Effect of lipid-based nutrient supplements on micronutrient status and hemoglobin among children with stunting: secondary analysis of a randomized controlled trial in Uganda.

BACKGROUND: Micronutrient deficiencies and anemia are widespread among children with stunting. OBJECTIVES: We assessed the effects of lipid-based nutrient supplements (LNS) containing milk protein (MP) and/or whey permeate (WP) on micronutrient status and hemoglobin (Hb) among children with stunting. METHODS: This was a secondary analysis of a randomized controlled trial. Children aged 12-59 mo with stunting were randomly assigned to LNS (100 g/d) with milk or soy protein and WP or maltodextrin for 12 wk, or no supplement. Hb, serum ferritin (S-FE), serum soluble transferrin receptor (S-TfR), plasma cobalamin (P-Cob), plasma methylmalonic acid (P-MMA), plasma folate (P-Fol), and serum retinol-binding protein (S-RBP) were measured at inclusion and at 12 wk. Data were analyzed using linear and logistic mixed-effects models. RESULTS: Among 750 children, with mean age ± SD of 32 ± 11.7 mo, 45% (n = 338) were female and 98% (n = 736) completed follow-up. LNS, compared with no supplementation, resulted in 43% [95% confidence interval (CI): 28, 60] greater increase in S-FE corrected for inflammation (S-FEci), 2.4 (95% CI: 1.2, 3.5) mg/L greater decline in S-TfR, 138 (95% CI: 111, 164) pmol/L greater increase in P-Cob, 33% (95% CI: 27, 39) reduction in P-MMA, and 8.5 (95% CI: 6.6, 10.3) nmol/L greater increase in P-Fol. There was no effect of LNS on S-RBP. Lactation modified the effect of LNS on markers of cobalamin status, reflecting improved status among nonbreastfed and no effects among breastfed children. LNS increased Hb by 3.8 (95% CI: 1.7, 6.0) g/L and reduced the odds of anemia by 55% (odds ratio: 0.45, 95% CI: 0.29, 0.70). MP compared with soy protein increased S-FEci by 14% (95% CI: 3, 26). CONCLUSIONS: LNS supplementation increases Hb and improves iron, cobalamin, and folate status, but not vitamin A status among children with stunting. LNS should be considered for children with stunting. This trial was registered at ISRCTN as 13093195.

Nutritional treatment of children 6-59 months with severely low weight-for-age z-score: a study protocol for a 3-arm randomized controlled trial.

BACKGROUND: Admission criteria that treat children with low mid-upper-arm circumference (MUAC), and low weight-for-height z-score (WHZ) are not aligned with the evidence on which children are at risk of mortality. An analysis of community-based cohort data from Senegal found that a combination of weight-for-age (WAZ) and MUAC criteria identified all children at risk of near-term death associated with severe anthropometric deficits. This study will address whether children with WAZ <-3 but MUAC ≥125 mm benefit from therapeutic feeding with ready-to-use therapeutic foods (RUTF) and whether a simplified protocol is non-inferior to the weight-based standard protocol. METHODS: This is a prospective individually randomized controlled 3-arm trial conducted in the Nara health district in Mali. Children aged 6-59 months presenting with MUAC ≥125 mm and WAZ <-3 will be randomized to (1) control group receiving no treatment, (2) simplified treatment receiving 1 sachet of RUTF daily until WAZ ≥-3 for 2 visits, (3) standard treatment receiving RUTF according to WHZ category: (a) WHZ <-3 receive 200 kcal/kg/day until WHZ ≥-2 for 2 visits, (b) WHZ ≥-3 but <-2 receive 1 sachet daily until WHZ ≥-2 for 2 visits or (c) WHZ ≥-2 receive no treatment. All children will be followed up first fortnightly for 12 weeks and then monthly until 6 months post-enrolment. The primary endpoint will be measured at 2 months with the primary outcome being WAZ as a continuous measure. Other outcomes include other anthropometric measurements and a secondary endpoint will be observed at 6 months. A total of 1397 children will be recruited including 209 in the control and 594 in both the simplified and standard arms. The sample size should enable us to conclude on the superiority of the simplified treatment compared to no treatment and on the non-inferiority of the simplified treatment versus standard treatment with a margin of non-inferiority of 0.2 WAZ. DISCUSSION: This trial aims to generate new evidence on the benefit of treating children with WAZ <-3 but MUAC ≥125 mm in order to guide the choice of admission criteria to malnutrition treatment and build evidence on the most efficient treatment protocol. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov: NCT05248516 on February 21, 2022.

Bovine colostrum to supplement the first feeding of very preterm infants: The PreColos randomized controlled trial.

