Oral nutritional supplementation with dietary counseling improves linear catch-up growth and health outcomes in children with or at risk of undernutrition: a randomized controlled trial.

Introduction: Childhood undernutrition is associated with increased morbidity, mortality and a high socio-economic burden. Methods: Supporting Pediatric GRowth and Health OUTcomes (SPROUT) is a randomized, controlled trial evaluating the effects of an oral nutritional supplement (ONS) with dietary counseling (DC; n = 164) compared to a DC-only group who continued consuming their habitual milk (n = 166; NCT05239208). Children aged 24-60 months who were at risk or with undernutrition, as defined by weight-for-age [WAZ] < -1 and height-for-age [HAZ] < -1 according to the WHO Growth Standards, and who also met the criterion of weight-for-height [WHZ] < 0, were enrolled in Vietnam. Results: ONS + DC had a larger WAZ increase at day 120 (primary endpoint) vs. DC (least squares mean, LSM (SE): 0.30 (0.02) vs. 0.13 (0.02); p < 0.001), and larger improvements in all weight, BMI and weight-for-height indices at day 30 and 120 (all p < 0.01). Height gain was larger in ONS + DC in all indices, including height-for-age difference [HAD; cm: 0.56 (0.07) vs. 0.10 (0.07); p < 0.001], at day 120. ONS + DC had larger arm muscle but not arm fat indices, higher parent-rated appetite, physical activity and energy levels, longer night sleep, fewer and shorter awakenings, and better sleep quality than DC. Conclusion: Adding ONS to DC, compared to DC-alone, improves growth in weight and height, linear catch-up growth, and health outcomes in children with or at risk of undernutrition.

Impact of a specialized oral nutritional supplement on quality of life in older adults following hospitalization: Post-hoc analysis of the NOURISH trial.

BACKGROUND & AIMS: Both during and after hospitalization, nutritional care with daily intake of oral nutritional supplements (ONS) improves health outcomes and decreases risk of mortality in malnourished older adults. In a post-hoc analysis of data from hospitalized older adults with malnutrition risk, we sought to determine whether consuming a specialized ONS (S-ONS) containing high protein and beta-hydroxy-beta-methylbutyrate (HMB) can also improve Quality of Life (QoL). METHODS: We analyzed data from the NOURISH trial-a randomized, placebo-controlled, multi-center, double-blind study conducted in patients with congestive heart failure, acute myocardial infarction, pneumonia, or chronic obstructive pulmonary disease. Patients received standard care + S-ONS or placebo beverage (target 2 servings/day) during hospitalization and for 90 days post-discharge. SF-36 and EQ-5D QoL outcomes were assessed at 0-, 30-, 60-, and 90-days post-discharge. To account for the missing QoL observations (27.7%) due to patient dropout, we used multiple imputation. Data represent differences between least squares mean (LSM) values with 95% Confidence Intervals for groups receiving S-ONS or placebo treatments. RESULTS: The study population consisted of 622 patients of mean age ±standard deviation: 77.9 ± 8.4 years and of whom 52.1% were females. Patients consuming placebo had lower (worse) QoL domain scores than did those consuming S-ONS. Specifically for the SF-36 health domain scores, group differences (placebo vs S-ONS) in LSM were significant for the mental component summary at day 90 (-4.23 [-7.75, -0.71]; p = 0.019), the domains of mental health at days 60 (-3.76 [-7.40, -0.12]; p = 0.043) and 90 (-4.88 [-8.41, -1.34]; p = 0.007), vitality at day 90 (-3.33 [-6.65, -0.01]; p = 0.049) and social functioning at day 90 (-4.02 [-7.48,-0.55]; p = 0.023). Compared to placebo, differences in LSM values for the SF-36 general health domain were significant with improvement in the S-ONS group at hospital discharge and beyond: day 0 (-2.72 [-5.33, -0.11]; p = 0.041), day 30 (-3.08 [-6.09, -0.08]; p = 0.044), day 60 (-3.95 [-7.13, -0.76]; p = 0.015), and day 90 (-4.56 [-7.74, -1.38]; p = 0.005). CONCLUSIONS: In hospitalized older adults with cardiopulmonary diseases and evidence of poor nutritional status, daily intake of S-ONS compared to placebo improved post-discharge QoL scores for mental health/cognition, vitality, social functioning, and general health. These QoL benefits complement survival benefits found in the original NOURISH trial analysis. CLINICAL TRIAL REGISTRATION: NCT01626742.

