Philippe Steenhout

Dynamics of human milk nutrient composition of women from singapore with a special focus on lipids

A recent report suggested that human milk (HM) composition not only changes with lactation stages but also vary according to gender of the offspring. In spite of available literature, the dynamic changes of HM composition still remain to be completely explored and characterized. Progress in analytical technologies together with quantitative sampling of HM allows for a better quantification of HM nutrients and thereby providing a deeper understanding of the dynamics of HM secretion.

Clinical trials prove the safety and efficacy of the probiotic strain Bifidobacterium Bb12 in follow-up formula and growing-up milks

SummaryClinical trials to prove the safety and efficacy of follow-up formulas and growing-up milks fortified with Bifidobacterium strain Bb12 (107–108/g formula powder) are summarized in this report. The strain Bb12 was selected because of its excellent survival during intestinal transit and adhesion to enterocytes. Double-blind, randomized, controlled feeding studies with Bb12 in the U.S., China, and Thailand demonstrated normal growth of healthy children between 4 and 36 months of age and catch-up growth in malnourished children. ”Colonization” with Bb12, which indicates survival during intestinal transit, was confirmed when Bb12 was given with milk-based formulas, but was not satisfactory with soy-based formulas. Feeding the milk-based formula with Bb12 resulted in protection from rotavirus infection, fewer periods with hard bowel movements and a lower incidence of diaper rash. Therefore, using follow-up formulas and growing-up milks with Bifidobacterium strain Bb12 is safe and can prevent diseases frequently seen in both industrialized and developing countries.ZusammenfassungKlinische Studien sind notwendig, um die Sicherheit und Wirksamkeit von Folge- und Kleinkindermilch zu beweisen, der Bifidobacterien vom Stamm Bb12 (107–108/Gramm Milchpulver) zugegeben wurden. Dieser Bakterienstamm wurde gewählt, weil er die Darmpassage überleben kann und eine Adhäsionsfähigkeit an Enterozyten besitzt. Randomisierte, kontrollierte Doppelblindstudien in den USA, China und Thailand zeigten, daß gesunde Kinder im Alter zwischen 4 und 36 Monaten bei Ernährung mit einer mit Bb12 versetzten Folgemilch normal wuchsen. Kinder mit Malnutrition zeigten ein Aufholwachstum. Bb12 konnte bei den Kindern im Stuhl nachgewiesen werden, die eine mit Bb12 versetzte Folge- oder Kleinkindermilch auf Kuhmilchbasis erhielten. Bei Ernährung mit Soyamilch, die mit Bb12 versetzt war, war das gastrointestinale Überleben der Bakterien jedoch nicht ausreichend. Die Ernährung mit Folge- oder Kleinkindermilch auf Kuhmilchbasis und Bb12 Zusatz führte zu einer niedrigeren Inzidenz von Rotavirus Infektionen, Obstipation und Windeldermatitis. Es konnte daher in den klinischen Studien einerseits die Sicherheit von Folge- und Kleinkindermilch mit Bb12 gezeigt werden, andererseits tragen diese Nahrungen zur Verhütung einiger Erkrankungen bei, die sowohl in Industrie- als auch in Entwicklungsländern häufig beobachtet werden.

The Effect of Bifidobacterium lactis on the Growth of Infants: A Pooled Analysis of Randomized Controlled Studies