BACKGROUND & AIMS: Gut immaturity leads to feeding difficulties in very preterm infants (<32 weeks gestation at birth). Maternal milk (MM) is the optimal diet but often absent or insufficient. We hypothesized that bovine colostrum (BC), rich in protein and bioactive components, improves enteral feeding progression, relative to preterm formula (PF), when supplemented to MM. Aim of the study is to determine whether BC supplementation to MM during the first 14 days of life shortens the time to full enteral feeding (120 mL/kg/d, TFF120). METHODS: This was a multicenter, randomized, controlled trial at seven hospitals in South China without access to human donor milk and with slow feeding progression. Infants were randomly assigned to receive BC or PF when MM was insufficient. Volume of BC was restricted by recommended protein intake (4-4.5 g/kg/d). Primary outcome was TFF120. Feeding intolerance, growth, morbidities and blood parameters were recorded to assess safety. RESULTS: A total of 350 infants were recruited. BC supplementation had no effect on TFF120 in intention-to-treat analysis [n (BC) = 171, n (PF) = 179; adjusted hazard ratio, aHR: 0.82 (95% CI: 0.64, 1.06); P = 0.13]. Body growth and morbidities did not differ, but more cases of periventricular leukomalacia were detected in the infants fed BC (5/155 vs. 0/181, P = 0.06). Blood chemistry and hematology data were similar between the intervention groups. CONCLUSIONS: BC supplementation during the first two weeks of life did not reduce TFF120 and had only marginal effects on clinical variables. Clinical effects of BC supplementation on very preterm infants in the first weeks of life may depend on feeding regimen and remaining milk diet. TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov: NCT03085277.

Effect of Milk Protein and Whey Permeate in Large-Quantity Lipid-Based Nutrient Supplement on Early Child Development among Children with Stunting: A Randomized 2 × 2 Factorial Trial in Uganda.

Stunting affects 22% children globally, putting them at risk of adverse outcomes including delayed development. We investigated the effect of milk protein (MP) vs. soy and whey permeate (WP) vs. maltodextrin in large-quantity, lipid-based nutrient supplement (LNS), and LNS itself vs. no supplementation, on child development and head circumference among stunted children aged 1-5 years. We conducted a randomized, double-blind, community-based 2 × 2 factorial trial in Uganda (ISRCTN1309319). We randomized 600 children to one of four LNS formulations (~535 kcal/d), with or without MP (n = 299 vs. n = 301) or WP (n = 301 vs. n = 299), for 12 weeks or to no supplementation (n = 150). Child development was assessed using the Malawi Development Assessment Tool. Data were analyzed using linear mixed-effects models. Children had a median [interquartile range] age of 30 [23; 41] months and mean ± standard deviation height-for-age z-score of -3.02 ± 0.74. There were no interactions between MP and WP for any of the outcomes. There was no effect of either MP or WP on any developmental domain. Although LNS itself had no impact on development, it resulted in 0.07 (95%CI: 0.004; 0.14) cm higher head circumference. Neither dairy in LNS, nor LNS in itself, had an effect on development among already stunted children.

Post-Recovery Relapse of Children Treated with a Simplified, Combined Nutrition Treatment Protocol in Mali: A Prospective Cohort Study.

The present study aimed to determine the 6-month incidence of relapse and associated factors among children who recovered from acute malnutrition (AM) following mid-upper arm circumference (MUAC)-based simplified combined treatment using the ComPAS protocol. A prospective cohort of 420 children who had reached a MUAC ≥ 125 mm for two consecutive measures was monitored between December 2020 and October 2021. Children were seen at home fortnightly for 6 months. The overall 6-month cumulative incidence of relapse [95%CI] into MUAC < 125 mm and/or edema was 26.1% [21.7; 30.8] and 1.7% [0.6; 3.6] to MUAC < 115 mm and/or edema. Relapse was similar among children initially admitted to treatment with a MUAC < 115 mm and/or oedema and among those with a MUAC ≥ 115 mm but <125 mm. Relapse was predicted by lower anthropometry both at admission to and discharge from treatment, and a higher number of illness episodes per month of follow-up. Having a vaccination card, using an improved water source, having agriculture as the main source of income, and increases in caregiver workload during follow-up all protected from relapse. Children discharged as recovered from AM remain at risk of relapsing into AM. To achieve reduction in relapse, recovery criteria may need to be revised and post-discharge strategies tested.

Effects of Mindful Eating and YogaDance among Overweight and Obese Women: An Exploratory Randomized Controlled Trial.