Pilot study on the impact of a carbohydrate loading drink on postprandial glycemic responses and gastric emptying in adults with prediabetes and type 2 diabetes mellitus.

BACKGROUND: Preoperative carbohydrate (CHO) loading improves patient outcomes but is not extensively studied in individuals with diabetes mellitus (DM), resulting in limited professional recommendations. This study examined postprandial glycemic responses and gastric emptying rates following consumption of a CHO drink in adults with and without DM. METHODS: A single-arm, nonrandomized pilot trial was conducted in adults without DM (non-DM) (47.5 ± 2.5 years), with pre-DM (55.8 ± 3.0 years), and with type 2 DM (56.2 ± 2.5 years). Following an overnight fast, participants consumed a 50 g CHO drink followed by 1.5 g liquid paracetamol. Venous blood samples were collected at baseline (ie, t = 0 min) and 15, 30, 45, 60, 90, 120, 150, 180, 210, and 240 min for plasma glucose and serum insulin and paracetamol concentrations to assess gastric emptying. RESULTS: Participants with DM were older and had a higher body mass index than non-DM participants (31.2 ± 0.9 vs 28.2 ± 0.9). Fasting glucose and hemoglobin A1c levels differed significantly across groups (non-DM: 95.4 ± 3.6 mg/dl and 5.2% ± 0.1%; pre-DM: 111.6 ± 3.6 mg/dl and 5.8% ± 0.1%; DM: 167.4 ± 3.6 mg/dl and 7.2% ± 0.1%). Compared with the non-DM group, DM had increased glucose responses at 30-180 min. Glucose returned to baseline at 150 min in the non-DM and pre-DM groups compared with 210 min in the DM group. Paracetamol concentrations were not significantly different between the non-DM and DM groups. CONCLUSION: Blood glucose returned to baseline within ~2.5 h in non-DM and pre-DM groups and ~3.5 h in participants with DM following ingestion of a CHO drink. No consistent differences in gastric emptying rates were observed between participants with and without DM.

Optimal Cutoffs for the Diagnosis of Sarcopenia in Older Chinese Adults.

Background: The optimal criteria for sarcopenia in the older Chinese population have not been defined. Consequently, this study aims to determine the optimal cutoffs of grip strength, appendicular skeletal muscle index (ASMI) using bioelectrical impedance analysis (BIA), and gait speed, comprising the best definition of sarcopenia for older Chinese populations. Methods: A total of 2,821 (1,398 men and 1,423 women) community-dwelling older people (≥60 years) and 409 (205 men and 204 women) young healthy adults (25-34 years) were recruited from three big cities in China. Besides gait speed and grip strength, we examined ASMI by BIA and dual-energy X-ray absorptiometry (DXA), comprising the three components of sarcopenia. DXA classification for low ASMI, 20th percentile among older adults in the study sample, was found to be best compared with the other existing classification, 1 SD and 2 SD below the mean for the young population, and was used as the gold standard to determine the optimal cutoffs of BIA using receiver operating characteristic curves (ROC). The cutoffs of handgrip strength and gait speed were determined following the same rule. Results: Using gender-specific 20th percentiles of DXA (6.53 kg/m2 for men and 5.40 kg/m2 for women), the cutoffs 7.05 kg/m2 for men and 5.85 kg/m2 for women were determined as optimal cutoffs of BIA by achieving the largest sensitivity (0.81, 95% CI: 0.63-0.93 for men and 0.90, 95% CI: 0.73-0.98 for women) and specificity greater than 0.80 (0.80, 95% CI: 0.72-0.87 for men and 0.81, 95% CI: 0.72-0.87 for women) in the ROC analysis. The 28.5 kg and 1.05 m/s for men and 18.6 kg and 1.01 m/s for women were determined as the cutoffs for handgrip strength and gait speed, respectively. Based on the derived cutoffs, 14.2% of men and 15.7% of women in the older Chinese study population were classified as sarcopenia. Conclusion: Notably, 7.05 kg/m2, 28.5 kg, and 1.05 m/s for men and 5.85 kg/m2, 18.6 kg, and 1.01 m/s for women were selected as the optimal cutoffs for low ASMI by BIA, handgrip strength, and gait speed, respectively. These optimal cutoffs will enhance practicability for screening sarcopenia in primary care and clinical settings.

