Objectives and Study

In vitro studies suggest that gastric casein coagulation and digestion of milk formula under simulated infant conditions are affected by casein micelle mineralisation. Casein micelle mineralisation may thus also impact overall digestion and absorption kinetics in vivo. This study therefore aimed to determine the effect of milk casein micelle mineralisation on milk protein digestion and absorption.

Methods

In a randomized cross-over study healthy males (n =15, age 30.9±13.8 years) were fed low or high casein micelle mineralization milk and underwent gastric magnetic resonance imaging (MRI) scans to determine gastric emptying (manual segmentation) and the degree of casein coagulation (image texture analysis). Blood samples were taken at baseline and up to 5 hours postprandially to determine amino acid absorption kinetics and changes in plasma insulin and glucose. Additionally, the contribution of whey and casein derived amino acids over time was determined.

Results

MRI analyses showed that gastric volume over time did not differ between treatments. However, the degree of casein coagulation was lower for low mineralization milk. Postprandial plasma amino acid kinetics showed that peak levels of casein-dominant amino acids, such as proline, were significantly higher in the low casein mineralization group, whereas whey-dominant amino acids, such as leucine, did not differ. Plasma insulin responses were in line with an initial higher level of branched-chain amino acids in the low mineralization condition although only valine was significantly different.

Conclusions

Mineral composition of milk can influence gastric coagulation with coherent effects on post prandial plasma amino acid kinetics and plasma insulin responses without impacting overall gastric emptying.

Objectives and Study

Recent results from the randomized double-blind controlled trial PRESTO showed that infants receiving amino acid-based formula (AAF) with or without synbiotics demonstrated effective symptom resolution and development of tolerance to cow’s milk (CM) in line with natural outgrowth and similarly to those receiving extensively hydrolysed formula.

The objective of the present analysis is to assess the rates of acquired tolerance to CM after 36 months in subjects who consumed AAF with or without synbiotics during a 1-year intervention period in early life as part of the PRESTO study (NTR3725).

Methods

Infants aged ≤ 13 months with confirmed IgE-mediated CM allergy were randomly assigned to receive either a hypoallergenic AAF (Nutricia, United Kingdom) containing synbiotics (prebiotic oligosaccharides: oligofructose, inulin; and probiotic strain Bifidobacterium breve M-16V; AAF-S) or a nutritionally similar AAF without synbiotics (AAF) for a 1-year period. Differences in CM tolerance development between groups were analysed 36 months after the start of the 1-year intervention using a logistic regression model including group, and age and CM IgE at baseline as fixed factors.

Results

The proportion of subjects (mean [±SD] age, 3.8±0.36 years) who developed CM tolerance after 36 months was similar in the group receiving AAF-S (47/60 [78%]) and in the group receiving AAF (49/66 [74%]) (p=0.253) (Figure 1). In those subjects who did not develop CM tolerance, CM-related symptoms were generally mild and there were no differences in symptoms’ prevalence or severity between the AAF-S and AAF groups.

Conclusions

A high proportion of children (about three-quarters) developed tolerance to CM 36 months after the start of a 1-year intervention period with AAF, with or without synbiotics. This proportion is comparable to natural outgrowth of CM allergy. These data suggest that the consumption of AAF and absence of exposure to CM peptides does not slow down CM tolerance acquisition.

Objectives and Study

Ingredients that focus on reducing the risk of obesity by maintaining a healthy gut microbiota and preventing obesity-related adverse effects may represent a management option appropriate in the pediatric population. The purpose of this study was to determine the effects of specialized nutrition carbohydrates for preventing obese-associated dysbiosis, as well as avoiding excessive fat deposition in an animal model of childhood obesity induced by feeding a high fat diet (HFD).

Methods

Growing rats were assigned to one of the three nutritional groups: LEAN group fed on standard rodent diet; OBE group fed on HFD containing rapid-digesting CHO; and SDC group fed on HFD containing slow-digesting CHO. A linear mixed-effects model was used to determine the abundance changes of gut microbiota, analyzed by 16S rRNA-based metagenomics. Short-chain fatty acids production was analyzed in feces by UPLC-MS/MS system. The effect of the diets on the lipid and glucose homeostasis were also analyzed.

Results

The specialized carbs ingredients (SDC) prevented the obese-associated dysbiosis, showing differences at the phylum levels (decreasing Firmicutes and increasing Bacteroidetes) and at the genus level (increasing Alistipes, Bifidobacterium, and Bacteroides) as compared to OBE group. Associated to these changes, the SDC group showed higher levels of acetate and propionate than OBE group. In the SDC group, body weight gain, body composition, insulin and leptin resistances and vascular risk factors were significant lower as compared to obesogenic group and closer to the values found in the lean group. Liver steatosis and systemic inflammation were observed after the consumption of OBE diet. Conversely, the SDC diet significantly prevented these obesity-associated comorbidities.

