Background: The benefits of short-term oral nutritional supplementation (ONS) in undernourished children are well-established. The benefits of long-term ONS in promoting longitudinal growth and health in children who are at risk of undernutrition have not been reported previously. Methods: In this 48-week prospective, single-arm, multicentre trial, 200 Filipino children aged 3-4 years with weight-for-height percentiles from 5th to 25th (WHO Child Growth Standards) were enrolled. Parents received dietary counselling at baseline, and at weeks 4 and 8. Two servings of ONS (450 mL) were consumed daily, providing 450 kcal, 13.5 g protein and micronutrients. Weight, height, dietary intake using 24-h dietary recalls, and physical activity and appetite using the visual analogue scales were assessed at baseline and weeks 4, 8, 16, 24, 32, 40 and 48. The number of sick days for acute illnesses was collected over the study period. Results: At baseline, mean age was 41.2 months with 50% being male. Weight-for-height percentiles showed the greatest increase in the first 4 weeks (12.1 and 12.8 percentiles, respectively, P < 0.0001) and remained significantly higher than baseline (P < 0.0001) but were relatively stable from week 4 onwards. Height-for-age percentiles increased steadily over time and became significantly higher than baseline from week 24 onwards (P < 0.0001). Appetite and physical activity scores at all post-baseline visits improved from baseline (P < 0.0001), and a reduction in the number of sick days from week 16 onwards was also observed (P < 0.0001). Higher parental education level, being male and higher baseline weight-for-height percentiles were significantly associated with higher ponderal and linear growth over time in repeated measures analysis of covariance. Conclusions: Intervention consisting of initial dietary counselling and continued ONS helped sustain normal growth after a catch-up growth in nutritionally at-risk children.

Background Bovine milk-derived oligosaccharides (MOS) containing primarily galacto-oligosaccharides with inherent levels of sialylated oligosaccharides can be added to infant formula to enhance the oligosaccharide profile. Objective To investigate the effects of a MOS-supplemented infant formula on gut microbiota and intestinal immunity. Methods In a double-blind, randomized, controlled trial, healthy-term formula-fed infants aged 21–26 days either received an intact protein cow's milk-based formula (control group, CG, n = 112) or the same formula containing 7.2 g MOS/L (experimental group, EG, n = 114) until age 6 months. Exclusively human milk-fed infants (HFI, n = 70) from an observational study served as reference. Fecal samples collected at baseline, 2.5 and 4 months of age were assessed for microbiota (16S ribosomal ribonucleic acid—based approaches), metabolites and biomarkers of gut health and immune response. Results At age 2.5 and 4 months, redundancy analysis (P = 0.002) and average phylogenetic distance (P &lt; 0.05) showed that the overall microbiota composition in EG was different from CG and closer to that of HFI. Similarly, EG caesarean-born infants were different from CG caesarean- or vaginally-born infants and approaching HFI vaginally-born infants. Relative bifidobacteria abundance was higher in EG vs. CG (P &lt; 0.05) approaching HFI. At age 4 months, counts of Clostridioides difficile and Clostridium perfringens were ∼90% (P &lt; 0.001) and ∼65% (P &lt; 0.01) lower in EG vs. CG, respectively. Mean (95%CI) fecal secretory immunoglobulin A (IgA) in EG was twice that of CG [70 (57,85) vs. 34 (28,42) mg/g, P &lt; 0.001] and closer to HFI. Fecal oral polio vaccine-specific IgA was ∼50% higher in EG vs. CG (P = 0.065). Compared to CG, EG and HFI had lower fecal calcium excretion (by ∼30%) and fecal pH (P &lt; 0.001), and higher lactate concentration (P &lt; 0.001). Conclusions Infant formula with MOS shifts the gut microbiota and metabolic signature closer to that of HFI, has a strong bifidogenic effect, reduces fecal pathogens, and improves intestinal immune response.

