Galacto-oligosaccharides are bifidogenic and safe at weaning: a double-blind randomized multicenter study.

OBJECTIVES: The primary objective of this study was to determine the bifidogenic effect of galacto-oligosaccharides (GOS) in a follow-on formula and the effects on other intestinal bacteria. Secondary objectives were the effects on stool characteristics, growth, and general well-being. PARTICIPANTS AND METHODS: In a multicenter, double-blind study, 159 healthy infants, formula-fed at enrollment (at 4-6 months), were randomized to an experimental follow-on formula supplemented with 5 g/L (GOS) (77 infants), or to a standard follow-on formula (control, 82 infants). Infants were evaluated at enrollment (study day 1 = sd1), after 6 weeks (study day 2 = sd2), and after an additional 12 weeks (study day 3 = sd3). At each study day, a fresh stool sample for the bacterial counts was collected, and the growth parameters were measured. At sd2, urinary specimens were collected for the evaluation of urinary osmolarity. RESULTS: At sd2 and sd3, the GOS group had a higher median number (colony-forming units per gram of stool) of bifidobacteria than did the control group (sd2 GOS 9.2 x 10(9) vs control 4.4 x 10(9), P = 0.012); (sd3 GOS 7.2 x 10(9) vs control 2.4 x 10(9), P = 0.027). Other bacteria did not show any significant differences between the 2 groups at all study days. The GOS produced softer stools but had no effect on stool frequency. The urinary osmolarity (mOsm/L) at sd2 was comparable in both groups. Supplementation had no influence on the incidence of gastrointestinal side effects or on the growth of the infants. CONCLUSIONS: These data indicate that the addition of GOS (5 g/L) to a follow-on formula positively influences the bifidobacteria flora and the stool consistency in infants during the supplementation period at weaning. No local or systemic side effects were recorded.

Which role for prebiotics at weaning?

It is now generally recognized that the intestinal microflora plays a key role for human health and well being. In fact, the gut ecosystem is involved in a number of biologic functions, such as direct and indirect antipathogen activity (nutritive competition, reduction of pH, production of short-chain fatty acids, maturation and protection of the mucosal barrier, etc), synthesis of vitamins, detoxification of potentially harmful substances, and maturation and regulation of the immune system. Weaning represents a crucial step in the development of the intestinal flora and, at the same time, corresponds to a very delicate phase of immunologic maturation. A safe and effective way to beneficially influence the intestinal microflora is the administration of prebiotics, which selectively promote the growth and/or activity of beneficial bacteria, such as bifidobacteria. Some of the studies, which investigated the microbiologic and clinical effectiveness of prebiotics have been conducted at weaning, reporting interesting results. Anyway, many of the promising beneficial effects evidenced still need to be confirmed by further large randomized trials.

Weaning preterm infants: an open issue.

Survival rates for very low birth weight (VLBW) and extremely low birth weight infants have substantially increased during the past few decades. Most of these infants pose new and difficult problems related in particular to neurodevelopmental outcome and growth impairment. In fact, a high percentage of very low birth weight infants fail to achieve their growth potential and experience postnatal growth restriction. Because of this in-hospital growth failure and nutrient deficits, correct nutritional intervention after hospital discharge must be instituted to avoid postnatal malnutrition and to correct the acquired deficit. Nutrient-enriched formulas for several months after discharge have shown some benefits, although their clinical value remains unclear. Weaning, which certainly represents a relevant source of nutrients for the preterm infant, has attracted little attention until now. There are no precise guidelines on this topic, and too often weaning practices are left totally to the parents, without considering the specific nutritional needs of the single infant.

Complementary feeding practices in preterm infants: an observational study in a cohort of Italian infants.

BACKGROUND: There are no evidence-based guidelines for weaning preterm infants, and the timing of weaning and the diet offered tend to reflect tradition and marketing rather than medical advice. PROCEDURES: In a survey of complementary feeding practices in preterm infants conducted at the University Hospital of Ferrara, Italy, we evaluated the effect of sex, gestational age (GA), birth weight (BW), and milk feeding, and of the mother's age, education, and professional status, on weaning. RESULTS: Complete data were available for 156 infants. Solid food was introduced, on average, 22.2 weeks after birth and 15.1 weeks after term; 6.5% of infants (considering chronological age) and 60.9% (considering corrected age) were weaned before 4 months; 18% of infants weighed <5 kg at weaning (most had low GA and BW). Among maternal factors, only age significantly influenced the weaning schedule. Milk feeding did not affect initiation of weaning; however, formula-fed infants, most of whom had lower GA and BW, were lighter and younger (from term) than were their counterparts. The first solid food was mashed fruit in 46.8% of cases. Meat and gluten were offered 5 and 7 weeks (average) after the initiation of weaning. CONCLUSIONS: A matter of concern emerging from our study is that in almost 50% of cases, the first solid food offered to infants is low in energy density, and its protein, iron, and zinc content is negligible. It is evident that despite the lack of a general consensus, mothers of preterm babies should receive customized instructions from family pediatricians and health caregivers about weaning.

Considerations and approaches in determining the protein and energy composition of preterm infant formulas.

