOMD 16S rDNA database of oral bacteria.Species richness in the oral samples did not differ between the EF and SF groups, but partial least square modeling identified a few taxa that were significantly associated with being in either group, e.g. lower level of Moraxella catarrhalis in the EF group. Infants in the BFR group had significantly lower species richness at 4 months of age and their microbiota pattern differed markedly from the formula-fed groups.Supplementation of infant formula with MFGM yielded moderate effects on the oral microbiome. Moraxella catarrhalis was less prevalent in infants fed EF than in those fed SF and may be associated with the decrease in otitis media seen in the same group.
Project description:The relationships between nutrition, metabolic response, early growth and later body weight have been investigated in human studies. The aim of this follow-up study was to assess the long-term effect of infant feeding on growth and to study whether the infant metabolome at the age of 4 months might predict anthropometry at 4 years of age. The Belgrade-Munich infant milk trial (BeMIM) was a randomized controlled trial in which healthy term infants received either a protein-reduced infant formula (1.89 g protein/100 kcal) containing alpha-lactalbumin enriched whey and long-chain polyunsaturated fatty acids (LC-PUFA), or a standard formula (2.2 g protein/100 kcal) without LC-PUFA, focusing on safety and suitability. Non-randomized breastfed infants were used as a reference group. Of the 259 infants that completed the BeMIM study at the age of 4 months (anthropometry assessment and blood sampling), 187 children participated in a follow-up visit at 4 years of age. Anthropometry including weight, standing height, head circumference, and percent body fat was determined using skinfolds (triceps, subscapular) and bioelectrical impedance analysis. Plasma metabolite concentration, collected in samples at the age of 4 months, was measured using flow-injection tandem mass spectrometry. A linear regression model was applied to estimate the associations between each metabolite and growth with metabolites as an independent variable. At 4 years of age, there were no significant group differences in anthropometry and body composition between formula groups. Six metabolites (Asn, Lys, Met, Phe, Trp, Tyr) measured at 4 months of age were significantly associated with changes in weight-for-age z-score between 1 to 4 months of age and BMI-for-age z-score (Tyr only), after adjustment for feeding group. No correlation was found between measured metabolites and long-term growth (up to 4 years of age). No long-term effects of early growth patterns were shown on anthropometry at 4 years of age. The composition of infant formula influences the metabolic profile and early growth, while long-term programming effects were not observed in this study.
Project description:Purpose: To evaluate effects on growth and infection rates of supplementing infant formula with the probiotic Lactobacillus paracasei ssp. paracasei strain F19 (F19) or bovine milk fat globule membrane (MFGM). Methods: In a double-blind, randomized controlled trial, 600 infants were randomized to a formula supplemented with F19 or MFGM, or to standard formula (SF). A breastfed group was recruited as reference (n = 200).The intervention lasted from age 21 ± 7 days until 4 months, and infants were followed until age one year. Results: Both experimental formulas were well tolerated and resulted in high compliance. The few reported adverse events were not likely related to formula, with the highest rates in the SF group, significantly higher than for the F19-supplemented infants (p = 0.046). Weight or length gain did not differ during or after the intervention among the formula-fed groups, with satisfactory growth. During the intervention, overall, the experimental formula groups did not have more episodes of diarrhea, fever, or days with fever than the breastfed infants. However, compared to the breastfed infants, the SF group had more fever episodes (p = 0.021) and days with fever (p = 0.036), but not diarrhea. Compared with the breastfed group, the F19-supplemented infants but not the other two formula groups had more visits/unscheduled hospitalizations (p = 0.015) and borderline more episodes of upper respiratory tract infections (p = 0.048). Conclusions: Both the MFGM- and F19-supplemented formulas were safe and well-tolerated, leading to few adverse effects, similar to the breastfed group and unlike the SF group. During the intervention, the MFGM-supplemented infants did not differ from the breastfed infants in any primary outcome.
Project description:Human milk oligosaccharides are important components of breast milk. We evaluated feeding tolerance of the human milk oligosaccharide 2'-fucosyllactose (2'FL) in a 100% whey, partially hydrolyzed infant formula with the probiotic Bifidobacterium animalis ssp lactis strain Bb12 (B lactis; Test) as compared with the same formula without 2'FL (Control) in a randomized controlled trial of healthy infants enrolled at 2 weeks of age (±5 days). After 6 weeks of feeding the assigned formula, the primary outcome of tolerance was assessed using the Infant Gastrointestinal Symptom Questionnaire. Stooling, vomiting, spit-up, crying, and fussing were compared between groups. Seventy-nine infants were enrolled and 63 completed the study per protocol (30 Test, 33 Control). Infant Gastrointestinal Symptom Questionnaire scores were similar between groups (Test 20.9 ± 4.8, Control 20.7 ± 4.3, P = .82). Partially hydrolyzed infant formula with 2'FL and B lactis is tolerated well, as confirmed by a validated multi-symptom index.