Background/Aims: Breast milk is the best source of nutrition for the growth of the newborn infant. It is therefore essential that mothers who cannot breastfeed or choose not to are provided with alternatives that closely match the composition and functionality of breast milk. This study aimed to investigate the growth effects of probiotic-supplemented formulas on both healthy and vulnerable populations of infants. Methods: A meta-analysis of data from 5 randomized controlled clinical trials that included infants fed formulas containing a probiotic Bifidobacterium lactis CNCM I-3446 was performed (n = 525). A sub-analysis was performed among infants of HIV-positive mothers (n = 120). Growth measurements (gain in weight and body mass index, BMI, from enrollment to 120 days) were compared between infants fed a formula containing B. lactis and those fed a control formula. Changes in length and Z-scores were also compared. Results: Formula with B.lactis was demonstrated to be at least as good as formula without B. lactis in the meta-analysis of 5 studies. The lower boundary of the 95% confidence interval (CI) of the differences in mean weight gain (95% CI 0.09–2.93 g/day) was above the predefined non-inferiority margin of –3.0 g/day. Moreover, among infants with HIV-positive mothers, weight gain of those taking B. lactis was significantly higher than of those not taking B. lactis, by 3.1 g/day (95% CI 0.4–5.8 g/day, p = 0.0226) and the BMI gains were significantly higher, by 6.4 g/m2/day (95% CI 0.0.3–12.5 g/m2/day, p = 0.0400). The corresponding weight for age and BMI Z-scores were also significantly higher, by 0.37 (95% CI 0.03–0.71, p = 0.0308) and by 0.42 (95% CI 0.02–0.83, p = 0.0377), respectively, whereas differences in length gain or length-for-age Z-score were not significant. Among infants in the non-HIV mothers group, there were no significant differences between infants fed formulas with or without B. lactis, for any of the growth parameters. Conclusions: The analysis suggests that B. lactis may have a positive effect on growth in vulnerable populations, specifically in infants born to mothers with HIV.

Impact of breast-feeding and high- and low-protein formula on the metabolism and growth of infants from overweight and obese mothers

Background:The combination of maternal obesity in early pregnancy and high protein intake in infant formula feeding might predispose to obesity risk in later life.Methods:This study assesses the impact of breast- or formula-feeding (differing in protein content by 1.65 or 2.7u2009g/100 kcal) on the metabolism of term infants from overweight and obese mothers. From birth to 3 mo of age, infants received exclusively either breast- or starter formula-feeding and until 6 mo, exclusively either a formula designed for this study or breast-feeding. From 6 to 12 mo, infants received complementary weaning food. Metabonomics was conducted on the infants’ urine and stool samples collected at the age of 3, 6, and 12 mo.Results:Infant formula-feeding resulted in higher protein-derived short-chain fatty acids and amino acids in stools. Urine metabonomics revealed a relationship between bacterial processing of dietary proteins and host protein metabolism stimulated with increasing protein content in the formula. Moreover, formula-fed infants were metabolically different from breast-fed infants, at the level of lipid and energy metabolism (carnitines, ketone bodies, and Krebs cycle).Conclusion:Noninvasive urine and stool metabolic monitoring of responses to early nutrition provides relevant readouts to assess nutritional requirements for infants’ growth.

Protein quality and quantity in cow's milk-based formula for healthy term infants: past, present and future.

The development of infant formula with optimized protein quality and quantity has been, and still is, the subject of intense investigation. A better understanding of the protein composition of breast milk and infant needs in association with technological breakthroughs in cows milk fractionation, has led to the development of infant formulas with a protein content that is closer to that of human milk. Today, infant formulas with a protein/energy ratio of 1.8 g/100 kcal are commercially available. These formulas have been shown to be safe and nutritionally adequate for term infants. However, the short-term and potentially long-term metabolic benefits of formulas with reduced protein content have still to be elucidated and are currently under investigation. In addition to providing amino acids as building blocks for growth, milk is the source of numerous bioactive factors/hormones which are involved in multiple physiological processes. Continuous efforts are being made to identify new bioactive compounds in human milk. However, a better understanding of their biological functions in suckling infants as well as a comparison with their bovine counterparts are needed. Technological processes, which preserve some bioactive factors in cows milk already exist. These processes could be applied to infant formulas.

Growth and safety evaluation of infant formulae containing oligosaccharides derived from bovine milk: a randomized, double-blind, noninferiority trial

