Change search
ReferencesLink to record
Permanent link

Direct link
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
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
Umeå University, Faculty of Social Sciences, Department of Psychology.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
Department of Nutrition, University of California, Davis, USA.
Show others and affiliations
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 as NCT00624689.

Place, publisher, year, edition, pages
American Society for Nutrition , 2014. Vol. 99, no 4, 860-868 p.
Keyword [en]
term infants; cognitive-development; 1st year; dietary-cholesterol; published evidence; brain-development; enriched formula; maternal control; clinical-trial; blood-pressure
National Category
URN: urn:nbn:se:umu:diva-86314DOI: 10.3945/ajcn.113.064295ISI: 000333173100013PubMedID: 24500150OAI: diva2:698500
Available from: 2014-02-22 Created: 2014-02-22 Last updated: 2014-06-27Bibliographically approved
In thesis
1. Effects of feeding term infants low energy low protein formula supplemented with bovine milk fat globule membranes
Open this publication in new window or tab >>Effects of feeding term infants low energy low protein formula supplemented with bovine milk fat globule membranes
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.
Umeå University medical dissertations, ISSN 0346-6612 ; 1644
infant formula, milk fat globule membranes, energy, protein, growth, cognition, parental control, infection, cholesterol, oral microbiota
National Category
Research subject
urn:nbn:se:umu:diva-88192 (URN)978-91-7601-044-0 (ISBN)
Public defence
2014-05-16, Sal E04, Biomedicinarhuset (byggnad R1), Norrlands Universitetssjukhus, Umeå, 13:00 (English)
Vinnova, 2009-00209
Available from: 2014-04-25 Created: 2014-04-24 Last updated: 2014-04-25Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Timby, NiklasDomellöf, ErikHernell, OlleDomellöf, Magnus
By organisation
PaediatricsDepartment of Psychology
In the same journal
American Journal of Clinical Nutrition

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 285 hits
ReferencesLink to record
Permanent link

Direct link