Influence of Feeding Types during the First Months of Life on Calciuria Levels in Healthy Infants: A Secondary Analysis from a Randomized Clinical Trial

Background/Aims: Dietary factors can modify calciuria. We aim to investigate urinary calcium excretion in healthy infants according to their protein. Methods: Secondary data analysis from a randomized clinical trial where healthy term infants were randomized after birth to a higher (HP) or lower (LP) protein content formula that was consumed until age 1 year. A non-randomized group of breastfed (BF) infants was used for reference. Anthropometry, dietary intakes and calciuria (calcium/creatinine ratios) from spot urine samples were assessed at ages 3 and 6 months. At 6 months, the kidney volumes were assessed using ultrasonography, and the serum urea and creatinine levels were determined. Results: BF infants showed the highest calciuria levels, followed by the HP and the LP groups (p < 0.001 for all comparisons). Either protein intakes or formula types modulated the calciuria in linear regression models adjusted for other influencing dietary factors. The usual cut-off values classified 37.8% (BF), 16.8% (HP) and 4.9% (LP) of the infants as hypercalciuric. Conclusions: Feeding types during the first months of life affect calciuria, with BF infants presenting the highest levels. We propose new cut-off values, based on feeding types, to prevent the overestimation in hypercalciuria diagnoses among BF infants

Infant feeding and later obesity risk

Some 30 years ago, G\ufcnter D\uf6rner proposed that exposure to hormones, metabolites and neurotransmitters during limited, sensitive periods of early development exert programming effects on disease risk in human adults. Early programming of long term health has since received broad scientific support and attention. For example, evidence increases for programming effects of infant feeding choices on later obesity risk. Meta-analyses of observational studies indicate that breast feeding reduces the odds ratio for obesity at school age by about 20%, relative to formula feeding, even after adjustment for biological and sociodemographic confounding variables. We hypothesized that breast feeding protects against later obesity by reducing the likelihood of high weight gain in infancy, and that this protection is caused at least partly by the lower protein supply with breast milk relative to standard infant formulae (the "Early Protein Hypothesis"). These hypotheses are tested in the European Childhood Obesity Project, a randomized double blind intervention trial in more than 1,000 infants in five European countries (Belgium, Germany, Italy, Poland, Spain). Formula fed infants were randomized to receive during the first year of life infant formulae and follow-on-formulae with higher or lower protein contents. Follow-up at 2 years of age shows that lower protein supply with formula normalizes early growth relative to a breast fed reference group and to the WHO growth reference. These results demonstrate that modification of infant feeding practice has an important potential for long-term health promotion and should prompt a review of the recommendations and policies for infant formula composition

Associations of <em>IGF-1 gene variants</em> and milk protein intake with IGF-I concentrations in infants at age 6 months - results from a randomized clinical trial.

OBJECTIVE: The interplay of genetic and nutritional regulation of the insulin-like growth factor-I axis in children is unclear. Therefore, potential gene-nutrient effects on serum levels of the IGF-I axis in a formula feeding trial were studied. DESIGN: European multicenter randomized clinical trial of 1090 term, formula-fed infants assigned to receive cow&#39;s milk-based infant and follow-on formulae with lower (LP: 1.25 and 1.6g/100mL) or higher (HP: 2.05 and 3.2g/100mL) protein contents for the first 12months of life; a comparison group of 588 breastfed infants (BF) was included. Eight single nucleotide polymorphisms (SNPs) of the IGF-1-(rs6214, rs1520220, rs978458, rs7136446, rs10735380, rs2195239, rs35767, and rs35766) and two of the IGFBP-3-(rs1496495, rs6670) gene were analyzed. Serum levels of total and free IGF-I, IGFBP-3 and the molar ratio IGF-1/IGFBP-3 at age 6months were regressed on determined SNPs and feeding groups in 501 infants. RESULTS: IGF-1-SNPs rs1520220, rs978458, and rs2195239 significantly increased total-IGF-I and molar-ratio IGF-I/IGFBP-3 by ~1.3ng/mL and ~1.3 per allele, respectively; compared to LP infants concentration and molar-ratio were increased in HP by ~1.3ng/mL and ~1.3 and decreased in BF infants by ~0.6ng/mL and ~0.6, respectively. IGFBP-3 was only affected by the BF group with ~450ng/mL lower levels than the LP group. No gene-feeding-group interaction was detected for any SNP, even without correction for multiple testing. CONCLUSIONS: Variants of the IGF-1-gene play an important role in regulating serum levels of the IGF-I axis but there is no gene-protein-interaction. The predominant nutritional regulation of IGF-I and IGFBP-3 gives further evidence that higher protein intake contributes to metabolic programming of growth

Supplementary Material for: Influence of Feeding Types during the First Months of Life on Calciuria Levels in Healthy Infants: A Secondary Analysis from a Randomized Clinical Trial

<p><b><i>Background/Aims:</i></b> Dietary factors can modify calciuria. We aim to investigate urinary calcium excretion in healthy infants according to their protein. <b><i>Methods:</i></b> Secondary data analysis from a randomized clinical trial where healthy term infants were randomized after birth to a higher (HP) or lower (LP) protein content formula that was consumed until age 1 year. A non-randomized group of breastfed (BF) infants was used for reference. Anthropometry, dietary intakes and calciuria (calcium/creatinine ratios) from spot urine samples were assessed at ages 3 and 6 months. At 6 months, the kidney volumes were assessed using ultrasonography, and the serum urea and creatinine levels were determined. <b><i>Results:</i></b> BF infants showed the highest calciuria levels, followed by the HP and the LP groups (<i>p</i> < 0.001 for all comparisons). Either protein intakes or formula types modulated the calciuria in linear regression models adjusted for other influencing dietary factors. The usual cut-off values classified 37.8% (BF), 16.8% (HP) and 4.9% (LP) of the infants as hypercalciuric. <b><i>Conclusions:</i></b> Feeding types during the first months of life affect calciuria, with BF infants presenting the highest levels. We propose new cut-off values, based on feeding types, to prevent the overestimation in hypercalciuria diagnoses among BF infants.</p