Many current treatment options for managing overweight and obesity consist of rather strict diet and exercise regimes that are difficult to implement as a lifelong routine. Therefore, alternative initiatives such as mindful eating and pleasure-oriented physical activity with more focus on implementation and enjoyment are needed to reverse the obesity epidemic. Mindful eating is an approach focusing on inner hunger and satiety signals. YogaDance is a novel exercise approach combining elements of yoga and dance. This study was a randomized controlled trial investigating the individual and combined effects of mindful eating and YogaDance. Participants were healthy, inactive women with overweight or obesity (body mass index ≥ 25 kg/m2 and/or waist circumference ≥ 80 cm) who were randomized to one of four groups for 8 weeks: mindful eating alone, YogaDance alone, the combination of mindful eating and YogaDance, or control. Fat mass was the primary outcome and secondary outcomes included body weight, waist circumference, and other physiological, behavioral, and quality-of-life outcomes. Sixty-one women were included in the study and randomized to mindful eating and YogaDance combined, YogaDance, mindful eating, or control. Fat mass was reduced by 1.3 kg (95% CI [-10.0, 7.3] kg; p = 0.77), 3.0 kg (95% CI [-11.1, 5.1] kg; p = 0.48), and 1.8 kg (95% CI [-10.1, 6.6] kg; p = 0.69) for the mindful eating, YogaDance, and combined mindful eating and YogaDance interventions, respectively, compared to the control, with corresponding effect sizes of 0.15, 0.34, and 0.21. In complete-case analyses, fat percent and waist circumference were reduced whereas mental quality of life and eating behavior were improved for mindful eating and mindful eating and YogaDance combined compared to the control. In conclusion, the study found modest benefits of an 8-week combination of mindful eating and YogaDance, corroborating findings in previous studies on mindful eating, yoga, and dance. However, the study had several limitations that should be taken into consideration, including low power due to a large drop-out as well as low to moderate training load and compliance. The trial was retrospectively registered (ISRCTN87234794).

Multidimensional individualized nutritional therapy for individuals with severe chronic obstructive pulmonary disease: study protocol for a registry-based randomized controlled trial.

BACKGROUND: Individuals with severe chronic obstructive pulmonary disease (COPD) are often at risk of undernutrition with low health-related quality of life (HRQoL). Undernutrition can worsen COPD and other comorbidities, be an independent predictor of morbidity and functional decline resulting in increased healthcare consumption and increased risk of death. Especially exacerbations and acute infections result in unintentional weight loss. The aim is to investigate the effect of an individualized nutritional intervention among individuals with severe COPD. METHODS: An open-label randomized controlled trial with two parallel groups. Participants are recruited from the pulmonary outpatient clinic at the Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital, North Zealand, Denmark, and randomly allocated to either the intervention (intervention + standard of care) or control group (standard of care). The intervention has a duration of 3 months and combines individual nutritional care with adherence support and practical tools. It contains 4 elements including an individual nutritional plan, regular contacts, adherence support, and weight diary. The primary outcome is a difference in HRQoL (EQ-5D-5L) between the intervention and control group 3 months after baseline. Difference in functional capacity (grip strength, 30-s stand chair test, and physical activity), disease-specific quality of life (COPD Assessment Test), anxiety and depression (Hospital Anxiety and Depression Scale), nutritional parameters (energy and protein intake), anthropometry (weight, body mass index, waist, hip, and upper arm circumference), body composition (total fat-free and fat mass and indices), and prognosis (exacerbations, oxygen therapy, hospital contacts, and mortality) 3 months after baseline will be included as secondary outcomes. Data will be collected through home visits at baseline and 1 and 3 months after baseline. DISCUSSION: Currently, nutritional care is a neglected area of outpatient care among individuals with severe COPD. If this patient-centered approach can demonstrate a positive impact on HRQoL, mortality, and hospital contacts, it should be recommended as part of end-of-life care for individuals with severe COPD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04873856 . Registered on May 3, 2021.

Serum cobalamin in children with moderate acute malnutrition in Burkina Faso: Secondary analysis of a randomized trial.

