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  • 1. Demmelmair, Hans
    et al.
    Prell, Christine
    Timby, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, Bo
    Benefits of Lactoferrin, Osteopontin and Milk Fat Globule Membranes for Infants2017In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 9, no 8, article id 817Article, review/survey (Refereed)
    Abstract [en]

    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.

  • 2.
    Domellöf, Erik
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Timby, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, Bo
    Department of Nutrition, University of California, Davis, USA.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Formula feeding supplemented with milk fat globule membranes  improves cognitive score in term infants at 12 months2013In: Developmental Medicine & Child Neurology, 55 (Suppl. S2): Abstracts of the European Academy of Childhood Disability 25th Annual Meeting, 10-12 October 2013, Newcastle-Gateshead, UK, Mac Keith Press , 2013, p. 50-50Conference paper (Refereed)
    Abstract [en]

    Introduction: Findings of enhanced cognitive development in breast‐fed compared with formula‐fed infants suggest that breast milk contains neurodevelopmentally beneficial components. Animal studies report positive behavioral effects of supplementation with components included in the bovine milkfat globule membrane fraction (MFGM). Behavioral effects of MFGM supplemented formula in human infants have not been studied. This study tested the hypothesis that infants fed an experimental formula (EF) supplemented with a bovine MFGM fraction would display a more favorable neurofunctional development than infants fed a standard formula (SF) at 12 months.

    Participants and Methods: Healthy term formula‐fed infants (n = 160) and a breast‐fed reference (BFR) group (n = 80) were included in a prospective double blind randomized trial before 2 months of age. Formula‐fed infants were randomized to receive EF or SF from inclusion until 6 months. At 12 months, cognitive, motor and verbal functions were tested using the Bayley Scales of Infant and Toddler Development‐III.

    Results: The cognitive score was significantly higher in the EF (105.8 ± 9.2) than SF (101.8 ± 8.0) group, but equal between the EF and BFR groups. No differences were found in motor or verbal score between the formula groups. The BFR group displayed higher verbal but not motor scores than the formula groups.

    Conclusion: In keeping with the hypothesis, feeding infants MFGM supplemented formula resulted in improved cognitive function at 12 months compared with a standard formula. The difference in cognitive score between the EF and SF groups is compliant with calculated differences between formula‐fed and breast‐fed infants in previous studies.

  • 3.
    Grip, Tove
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Dyrlund, Thomas S.
    Ahonen, Linda
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hyötyläinen, Tuulia
    Knip, Mikael
    Lönnerdal, Bo
    Oresic, Matej
    Timby, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Serum, plasma and erythrocyte membrane lipidomes in infants fed formula supplemented with bovine milk fat globule membranes2018In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 84, no 5, p. 726-732Article in journal (Refereed)
    Abstract [en]

    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.

  • 4. He, Xuan
    et al.
    Parenti, Mariana
    Grip, Tove
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lonnerdal, Bo
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Timby, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Slupsky, Carolyn M.
    Metabolic phenotype of breast-fed infants, and infants fed standard formula or bovine MFGM supplemented formula: a randomized controlled trial2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 339Article in journal (Refereed)
    Abstract [en]

    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.

  • 5. He, Xuan
    et al.
    Parenti, Mariana
    Grip, Tove
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, Bo
    Timby, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Slupsky, Carolyn M.
    Fecal microbiome and metabolome of infants fed bovine MFGM supplemented formula or standard formula with breast-fed infants as reference: a randomized controlled trial2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 11589Article in journal (Refereed)
    Abstract [en]

    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.

  • 6.
    Hernell, Olle
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Timby, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, Bo
    Clinical Benefits of Milk Fat Globule Membranes for Infants and Children2016In: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 173, p. S60-S65Article in journal (Refereed)
    Abstract [en]

    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 firm conclusions on the effects of MFGM supplementation on the health and development of infants can be drawn.