Growth, Tolerance, and Compliance of Infants Fed an Extensively Hydrolyzed Infant Formula with Added 2'-FL Fucosyllactose (2'-FL) Human Milk Oligosaccharide.

BACKGROUND: The purpose of this study was to evaluate the growth, tolerance and compliance effects of an extensively hydrolyzed formula with added 2'-FL in an intended use population of infants. METHODS: A non-randomized, single-group, multicenter study was conducted. Infants (0-60 days of age) with suspected food protein allergy, persistent feeding intolerance, or presenting conditions where an extensively hydrolyzed formula (eHF) was deemed appropriate were enrolled in a 2-month feeding trial. The primary outcome was maintenance of weight for age z-score during the study. Weight, length, head circumference, formula intake, tolerance measures, clinical symptoms and questionnaires were collected. Forty-eight infants were enrolled and 36 completed the study. RESULTS: Weight for age z-scores of infants showed a statistically significant improvement from study day 1 to study day 60 (0.32 ± 0.11, p = 0.0078). CONCLUSIONS: Overall, the results of the study demonstrate that the study formula was well tolerated, safe and supported growth in the intended population.

Reduced mortality risk in malnourished hospitalized older adult patients with COPD treated with a specialized oral nutritional supplement: Sub-group analysis of the NOURISH study.

BACKGROUND: Hospitalized, malnourished older adults with chronic obstructive pulmonary disease (COPD) have an elevated risk of readmission and mortality. OBJECTIVE: Post-hoc, sub-group analysis from the NOURISH study cohort examined the effect of a high-protein oral nutritional supplement (ONS) containing HMB (HP-HMB) in malnourished, hospitalized older adults with COPD and to identify predictors of outcomes. METHODS: The NOURISH study (n = 652) was a multicenter, randomized, placebo-controlled, double-blind trial. The COPD subgroup (n = 214) included hospitalized, malnourished (based on Subjective Global Assessment), older adults (≥65 y), with admission diagnosis of COPD who received either standard-of-care plus HP-HMB (n = 109) or standard-of-care and a placebo supplement (n = 105) prescribed 2 servings/day from within 3 days of hospital admission (baseline) and up to 90 days after discharge. The primary study outcome was a composite endpoint of incidence of death or non-elective readmission up to 90-day post-discharge, while secondary endpoints included changes in hand-grip strength, body weight, and nutritional biomarkers over time. Categorical outcomes were analyzed using Cochran-Mantel-Haenszel tests, longitudinal data by repeated measures analysis of covariance; and changes from baseline by analysis of covariance. p-values ≤ 0.05 were considered statistically significant. Multivariate logistic regression was used to model predictors of the primary outcome and components. RESULTS: In patients with COPD, 30, 60, and 90-day hospital readmission rate did not differ, but in contrast, 30, 60, and 90-day mortality risk was approximately 71% lower with HP-HMB supplementation relative to placebo (1.83%, 2.75%, 2.75% vs. 6.67%, 9.52% and 10.48%, p = 0.0395, 0.0193, 0.0113, resp.). In patients with COPD, compared to placebo, intake of HP-HMB resulted in a significant increase in handgrip strength (+1.56 kg vs. -0.34 kg, p = 0.0413) from discharge to day 30; increased body weight from baseline to hospital discharge (0.66 kg vs. -0.01 kg, p < 0.05) and, improvements in blood nutritional biomarker concentrations. The multivariate logistic regression predictors of the death, readmission or composite endpoints in these COPD patients showed that participants who were severely malnourished (p = 0.0191) and had a Glasgow prognostic score (GPS) Score of 1 or 2 had statistically significant odds of readmission or death (p = 0.0227). CONCLUSIONS: Among malnourished, hospitalized patients with COPD, supplementation with HP-HMB was associated with a markedly decreased mortality risk, and improved handgrip strength, body weight, and nutritional biomarkers within a 90-day period after hospital discharge. This post-hoc, subgroup analysis highlights the importance of early identification of nutritional risk and administration of high-protein ONS in older, malnourished patients with COPD after hospital admission and continuing after hospital discharge.

Specialized oral nutritional supplement (ONS) improves handgrip strength in hospitalized, malnourished older patients with cardiovascular and pulmonary disease: A randomized clinical trial.

