Niklas Timby

Neurodevelopment, nutrition, and growth until 12 mo of age in infants fed a low-energy, low-protein formula supplemented with bovine milk fat globule membranes: a randomized controlled trial

BACKGROUNDnObservational studies have indicated that differences in the composition of human milk and infant formula yield benefits in cognitive development and early growth for breastfed infants.nnnOBJECTIVEnThe objective was to test the hypothesis that feeding an infant formula with reduced energy and protein densities and supplemented with bovine milk fat globule membrane (MFGM) reduces differences in cognitive development and early growth between formula-fed and breastfed infants.nnnDESIGNnIn a prospective, double-blind, randomized controlled trial, 160 infants <2 mo of age were randomly assigned to be fed an MFGM-supplemented, low-energy, low-protein experimental formula (EF) or a standard formula (SF) until 6 mo of age. The energy and protein contents of the EF and SF were 60 and 66 kcal/100 mL and 1.20 and 1.27 g/100 mL, respectively. A breastfed reference (BFR) group consisted of 80 infants.nnnRESULTSnAt 12 mo of age, the cognitive score (mean ± SD) on testing with the Bayley Scales of Infant and Toddler Development, Third Edition, was significantly higher in the EF group than in the SF group (105.8 ± 9.2 compared with 101.8 ± 8.0; P = 0.008) but was not significantly different from that in the BFR group (106.4 ± 9.5; P = 0.73). The EF group ingested larger volumes of formula than did the SF group (864 ± 174 compared with 797 ± 165 mL/d; P = 0.022), fully compensating for the lower energy density. No significant differences in linear growth, weight gain, body mass index, percentage body fat, or head circumference were found between the EF and SF groups.nnnCONCLUSIONSnMFGM supplementation to infant formula narrows the gap in cognitive development between breastfed and formula-fed infants. Between 2 and 6 mo of age, formula-fed term infants have the capacity to upregulate their ingested volumes when the energy density of formula is reduced from 66 to 60 kcal/100 mL.

Infections in infants fed formula supplemented with bovine milk fat globule membranes

Objectives: Observational studies have shown that even in high-income countries formula-fed infants have a higher incidence of acute otitis media (AOM), and gastrointestinal and respiratory tract infections during the first year of life compared with breast-fed infants. We hypothesized that components of the milk fat globule membrane (MFGM) may be responsible for some of these differences and that supplementation with bovine MFGM would decrease the infectious morbidity in formula-fed infants. Methods: In a double-blind randomized controlled trial, 160 formula-fed infants received experimental formula (EF) supplemented with bovine MFGM (EF) or unsupplemented standard formula (SF) from <2 months until 6 months of age. A breast-fed reference group consisted of 80 infants. Disease symptoms, health care contacts, and medication were recorded by the parents until 12 months of age. Serum immunoglobulin G for 10 pneumococcal serotypes was analyzed at 6 months of age. Results: The cumulative incidence of AOM during the intervention was lower in the EF group than in the SF group (1% vs 9%, Pu200a=u200a0.034), and did not differ from the breast-fed reference group (0%, Pu200a=u200a1.0). The incidence (25% vs 43%, Pu200a=u200a0.021) and longitudinal prevalence (Pu200a=u200a0.012) of antipyretic use were significantly lower in the EF group than in the SF group. Serum immunoglobulin G concentrations against pneumococcal serotypes 1, 5, and 14 were lower in the EF group than in the SF group. Conclusions: Supplementation of formula with bovine MFGM reduces the risk of AOM, decreases antipyretics use in formula-fed infants, and has immunomodulatory effects on humoral response against pneumococcus vaccine.

Clinical Benefits of Milk Fat Globule Membranes for Infants and Children.

The milk fat globule membrane (MFGM) in breast milk contains many bioactive components. Infant formulas traditionally have been devoid of the MFGM fraction, but dairy technology now has made the addition of bovine MFGM technically feasible. We identified 6 double-blinded randomized controlled trials exploring the effects of MFGM supplementation on the diets of infants or children. Results suggest that supplementation is safe and indicate positive effects on both neurodevelopment and defense against infections. MFGM supplementation of infant formula may narrow the gap in cognitive performance and infection rates between breastfed and formula-fed infants. Because of the small number of studies and the heterogeneity of interventions, more high-quality double-blinded randomized controlled trials are needed, with well characterized and clearly defined MFGM fractions, before firmxa0conclusions on the effects of MFGM supplementation on the health and development of infants can be drawn.

Cardiovascular risk markers until 12 mo of age in infants fed a formula supplemented with bovine milk fat globule membranes

Background:Some of the health advantages of breast-fed as compared to formula-fed infants have been suggested to be due to metabolic programming effects resulting from early nutrition.Methods:In a prospective double-blinded randomized trial, 160 infants <2 mo of age were randomized to experimental formula (EF) with added milk fat globule membrane (MFGM) or standard formula (SF) until 6 mo of age. A breast-fed reference (BFR) group consisted of 80 infants. Measurements were made at inclusion and at 4, 6, and 12 mo of age.Results:During the intervention, the EF group had higher total serum cholesterol concentration than the SF group, reaching the level of the BFR group. The EF group had a low-density lipoprotein to high-density lipoprotein ratio not significantly different from the SF group but lower than the BFR group.Conclusion:Supplementation of infant formula with MFGM modified the fat composition of the formula and narrowed the gap between breast-fed and formula-fed infants with regard to serum lipid status at 12 mo.