Project description:Human milk contains nutritional, immunoprotective and developmental components that support optimal infant growth and development. The milk fat globule membrane (MFGM) is one unique component, comprised of a tri-layer of polar lipids, glycolipids, and proteins, that may be important for brain development. MFGM is not present in most infant formulas. We tested the effects of bovine MFGM supplementation on reflex development and on brain lipid and metabolite composition in rats using the "pup in a cup" model. From postnatal d5 to d18, rats received either formula supplemented with MFGM or a standard formula without MFGM; a group of mother-reared animals was used as reference/control condition. Body and brain weights did not differ between groups. MFGM supplementation reduced the gap in maturation age between mother-reared and standard formula-fed groups for the ear and eyelid twitch, negative geotaxis and cliff avoidance reflexes. Statistically significant differences in brain phospholipid and metabolite composition were found at d13 and/or d18 between mother-reared and standard formula-fed groups, including a higher phosphatidylcholine:phosphatidylethanolamine ratio, and higher phosphatidylserine, glycerol-3 phosphate, and glutamine in mother-reared compared to formula-fed pups. Adding MFGM to formula narrowed these differences. Our study demonstrates that addition of bovine MFGM to formula promotes reflex development and alters brain phospholipid and metabolite composition. Changes in brain lipid metabolism and their potential functional implications for neurodevelopment need to be further investigated in future studies.
Project description:BACKGROUND & METHODS:To examine the relationship between breastfeeding and maternally-rated infant temperament at age 3 months, 316 infants in the prospective Cambridge Baby Growth Study, UK had infant temperament assessed at age 3 months by mothers using the Revised Infant Behavior Questionnaire, which produces scores for three main dimensions of temperament derived from 14 subscales. Infant temperament scores were related to mode of infant milk feeding at age 3 months (breast only; formula milk only; or mixed) with adjustment for infant's age at assessment and an index of deprivation. RESULTS:Infant temperament dimension scores differed across the three infant feeding groups, but appeared to be comparable between exclusive breast-fed and mixed-fed infants. Compared to formula milk-fed infants, exclusive breast-fed and mixed-fed infants were rated as having lower impulsivity and positive responses to stimulation (adjusted mean [95% CI] "Surgency/Extraversion" in formula-fed vs. mixed-fed vs. breast-fed groups: 4.3 [4.2-4.5] vs. 4.0 [3.8-4.1] vs. 4.0 [3.9-4.1]; p-heterogeneity?=?0.0006), lower ability to regulate their own emotions ("Orienting/Regulation": 5.1 [5.0-5.2], vs. 4.9 [4.8-5.1] vs. 4.9 [4.8-5.0]; p?=?0.01), and higher emotional instability ("Negative affectivity": 2.8 [2.6-2.9] vs. 3.0 [2.8-3.1] vs. 3.0 [2.9-3.1]; p?=?0.03). CONCLUSIONS:Breast and mixed-fed infants were rated by their mothers as having more challenging temperaments in all three dimensions; particular subscales included greater distress, less smiling, laughing, and vocalisation, and lower soothability. Increased awareness of the behavioural dynamics of breastfeeding, a better expectation of normal infant temperament and support to cope with difficult infant temperament could potentially help to promote successful breastfeeding.
Project description:BACKGROUND/OBJECTIVES: Protein concentration is lower in human milk (HM) than in infant formula. The objective of this study was to evaluate the effect of an α-lactalbumin-enriched formula with a lower protein concentration on infant growth, protein markers and biochemistries. SUBJECTS/METHODS: Healthy term formula-fed (FF) infants 5-14 days old were randomized in this controlled, double-blind trial to standard formula (SF: 14.1 g/l protein, 662 kcal/l) group (n=112) or experimental formula (EF: 12.8 g/l protein, 662 kcal/l) group (n=112) for 120 days; a HM reference group (n=112) was included. Primary outcome was weight gain (g/day) from D0 to D120. Secondary outcomes included serum albumin, plasma amino acids insulin and incidence of study events. Anthropometric measures were expressed as Z-scores using 2006 World Health Organization growth standards. RESULTS: A total of 321 of the 336 infants (96%) who enrolled, completed the study. Mean age was 9.6 (±2.9) days; 50% were girls. Mean weight gain (g/day) did not significantly differ between SF vs EF (P=0.67) nor between EF vs HM (P=0.11); however weight gain (g/day) was significantly greater in the SF vs HM group (P=0.04). At day 120, mean weight-for-age Z-score (WAZ) and weight-for-length Z-score (WLZ) did not significantly differ between SF vs EF nor EF vs HM; however the WAZ was significantly greater in SF vs HM (P=0.025). Secondary outcomes were within normal ranges for all groups. Incidence of study events did not differ among groups. CONCLUSIONS: α-Lactalbumin-enriched formula containing 12.8 g/l protein was safe and supported age-appropriate growth; weight gain with EF was intermediate between SF and HM groups and resulted in growth similar to HM-fed infants in terms of weight gain, WAZ and WLZ.