BackgroundA limited number of nondigestible oligosaccharides are available for use in infant formula. This study evaluated growth and safety in infants fed formula supplemented with a mixture of bovine milk-derived oligosaccharides (BMOS). This mixture, which was generated from whey permeate, contains galactooligosaccharides and other oligosaccharides from bovine milk, such as 3′- and 6′-sialyllactose. We hypothesized that growth in infants fed BMOS-supplemented formula would be noninferior to that in infants fed standard formula.MethodsHealthy term infants ≤14xa0days old were randomly assigned to standard formula (control; nu2009=u200984); standard formula with BMOS (IF-BMOS; nu2009=u200999); or standard formula with BMOS and probiotics (Bifidobacterium longum, Lactobacillus rhamnosus) (IF-BMOSu2009+u2009Pro; nu2009=u200998). A breastfed reference group was also enrolled (nu2009=u200930). The primary outcome was mean weight gain/day from enrollment to age 4xa0months (noninferiority margin: −3.0xa0g/day).Results189 (67.3%) formula-fed infants were included in the primary analysis. Mean differences in weight gain between the control and IF-BMOS and IF-BMOSu2009+u2009Pro groups were <1xa0g/day, with 97.5% confidence intervals above −3.0xa0g/day, indicating noninferior weight gain in the BMOS formula groups. Compared with control, infants in the BMOS groups had more frequent (pu2009<u20090.0001) and less hard (pu2009=u20090.0003) stools. No significant differences were observed between the control and BMOS groups in caregivers’ reports of flatulence, vomiting, spitting up, crying, fussing, and colic. When based on clinical evaluation by the investigator, the incidence of colic was higher (pu2009=u20090.01) in IF-BMOS than in control; the incidence of investigator-diagnosed colic was not significantly different in control and IF-BMOSu2009+u2009Pro (pu2009=u20090.15). Stool bifidobacteria and lactobacilli counts were higher with IF-BMOSu2009+u2009Pro compared with control (pu2009<u20090.05), whereas Clostridia counts were lower (pu2009<u20090.05) in both BMOS groups compared with control.ConclusionsInfant formula containing BMOS either with or without probiotics provides adequate nutrition for normal growth in healthy term infants. Further studies are needed to fully explore the digestive tolerance of BMOS formula.Trial registrationClinicalTrials.gov NCT01886898. Registered 24 June 2013.

Effect of dietary protein on plasma insulin-like growth factor-1, growth, and body composition in healthy term infants: a randomised, double-blind, controlled trial (Early Protein and Obesity in Childhood (EPOCH) study).

The effect of protein intake on growth velocity in infancy may be mediated by insulin-like growth factor-1 (IGF-1). This study aimed to determine the effects of formulae containing 1·8 (F1·8) or 2·7 g (F2·7) protein/418·4 kJ (100 kcal) on IGF-1 concentrations and growth. Healthy term infants were randomly assigned to receive F1·8 (n 74) or F2·7 (n 80) exclusively for the first 4 months of life. A group of breast-fed infants (n 84) was followed-up simultaneously (reference). Growth and body composition were measured at 0·5, 4, 6, 12, 36, 48 and 60 months of life. The IGF-1 concentrations at 4 months (primary outcome) were similar in the F1·8 (67·1 (sd 20·8) ng/l; n 70) and F2·7 (71·2 (sd 27·5) ng/l; n 73) groups (P=0·52). Both formula groups had higher IGF-1 concentrations than the breast-fed group at 4 and 9 months of age (P≤0·0001). During the first 60 months of life, anthropometric parameters in the F1·8 group were lower compared with the F2·7 group, and the differences were significant for head circumference from 2 to 60 months, body weight at 4 and 6 months and length at 9, 12 and 36 months of age. There were no significant differences in body composition between these two groups at any age. We conclude that, in formula-fed infants, although increased protein intake did not affect the IGF-1 concentration during the first 12 months of life, it did affect length and head circumference growth, suggesting that factors other than IGF-1 could play roles in determining growth velocity.

A pilot study on the application of a symptom-based score for the diagnosis of cow’s milk protein allergy

Objective: A challenge is the recommended test to diagnose cow’s milk protein allergy. However, many parents and physicians prefer to not challenge because the procedure may cause (severe) symptoms. In clinical routine, diagnostic testing is only available for IgE-mediated allergy. The aim of this study was to test the diagnostic accuracy of a symptom-based score to select infants at risk of having cow’s milk protein allergy. Methods: A symptom-based score was developed and consensus was reached that a score of ≥12 would select infants at risk of cow’s milk protein allergy. Diagnosis of cow’s milk protein allergy was demonstrated with a positive challenge after 1-month elimination diet. Results: An open challenge was performed in 85/116 (73%) infants suspected of cow’s milk protein allergy based on a symptom-based score ≥ 12 and was positive in 59/85 (69%). Although “a challenge test” was planned in the protocol, 27% of the parents refused the challenge. The mean decrease after 1 month of elimination diet with an extensive hydrolysate was −8.07 (95% confidence interval = −8.74, −7.40). If the symptom-based score during the elimination diet decreased to 6 or lower, 80% of the infants had a positive challenge test. If the symptom-based score remained >7, the challenge test was positive in only 48% (p < 0.001). Conclusion: In daily practice, a symptom-based score of ≥12 is a useful tool to select infants at risk of cow’s milk protein allergy. If an elimination diet reduces the symptom-based score to ≤6, the challenge test is positive in 80%.