BACKGROUND: Among children with moderate acute malnutrition (MAM) the level of serum cobalamin (SC) and effect of food supplements are unknown. We aimed to assess prevalence and correlates of low SC in children with MAM, associations with hemoglobin and development, and effects of food supplements on SC. METHODS AND FINDINGS: A randomized 2 × 2 × 3 factorial trial was conducted in Burkina Faso. Children aged 6 to 23 months with MAM received 500 kcal/d as lipid-based nutrient supplement (LNS) or corn-soy blend (CSB), containing dehulled soy (DS) or soy isolate (SI) and 0%, 20%, or 50% of total protein from milk for 3 months. Randomization resulted in baseline equivalence between intervention groups. Data on hemoglobin and development were available at baseline. SC was available at baseline and after 3 and 6 months. SC was available from 1,192 (74.1%) of 1,609 children at baseline. The mean (±SD) age was 12.6 (±5.0) months, and 54% were females. Low mid-upper arm circumference (MUAC; <125 mm) was found in 80.4% (958) of the children and low weight-for-length z-score (WLZ; <-2) in 70.6% (841). Stunting was seen in 38.2% (456). Only 5.9% were not breastfed. Median (IQR) SC was 188 (137; 259) pmol/L. Two-thirds had SC ≤222 pmol/L, which was associated with lower hemoglobin. After age and sex adjustments, very low SC (<112 pmol/L) was associated with 0.21 (95% CI: 0.01; 0.41, p = 0.04) and 0.24 (95% CI: 0.06; 0.42, p = 0.01) z-score lower fine and gross motor development, respectively. SC data were available from 1,330 (85.9%) of 1,548 children followed up after 3 months and 398 (26.5%) of the 1,503 children after 6 months. Based on tobit regression, accounting for left censored data, and adjustments for correlates of missing data, the mean (95% CI) increments in SC from baseline to the 3- and 6-month follow-up were 72 (65; 79, p < 0.001) and 26 (16; 37, p < 0.001) pmol/L, respectively. The changes were similar among the 310 children with SC data at all 3 time points. Yet, the increase was 39 (20; 57, p < 0.001) pmol/L larger in children given LNS compared to CSB if based on SI (interaction, p < 0.001). No effect of milk was found. Four children died, and no child developed an allergic reaction to supplements. The main limitation of this study was that only SC was available as a marker of status and was missing from a quarter of the children. CONCLUSIONS: Low SC is prevalent among children with MAM and may contribute to impaired erythropoiesis and child development. The SC increase during supplementation was inadequate. The bioavailability and adequacy of cobalamin in food supplements should be reconsidered. TRIAL REGISTRATION: ISRCTN Registry ISRCTN42569496.

Vitamin D biomarkers for Dietary Reference Intake development in children: a systematic review and meta-analysis.

BACKGROUND: Circulating 25-hydroxyvitamin D [25(OH)D] has been the accepted vitamin D exposure/intake biomarker of choice within recent DRI exercises, but use of other vitamin D-related biomarkers as well as functional markers has been suggested. These may be of value in future vitamin D DRI exercises, such as the FAO/WHO's one for young children. OBJECTIVES: To systematically review the usefulness of circulating 25(OH)D, parathyroid hormone (PTH), free and bioavailable 25(OH)D, C3-epimer of 25(OH)D, vitamin D3, 24,25-dihydroxyvitamin D [24,25(OH)2D], and bone turnover markers and calcium absorption as vitamin D biomarkers for DRI development in children. METHODS: Methods included structured searches of published articles, full-text reviews, data extraction, quality assessment, meta-analysis, and random-effects meta-regression. RESULTS: Fifty-nine vitamin D supplementation randomized controlled trials (RCTs) were included (39 in infants/children as the priority group and the remainder in adults since pediatric studies were absent/limited). Vitamin D supplementation significantly raised circulating 25(OH)D in infants and children, but the response was highly heterogeneous [weighted mean difference (WMD): 27.7 nmol/L; 95% CI: 22.9, 32.5; 27 RCTs; I2 = 93%]. Meta-regression suggested an increase by 1.7 nmol/L (95% CI: 0.7, 2.6) in serum 25(OH)D per each 100-IU increment in vitamin D intake (P = 0.0005). Vitamin D supplementation had a significant effect on circulating 24,25(OH)2D (WMD: 3.4 nmol/L; 95% CI: 2.4, 4.5; 13 RCTs; I2 = 95%), with a dose-response relation (+0.15 nmol/L per 100 IU; 95% CI: -0.01, 0.29). With circulating PTH, although there was a significant effect of vitamin D on WMD (P = 0.05), there was no significant dose-response relation (P = 0.32). Pediatric data were too limited in relation to the usefulness of the other biomarkers. CONCLUSIONS: Circulating 25(OH)D may be a useful biomarker of vitamin D exposure/intake for DRI development in infants and children. Circulating 24,25(OH)2D also showed some promise, but further data are needed, especially in infants and children.

Individual participant data (IPD)-level meta-analysis of randomised controlled trials to estimate the vitamin D dietary requirements in dark-skinned individuals resident at high latitude.

