Growth of infants born to HIV-positive mothers fed a whey-adapted acidified starter formula with prebiotics and nucleotides

Objectives: The objectives of this study were to evaluate whether infants born to known HIV-positive mothers, but who were not themselves infected with HIV and who were fed a chemically acidified starter formula with prebiotics with or without nucleotides during their first six months, displayed growth rates equal to uninfected infants fed a chemically acidified starter formula without prebiotics or nucleotides.Design: The design was a multi-centre, double-blinded randomised controlled trial.Setting: The study was carried out in four academic hospitals, three in Johannesburg and one in Cape Town, South Africa.Subjects and intervention: The subjects were newborn infants born to consenting HIV-positive women who had previously decided not to breast feed. The infants were randomised to receive one of three milk formulas. The intervention comprised chemically acidified formula without prebiotics or nucleotides, with prebiotics only, or with prebiotics and nucleotides.Outcome measures: The outcome measures were the growth parameters through the first six months of life.Results: Of the 150 randomised infants, 50 did not complete the study and 16 (12.8% of those tested) were infected with HIV, leaving 84 infants available for analysis. All three formulas were tolerated well, with no differences in growth parameters seen with the addition of prebiotics and nucleotides. The growth rates of the study infants up to the age of six months were very good, showing an increase in Z-scores from negative values at the time of enrolment in the first week after birth to around zero for length and > 0.5 for weight.Conclusions: The three chemically acidified formulas were tolerated well and resulted in good growth over the first six months of life. No benefits were seen with the addition of prebiotics or nucleotides. The growth rates were similar to those found in previous studies of ours on biologically acidified formulas. The chemical acidification of infant formulas appears to be a realistic alternative to biological acidification should an acidified formula be required.Keywords: milk formula; acidification; probiotics; nucleotides; infant growt

Assay of D-lactate in urine of infants and children with reference values taking into account data below detection limit.

Accumulation of D-lactic acid produced by intestinal bacteria such as streptococci and lactobacilli has been extensively studied in ruminants [1-4]. In humans an increased production of D-lactate by intestinal bacteria under pathological conditions such as the short bowel syndrome can cause metabolic acidosis [5-8]. Since the lactate assays routinely used only measure L-lactate we developed a sensitive method of D-lactate quantification and established reference values in spot urines of infants and children (0 to 4 years of age). The enzymatic method with fluorimetric quantification of NADH is linear up to 2 mmol/l. It has a detection limit of 3.4 micromol/l. Among structurally related organic acids an interference was found only for L-lactate and DL-2-hydroxybutyrate at concentrations which are way beyond their physiological excretion. One hundred and sixty five spot urines of healthy Swiss (S), Austrian (A), German (G) and Chilean (CHI) infants aged from 0 to 4 years were analyzed. The distribution of the data is close to a lognormal one. Values below the detection limit were simulated and age groups were formed. In all populations D-lactate excretion was found highest during the first year of life; it declines with age during infancy and remains stable from 2.5 to 4 years of age. We show that D-lactate is excreted physiologically by healthy infants and children below 4 years of age and present reference values for D-lactate excretion which show some differences between the populations tested

Reference values of amino acids and of common clinical chemistry in plasma of healthy infants aged 1 and 4 months.

OBJECTIVE: To compare plasma levels of amino acids and clinical chemistry parameters in healthy infants at 1 and 4 months of age and to establish corresponding reference limits. METHODS: Data of three multicenter studies assessing the safety of new infant formulas were used. During these studies infants of both age-groups were either breast-fed or received formulas of low or high protein content. All samples were analyzed centrally in the same accredited laboratory. RESULTS: Plasma was collected from 521 infants in total, 157 boys and 135 girls aged 1 month and 121 boys and 108 girls aged 4 months. At the age of 1 month, 62 infants had received exclusively breast milk, 198 exclusively formula, and 27 both; in the 4-months age group corresponding numbers were 49, 158 and 18, respectively; for 9 infants, diet was unknown. Concentrations of most amino acids and clinical chemistry parameters differed significantly between both ages. Regardless of age, most plasma amino acid levels were comparable or lower in breast-fed than in formula-fed infants whereas at 1 month of age most clinical chemistry parameters were higher. While in breast-fed infants the plasma urea concentration decreased over 4 months of age, it increased in formula-fed infants. There were significant differences between infants fed a low and high protein formula. At both ages, high protein formulas resulted in significantly higher threonine, 2-aminobutyrate, and urea concentrations. CONCLUSIONS: For clinical use, age- and diet specific reference limits in infants are warranted

Urinary D-lactate excretion in infants receiving Lactobacillus johnsonii with formula.