Normal growth of infants receiving an infant formula containing Lactobacillus reuteri, galacto-oligosaccharides, and fructo-oligosaccharide: a randomized controlled trial.

BackgroundThe safety of an infant formula containing a new mixture of the prebiotics galacto-oligosaccharides (GOS) and fructo-oligosaccharide (FOS) and the probiotic Lactobacillus reuteri needs to be evaluated.MethodsHealthy term infants in Singapore were randomly assigned (using computer-generated allocation sequences) to receive exclusively an experimental infant formula containing L. reuteri, GOS (5.50 g/L), and FOS (0.36 g/L) or a control formula containing only L. reuteri from enrollment (7–14 days of age) to 4 months of age. The primary objective of this trial was to demonstrate that weight change between birth and 4 months of age in infants fed the experimental formula was not inferior to World Health Organization (WHO) Child Growth standards. The non-inferiority margin was −0.5 standard deviations (SD). The secondary objectives were to compare changes in anthropometric measurements (weight, length, body mass index, and head circumference), digestive tolerance, stool bacterial counts, urinary D- and L- lactate concentrations, and adverse events in the two formula groups.ResultsThe intention-to-treat (ITT) population included all randomized infants stratified by gender, (experimental group, Nu2009=u200968 and control group, Nu2009=u200972). The per-protocol (PP) population included 61 infants in the experimental and 62 infants in the control groups. The change in weight-for-age z-score between birth and 4xa0months was +0.93 (95% confidence interval [CI]: +0.63 to +1.23) SD in the experimental group and +0.92 (95% CI: +0.62 to +1.22) SD in the control group in the PP population, indicating non-inferior weight gain in both formulas groups compared with WHO standards. The ITT population had similar results. Liquid stools occurred more frequently in the experimental compared with the control group and median bifidobacteria, lactobacilli, and enterococci counts were higher in the experimental group (pu2009<u20090.05). Other secondary outcomes were not significantly different between groups.ConclusionsInfant formula containing L. reuteriu2009+u2009GOS/FOS supports normal growth and is safe.Trial registrationClinicalTrial.gov: NCT01010113

Pooled Analysis of the Cow's Milk-related-Symptom-Score (CoMiSS™) as a Predictor for Cow's Milk Related Symptoms

Purpose The diagnosis of cows milk (CM) allergy is a challenge. The Cows Milk-related-Symptom-Score (CoMiSS™) was developed to offer primary health care providers a reliable diagnostic tool for CM related symptoms. The predictive prospective value of the CoMiSS™ was evaluated in three clinical trials. Methods Pooled analyses of the three studies were conducted based on regressing the results of the month-1 challenge test on the month-1 CoMiSS™, adjusting for baseline CoMiSS™ using a logistic regression model. In addition a logistic regression model was also fitted to the month-1 challenge test result with the change in CoMiSS™ from baseline as a predictor. Results Results suggest that infants having a low CoMiSS™ (median, 5) after 1 month dietary treatment free from intact CM protein have a significant risk of having a positive challenge test (odds ratio, 0.83; 95% confidence interval, 0.75-0.93; p=0.002). Pooled data suggest that the change in CoMiSS™ from baseline to month-1 can predict CM related symptoms as a confirmed diagnosis according to the challenge test at month-1. However, in order to validate such a tool, infants without CM related symptoms would also need to be enrolled in a validation trial. A concern is that it may not be ethical to expose healthy infants to a therapeutic formula and a challenge test. Conclusion Pooled data analysis emphasizes that the CoMiSS™ has the potential to be of interest in infants suspected to have CM-related-symptoms. A prospective validation trial is needed.