BACKGROUND & AIMS: Oral Nutritional Supplements (ONS) are used to treat malnutrition and improve clinical outcomes in malnourished patients. Poor handgrip strength (HGS) is associated with an increased risk of mortality, disability and other adverse health consequences. This analysis examined the effect of a specialized ONS on HGS and its relationship to nutritional status in hospitalized, older adults with malnutrition who were participants in the NOURISH trial. METHODS: We enrolled older (≥65years), malnourished (Subjective Global Assessment [SGA] class B/C) adults hospitalized for cardiovascular and pulmonary events: congestive heart failure, acute myocardial infarction, pneumonia and/or chronic obstructive pulmonary disease exacerbation in a double-blind, randomized, placebo-controlled trial (NOURISH study). During hospitalization and until 90 days after discharge, participants received standard-of-care plus a high protein and beta-hydroxy-beta-methylbutyrate containing ONS (S-ONS; n = 328) or a placebo supplement (n = 324), aimed at 2 servings/day. HGS was evaluated by dynamometer at baseline, hospital discharge, day (d) 30, d60, and d90 post-discharge. RESULTS: Post hoc, repeated measures analysis of data at discharge, d30, d60, and d90 showed significantly higher HGS in the S-ONS vs. the placebo group in the evaluable group (Least Squares Means ± Standard Error: (23.25 ± 0.25 vs. 22.63 ± 0.25, p = 0.043). At d90, there was a significant positive association between HGS and nutritional status (SGA) improvements in the entire cohort: 49% of participants with increased HGS from discharge had improved nutritional status versus 31% with unchanged or decreased HGS (p = 0.003). HGS and the scores on the Katz index of independence in activities of daily living (ADL) were positively associated at all visits including all ITT subjects (Pearson's r range: 0.24 to 0.34, all p < 0.0001). CONCLUSIONS: S-ONS provided during hospitalization and up to 90 days post-discharge improves HGS in malnourished older adults following cardiovascular and pulmonary events and may contribute to improvement in patients' overall recovery. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov NCT01626742.

Efficacy of Soy-Based Formulas in Alleviating Gastrointestinal Symptoms in Infants With Milk-Based Formula Intolerance: A Randomized Clinical Trial.

A randomized, blinded pilot clinical study was conducted to assess gastrointestinal (GI) tolerance in healthy, full-term infants (2-9 weeks old), whose pediatricians recommended a formula change due to perceived cow's milk formula intolerance. Infants were randomized and exclusively fed either a commercial control soy formula (SF; n = 22), an experimental partially hydrolyzed SF (10% hydrolyzed, n = 23), or a 5% hydrolyzed SF (n = 26) for 2 weeks. Age-matched reference cohorts (n = 72) with no GI intolerance on milk-based formula were assessed in parallel. Results indicated that all SF-fed groups contributed to reduction (P < .05) in common GI tolerance symptoms to levels not different from the non-symptomatic reference cohort at study end. The control SF group had more reduced fussiness, gas, and crying and higher formed stools versus hydrolyzed SF groups. In conclusion, the study suggests that SFs reduced GI intolerance symptoms in otherwise healthy infants with poor tolerance on milk-based formulas.

Specialized High-Protein Oral Nutrition Supplement Improves Home Nutrient Intake of Malnourished Older Adults Without Decreasing Usual Food Intake.

BACKGROUND: Reduced nutrient intake is common in patients after hospitalization, contributing to increased risk for readmission and mortality. Oral nutrition supplements can improve nutrition status and clinical outcomes, but intake of food is prioritized by clinicians. This study examines the impact of a high-protein oral nutrition supplement (S-ONS) on nutrient intake post discharge. METHODS: In a subset of patients (14 S-ONS and 16 placebo) from the NOURISH (Nutrition effect On Unplanned ReadmIssions and Survival in Hospitalized patients) trial, 24-hour dietary recalls were conducted on 3 randomly selected days during the weeks of 30, 60, and 90 days post discharge. Nutrient intake was estimated using Nutrition Data System for Research software. Adequate energy and protein intake were defined as 30 kcal/kg/d and 1.2 g/kg/d, respectively. Dietary Reference Intakes (DRIs) were used for other nutrients. RESULTS: Less than half of patients met the requirements for energy, protein, and 12 micronutrients from food intake alone during the study. Energy and protein intakes from food were not diminished relative to placebo. Considering nutrient intake from both food and S-ONS, 50% and 71% of patients receiving S-ONSs met energy and protein goals respectively at 90 days (compared with 29% and 36%, in the placebo group), and 100% met the DRI for total carbohydrate, iron, phosphorus, copper, selenium, thiamin, and riboflavin at all time points, all of which were consumed at higher amounts vs placebo. CONCLUSION: Three months of S-ONS consumption increases intake of numerous nutrients without decreasing nutrient intake from food in older malnourished adults post discharge.

