Growth, Nutrition, and Cytokine Response of Breast-fed Infants and Infants Fed Formula With Added Bovine Osteopontin

J Pediatr Gastroenterol Nutr. 2016 Apr;62(4):650-7. doi: 10.1097/MPG.0000000000001005.


Objectives: Breast milk contains a high concentration of osteopontin (OPN), a protein having multiple functions. In contrast, infant formula is low in OPN. A randomized clinical trial was performed to evaluate effects of adding a highly enriched bovine OPN fraction to formula, and infants whose mothers had already decided not to breast-feed were recruited. They were fed regular formula (F0) or the same formula with bovine OPN at 65 (F65) or 130 (F130) mg/L (50% and 100% of human milk level, respectively) from 1 to 6 months of age and were compared with a reference group of breast-fed (BF) infants.

Methods: Morbidity was recorded daily and 3-day dietary records collected monthly. Anthropometry was assessed monthly, and blood samples were taken at 1, 4, and 6 months of age. Hematology and iron status, serum cytokines, plasma amino acids, and blood urea nitrogen were analyzed.

Results: Formulas were well tolerated and there were no significant differences in formula intake or growth among the formula-fed groups. The F130 group had significantly lower plasma threonine than the F0 and F65 groups, and significantly lower plasma branched-chain amino acids (BCAAs) than the F0 group and, thus, was closer to BF infants. Plasma TNF-α was higher in formula-fed infants than in BF infants. Among the formula-fed groups, the proinflammatory cytokine TNF-α was significantly lower in the F65 and F130 groups than in the F0 group, suggesting that OPN downregulates inflammatory cytokines and thus affects immune function.

Conclusions: Addition of OPN to infant formula changes amino acid metabolism and cytokine responses of FF infants and makes them more similar to BF infants. The lower prevalence of pyrexia in the F130 infants than in F0 infants suggests that adding OPN may confer health benefits.

Trial registration: NCT00970398.

Publication types

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

MeSH terms

  • Amino Acids / blood
  • Amino Acids / metabolism
  • Animals
  • Blood Urea Nitrogen
  • Breast Feeding*
  • Cattle
  • Child Development*
  • China / epidemiology
  • Cytokines / blood
  • Cytokines / metabolism
  • Double-Blind Method
  • Female
  • Fever / epidemiology
  • Fever / immunology
  • Fever / prevention & control
  • Hospitals, Pediatric
  • Humans
  • Immune System / growth & development*
  • Immune System / immunology
  • Immune System / metabolism
  • Incidence
  • Infant Formula* / adverse effects
  • Infant Formula* / chemistry
  • Infant, Newborn
  • Male
  • Milk Proteins / administration & dosage
  • Milk Proteins / adverse effects
  • Milk Proteins / therapeutic use*
  • Nutritional Status*
  • Osteopontin / administration & dosage
  • Osteopontin / adverse effects
  • Osteopontin / therapeutic use*
  • Prevalence


  • Amino Acids
  • Cytokines
  • Milk Proteins
  • Osteopontin

Associated data