Neurodevelopment and growth until 6.5 years of infants who consumed a low-energy, low-protein formula supplemented with bovine milk fat globule membranes: a randomized controlled trial.

BACKGROUND: We previously reported results from a randomized controlled trial in which we found that Swedish infants consuming an experimental low-energy, low-protein formula (EF) supplemented with bovine milk fat globule membranes (MFGMs) until 6 mo of age had several positive outcomes, including better performance in the cognitive domain of Bayley Scales of Infant and Toddler Development 3rd Edition at 12 mo of age, and higher plasma cholesterol concentrations during the intervention, than infants consuming standard formula (SF). OBJECTIVES: We aimed to evaluate neurodevelopment, growth, and plasma cholesterol status at 6 and 6.5 y of age in the same study population. METHODS: We assessed cognitive and executive functions using the Wechsler Intelligence Scale for Children 4th Edition (WISC-IV), Brown Attention-Deficit Disorder Scales for Children and Adolescents (Brown-ADD), and Quantified Behavior (Qb) tests, and behavior using the Child Behavior Checklist (CBCL) and Teacher's Report Form (TRF), at 6.5 y of age. Anthropometrics and plasma lipids were assessed at 6 y of age. RESULTS: There were no differences between the EF and SF groups in any of the subscales in WISC-IV or Brown-ADD at 6.5 y of age, in the proportion of children with scores outside the normal range in the Qb test, nor in clinical or borderline indications of problems in adaptive functioning from parental and teacher's scoring using the CBCL and TRF. There were no differences between the EF and SF groups in weight, length, or head or abdominal circumferences, nor in plasma concentrations of homocysteine, lipids, insulin, or glucose. CONCLUSIONS: Among children who as infants consumed a low-energy, low-protein formula supplemented with bovine MFGMs, there were no effects on neurodevelopment, growth, or plasma cholesterol status 6-6.5 y later.

Publisher Correction: Metabolic phenotype of breast-fed infants, and infants fed standard formula or bovine MFGM supplemented formula: a randomized controlled trial.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Fecal microbiome and metabolome of infants fed bovine MFGM supplemented formula or standard formula with breast-fed infants as reference: a randomized controlled trial.

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.

Physiological Effects of Feeding Infants and Young Children Formula Supplemented with Milk Fat Globule Membranes.

Dietary supplementation with bovine milk fat globule membrane (MFGM) concentrates has recently emerged as a possible means to improve the health of infants and young children. Formula-fed infants are of special interest since infant formulas traditionally have lower concentrations of biologically active MFGM components than human milk. We identified 6 double-blind randomized controlled trials (DBRCT) exploring the effects of supplementing the diet of infants and children with bovine MFGM concentrates. Two studies found a positive effect on cognitive development in formula-fed infants. Three studies found a protective effect against infections at different ages during infancy and early childhood. We conclude that supplementation with MFGM during infancy and childhood appears safe, and the studies indicate positive effects on both neurodevelopment and defense against infections, especially in formula-fed infants. However, due to the small number of studies and the heterogeneity of interventions and outcomes, more high-quality DBRCTs are needed before firm conclusions can be drawn on the likely health benefits of MFGM supplementation to infants and children.

Metabolic phenotype of breast-fed infants, and infants fed standard formula or bovine MFGM supplemented formula: a randomized controlled trial.

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.

Serum, plasma and erythrocyte membrane lipidomes in infants fed formula supplemented with bovine milk fat globule membranes.

BACKGROUND: Supplementation of formula with bovine milk fat globule membranes has been shown to narrow the gap in immunological and cognitive development between breast-fed and formula-fed infants. METHOD: In a double-blinded randomized controlled trial 160 formula-fed infants received an experimental formula (EF), supplemented with bovine milk fat globule membranes, or standard formula until 6 months of age. A breast-fed reference group was recruited. Lipidomic analyses were performed on plasma and erythrocyte membranes at 6 months and on serum at 4 and 12 months of age. RESULTS: At 6 months of age, we observed a significant separation in the plasma lipidome between the two formula groups, mostly due to differences in concentrations of sphingomyelins (SM), phosphatidylcholines (PC), and ceramides, and in the erythrocyte membrane lipidome, mostly due to SMs, PEs and PCs. Already at 4 months, a separation in the serum lipidome was evident where SMs and PCs contributed. The separation was not detected at 12 months. CONCLUSIONS: The effect of MFGM supplementation on the lipidome is likely part of the mechanisms behind the positive cognitive and immunological effects of feeding the EF previously reported in the same study population.