CONTEXT AND PURPOSE: There is an urgent need to develop vitamin D dietary recommendations for dark-skinned populations resident at high latitude. Using data from randomised controlled trials (RCTs) with vitamin D3-supplements/fortified foods, we undertook an individual participant data-level meta-regression (IPD) analysis of the response of wintertime serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among dark-skinned children and adults residing at ≥ 40° N and derived dietary requirement values for vitamin D. METHODS: IPD analysis using data from 677 dark-skinned participants (of Black or South Asian descent; ages 5-86 years) in 10 RCTs with vitamin D supplements/fortified foods identified via a systematic review and predefined eligibility criteria. Outcome measures were vitamin D intake estimates across a range of 25(OH)D thresholds. RESULTS: To maintain serum 25(OH)D concentrations ≥ 25 and 30 nmol/L in 97.5% of individuals, 23.9 and 27.3 µg/day of vitamin D, respectively, were required among South Asian and 24.1 and 33.2 µg/day, respectively, among Black participants. Overall, our age-stratified intake estimates did not exceed age-specific Tolerable Upper Intake Levels for vitamin D. The vitamin D intake required by dark-skinned individuals to maintain 97.5% of winter 25(OH)D concentrations ≥ 50 nmol/L was 66.8 µg/day. This intake predicted that the upper 2.5% of individuals could potentially achieve serum 25(OH)D concentrations ≥ 158 nmol/L, which has been linked to potential adverse effects in older adults in supplementation studies. CONCLUSIONS: Our IPD-derived vitamin D intakes required to maintain 97.5% of winter 25(OH)D concentrations ≥ 25, 30 and 50 nmol/L are substantially higher than the equivalent estimates for White individuals. These requirement estimates are also higher than those currently recommended internationally by several agencies, which are based predominantly on data from Whites and derived from standard meta-regression based on aggregate data. Much more work is needed in dark-skinned populations both in the dose-response relationship and risk characterisation for health outcomes. TRAIL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews (Registration Number: CRD42018097260).

A protein-supplemented very-low-calorie diet does not mitigate reductions in lean mass and resting metabolic rate in subjects with overweight or obesity: A randomized controlled trial.

BACKGROUND & AIMS: The European Food Safety Authority recently recommended an increase in the protein content of total diet replacement (TDR) products from 50 to 75 g/day. The rationale was to minimize reductions in lean mass (LM) and resting metabolic rate (RMR) that occur with weight loss, and thereby facilitate maintenance of lost weight. We sought to directly compare the efficacy of TDR regimens with the new vs the current protein requirement. METHODS: We randomized 108 adults with overweight or obesity (body mass index 28-40 kg/m2) to very-low-calorie diets (VLCD) with either 52 or 77 g/day protein for 8 weeks (total energy intake of 600 or 700 kcal/day, respectively). LM was determined by dual energy X-ray absorptiometry and RMR by indirect calorimetry. RESULTS: Attrition rate was 22% in both groups. Both VLCDs decreased body weight, fat mass, LM, and RMR (all P < 0.05). Significant time-by-group interactions were detected for weight and fat mass (both P < 0.05), with corresponding reductions being smaller in the higher-protein than the standard-protein VLCD, likely because of the added calories. On the other hand, reductions in LM (6% from baseline) and RMR (9-10% from baseline) did not differ between groups (P = 0.155 and P = 0.389, respectively), and the contribution of LM to total weight loss was identical (27 ± 2% of lost weight, P = 0.973). CONCLUSIONS: Our results indicate that the proposed increase in the protein content of TDR products does not attenuate reductions in LM and RMR in individuals with overweight and obesity who are treated with <800 kcal/day VLCDs for 2 months. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov # NCT04156165.

The effect of milk and rapeseed protein on growth factors in 7-8 year-old healthy children - A randomized controlled trial.

OBJECTIVE: Milk protein may stimulate linear growth through insulin-like growth factor-1 (IGF-1). However, the effect of plant proteins on growth factors is largely unknown. This study assesses the effect of combinations of milk and rapeseed protein versus milk protein alone on growth factors in children. DESIGN: An exploratory 3-armed randomized, double-blind, controlled trial was conducted in 129 healthy 7-8 year-old Danish children. Children received 35 g milk and rapeseed protein (ratio 54:46 or 30:70) or 35 g milk protein per day for 4 weeks. The primary outcome was difference in IGF-1 changes between intervention groups after 4 weeks. Secondary outcomes included changes in IGF-1 after 1 week and changes in insulin-like growth factor binding protein-3 (IGFBP-3), IGF-1/IGFBP-3, insulin, height, weight and body composition after 1 and 4 weeks. Results were analysed by multiple linear mixed-effect models. RESULTS: There were no differences in changes of plasma IGF-1, insulin-like growth factor binding protein-3 (IGFBP-3), IGF-1/IGFBP-3 ratio or insulin between groups after 1 or 4 weeks based on 89 complete cases (P > 0.10). IGF-1 increased by 13.7 (95% CI 9.7;17.7) ng/mL and 18.0 (14.0;22.0) ng/mL from baseline to week 1 and 4, respectively, a 16% increase during the intervention. Similarly, insulin increased by 31% (14; 50) and 33% (16; 53) from baseline to week 1 and 4. Fat-free mass index (FFMI) increments were higher with milk alone than rapeseed blends (P < 0.05), coinciding with a trend towards a lower height increment. Body mass index increased within all groups (P < 0.05), mainly due to an increase in FFMI (P < 0.01). CONCLUSION: There were no differences in changes of growth factors between the combinations of milk and rapeseed protein and milk protein alone in healthy, well-nourished children with a habitual intake of milk. Within groups, growth factors increased considerably. Future studies are needed to investigate how intakes of plant and animal proteins affect childhood growth.

