Tolerance of a standard intact protein formula versus a partially hydrolyzed formula in healthy, term infants

<p>Abstract</p> <p>Background</p> <p>Parents who perceive common infant behaviors as formula intolerance-related often switch formulas without consulting a health professional. Up to one-half of formula-fed infants experience a formula change during the first six months of life.</p> <p>Methods</p> <p>The objective of this study was to assess discontinuance due to study physician-assessed formula intolerance in healthy, term infants. Infants (335) were randomized to receive either a standard intact cow milk protein formula (INTACT) or a partially hydrolyzed cow milk protein formula (PH) in a 60 day non-inferiority trial. Discontinuance due to study physician-assessed formula intolerance was the primary outcome. Secondary outcomes included number of infants who discontinued for any reason, including parent-assessed.</p> <p>Results</p> <p>Formula intolerance between groups (INTACT, 12.3% vs. PH, 13.7%) was similar for infants who completed the study or discontinued due to study physician-assessed formula intolerance. Overall study discontinuance based on parent- vs. study physician-assessed intolerance for all infants (14.4 vs.11.1%) was significantly different (P = 0.001).</p> <p>Conclusion</p> <p>This study demonstrated no difference in infant tolerance of intact vs. partially hydrolyzed cow milk protein formulas for healthy, term infants over a 60-day feeding trial, suggesting nonstandard partially hydrolyzed formulas are not necessary as a first-choice for healthy infants. Parents frequently perceived infant behavior as formula intolerance, paralleling previous reports of unnecessary formula changes.</p> <p>Trial Registration</p> <p>clinicaltrials.gov: NCT00666120</p

Higher Protein Intake Improves Length, Not Weight, z Scores in Preterm Infants

Objective: The aim of the study was to evaluate the relation between nutritional intake (kilocalories, protein) and weight and length growth in preterm infants, and to describe their metabolic tolerance with a focus on those with high protein intake (≥4.6 g · kg−1 · day−1). Methods: Secondary analysis of data from appropriate-for-gestational age preterm infants in a 28-day randomized clinical trial that evaluated growth, tolerance, and safety of a new ultraconcentrated liquid human milk fortifier (original study n = 150). This subset of 56 infants had complete growth and nutrition data and met criteria for the original study\u27s “efficacy analysis” (eg, \u3e80% of kilocalorie intake from study diet). Nutritional intake was estimated, not actual. Regressions were used to test cumulative kilocalories and protein as the predictors of 28-day change in weight and length z scores (growth status), and to evaluate protein tolerance. Results: Average intake was 118 ± 8 kcal · kg−1 · day−1 and 4.3 ± 0.4 g protein · kg−1 · day−1, with 16 ± 3 g · kg−1 · day−1 and 1.1 ± 0.2 cm/week growth for 28 days. Cumulative total kilocalories and protein were significant predictors of improved length z score (P = 0.0054, 0.0005) but not weight z score change. Regression models indicated that protein not kilocalories explained the improvement in length z score, with protein explaining 19% of the variability. The high protein group averaged 4.6 to 5.5 g · kg−1 · day−1 (n = 16). Protein tolerance was adequate for all of the study infants based on metabolic measures (blood urea nitrogen, serum carbon dioxide, pH). Conclusions: Higher cumulative protein intake was tolerated and overall lessened the commonly occurring decline in the length but not weight growth status in a 28-day study of preterm infants

Infant behavioral state and stool microbiome in infants receiving Lactocaseibacillus rhamnosus GG in formula: randomized controlled trial

Background Our aim was to evaluate infant behavioral state, stool microbiome profile and calprotectin in infants with infantile colic receiving a partially hydrolyzed protein formula with or without added Lacticaseibacillus (formerly Lactobacillus) rhamnosus GG (LGG). Methods In this single-center, double-blind, controlled, parallel, prospective study, term infants (14–28 days of age) identified with colic (using modified Wessel’s criteria: cried and/or fussed ≥ 3 h/day for ≥ 3 days/week, in a one-week period) were randomized to receive one of two formulas over a three-week feeding period: marketed partially hydrolyzed cow’s milk-based infant formula (PHF, n = 35) or a similar formula with added LGG (PHF-LGG, n = 36). Parent-reported infant behavior was recorded at three time points (Study Days 2–4, 10–12, and 18–20). Duration (hours/day) of crying/fussing (averaged over each three-day period) was the primary outcome. Stool samples were collected at Baseline and Study End (Days 19–21) to determine stool LGG colonization (by qPCR) and microbial abundance (using 16S rRNA gene sequencing) and calprotectin (μg/g). Results Duration of crying/fussing (mean ± SE) decreased and awake/content behavior increased over time with no significant group differences over the course of the study. There were no group differences in the percentage of infants who experienced colic by study end. Colic decreased by Study End vs Baseline in both groups. Change in fecal calprotectin also was similar between groups. Comparing Study End vs Baseline, LGG abundance was greater in the PHF-LGG group (P < 0.001) whereas alpha diversity was greater in the PHF group (P = 0.022). Beta diversity was significantly different between PHF and PHF-LGG at Study End (P = 0.05). By study end, relative abundance of L. rhamnosus was higher in the PHF-LGG vs PHF group and vs Baseline. Conclusions In this pilot study of infants with colic, both study formulas were well tolerated. Crying/fussing decreased and awake/content behavior increased in both study groups over the course of the study. Study results demonstrate a successful introduction of the probiotic to the microbiome. The partially hydrolyzed protein formula with added LGG was associated with significant changes in the gut microbiome.ISSN:1471-243

Effect of Bovine Milk Fat Globule Membrane and Lactoferrin in Infant Formula on Gut Microbiome and Metabolome at 4 Months of Age

Background Milk fat globule membrane (MFGM) and lactoferrin (LF) are human-milk bioactive components demonstrated to support gastrointestinal and immune development. Significantly fewer diarrhea and respiratory-associated adverse events through 18 mo of age were previously reported in healthy term infants fed a cow-milk–based infant formula with an added source of bovine MFGM and bovine LF through 12 mo of age. Objectives The aim was to compare microbiota and metabolite profiles in a subset of study participants. Methods Stool samples were collected at baseline (10–14 d of age) and day 120. Bacterial community profiling was performed via 16S rRNA gene sequencing and alpha and beta diversity were analyzed (QIIME 2). Differentially abundant taxa were determined using linear discriminant analysis effect size (LefSE) and visualized (Metacoder). Untargeted stool metabolites were analyzed (HPLC/MS) and expressed as the fold-change between group means (control to MFGM+LF ratio). Results Alpha diversity increased significantly in both groups from baseline to 4 mo. Subtle group differences in beta diversity were demonstrated at 4 mo (Jaccard distance; R2 = 0.01, P = 0.042). Specifically, Bacteroides uniformis and Bacteroides plebeius were more abundant in the MFGM+LF group at 4 mo. Metabolite profile differences for MFGM+LF versus control included lower fecal medium-chain fatty acids, deoxycarnitine, and glycochenodeoxycholate, and some higher fecal carbohydrates and steroids (P < 0.05). After applying multiple test correction, the differences in stool metabolomics were not significant. Conclusions Addition of bovine MFGM and LF in infant formula was associated with subtle differences in stool microbiome and metabolome by 4 mo of age, including increased prevalence of Bacteroides species. Stool metabolite profiles may be consistent with altered microbial metabolism. This trial was registered at https://clinicaltrials.gov as NCT02274883.ISSN:2475-299