title: Effect of dietary nucleotide supplementation on growth and immune function in term infants: a randomized controlled trial.
abstract: OBJECTIVE
  To examine the effect of nucleotide (NT)-supplemented cow's milk-based formula on growth and biochemical indices of immune function in healthy infants.
  
  
  METHODS
  Randomized controlled trial (RCT) of formula-fed term infants allocated to control formula with an innate level of NT at 10 mg/l (n = 102), or formula fortified with NT at 33.5 mg/l (n = 98). A parallel group of 125 breastfed infants followed the same protocol as a reference.
  
  
  METHODS
  Growth was assessed at enrolment, 7 weeks, 4 months and 7 months of age. Natural killer cell activity, cytokine production and lymphocyte subpopulations were assessed at 7 weeks of age. Antibody responses to diphtheria toxoid, tetanus toxoid and Haemophilus influenzae type b (Hib) immunizations were measured at 7 months of age.
  
  
  RESULTS
  NT supplementation did not influence the growth of formula fed infants or any markers of immunity measured at 7 weeks of age. Antibody responses to tetanus toxoid were higher in the NT-supplemented group (n = 68) compared with the control group (n = 70) at 7 months of age (median (5th, 95% percentile): 1.57(0.42, 3.43) vs 1.01(0.41, 4.66) IU/ml, P < 0.03). A difference between treatments was seen in response to diphtheria toxoid but this effect disappeared when adjusted for hepatitis B immunization at birth. There was no effect of treatment on antibody responses to Hib immunization.
  
  
  CONCLUSIONS
  Supplementation of formulas with NT at 33.5 mg/l resulted in a modest improvement in antibody response consistent with RCTs that used higher levels of NT supplementation. Whether this translates to clinical benefits in well-nourished infants requires further study.
  
  
  BACKGROUND
  Supported by a grant from Wyeth Nutrition. Dr Makrides was supported by an RD Wright Fellowship from the National Health and Medical Research Council of Australia and Dr Gibson was partially supported by the MS McLeod Research Trust and a Senior Research Fellowship from the National Health and Medical Research Council of Australia.
authors.affiliation: Child Health Research Institute, Flinders Medical Centre and Flinders University, Bedford Park, SA, Australia.
authors.forename: J S
authors.initials: JS
authors.lastname: Hawkes
authors.forename: R A
authors.initials: RA
authors.lastname: Gibson
authors.forename: D
authors.initials: D
authors.lastname: Roberton
authors.forename: M
authors.initials: M
authors.lastname: Makrides
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D005260:Female; D005527:Food, Fortified; D006128:Growth / Q000187:drug effects* / Q000502:physiology; D018073:Haemophilus Vaccines / Q000276:immunology*; D019741:Haemophilus influenzae type b / Q000276:immunology; D006801:Humans; D007223:Infant; D041943:Infant Formula / Q000737:chemistry*; D007227:Infant Nutritional Physiological Phenomena; D008895:Milk, Human / Q000737:chemistry; D009711:Nucleotides / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D018073:Haemophilus Vaccines; D009711:Nucleotides