Dietary Nucleotides and Early Growth in Formula-Fed Infants: A Randomized Controlled Trial

BACKGROUND: Dietary nucleotides are nonprotein nitrogenous compounds that are found in high concentrations in breast milk and are thought to be conditionally essential nutrients in infancy. A high nucleotide intake has been suggested to explain some of the benefits of breastfeeding compared with formula feeding and to promote infant growth. However, relatively few large-scale randomized trials have tested this hypothesis in healthy infants.

OBJECTIVE: We tested the hypothesis that nucleotide supplementation of formula benefits early infant growth.

PATIENTS AND METHODS: Occipitofrontal head circumference, weight, and length were assessed in infants who were randomly assigned to groups fed nucleotide-supplemented (31 mg/L; n = 100) or control formula without nucleotide supplementation (n = 100) from birth to the age of 20 weeks, and in infants who were breastfed (reference group; n = 101).

RESULTS: Infants fed with nucleotide-supplemented formula had greater occipitofrontal head circumference at ages 8, 16, and 20 weeks than infants fed control formula (mean difference in z scores at 8 weeks: 0.4 [95% confidence interval: 0.1–0.7]; P = .006) even after adjustment for potential confounding factors (P = .002). Weight at 8 weeks and the increase in both occipitofrontal head circumference and weight from birth to 8 weeks were also greater in infants fed nucleotide-supplemented formula than in those fed control formula.

CONCLUSIONS: Our data support the hypothesis that nucleotide supplementation leads to increased weight gain and head growth in formula-fed infants. Therefore, nucleotides could be conditionally essential for optimal infant growth in some formula-fed populations. Additional research is needed to test the hypothesis that the benefits of nucleotide supplementation for early head growth, a critical period for brain growth, have advantages for long-term cognitive development.