Review of the Clinical Experiences of Feeding Infants Formula Containing the Human Milk Oligosaccharide 2'-Fucosyllactose.

Human milk oligosaccharides (HMOs) are the third most abundant solid component in human milk after lactose and lipids. Preclinical research has demonstrated that HMOs and specifically 2'-fucosyllactose (2'-FL) are more than a prebiotic and have multiple functions, including immune, gut, and cognition benefits. Previously, human milk has been the only source for significant levels of HMOs. The most abundant HMO in most mothers' breast milk is 2'-FL. Recently, 2'-FL has been synthesized and shown to be structurally identical to the 2'-FL found in human milk. 2'-FL HMO is now available in some commercial infant formulas. The purpose of this narrative review was to summarize the clinical experiences of feeding infant formula supplemented with the HMO, 2'-FL. Most of these studies investigated standard intact milk protein-based infant formulas containing 2'-FL, and one evaluated a partially hydrolyzed whey-based formula. Collectively, these clinical experiences demonstrated that 2'-FL being added to infant formula was safe, well-tolerated, and absorbed and excreted with similar efficiency to 2'-FL in human milk. Further, infants that were fed formula with 2'-FL had immune benefits, fewer parent-reported respiratory infections, and improved symptoms of formula intolerance. Ultimately, infant formula with 2'-FL supports immune and gut health and is closer compositionally and functionally to human milk.

Comparison of Growth of Healthy Term Infants Fed Extensively Hydrolyzed Protein- and Amino Acid-Based Infant Formulas.

The aim of this narrative review was to assess published growth data for healthy, term, infants consuming extensively hydrolyzed protein-based (EHF), or amino acid-based formulas (AAF). These data may be of use to clinicians managing infants with medical conditions consuming these products. A search was conducted using key terms: amino acid-based, hydrolysate, hydrolyzed, hydrolysed, infant formula, infant formulae or formulas, baby formula, or formulae or formulas, infant, infants, infantile, and growth. Seven controlled, randomized, prospective growth trials of healthy term infants fed EHFs or AAFs at similar time points during the first four months of age met these and other criteria, including that the trial was published in a peer-reviewed journal, subjects were enrolled by ≤14 days of age and were exclusively formula-fed at entry and throughout the duration of the trial, and infants were assessed at regular intervals with weight measures available ideally at 14 days, one, two, three, and four months of age. Results suggested that healthy infants receiving commonly available EHFs and AAFs do not appear to experience accelerated growth as reported for infants fed many standard formulas. Differences in growth patterns were observed with some formulas supporting normative growth patterns during the first four months but others appearing to support markedly lower growth patterns. These observations should be confirmed in well-designed prospective randomized trials. Until that time, it is recommended that EHFs and AAFs be chosen carefully with individual patient needs considered.

A Randomized Controlled Multicenter Trial of an Investigational Liquid Nutritional Formula in Women with Cyclic Breast Pain Associated with Fibrocystic Breast Changes.

OBJECTIVE: A randomized, multicenter, controlled double-blind trial was performed in women with cyclic breast pain (mastalgia) associated with fibrocystic breast changes (FBCs) to determine whether a nutritional formula reduced breast pain and/or nodularity. STUDY DESIGN: Women were randomized to receive a specifically designed liquid formulation (n = 93) (1 g gamma-linolenic acid [GLA], 750 µg iodine, and 70 µg selenium) or control formula (n = 95) (without GLA, iodine, and selenium) daily for three cycles. Women recorded breast pain, medications, and menstrual signs daily using interactive voice-response system. Nodularity was determined by physical breast examination. RESULTS: Breast pain scores decreased similarly in the experimental (-32.2%) and control (-33.1%) groups (p = 0.64). Nodularity was reduced in the experimental, but not the control group (p = 0.03). Among women who continued pain medication, the amount was reduced in the experimental group relative to controls (p = 0.02). CONCLUSION: Women with FBC using the formula containing GLA, iodine, and selenium experienced reduced nodularity and in those women who took over-the-counter breast pain medication, a decrease in the quantity of pain medication was observed.

