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Background: Development of body composition (BC) may be disrupted in children with stunting. Such disruption may affect the later risk of excess adiposity and metabolic health, yet few studies have investigated correlates of BC in children with stunting., Objectives: We aimed to investigate nutritional status, infection and inflammation, breastfeeding behaviors, and other factors as correlates of BC in children with stunting., Methods: Among Ugandan children with a height-for-age z-score <-2, BC was estimated using bioelectrical impedance analysis and compared with United Kingdom references. We used multiple linear regression analysis to identify correlates of fat mass (FM), fat-free mass (FFM), FM-index (FMI), and FFM index (FFMI) and height, adjusting for gender and age., Results: In 750 children aged 1-5 y, FMI was 0.46 (95% confidence interval [CI]: 0.38, 0.54] and FFMI 0.18 [95% CI: 0.11, 0.26) z-scores lower than United Kingdom references. Elevated serum α 1 -acid glycoprotein was associated with 1.14 [0.76, 1.52] cm lower height, 0.50 [0.35, 0.65] kg/m 2 less FFMI, and 0.48 [0.31, 0.66] kg/m 2 greater FMI. Similar, weaker, associations for elevated serum C-reactive protein were detected. A positive malaria rapid test was associated with 0.64 [0.25, 1.02] cm shorter height, but 0.36 [0.18, 0.54] kg/m 2 greater FMI. Anemia (according to hemoglobin) was associated with 0.20 [0.07, 0.33] kg less FFM in proportion to shorter height. Longer breastfeeding duration was associated with 0.03 [0.02, 0.04] kg greater FFM per month, in proportion to greater height., Conclusions: These children exhibited deficits in FM and FFM, proportionally to their stunted height, compared with United Kingdom references. Systemic inflammation correlated inversely with linear growth and FFM but positively with fatness, making it a possible target for intervention where fat-free tissue accretion is desirable. Longer breastfeeding may offer protection to lean linear growth, but findings for micronutrients were less clear. Longitudinal studies are warranted to support these findings. The study was registered at www.isrctn.com (Ref. ISRCTN13093195)., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Millions of children under 5 years in low- and middle-income countries fail to attain their development potential with accruing short- and long-term consequences. Low length/height for age (stunting) is known to be a key factor, but there is little data on how child characteristics are linked with developmental changes among children with stunting. We assessed the socioeconomic, household, anthropometric, and clinical predictors of change in early child development (ECD) among 1-5-year-old children with stunting. This was a prospective cohort study nested in a randomized trial testing effects of lipid-based nutrient supplementation among children with stunting in Uganda. Development was assessed using the Malawi Development Assessment Tool (MDAT). Multiple linear regression analysis was used to assess for predictors of change. We included 750 children with mean ±SD age of 30.2 ±11.7 months 45% of whom were female. After 12 weeks, total MDAT z-score increased by 0.40 (95%CI: 0.32; 0.48). Moderate vs severe stunting, higher fat-free mass, negative malaria test and no inflammation (serum α-1-acid glycoprotein <1 g/l) at baseline predicted greater increase in ECD scores. Older age and fat mass gain predicted a lesser increase in ECD. Our findings reinforce the link between stunting and development with more severely stunted children having a lesser increase in ECD scores over time. Younger age, freedom from malaria and inflammation, and higher fat-free mass at baseline, as well as less gain of fat mass during follow-up predicted a higher increase in developmental scores in this study. Thus, supporting fat-free mass accretion, focusing on younger children, and infection prevention may improve development among children with stunting., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: HF has received research grants from Arla Food for Health, HF and BG have received research grants from the Danish Dairy Research Foundation, and finally HF, BG, SF and AB have had research collaboration with Nutriset, the producer of LNS. Other authors declare no financial relationships with any organisations that might have an interest in the submitted work in the previous five years and declare no other relationships or activities that could appear to have influenced the submitted work., (Copyright: © 2024 Mbabazi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Many children in low- and middle-income countries are not attaining their developmental potential. Stunting is associated with poor child development, but it is not known which correlates of stunting are impairing child development. We explored potential socioeconomic, nutritional, clinical, and household correlates of early child development among 12-59-month-old children with stunting in a cross-sectional study in Uganda. Development was assessed using the Malawi Development Assessment Tool (MDAT) across four domains of gross and fine motor, language, and social skills. Linear regression analysis was used to assess correlates of development in the four domains and total MDAT score. Of 750 children included, the median [interquartile range] age was 30 [23-41] months, 55% of the children resided in rural settings with 21% from female-headed households and 47% of mothers had no schooling. The mean ± standard deviation height-for-age z-score (HAZ) was -3.02 ± 0.74, 40% of the children had a positive malaria test and 65% were anaemic (haemoglobin < 110 g/L). One-third had children's books at home, majority (96%) used household objects to play with and