Conclusions

In this animal model of childhood obesity, the consumption of SDC might preserve the gut microbiota composition from dysbiosis and its adverse metabolic complications.

Objectives and Study

Acute diarrhea continues to be a leading cause of morbidity, hospitalization, and mortality worldwide. Probiotics have been proposed as a complementary therapy in the treatment of acute diarrhea. The goal of this study is to assess the efficacy and safety of Lactobacillus rhamnosus LRa05, as an adjunct to the treatment of acute watery diarrhea in children with a randomized, double-blinded, placebo-controlled study design.

Methods

Eligible diarrheal children were randomized into intervention group (IG, n=57, conventional treatment for diarrhea in combination with probiotic) and control group (CG, n=53, conventional treatment for diarrhea without probiotic). The primary assessments of this study were duration of diarrhea and the improvement in diarrhea symptoms. Fecal samples were collected from all children before and after intervention to measure levels of sIgA, calprotectin, human beta-defensin 2 (HBD-2), and cathelicidin (LL-37), and to analyze the gut microbiome (GM) composition.

Results

After the intervention, the total duration of diarrhea in the IG (122.4±13.5 h) was significantly shorter than that in the CG (138.7±16.4 h, p <0.001). More children in the IG showed improvements in diarrhea (defined as a decrease in fecal frequency to no more than four times per day and an improved fecal consistency within 72 h after treatment) than those in the CG for both per protocol analysis (70.2% vs 45.3%, p=0.008) and intention-to-treat analysis (66.7% vs. 40.0%, p=0.003). The LL-37 levels in the IG was markedly higher than that in the CG after the intervention (4349.35±1143.86 pg/g vs. 3679.49±871.18 pg/g, p=0.042). The intervention led to higher abundance of Bifidobacterium longum and lower abundance of Enterococcus faecium, Lactobacillus rhamnosus, and Bacteroides fragilis (p<0.05).

Conclusions

Administration of the Lactobacillus rhamnosus LRa05 at a dose of 5×10⁹ CFU/day to children aged 0-3 years resulted in shorter duration of diarrhea, faster improvement in fecal consistency, and beneficial changes in GM composition.

Objectives and Study

Infancy is a critical period for brain and cognitive growth that is sensitive to intake of key nutrients, such as long-chain polyunsaturated fatty acids, sphingomyelin, and other phospholipids. Bovine milk fat globule membrane (bMFGM) is a source of phospholipids that may impact early neurodevelopment. We examined the effect of bMFGM intake on developing brain myelination and cognitive ability by comparing children in an observational study who received infant formula either without (Standard) or with added bMFGM (bMFGM+).

Methods

Healthy full-term infants were drawn from a longitudinal neurodevelopmental study with continuous enrollment since 2010. Matched cohorts of 28 and 23 infants were selected who had multiple MRI scans between 0 and 2 years of age and had exclusively received either Standard or bMFGM+ formula. Both formulas differed nutritionally only in bMFGM content. 3T MRI scanning was performed to quantify myelin development throughout the brain, and cognitive abilities were assessed using the Mullen Scales of Early Learning (MSEL).

Following MRI processing and alignment, mean longitudinal trajectories of myelination were calculated for each infant group and compared throughout the brain using a series of general nonlinear mixed-effects models. Development of verbal, non-verbal, and overall cognitive ability was also compared between groups using linear mixed-effects models.

Results

Brain imaging results reveal significantly enhanced myelination rate and overall content in infants receiving bMFGM+ formula compared to Standard (Figs.1a and b), particularly throughout motor-related regions (corpus callosum, cerebellum, and parietal cortex). Non-verbal cognitive MSEL scores were also significantly higher in the bMFGM+ group (Fig. 1c).

Conclusions

These results demonstrate enhanced brain structure and function associated with dietary intake of bMFGM in infancy, consistent with emerging evidence for the importance of phospholipid and sphingomyelin intake for neurodevelopment.

Objectives and Study

Preterm infants are at risk for impaired oral feeding and often require feeding tubes (FT), either nasogastric tubes (NGT) or surgically placed gastrostomy tubes (GT), to facilitate discharge from the neonatal intensive care unit (NICU). Little is known about their long-term feeding outcomes. This study aimed to determine the factors associated with full oral feeding by 12-months corrected age (CA) in infants discharged with a FT. Secondary aims included growth outcomes and FT complications.

Methods

This was a single-center retrospective study of infants ≤30 weeks gestational age (GA) discharged from a Level IV NICU with a FT between 2012-2020. Exclusions: infants that were deceased before 12-months CA, lost to follow-up, or those diagnosed with a condition that could independently affect oral feeding. Clinical characteristics and outcomes were compared.