Optimal early nutritional support is considered a crucial issue in the care of the preterm infant, particularly of those with very low- or extremely low-brithweight. Unfortunately, this goal is seldom satisfactorily attained. Several conditions such as hypoxia, acidosis, patent ductus arteriosus, drug therapy, reduced intestinal motility may interfere with an adequate nutritional delivery in the early neonatal period. Moreover, there is still concern about metabolic and intestinal tolerance of the currently suggested intakes and a lack of uniformity in the nutritional program among different NICUs. Finally, the vast majority of the available preterm formulas are not fully adequate to the real nutritional needs of these infants. Inadequate protein content and inappropriate protein energy ratio of most preterm formulas represent a matter of major concern, since there is a strict relationship between formula composition and the quantity and quality of weight gain. As a consequence there is a need of at least two milk formulas for different preterm infants: one for LBW and VLBW infants, the other for preterm infants weighing >1500 g.

Galacto-oligosaccharides and long-chain fructo-oligosaccharides as prebiotics in infant formulas: a review.

UNLABELLED: The present review summarizes clinical and experimental data concerning the possible effects of a prebiotic mixture of short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides. The results from several studies, made up of over 400 preterm and term infants, clearly demonstrate that the prebiotic mixture under examination specifically stimulates the growth of bifidobacteria and lactobacilli and reduces the growth of pathogens. As a consequence of the changed intestinal flora by the dietary galacto-oligosaccharides and fructo-oligosaccharides, the faecal pH values and the short-chain fatty acid pattern were similar to those found in breastfed infants. In addition, the stool consistency was the same as in breastfed infants. In vitro experiments have demonstrated that the specific short-chain fatty acid pattern, at a pH similar to that found in faecal samples of breastfed infants, reduces the growth of pathogens in a dose-dependent manner but does not influence the growth of bifidobacteria and lactobacilli. In an animal vaccination model, the prebiotic mixture improved the response to vaccination. In an allergy model (sensitization by ovalbumin), the allergic reaction was reduced by the prebiotic mixture. The data obtained from animal experiments are in agreement with preliminary data from clinical trials which indicate a reduced allergic response (reduced plasma IgE/IgG4 ratio) and reduced episodes of upper airway infection during the first year of life. CONCLUSION: Experimental evidence demonstrates that the prebiotic mixture employed in these studies modulates the intestinal flora and modulates the immune system as human milk does. There are sufficient experimental data to put forward the hypothesis that substances like the prebiotic mixture under study will substantially contribute to the improvement of the protective properties of infant formulas.

Z-score of weight for age of infants with atopic dermatitis and cow's milk allergy fed with a rice-hydrolysate formula during the first two years of life.

BACKGROUND: Recently, rice-based formulas have been widely used in hypoallergenic diets, but data on nutritional values are scarce. AIM: To evaluate the growth of infants fed with a rice-based hydrolysate formula, compared to those infants fed with a soy formula or an extensively hydrolysed casein formula, in the first 2 y of life. METHODS: A total of 88 infants were enrolled between March 2002 and March 2004. Fifty-eight infants with atopic dermatitis (AD) and cow's milk allergy (CMA), confirmed by open challenge, were enrolled as study group: 15 were fed with a rice-based hydrolysate formula (RHF), 17 with a soy-based formula (SF) and 26 with an extensively hydrolysed casein formula (eHCF). Thirty infants with AD without cow's milk allergy were recruited as a control group (CG) and fed with a free diet. Weight was recorded on enrolment and at 3-monthly intervals in the first year of life, and at 6-monthly intervals in the second year. Infants were weighed naked, before feeding, by means of an electronic integrating scale. The z-scores of weight for age were calculated. STATISTICS: One-way analysis of variance and Student's t-test were used for statistical comparison. Significance was set at p<0.05. RESULTS: No significant differences between the RHF, SF and eHCF groups were observed for the z-score of weight for age during the first 2 y of life, but a significantly lower difference was seen in the RHF group compared to the control group in the intervals 9 mo-1 y (p=0.025) and 1-1.5 y (p=0.020) of age. In contrast, the SF and eHCF groups were comparable to the control group, but the eHCF group was significantly lower (p=0) in the first trimester of life. CONCLUSION: Even if our findings show no significant difference between RHF and control, low weight observed in infants fed with RHF raises doubts about the nutritional adequacy of rice-hydrolysate formulas.

Different pre-term formulas for different pre-term infants.

Optimal nutrition is one of the most important aspects in the care of pre-term infants, especially for the gestationally youngest ones. These infants should receive a supply of nutrients that can sustain growth similar to that of a third trimester normal foetus. Traditional pre-term formulas do not ensure an optimal protein supply except when fed at high volumes, with an excess of fat and carbohydrates. Formulas with a protein content of 2-2.5 g 100ml(-1) and a protein/energy (P:E) ratio of less than 3g 100 kcal(-1) are not the best choice for the very low birth weight (VLBW) infants. We have tested a new formulation designed for the nutrition of the VLBW infants that is characterised by a protein content of 2.9 g 100ml(-1) and a P:E ratio of 3.5 g 100 kcal(-1). The milk formula was well tolerated and associated with better weight gain compared with fortified breast milk (18.1 vs. 15.2 g kg(-1)day(-1); p=0.0015). These results were obtained with a noticeably lower fluid supply (157 vs. 177 ml kg day(-1); p<0.0001) and lower energy intake (130 vs. 151 kcal kg(-1)day(-1); p<0.0001). Infant length and head circumference did not differ significantly between groups. Currently, the use of a formula with a P:E ratio of 3.5 g 100 kcal(-1) appears to be safe and to represent the best choice available for the gestationally youngest infants.