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Effect of dietary nucleotide supplementation on growth and immune function in term infants: a randomized controlled trial

European Journal of Clinical Nutrition volume 60, pages 254–264 (2006)Cite this article

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.

Design:

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.

Outcome measures:

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.

Sponsorship:

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.

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Acknowledgements

We thank Suzanne McCusker, Jenni Scambiatterra, Heather Garreffa, Jo White, Jo Collins, Judy Bettes, Kathy Byrt, Sarah Russell, Elizabeth Roberton, Warren Higgs, Michelle Clarke, Lisa Smithers, Jacki Aldis, Helen Marshall, Ela Zielinski, Mark Neumann, Julie Lewis and the staff of the postnatal ward at the WCH and Lindy Harkness and the staff of the immunization clinic at the WCH for their administrative, clinical and technical support. Financial support and formula for the study came from Wyeth Nutrition and William Goldman, Kathryn Pramuk and Paul Zimmer made contributions to the study design and provided valuable comments on the manuscript. Source document verification was made by a representative from Wyeth Nutrition.

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Authors and Affiliations

  1. Child Health Research Institute, Flinders Medical Centre and Flinders University, Bedford Park, SA, Australia

    J S Hawkes, R A Gibson & M Makrides

  2. Child Health Research Institute, Women's and Children's Hospital, North Adelaide, SA, Australia

    R A Gibson & M Makrides

  3. Department of Paediatrics, University of Adelaide, SA, Australia

    R A Gibson, D Roberton & M Makrides

Authors
  1. J S Hawkes
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  2. R A Gibson
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  3. D Roberton
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  4. M Makrides
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Corresponding author

Correspondence to M Makrides.

Additional information

Guarantors: JS Hawkes, RA Gibson and M Makrides.

Contributors: JSH, RAG and MM designed the study and were the steering committee who monitored and managed the trial. MM chaired the steering committee and managed the clinical aspects of the trial. JSH managed the laboratory analyses and wrote the report with contributions from all co-authors. DR was responsible for the immunization response analyses. All data were managed, analysed and interpreted by the trial steering committee in Adelaide.

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Hawkes, J., Gibson, R., Roberton, D. et al. Effect of dietary nucleotide supplementation on growth and immune function in term infants: a randomized controlled trial. Eur J Clin Nutr 60, 254–264 (2006). https://doi.org/10.1038/sj.ejcn.1602310

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  • DOI: https://doi.org/10.1038/sj.ejcn.1602310

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