The Role of Milk Protein and Whey Permeate in Lipid-based Nutrient Supplements on the Growth and Development of Stunted Children in Uganda: A Randomized Trial Protocol (MAGNUS).

Stunting is associated with cognitive impairment and later chronic disease. Previous trials to prevent stunting have had little effect, and no trials seem to have provided larger amounts of energy and high-quality proteins to already stunted children. We aimed to assess the effects of milk protein (MP) and whey permeate (WP) in large-quantity lipid-based nutrient supplements (LNS-LQ), among stunted children, on linear growth and child development. This was a randomized, double-blind, 2-by-2 factorial trial. Stunted children aged 12-59 mo from eastern Uganda (n = 750) were randomly assigned to receive 100 g LNS-LQ with or without MP and WP (n = 4 × 150) or no supplement (n = 150) for 3 mo. The primary outcomes were change in knee-heel and total length. Secondary outcomes included child development, body composition, anthropometry, and hemoglobin. Micronutrient status, intestinal function, and microbiota were also assessed. Our findings will contribute to an understanding of the role of milk ingredients and LNS in linear catch-up growth. This trial was registered at www.isrctn.com as ISRCTN13093195.

Individual participant data (IPD)-level meta-analysis of randomised controlled trials with vitamin D-fortified foods to estimate Dietary Reference Values for vitamin D.

CONTEXT AND PURPOSE: Individual participant data-level meta-regression (IPD) analysis is superior to meta-regression based on aggregate data in determining Dietary Reference Values (DRV) for vitamin D. Using data from randomized controlled trials (RCTs) with vitamin D3-fortified foods, we undertook an IPD analysis of the response of winter serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among children and adults and derived DRV for vitamin D. METHODS: IPD analysis using data from 1429 participants (ages 2-89 years) in 11 RCTs with vitamin D-fortified foods identified via a systematic review and predefined eligibility criteria. Outcome measures were vitamin D DRV estimates across a range of serum 25(OH)D thresholds using unadjusted and adjusted models. RESULTS: Our IPD-derived estimates of vitamin D intakes required to maintain 97.5% of winter 25(OH)D concentrations ≥ 25 and ≥ 30 nmol/L are 6 and 12 µg/day, respectively (unadjusted model). The intake estimates to maintain 90%, 95% and 97.5% of concentrations ≥ 50 nmol/L are 33.4, 57.5 and 92.3 µg/day, respectively (unadjusted) and 17.0, 28.1 and 43.6 µg/day, respectively (adjusted for mean values for baseline serum 25(OH)D, age and BMI). CONCLUSIONS: IPD-derived vitamin D intakes required to maintain 90%, 95% and 97.5% of winter 25(OH)D concentrations ≥ 50 nmol/L are much higher than those derived from standard meta-regression based on aggregate data, due to the inability of the latter to capture between person-variability. Our IPD provides further evidence that using food-based approaches to achieve an intake of 12 µg/day could prevent vitamin D deficiency (i.e., serum 25(OH)D < 30 nmol/L) in the general population.

Utility of bio-electrical impedance vector analysis for monitoring treatment of severe acute malnutrition in children.

BACKGROUND & AIMS: Change in hydration is common in children with severe acute malnutrition (SAM) including during treatment, but is difficult to assess. We investigated the utility of bio-electrical impedance vector analysis (BIVA), a quick non-invasive method, for indexing hydration during treatment. METHODS: We studied 350 children 0·5-14 years of age with SAM (mid-upper arm circumference <11·0 cm or weight-for-height <70% of median, and/or nutritional oedema) admitted to a hospital nutrition unit, but excluded medically unstable patients. Weight, height (H), resistance (R), reactance (Xc) and phase angle (PA) were measured and oedema assessed. Similar data were collected from 120 healthy infants and preschool/school children for comparison. Means of height-adjusted vectors (R/H, Xc/H) from SAM children were interpreted using tolerance and confidence ellipses of corresponding parameters from the healthy children. RESULTS: SAM children with oedema were less wasted than those without (p < 0·001), but had BIVA parameters that differed more from those of healthy children (P < 0·05) than those non-oedematous. Initially, both oedematous and non-oedematous SAM children had mean vectors outside the reference 95% tolerance ellipse. During treatment, mean vectors migrated differently in the two SAM groups, indicating fluid loss in oedematous patients, and tissue accretion in non-oedematous patients. At admission, R/H was lower (oedematous) or higher (non-oedematous) among children who died than those who exited the hospital alive. CONCLUSIONS: BIVA can be used in children with SAM to distinguish tissue-vs. hydration-related weight changes during treatment, and also identify children at high risk of death enabling early clinical interventions.

