Abstract

Introduction: Nucleotide (NT) supplemented infant formulas have been commercially available for a number of years despite the fact that clinical efficacy of NT supplementation has not been well established in randomised controlled trials. Our aim was to assess the effect of NT-supplemented formula on infant growth and biochemical indices of immune function. Methods: This was a randomised controlled double blind trial of NT-supplementation in formula fed infants. Eligible infants were healthy, born at term and had a birth weight greater 2500g. Study outcome measures included lymphocyte subsets (CD4, CD8, NK), NK cell activity and cytokine production at 7 weeks of age, and plasma antibody concentrations of tetanus, diphtheria and haemophilus influenzae B at 7 months of age. Growth was assessed at 7 weeks, 4 and 7 months of age. An unblinded reference group of breastfed infants was also included. Primary comparisons were made between the infants in the randomised groups. Secondary analyses included comparisons with breastfed infants. Results: 89/98 formula fed infants allocated to the NT-supplemented formula, 98/102 infants allocated to the control formula and 116/124 breastfed infants completed the trial to 7 months of age. Growth of NT-supplemented and control formula fed infants did not differ. There were no differences in the proportion or absolute number of lymphocyte subsets, NK cell activity, or cytokine production between any groups. IgG antibody concentrations to diphtheria (median 0.36 [0.09, 1.22] vs 0.27 [0.08, 1.65], n=138) and tetanus (median 1.57 [0.42, 3.43] vs 1.01 [0.41, 4.66], n=138) were sigificantly higher in infants fed NT-supplemented formula compared with control infants. These differences were not sustained in the three-way comparison including breastfed infants. Conclusion: NT-supplementation of infant formula does not alter the growth of formula fed infants and may improve antibody responses to diphtheria and tetanus vaccines in comparison with control formula. The clinical significance of this change in plasma antibody concentrations requires further investigation.

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