Results

217 infants were included: 130 discharged with an NGT and 87 with a GT. By 12-months CA, 55% of infants achieved full oral feeding. More infants discharged with an NGT achieved full oral feeding compared to those discharged with a GT (76% vs 21%, p <0.001), with a median time to oral feeds of 2.18 months after discharge (IQR 0.87-5.02), (Figure 1). At 12-months CA, those achieving full oral feeds, compared to infants still requiring a FT, had significantly less bronchopulmonary dysplasia, home oxygen on discharge, ventilator days, pulmonary hypertension, and aspiration on swallow studies (Figure 2). Infants achieving full oral feeds had higher length z-scores than those with continued need for FT, median of -0.83 compared to -2.00 (p<0.001), respectively. Infants with a GT experienced more FT complications, 63% compared to 18% in the NGT group (p<0.000).

Conclusions

Most infants discharged with an NGT achieved full oral feeding by 12-months CA. Certain characteristics were associated with continued need for FT. These findings can guide FT selection at discharge and follow-up.

Objectives and Study

Maternal diet during pregnancy could be a potential target for overweight/obesity prevention in the pediatric age. Mediterranean Diet (MD) is considered one of the healthiest dietary models exerting protective effects against overweight/obesity. The Mediterranean Diet during Pregnancy (PREMEDI) study has been designed to evaluate the effects of a personalized nutritional counseling to promote MD during pregnancy on the occurrence of overweight/obesity at 24 months in the offspring.

Methods

The PREMEDI study was a multicenter randomized controlled, parallel groups, prospective trial. 95 healthy women (mean age 36 years) at their first trimester of pregnancy were randomly allocated to receive the standard obstetrical and gynecological follow up plus a nutritional counseling to promote MD (Group 1, n= 45) or standard obstetrical and gynecological follow up alone (Group 2, n= 50). We evaluated pediatric overweight/obesity rate at 24 months, and leptin gene DNA methylation rate in cord blood mononuclear cells (PBMCs). Furthermore, the maternal MD adherence during pregnancy (assessed through the MeDiet Score questionnaire) was also evaluated.

Results

At the age of two years, the rate of overweight/obesity was significantly lower in children of women enrolled in Group 1 (29.4% vs. 53.7 %, p<0.05). This effect paralleled with higher leptin gene DNA methylation rate (30.4% vs. 16.9%, p<0.001) in cord blood PBMCs. A low baseline MD adherence was observed in both groups. The nutritional counseling promoted an optimal MD adherence (MedDiet SCORE>9) starting from the second trimester to the end of pregnancy. The result was sustained until the end of pregnancy.

Conclusions

The nutritional counseling aimed at promoting MD adherence during pregnancy could be an effective strategy against pediatric overweight/obesity. This effect could be mediated, at least in part, by an epigenetic modulation of leptin expression.

Objectives and Study

To assess the effectiveness of nutritional supplementation during the first 1000-days to reduce the prevalence of low birth weight and stunting in children at 24 months of age.

Methods

In this cluster randomized controlled trial, we enrolled women from two rural districts of Pakistan during their pregnancy. Out of 29 clusters, we randomly allocated 6 clusters to the intervention and control each. Pregnant women received a monthly supply of 5 kg (i.e., 165 grams/day) of wheat soya blend plus (WSB+) during pregnancy and the first six months of their lactation period. In addition, their children received lipid-based nutrient supplement - medium-quantity (LNSMQ) between 6-23 months of age.

Results

Two thousand thirty pregnant women (1017 in the intervention group and 1013 in the control group) were enrolled. Monthly follow-ups were conducted. At 24 months of age, we captured data from 699 (78%) of 892 live births in the intervention group and 653 (76%) of 853 live births in the control group. There was a significant difference in mean length (49.4 cm vs 48.9 cm, p =0.027), weight (3.1 kg vs 3.0 kg, p =0.013), length for age z-scores (-1.2 vs -1.5, p =0.004) and weight for age z-scores (-1.2 vs -1.5, p =0.015) among infants in the intervention compared to control group. At 24 months of age, a significant difference in the prevalence of stunting (absolute difference, 10.2%, 95% CI 18.2 to 2.3, p =0.017) and underweight (absolute difference, 13.7%, 95% CI 20.3 to 7.0, p =0.001) were observed in the intervention as compared to the control group.

Conclusions

Provision of supplementation during the first 1000-days of life improved child linear growth and reduced stunting in children at 24 months. This intervention can be scaled-up in similar settings to lower the prevalence of low birthweight and stunting in children under two years of age.