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

Am J Clin Nutr. 2014 Apr;99(4):860-8. doi: 10.3945/ajcn.113.064295. Epub 2014 Feb 5.


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.

Trial registration: NCT00624689.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Height*
  • Body Mass Index
  • Breast Feeding
  • Cattle
  • Child Development*
  • Cognition*
  • Diet, Protein-Restricted
  • Double-Blind Method
  • Energy Intake
  • Female
  • Glycolipids / metabolism*
  • Glycoproteins / metabolism*
  • Humans
  • Infant
  • Infant Behavior
  • Infant Formula* / chemistry
  • Infant, Newborn
  • Lipid Droplets
  • Longitudinal Studies
  • Male
  • Motor Skills
  • Neurogenesis*
  • Sweden
  • Verbal Behavior
  • Weight Gain*


  • Glycolipids
  • Glycoproteins
  • milk fat globule

Associated data