Impact of food supplements on early child development in children with moderate acute malnutrition: A randomised 2 x 2 x 3 factorial trial in Burkina Faso.

BACKGROUND: Lipid-based nutrient supplements (LNS) and corn-soy blends (CSBs) with varying soy and milk content are used in treatment of moderate acute malnutrition (MAM). We assessed the impact of these supplements on child development. METHODS AND FINDINGS: We conducted a randomised 2 × 2 × 3 factorial trial to assess the effectiveness of 12 weeks' supplementation with LNS or CSB, with either soy isolate or dehulled soy, and either 0%, 20%, or 50% of protein from milk, on child development among 6-23-month-old children with MAM. Recruitment took place at 5 health centres in Province du Passoré, Burkina Faso between September 2013 and August 2014. The study was fully blinded with respect to soy quality and milk content, while study participants were not blinded with respect to matrix. This analysis presents secondary trial outcomes: Gross motor, fine motor, and language development were assessed using the Malawi Development Assessment Tool (MDAT). Of 1,609 children enrolled, 54.7% were girls, and median age was 11.3 months (interquartile range [IQR] 8.2-16.0). Twelve weeks follow-up was completed by 1,548 (96.2%), and 24 weeks follow-up was completed by 1,503 (93.4%); follow-up was similar between randomised groups. During the study, 4 children died, and 102 children developed severe acute malnutrition (SAM). There was no difference in adverse events between randomised groups. At 12 weeks, the mean MDAT z-scores in the whole cohort had increased by 0.33 (95% CI: 0.28, 0.37), p < 0.001 for gross motor; 0.26 (0.20, 0.31), p < 0.001 for fine motor; and 0.14 (0.09, 0.20), p < 0.001 for language development. Children had larger improvement in language z-scores if receiving supplements with milk (20%: 0.09 [-0.01, 0.19], p = 0.08 and 50%: 0.11 [0.01, 0.21], p = 0.02), although the difference only reached statistical significance for 50% milk. Post hoc analyses suggested that this effect was specific to boys (interaction p = 0.02). The fine motor z-scores were also improved in children receiving milk, but only when 20% milk was added to CSB (0.18 [0.03, 0.33], p = 0.02). Soy isolate over dehulled soy increased language z-scores by 0.07 (-0.01, 0.15), p = 0.10, although not statistically significant. Post hoc analyses suggested that LNS benefited gross motor development among boys more than did CSB (interaction p = 0.04). Differences between supplement groups did not persist at 24 weeks, but MDAT z-scores continued to increase post-supplementation. The lack of an unsupplemented control group limits us from determining the overall effects of nutritional supplementation for children with MAM. CONCLUSIONS: In this study, we found that child development improved during and after supplementation for treatment of MAM. Milk protein was beneficial for language and fine motor development, while suggested benefits related to soy quality and supplement matrix merit further investigation. Supplement-specific effects were not found post-intervention, but z-scores continued to improve, suggesting a sustained overall effect of supplementation. TRIAL REGISTRATION: ISRCTN42569496.

Potato Fibers Have Positive Effects on Subjective Appetite Sensations in Healthy Men, but Not on Fecal Fat Excretion: A Randomized Controlled Single-Blind Crossover Trial.

Dietary fibers can affect appetite and gut metabolism, but the effect of the novel potato fibers FiberBind and rhamnogalacturonan I (RG-I) is unknown. We, therefore, aimed to investigate the effect of daily intake of FiberBind and RG-I on appetite sensations and fecal fat excretion. In a single-blinded, randomized, three-way crossover trial, wheat buns with FiberBind, RG-I, or low fiber (control) were consumed by 18 healthy men during a 21-day period. Appetite sensation and blood samples during a 3 h meal test, fecal fat content, and ad libitum energy intake were assessed after each period. Compared to RG-I and control, FiberBind caused a higher composite satiety score (6% ± 2% and 5% ± 2%), lower prospective food consumption (5% ± 2% and 6% ± 2%), and lower desire to eat (7% ± 3% and 6% ± 3%) (all p < 0.05). FiberBind also caused higher satiety (6% ± 2%) and fullness (9% ± 3%) compared to RG-I (all p < 0.01). No effects on fecal fat excretion or energy intake were found. The RG-I fiber caused higher postprandial glucose concentration compared to FiberBind (p < 0.05) and higher insulin concentration at 180 min compared to control (p < 0.05). Compared to the control, RG-I and FiberBind lowered peak insulin concentration (both p < 0.05) and delayed time to peak for glucose (both p < 0.05). In conclusion, FiberBind intake could be beneficial for appetite regulation, but neither FiberBind nor RG-I affected fecal fat excretion or energy intake.