Readmission and mortality in malnourished, older, hospitalized adults treated with a specialized oral nutritional supplement: A randomized clinical trial.

BACKGROUND: Hospitalized, malnourished older adults have a high risk of readmission and mortality. OBJECTIVE: Evaluation of a high-protein oral nutritional supplement (HP-HMB) containing beta-hydroxy-beta-methylbutyrate on postdischarge outcomes of nonelective readmission and mortality in malnourished, hospitalized older adults. DESIGN: Multicenter, randomized, placebo-controlled, double-blind trial. SETTING: Inpatient and posthospital discharge. PATIENTS: Older (≥65 years), malnourished (Subjective Global Assessment [SGA] class B or C) adults hospitalized for congestive heart failure, acute myocardial infarction, pneumonia, or chronic obstructive pulmonary disease. INTERVENTIONS: Standard-of-care plus HP-HMB (n = 328) or a placebo supplement (n = 324), 2 servings/day. MEASUREMENTS: Primary composite endpoint was 90-day postdischarge incidence of death or nonelective readmission. Other endpoints included 30- and 60-day postdischarge incidence of death or readmission, length of stay (LOS), SGA class, body weight, and activities of daily living (ADL). RESULTS: The primary composite endpoint was similar between HP-HMB (26.8%) and placebo (31.1%). No between-group differences were observed for 90-day readmission rate, but 90-day mortality was significantly lower with HP-HMB relative to placebo (4.8% vs. 9.7%; relative risk 0.49, 95% confidence interval [CI], 0.27 to 0.90; p = 0.018). The number-needed-to-treat to prevent 1 death was 20.3 (95% CI: 10.9, 121.4). Compared with placebo, HP-HMB resulted in improved odds of better nutritional status (SGA class, OR, 2.04, 95% CI: 1.28, 3.25, p = 0.009) at day 90, and an increase in body weight at day 30 (p = 0.035). LOS and ADL were similar between treatments. LIMITATIONS: Limited generalizability; patients represent a selected hospitalized population. CONCLUSIONS: Although no effects were observed for the primary composite endpoint, compared with placebo HP-HMB decreased mortality and improved indices of nutritional status during the 90-day observation period. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.govNCT01626742.

Growth of healthy term infants fed ready-to-feed and powdered forms of an extensively hydrolyzed casein-based infant formula: a randomized, blinded, controlled trial.

Extensively hydrolyzed formulas present a complex matrix subject to adverse conditions during manufacture that could influence growth and tolerance of infants fed these formulas. A masked, randomized, parallel growth study was conducted in infants fed a ready-to-feed (RTF) or powdered (PWD) form of an extensively hydrolyzed casein-based formula. Infants were enrolled between 0 and 9 days and studied to 112 days of age. Growth, formula intake, and stool patterns were assessed. There were no significant differences between groups in weight, length, head circumference, or their respective gains. Tolerance was similar between groups except that the RTF group had greater formula intakes and passed more stools/day compared to the PWD group. This study demonstrates that the PWD formulation of this RTF formula supports similar growth and tolerance in infants during the first 4 months of life.

Evaluation of a free amino acid-based formula in infants with presumptive food protein-induced proctocolitis.

OBJECTIVE: Food protein-induced proctocolitis usually occurs early in life and is characterized by blood-streaked stools and pain during defecation in an otherwise healthy infant. While many infants with food protein-induced proctocolitis respond well to a casein hydrolysate formula, some require an amino acid-based formula. The objective of the study was to measure the change in physician-rated symptom score from enrollment to study completion in infants with presumptive food protein-induced proctocolitis fed with a specific amino acid-based formula. METHODS: In this study, infants ≤6 months of age diagnosed with presumptive food protein-induced proctocolitis received an amino acid-based formula for 42 days. Intake, stool patterns, weight, stool occult blood, and questionnaires assessing infant feeding and stool patterns and parental formula satisfaction were collected. RESULTS: The full analysis set included 43 infants. The mean age at enrollment was 59 ± 5 days. A significant improvement was observed from enrollment to exit in physician-rated symptom score (9.1 ± 0.5 to 4.8 ± 0.5, p < 0.0001), the number of infants with occult blood in stool, and weight-for-age Z-scores during the study. Parental satisfaction with the formula was high. CONCLUSION: The results confirm that the amino acid-based formula studied is efficacious for managing symptoms of presumptive food protein-induced proctocolitis.

