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Effects of feeding term infants low energy low protein formula supplemented with bovine milk fat globule membranes
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
2014 (English)Doctoral 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.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet , 2014. , 55 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1644
Keyword [en]
infant formula, milk fat globule membranes, energy, protein, growth, cognition, parental control, infection, cholesterol, oral microbiota
National Category
Pediatrics
Research subject
Pediatrics
Identifiers
URN: urn:nbn:se:umu:diva-88192ISBN: 978-91-7601-044-0 (print)OAI: oai:DiVA.org:umu-88192DiVA: diva2:714006
Public defence
2014-05-16, Sal E04, Biomedicinarhuset (byggnad R1), Norrlands Universitetssjukhus, Umeå, 13:00 (English)
Opponent
Supervisors
Funder
Vinnova, 2009-00209
Available from: 2014-04-25 Created: 2014-04-24 Last updated: 2014-04-25Bibliographically approved
List of papers
1. 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 trial1,2,3
Open this publication in new window or tab >>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 trial1,2,3
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2014 (English)In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 99, no 4, 860-868 p.Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
American Society for Nutrition, 2014
Keyword
term infants; cognitive-development; 1st year; dietary-cholesterol; published evidence; brain-development; enriched formula; maternal control; clinical-trial; blood-pressure
National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-86314 (URN)10.3945/ajcn.113.064295 (DOI)000333173100013 ()24500150 (PubMedID)
Available from: 2014-02-22 Created: 2014-02-22 Last updated: 2017-12-05Bibliographically approved
2. Parental feeding control in relation to feeding mode and growth pattern in early infancy
Open this publication in new window or tab >>Parental feeding control in relation to feeding mode and growth pattern in early infancy
2014 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, no 10, 1072-1077 p.Article in journal (Refereed) Published
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.

Keyword
breast-feeding, bottle-feeding
National Category
Pediatrics
Research subject
Pediatrics
Identifiers
urn:nbn:se:umu:diva-88187 (URN)10.1111/apa.12721 (DOI)000342753400021 ()
Funder
Vinnova, 2009-00209
Available from: 2014-04-24 Created: 2014-04-24 Last updated: 2017-12-05Bibliographically approved
3. Infections in infants fed formula supplemented with bovine milk fat globule membranes
Open this publication in new window or tab >>Infections in infants fed formula supplemented with bovine milk fat globule membranes
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2015 (English)In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 60, no 3, 384-389 p.Article in journal (Other academic) Published
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.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2015
Keyword
breast-feeding, infant formula, infections, milk fat globule membranes, otitis media
National Category
Pediatrics Nutrition and Dietetics Gastroenterology and Hepatology
Research subject
Pediatrics
Identifiers
urn:nbn:se:umu:diva-88188 (URN)10.1097/MPG.0000000000000624 (DOI)000350527100023 ()25714582 (PubMedID)
Funder
VINNOVA, 2009-00209
Available from: 2014-04-24 Created: 2014-04-24 Last updated: 2017-12-05Bibliographically approved
4. Cardiovascular risk markers until 12 months of age in infants fed a formula supplemented with bovine milk fat globule membranes
Open this publication in new window or tab >>Cardiovascular risk markers until 12 months of age in infants fed a formula supplemented with bovine milk fat globule membranes
(English)Manuscript (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.

Keyword
Cardiovascular disease, infant formula, cholesterol, breast-feeding
National Category
Pediatrics
Research subject
Pediatrics
Identifiers
urn:nbn:se:umu:diva-88190 (URN)
Funder
Vinnova, 2009-00209
Available from: 2014-04-24 Created: 2014-04-24 Last updated: 2014-04-25Bibliographically approved
5. Characterization and in vitro properties of oral lactobacilli in breastfed infants
Open this publication in new window or tab >>Characterization and in vitro properties of oral lactobacilli in breastfed infants
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2013 (English)In: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 13, 193- p.Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
BioMed Central, 2013
Keyword
Lactobacillus, L.gasseri, Growth, Adhesion, Gp340, Breastfed infants
National Category
Pediatrics Dentistry
Identifiers
urn:nbn:se:umu:diva-80436 (URN)10.1186/1471-2180-13-193 (DOI)000323427400001 ()
Available from: 2013-09-20 Created: 2013-09-17 Last updated: 2017-12-06Bibliographically approved

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