Characterization and in vitro properties of oral lactobacilli in breastfed infants

BackgroundLactobacillus species can contribute positively to general and oral health and are frequently acquired by breastfeeding in infancy. The present study aimed to identify oral lactobacilli in breast and formula-fed 4 month-old infants and to evaluate potential probiotic properties of the dominant Lactobacillus species detected. Saliva and oral swab samples were collected from 133 infants who were enrolled in a longitudinal study (n=240) examining the effect of a new infant formula on child growth and development. Saliva was cultured and Lactobacillus isolates were identified from 16S rRNA gene sequences. Five L. gasseri isolates that differed in 16S rRNA sequence were tested for their ability to inhibit growth of selected oral bacteria and for adhesion to oral tissues. Oral swab samples were analyzed by qPCR for Lactobacillus gasseri.Results43 (32.3%) infants were breastfed and 90 (67.7%) were formula-fed with either a standard formula (43 out of 90) or formula supplemented with a milk fat globule membrane (MFGM) fraction (47 out of 90). Lactobacilli were cultured from saliva of 34.1% breastfed infants, but only in 4.7% of the standard and 9.3% of the MFGM supplemented formula-fed infants. L. gasseri was the most prevalent (88% of Lactobacillus positive infants) of six Lactobacillus species detected. L. gasseri isolates inhibited Streptococcus mutans binding to saliva-coated hydroxyapatite, and inhibited growth of S. mutans, Streptococcus sobrinus, Actinomyces naeslundii, Actinomyces oris, Candida albicans and Fusobacterium nucleatum in a concentration dependent fashion. L. gasseri isolates bound to parotid and submandibular saliva, salivary gp340 and MUC7, and purified MFGM, and adhered to epithelial cells. L. gasseri was detected by qPCR in 29.7% of the oral swabs. Breastfed infants had significantly higher mean DNA levels of L. gasseri (2.14 pg/uL) than infants fed the standard (0.363 pg/uL) or MFGM (0.697 pg/uL) formula.ConclusionsLactobacilli colonized the oral cavity of breastfed infants significantly more frequently than formula-fed infants. The dominant Lactobacillus was L. gasseri, which was detected at higher levels in breastfed than formula-fed infants and displayed probiotic traits in vitro.

Oral Microbiota in Infants Fed a Formula Supplemented with Bovine Milk Fat Globule Membranes : A Randomized Controlled Trial

Background 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. Objectives 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. Methods 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. Results 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. Conclusions 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.

Benefits of Lactoferrin, Osteopontin and Milk Fat Globule Membranes for Infants

The provision of essential and non-essential amino acids for breast-fed infants is the major function of milk proteins. In addition, breast-fed infants might benefit from bioactivities of milk proteins, which are exhibited in the intestine during the digestive phase and by absorption of intact proteins or derived peptides. For lactoferrin, osteopontin and milk fat globule membrane proteins/lipids, which have not until recently been included in substantial amounts in infant formulas, in vitro experiments and animal models provide a convincing base of evidence for bioactivities, which contribute to the protection of the infant from pathogens, improve nutrient absorption, support the development of the immune system and provide components for optimal neurodevelopment. Technologies have become available to obtain these compounds from cow´s milk and the bovine compounds also exhibit bioactivities in humans. Randomized clinical trials with experimental infant formulas incorporating lactoferrin, osteopontin, or milk fat globule membranes have already provided some evidence for clinical benefits. This review aims to compare findings from laboratory and animal experiments with outcomes of clinical studies. There is good justification from basic science and there are promising results from clinical studies for beneficial effects of lactoferrin, osteopontin and the milk fat globule membrane complex of proteins and lipids. Further studies should ideally be adequately powered to investigate effects on clinically relevant endpoints in healthy term infants.

Parental feeding control in relation to feeding mode and growth pattern during early infancy

A high level of parental control of feeding and disturbed energy self‐regulation has previously been suggested as a mechanism for the accelerated growth observed in formula‐fed compared with breast‐fed infants. This study explored factors associated with parental control of feeding in a population of formula‐fed infants with high levels of self‐regulation.

Supplementation of Infant Formula with Bovine Milk Fat Globule Membranes

Studies have shown that supplementation of infant formula with bovine milk fat globule membranes (MFGMs) may substantially narrow the gap in health outcomes between formula-fed and breastfed infants. In one study, consumption of a formula supplemented with a lipid-rich MFGM concentrate between 2 and 6 mo of age improved cognitive performance at 24 wk of age. In another study, a formula supplemented with a protein-rich MFGM concentrate given between 2 and 6 mo of age improved cognitive performance at 12 mo of age, decreased infectious morbidity until 6 mo of age, and yielded serum cholesterol concentrations closer to those of breastfed infants. A third study that assessed the safety of supplementing infant formula with a lipid-rich or a protein-rich MFGM concentrate found a noninferior weight gain for both groups compared with a nonsupplemented formula. In this study, there was an increased risk of eczema in the protein-rich group, but no serious adverse events. Infant formulas with supplemental MFGMs have been launched on the market in several countries. However, the evidence base must still be considered quite limited. Based on 3 randomized controlled trials that are not comparable, the intervention seems safe, but there is not enough evidence for a general recommendation on which MFGM fraction to use and at what concentration as formula supplement for a given outcome.

Comment on “Safety and Tolerance Evaluation of Milk Fat Globule Membrane-Enriched Infant Formulas: A Randomized Controlled Multicenter Non-Inferiority Trial in Healthy Term Infants”

Comment on Safety and Tolerance Evaluation of Milk Fat Globule Membrane-Enriched Infant Formulas : A Randomized Controlled Multicenter Non-Inferiority Trial in Healthy Term Infants