  • 7.
    Timby, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Effects of feeding term infants low energy low protein formula supplemented with bovine milk fat globule membranes2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background Observational studies have shown that early nutrition influences short- and long-term health of infants. Formula-fed infants have higher protein and energy intakes and lower intakes of several biologically active components present in human milk. Some of these are present in the milk fat globule membrane (MFGM). The aim of the present study was to examine the effects of feeding term infants an experimental low energy low protein formula supplemented with bovine milk fat globule membranes. Our hypothesis was that infants fed experimental formula (EF), compared to infants fed standard formula (SF), would have outcomes more similar to a breast-fed reference (BFR) group.

    Methods In a double-blinded randomized controlled trial, 160 exclusively formula-fed, healthy, term infants were randomized to receive EF or SF from <2 to 6 months of age. A BFR group consisted of 80 breast-fed infants. Measurements were made at baseline, 4, 6 and 12 months of age. The EF had lower energy (60 vs. 66 kcal/100 mL) and protein (1.20 vs. 1.27 g/100 mL) concentrations, and was supplemented with a bovine MFGM concentrate.

    Results At 12 months of age, the EF group performed better than the SF group in the cognitive domain of Bayley Scales of Infant Development, 3rd Ed. During the intervention, the EF group had a lower incidence of acute otitis media than the SF group, less use of antipyretics and the EF and SF groups differed in concentrations of s-IgG against pneumococci. The formula-fed infants regulated their intakes by increasing meal volumes. Thus, there were no differences between the EF and SF groups in energy or protein intakes, blood urea nitrogen, insulin or growth including body fat percent until 12 months of age. Pressure-to-eat score at 12 months of age was reported lower by parents of formula-fed infants than by parents of breast-fed infants, indicating a low level of parental control of feeding in the formula-fed groups. Neither high pressure-to-eat score nor high restrictive score was associated with formula feeding. During the intervention, the EF group gradually reached higher serum cholesterol concentrations than the SF group, and closer to the BFR group. At 4 months of age, there was no significant difference in the prevalence of lactobacilli in saliva between the EF and SF groups.

    Conclusions Supplementation of infant formula with a bovine MFGM fraction enhanced both cognitive and immunological development in formula-fed infants. Further, the intervention narrowed the gap in serum cholesterol concentrations between formula-fed and breast-fed infants. The lower energy and protein concentrations of the EF were totally compensated for by a high level of self-regulation of intake which might, at least partly, be explained by a low level of parental control of feeding in the study population. The findings are of importance for further development of infant formulas and may contribute to improved short- and long-term health outcomes for formula-fed infants.

  • 8.
    Timby, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Erik
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, Bo
    Department of Nutrition, University of California, Davis, USA.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    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 trial1,2,32014In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 99, no 4, p. 860-868Article in journal (Refereed)
    Abstract [en]

    Background: Observational 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

    Objective: The 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.

    Design: In 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.

    Results: At 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.

    Conclusions: MFGM 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. This trial was registered at clinicaltrials.gov as NCT00624689.

  • 9.
    Timby, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lif Holgerson, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lonnerdal, Bo
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Oral Microbiota in Infants Fed a Formula Supplemented with Bovine Milk Fat Globule Membranes: A Randomized Controlled Trial2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 1, article id e0169831Article in journal (Refereed)
    Abstract [en]

    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 micro biome. 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.

  • 10.
    Timby, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lonnerdal, Bo
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Supplementation of Infant Formula with Bovine Milk Fat Globule Membranes2017In: Advances in Nutrition, ISSN 2161-8313, Vol. 8, no 2, p. 351-355Article, review/survey (Refereed)
    Abstract [en]

    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.

  • 11.
    Timby, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, Bo
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    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"2015In: Clinical Medicine Insights: Pediatrics, ISSN 1179-5565, Vol. 9, p. 63-64Article in journal (Refereed)
  • 12.
    Timby, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, Bo
    University of California, Davis.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Parental feeding control in relation to feeding mode and growth pattern in early infancy2014In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, no 10, p. 1072-1077Article in journal (Refereed)
    Abstract [en]

    Aim: 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.