Human milk oligosaccharides play a key role in the maturation of the infant gut microbiome and immune system and are hypothesized to affect growth. This study examined the temporal changes of 24 HMOs and their associations to infant growth and appetitive traits in an exploratory, prospective, observational, study of 41 Filipino mother-infant dyads. Exclusively breastfed, healthy, term infants were enrolled at 21–26 days of age (≈ 0.75 mo) and followed for 6 months. Infant growth measures and appetitive traits were collected at visit 1 (V1) (≈ 0.75 mo), V2 (≈ 1.5 mo), V3 (2.5 mo), V4 (2.75 mo), V5 (4 mo), and V6 (6 mo), while HMOs were measured at V1, V2, V3 and V5. Overall exposure to each HMO was summarized as area under the curve from baseline to 4 months of age and examined in association with each measure of growth at 6 months using linear regression adjusted for maternal age at birth, infant sex, birth weight, and mode of delivery. We saw modest associations between several HMOs and infant growth parameters. Our results suggest that specific HMOs, partly as proxy for milk groups (defined by Secretor and Lewis status), may be associated with head circumference and length, increasing their relevance especially in populations at the lower end of the WHO growth curve. We did not identify the same HMOs associated with infant appetitive traits, indicating that at least in our cohort, changes in appetite were not driving the observed associations between HMOs and growth.Clinical trial registration: NCT03387124.

Nutrient deficiencies during childhood have adverse effects on child growth and health. In a single-arm 48-week long-term intervention, we previously reported the efficacy of oral nutritional supplementation (ONS) and dietary counselling on catch-up growth and growth maintenance in nutritionally at-risk Filipino children. The present analysis was done to assess the contributing effects of ONS to nutritional adequacy, dietary diversity, food intake and longitudinal growth. ONS (450 ml) was consumed daily providing 450 kcal (1880 kJ) and at least 50 % of micronutrient requirements among 200 children aged 3–4 years with weight-for-height percentiles between 5th and 25th (WHO Growth Standards). Weight, height and dietary intakes using 24-h food recalls were measured at baseline, and at weeks 4, 8, 16, 24, 32, 40 and 48. Nutrient adequacy and dietary diversity score (DDS) were calculated. Generalised estimating equations were used to assess the effects of total nutrient intakes, DDS, ONS compliance and sociodemographic factors on longitudinal growth. The percentages of children with adequate intake of energy, protein, Fe, Ca and some vitamins at each post-baseline visit were improved from baseline, reaching 100 % for most nutrients. DDS was also increased from baseline and reached significance from week 16 onwards (P < 0·01). Male children, total energy intake and parental employment status were associated with weight-for-height percentile gain (P < 0·05), whereas higher parental education level and ONS compliance were significantly associated with height-for-age percentile gain over time (P < 0·05). Long-term ONS intervention did not interfere with normal food intake and helped promote nutritional adequacy and growth of Filipino children.

Background Adding bovine milk-derived oligosaccharides (MOS) enhances the oligosaccharide profile of infant formula. This study aimed to evaluate the safety and efficacy of a MOS-supplemented infant formula. Methods In this double-blind randomized controlled trial, healthy infants 21–26 days old were either assigned to bovine milk-based, alpha-lactalbumin, and sn-2 palmitate enriched infant formula (control, n = 115) or the same formula with 7.2 g MOS/L (test, n = 115) until aged 6 months. Co-primary endpoints were weight gain through 4 months and stool consistency (validated scale: 1 = watery to 5 = hard). Secondary endpoints included parent-reported GI tolerance, health-related quality of life (HRQoL), and adverse events (AEs). Results Weight gain was similar (p = 0.695); the difference between test and control (mean; 95% CI: 0.29; −1.15, 1.73 g/day) was above the non-inferiority margin (−3 g/day). Test had softer stools than control (mean difference in stool consistency score: −0.31; 95% CI: −0.42, −0.21; P < 0.0001); fewer parental reports of harder stools (OR = 0.32, 95% CI: 0.20, 0.49; P < 0.0001) and less difficulties in passing stool (OR = 0.25, 95% CI: 0.09, 0.65; P = 0.005). Parent-reported GI tolerance and HRQoL were similar between groups as were the overall low AEs. Conclusions MOS-supplemented infant formula is safe and well-tolerated while supporting normal infant growth and promotes softer stooling pattern without increasing parent-reported and physician-confirmed adverse health concerns. Impact This is the first study investigating the addition of bovine milk-derived oligosaccharides to an infant formula enriched with alpha-lactalbumin and elevated levels of sn-2 palmitate, providing safety and efficacy data for such a formula. Term infant formula supplemented with 7.2 g bovine milk-derived oligosaccharides per liter supported normal infant growth, was well-tolerated and safe. Addition of bovine milk-derived oligosaccharides to term infant formula promoted softer stooling pattern and reduced difficulties in passing stool. The study shows that bovine milk-derived oligosaccharide supplemented infant formula is a safe and effective option for healthy term infants who are formula-fed.