BACKGROUND/AIMS: Supplementation with certain probiotics can improve gut microbial flora and immune function but should not have adverse effects. This study aimed to assess the risk of D-lactate accumulation and subsequent metabolic acidosis in infants fed on formula containing Lactobacillus johnsonii (La1). METHODS: In the framework of a double-blind, randomized controlled trial enrolling 71 infants aged 4-5 months, morning urine samples were collected before and 4 weeks after being fed formulas with or without La1 (1 x 10(8)/g powder) or being breastfed. Urinary D- and L-lactate concentrations were assayed by enzymatic, fluorimetric methods and excretion was normalized per mol creatinine. RESULTS: At baseline, no significant differences in urinary D-/L-lactate excretion among the formula-fed and breastfed groups were found. After 4 weeks, D-lactate excretion did not differ between the two formula groups, but was higher in both formula groups than in breastfed infants. In all infants receiving La1, urinary D-lactate concentrations remained within the concentration ranges of age-matched healthy infants which had been determined in an earlier study using the same analytical method. Urinary L-lactate also did not vary over time or among groups. CONCLUSIONS: Supplementation of La1 to formula did not affect urinary lactate excretion and there is no evidence of an increased risk of lactic acidosis

Effects of probiotic or prebiotic supplemented milk formulas on fecal microbiota composition of infants

The aim of the study was to evaluate whether supplementation of milk-formulas with prebiotic fructooligosaccharides or a probiotic, Lactobacillus johnsonii La1 (La1), could modulate the composition of the fecal microbiota of formula-fed infants, compared to breastfed (BF) infants. Ninety infants close to 4 months of age were randomized into one of three groups to be blindly assigned to receive for 13 weeks: a) an infant formula (Control), b) the same formula with fructo-oligosaccharides (Prebio), or c) with La1 (Probio). At the end of this period, all infants received the control formula for 2 additional weeks. Twenty-six infants, breastfed throughout the study, were recruited to form group BF. Fecal samples were obtained upon enrolment and after 7 and 15 weeks. Bacterial populations were assessed with classical culture techniques and fluorescent in situ hybridisation (FISH). Seventy-six infants completed the study. On enrolment, higher counts of Bifidobacterium and Lactobacillus and lower counts of enterobacteria were observed in BF compared to the formula-fed infants; these differences tended to disappear at weeks 7 and 15. No major differences for Clostridium, Bacteroides or Enterococcus were observed between the groups or along the follow up. Probio increased fecal Lactobacillus counts (P<0.001); 88% of the infants in this group excreted live La1 in their stools at week 7 but only 17% at week 15. Increased Bifidobacterium counts were observed at week 7 in the 3 formula groups, similar to BF infants. These results confirm the presence of higher counts of bifidobacteria and lactobacilli in the microbiota of BF infants compared to formula-fed infants before dietary diversification, and that La1 survives in the infant digestive tract

Whey predominant, whey modified infant formula with protein/energy ratio of 1.8 g/100 kcal: adequate and safe for term infants from birth to four months.

BACKGROUND: Protein quality of breast milk is superior to that of formula proteins. To ensure that the protein intake is sufficient, starter formulas with conventional protein composition provide a protein/energy ratio of 2.2-2.5 g per 100 kcal to infants, which is much higher than that supplied with breast milk. Several studies have shown that formula-fed infants have higher plasma or serum urea concentrations than breast-fed infants do. We tested if feeding formulas with improved protein quality and a protein content corresponding to the minimum level that is consistent with international recommendations (1.8 g/100 kcal) allows patients to achieve normal growth and plasma urea concentrations. METHODS: Healthy term infants were enrolled into the study and were either breast-fed or randomly assigned to three formula-fed groups. Formula-fed infants received either a standard formula with a protein/energy ratio of 2.2 g/100 kcal, whereas the two other groups received formulas with a protein/energy ratio of 1.8g/100 kcal differing mainly by their source of protein. Subjects received breast milk or these formulas ad libitum as the sole source of energy from birth to four months of age in a controlled blind design (except for the breast-fed group). Anthropometric measurements (body weight and length) were obtained at birth, at 30, 60, 90, and 120 days. Energy and protein intakes were calculated from three-day dietary records. Blood was collected for biochemical measurements at 30, 60, and 120 days. RESULTS: No differences were found between the four feeding groups for weight- and length-gains or for body mass indices (BMI). No differences in energy intakes between the formula-fed groups could be found, whereas protein intakes were less in infants fed the 1.8 g/100 kcal formulas. Plasma urea levels of the infants fed the 1.8 g/100 kcal formulas were closer to those found in the breast-fed infants. CONCLUSION: Improvement of the amino acid profile permits a whey predominant starter formula with 1.8 g protein per 100 kcal to meet the needs of normal term infants during the first four months of life