    Methods: We included 141 formula-fed and 72 breast-fed infants from a randomised controlled trial, who were prospectively followed from under 2 months of age to 12 months of age. Anthropometry was recorded at baseline, 4, 6 and 12 months of age. Parental feeding control was assessed using a Child Feeding Questionnaire at 4 and 12 months.

    Results: The formula-fed groups fully compensated for different energy and protein densities by regulating their volume intakes. Parents of formula-fed infants had a lower pressure to eat score at 12 months than parents of breast-fed infants. A high parental restrictive score at 12 months was associated with weight at 12 months and high parental pressure to eat score at 12 months with body mass index at 12 months. Neither were associated with feeding mode.

    Conclusion: Formula-fed infants had a high level of energy self-regulation and were subjected to low parental control. Parental control of feeding was mainly influenced by infant growth.

  • 13.
    Timby, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Vaarala, Outi
    Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland.
    Melin, Merit
    Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland.
    Lönnerdal, Bo
    University of California, Davis.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Infections in infants fed formula supplemented with bovine milk fat globule membranes2015In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 60, no 3, p. 384-389Article in journal (Other academic)
    Abstract [en]

    Objectives: Observational studies have shown that even in high-income countries formula-fed infants have a higher incidence of acute otitis media (AGM), 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%, P = 0.034), and did not differ from the breast-fed reference group (0%, P = 1.0). The incidence (25% vs 43%, P = 0.021) and longitudinal prevalence (P = 0.012) 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.

  • 14.
    Timby, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, Bo
    Department of Nutrition, University of California, Davis, California.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Cardiovascular risk markers until 12 mo of age in infants fed a formula supplemented with bovine milk fat globule membranes2014In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 76, no 4, p. 394-400Article in journal (Refereed)
    Abstract [en]

    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.

  • 15.
    Timby, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, Bo
    University of California, Davis.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Cardiovascular risk markers until 12 months of age in infants fed a formula supplemented with bovine milk fat globule membranesManuscript (preprint) (Other academic)
    Abstract [en]

    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 months of age were randomized to experimental formula (EF) with added milk fat globule membrane or standard formula (SF) until 6 months of age. A breast-fed reference (BFR) group consisted of 80 infants. Measurements were made at inclusion, 4, 6 and 12 months 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 months.

  • 16.
    Timby, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Stattin, Eva-Lena
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Kristiansen, Ingela
    Pediatric Clinic, Östersund Hospital, Sweden.
    Eriksson, Urban
    Pediatric Clinic, Östersund Hospital, Sweden.
    Erikson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Early onset autosomal dominant spinocerebellar ataxia with miosis: Four cases2008In: European journal of paediatric neurology, ISSN 1090-3798, E-ISSN 1532-2130, Vol. 12, no 1, p. 38-40Article in journal (Other academic)
    Abstract [en]

    Previously, at least 29 different forms of autosomal dominant spinocerebellar ataxias (SCAs) have been described. We describe a family with four members through three generations with autosomal dominant ataxia in combination with miosis and hyperreflexia. This family's ataxia does not match any of the previously described SCAs and is probably a novel form of SCA. To continue with the search for the genetic background of this disease, more cases are needed.

  • 17.
    Vestman, Nelly Romani
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Timby, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Holgerson, Pernilla Lif
    Umeå University, Faculty of Medicine, Department of Odontology.
    Kressirer, Christine A
    Claesson, Rolf
    Umeå University, Faculty of Medicine, Department of Odontology.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Öhman, Carina
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Tanner, Anne CR
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Characterization and in vitro properties of oral lactobacilli in breastfed infants2013In: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 13, p. 193-Article in journal (Refereed)
    Abstract [en]

    Background: Lactobacillus 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.

    Results: 43 (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.

    Conclusions: Lactobacilli colonized the oral cavity of breastfed infants significantly more frequently than formulafed 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.

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