Association between admission criteria and body composition among young children with moderate acute malnutrition, a cross-sectional study from Burkina Faso.

Children with moderate acute malnutrition (MAM) are treated based on low weight-for-length z-score (WLZ), low mid-upper arm circumference (MUAC) or both. This study aimed to assess associations of admission criteria and body composition (BC), to improve treatment of MAM. We undertook a cross-sectional study among 6-23 months old Burkinabe children with MAM. Fat-free (FFM) and fat mass (FM) were determined by deuterium dilution and expressed as FFM (FFMI) and FM index (FMI). Of 1,489 children, 439 (29.5%) were recruited by low MUAC only (MUAC-O), 734 (49.3%) by low WLZ and low MUAC (WLZ-MUAC) and 316 (21.2%) by low WLZ only (WLZ-O). Thus, 1,173 (78.8%) were recruited by low MUAC, with or without low WLZ (ALL-MUAC). After adjustments, WLZ-O had 89 g (95% confidence interval (CI) 5; 172) lower FFM compared to MUAC-O. Similarly, WLZ-O had 0.89 kg/m2 (95% CI 0.77; 1.01) lower FFMI compared to MUAC-O, whereas there was no difference for FMI. However, boys included by WLZ-O compared to MUAC-O had 0.21 kg/m2 (95% CI 0.05; 0.38) higher FMI. In contrast, girls included by WLZ-O had 0.17 (95% CI 0.01; 0.33) kg/m2 lower FMI compared to MUAC-O (interaction, p = 0.002). We found that different criteria for admission into MAM treatment programmes select children with differences in BC, especially FFMI.Trial registration: ISRCTN42569496.

Vitamin A and iron status of children before and after treatment of uncomplicated severe acute malnutrition.

BACKGROUND & AIMS: Treatment of children with uncomplicated severe acute malnutrition (SAM) is based on ready-to-use therapeutic foods (RUTF) and aims for quick regain of lost body tissues while providing sufficient micronutrients to restore diminished body stores. Little evidence exists on the success of the treatment to establish normal micronutrient status. We aimed to assess the changes in vitamin A and iron status of children treated for SAM with RUTF, and explore the effect of a reduced RUTF dose. METHODS: We collected blood samples from children 6-59 months old with SAM included in a randomised trial at admission to and discharge from treatment and analysed haemoglobin (Hb) and serum concentrations of retinol binding protein (RBP), ferritin (SF), soluble transferrin receptor (sTfR), C-reactive protein (CRP) and α1-acid glycoprotein (AGP). SF, sTfR and RBP were adjusted for inflammation (CRP and AGP) prior to analysis using internal regression coefficients. Vitamin A deficiency (VAD) was defined as RBP < 0.7 µmol/l, anaemia as Hb < 110 g/l, storage iron deficiency (sID) as SF < 12 µg/l, tissue iron deficiency (tID) as sTfR > 8.3 mg/l and iron deficiency anaemia (IDA) as both anaemia and sID. Linear and logistic mixed models were fitted including research team and study site as random effects and adjusting for sex, age and outcome at admission. RESULTS: Children included in the study (n = 801) were on average 13 months of age at admission to treatment and the median treatment duration was 56 days [IQR: 35; 91] in both arms. Vitamin A and iron status markers did not differ between trial arms at admission or at discharge. Only Hb was 1.7 g/l lower (95% CI -0.3, 3.7; p = 0.088) in the reduced dose arm compared to the standard dose, at recovery. Mean concentrations of all biomarkers improved from admission to discharge: Hb increased by 12% or 11.6 g/l (95% CI 10.2, 13.0), RBP increased by 13% or 0.12 µmol/l (95% CI 0.09, 0.15), SF increased by 36% or 4.4 µg/l (95% CI 3.1, 5.7) and sTfR decreased by 16% or 1.5 mg/l (95% CI 1.0, 1.9). However, at discharge, micronutrient deficiencies were still common, as 9% had VAD, 55% had anaemia, 35% had sID, 41% had tID and 21% had IDA. CONCLUSION: Reduced dose of RUTF did not result in poorer vitamin A and iron status of children. Only haemoglobin seemed slightly lower at recovery among children treated with the reduced dose. While improvement was observed, the vitamin A and iron status remained sub-optimal among children treated successfully for SAM with RUTF. There is a need to reconsider RUTF fortification levels or test other potential strategies in order to fully restore the micronutrient status of children treated for SAM.