Effect of dietary ribonucleotides on infant immune status. Part 2: Immune cell development.

The objective of this study was to determine whether dietary ribonucleotides alter immune cell phenotypes or function in the first year of life. Newborn term infants in a double-blind, 12-mo, multicenter trial were randomized to cow milk formula groups with (FN, n = 138) or without (F, n = 147) 72 mg/L supplemental ribonucleotides. A nonrandomized HMF cohort (n = 192) was concurrently enrolled. Eighty-eight immune blood cell types were characterized by flow cytometry. Data were analyzed by multivariate ANOVA (MANOVA), ANOVA, and repeated measures analysis (RMA), with adjustments made for multiple comparisons. Ribonucleotide feeding changed subpopulations of T and natural killer (NK) cells. FN had higher numbers and percentages of memory/effector (M/E) cytotoxic/suppressor (CD45R0(+)CD8(+), RMA) T, Fas(+) M/E (CD45R0(+)CD95(+)CD3(+), 6 mo) T, and CD56(+)CD16(-) NK cells (CD56(+)CD16(-)CD3(-)CD8(-), 12 mo), and higher percentages of M/E helper (CD45R0(+)CD4(+), RMA) T, Tc1 (IFN gamma(+)CD4(-)CD3(+), RMA), total interferon (IFN)gamma T (IFN gamma(+)CD4(+/-)CD3(+), RMA), Th2 (IL-4(+)CD4(+)CD3(+), 7 mo), and CD57(+) NK-T cells (CD57(+)CD56(-)CD3(+), 6 mo, 7 mo) compared with F. Percentages of naive helper T (CD45RA(+)CD4(+), 12 mo) and numbers and percentages of CD56(+) NK-T cells (CD56(+)CD16(-)CD3(+)CD8(-), 2 mo, 6 mo) were lower in FN than F. Percentages of M/E cytotoxic/suppressor, Th2, and CD56(+)CD16(-) NK cells in FN were significantly higher than F but were not different from HMF, whereas F was significantly lower than HMF. Ribonucleotide supplementation of infant formula supported increased T-cell maturation and affected immunoregulatory NK cell subsets. These FN-associated immune cell profiles either did not differ from those infants fed HMF or tended to be more like those fed HMF than those fed F.

Effect of dietary ribonucleotides on infant immune status. Part 1: Humoral responses.

The objective of this study was to further explore previously identified effects of supplemental ribonucleotides on infant immune status as measured by antibody responses to routine infant immunizations. Infants were randomized to a milk-based formula with (FN, n = 138) or without (F, n = 147) 72 mg ribonucleotides/L. A cohort of human milk-fed (HMF, n = 192) infants was also followed. Subjects were given Haemophilus influenzae type b (Hib), diphtheria tetanus acellular pertussis, and oral poliovirus vaccinations at 2, 4, and 6 mo of age, and specific antibody responses were assessed at 2, 6, 7, and 12 mo. Growth and safety data were also monitored. Using a two-group repeated measures analysis (RMA), FN-fed infants had significantly higher poliovirus type 1 neutralizing antibody (PV-VN1) responses than F-fed infants (p = 0.045). Using three-group RMA, PV-VN1 responses in HMF infants were not different from FN-fed infants, while HMF-fed infant PV-VN1 responses were significantly higher than F-fed infants at 6 (p = 0.0004) and 12 mo (p = 0.0001). FN-fed infants had responses to Hib Farr, diphtheria, tetanus toxoid, oral poliovirus-specific IgA, and PV-VN3 not significantly different from those of F and HMF infants. Growth, gastrointestinal tolerance, and adverse events were equivalent among the three groups. The FN-associated increase in PV-VN1 response and nonstatistically significant trends toward increased Hib and diphtheria antibody responses were consistent with observations from earlier studies, indicating immune benefits of nucleotide supplementation of infant formula.