most of them (70%) used toys as pretence items like those to mimic cooking. After age, sex, and site adjustments, HAZ (0.24, 95% confidence interval [CI]: 0.14-0.33) and head circumference (0.07, 95% CI: 0.02-0.12) were positive correlates of total MDAT score, whereas weight-for-height z-score (WHZ) was not. Current breastfeeding was associated with 0.41 (95% CI: 0.17-0.65) lower total MDAT score. Children from households with a single income earner had 0.22 (95% CI: 0.06-0.37) lower total MDAT score. Furthermore, severe food insecurity, inflammation and positive malaria test were associated with lower scores for motor development. All family care indicator subscales (FCIs) positively correlated with the total MDAT score and this association was independent of household's socioeconomic status. In conclusion, stunting degree, head circumference, number of household income earners and stimulation by improved FCIs correlate with early child development among stunted children. The negative association with prolonged breastfeeding is likely due to reverse causality. Identified correlates may inform initiatives to support children with stunting attain their development potential., (© 2024 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

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., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Environmental enteric dysfunction (EED) is associated with stunting. Citrulline, produced in mature enterocytes, may be a valuable biomarker of small intestinal enterocyte mass in the context of EED., Objectives: We aimed to explore the correlates of plasma citrulline (p-cit) in children with stunting., Methods: In a cross-sectional study using baseline data from the community-based MAGNUS (milk affecting growth, cognition and the gut in child stunting) trial (ISRCTN13093195), we explored potential correlates of p-cit in Ugandan children with stunting aged 12-59 mo. Using linear regression in univariate and multivariate models, we explored associations with socioeconomics, diet, micronutrient status, and water, sanitation, and hygiene characteristics. The influence of covariates age, fasting, and systemic inflammation were also explored., Results: In 750 children, the mean ± standard deviation age was 32.0 ± 11.7 mo, and height-for-age z-score was -3.02 ± 0.74. P-cit, available for 730 children, differed according to time fasted and was 20.7 ± 8.9, 22.3 ± 10.6 and 24.2 ± 13.1 μmol/L if fasted <2, 2-5 and >5 h, respectively. Positive correlates of p-cit were age [0.07; 95% confidence interval (CI): 0.001, 0.15 μmol/L] and log 10 serum insulin-like growth factor-1 (8.88; 95% CI: 5.09, 12.67 μmol/L). With adjustment for systemic inflammation, the association with serum insulin-like growth factor-1 reduced (4.98; 95% CI: 0.94, 9.03 μmol/L). Negative correlates of p-cit included food insecurity, wet season (-3.12; 95% CI: -4.97, -1.26 μmol/L), serum C-reactive protein (-0.15; 95% CI: -0.20, -0.10 μmol/L), serum α 1 -acid glycoprotein (-5.34; 95% CI: -6.98, -3.70 μmol/L) and anemia (-1.95; 95% CI: -3.72, -0.18 μmol/L). Among the negatively correlated water, sanitation, and hygiene characteristics was lack of soap for handwashing (-2.53; 95% CI: -4.82, -0.25 μmol/L). Many associations attenuated with adjustment for inflammation., Conclusions: Many of the correlates of p-cit are characteristic of populations with a high EED prevalence. Systemic inflammation is strongly associated with p-cit and is implicated in EED and stunting. Adjustment for systemic inflammation attenuates many associations, reflecting either confounding, mediation, or both. This study highlights the complex interplay between p-cit and systemic inflammation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In low-income countries, undernutrition and infections play a major role in childhood anemia. Stunted children may be at particular risk of anemia. In a cross-sectional study nested in a nutrition trial among 12-59-month-old stunted children in eastern Uganda, we measured hemoglobin (Hb) and markers of iron, cobalamin, folate and vitamin A status. We assessed low micronutrient status, socio-demography, stunting severity, inflammation and malaria as correlates of Hb and anemia using linear and logistic regression analyses, respectively. Of 750 stunted children, the mean ± SD age was 32.0 ± 11.7 months and 55% (n = 412) were male. The mean Hb was 104 ± 15 g/L and 65% had anemia, Hb < 110 g/L. In a multivariable model with age, sex and inflammation, the following were associated with lower Hb: serum ferritin < 12 µg/L (-5.6 g/L, 95% CI: -8.6; -2.6), transferrin receptors > 8.3 mg/L (-6.2 g/L, 95% CI: -8.4; -4.0), plasma folate <20 nmol/L (-4.6 g/L, 95% CI: -8.1;-1.1), cobalamin < 222 pmol/L (-3.0 g/L, 95% CI: -5.4; -0.7) and serum retinol-binding protein < 0.7 µmol/L (-2.0 g/L, 95% CI: -4.1; 0.2). In addition, severe stunting, inflammation and malaria were negative correlates. Anemia is common among stunted children in eastern Uganda; micronutrient deficiencies, inflammation and malaria are associated with low Hb.

Micronutrient deficiencies and stunting are prevalent. We assessed correlates of iron, cobalamin, folate, and vitamin A biomarkers in a cross-sectional study of stunted children aged 12-59 months in eastern Uganda. The biomarkers measured were serum ferritin (S-FE), soluble transferrin receptor (S-TfR), retinol binding protein (S-RBP), plasma cobalamin (P-Cob), methylmalonic acid (P-MMA), and folate (P-Fol). Using linear regression, we assessed socio-demography, stunting severity, malaria rapid test, and inflammation as correlates of micronutrient biomarkers. Of the 750 children, the mean (SD) age was 32.0 (11.7) months, and 45% were girls. Iron stores were depleted (inflammation-corrected S-FE < 12 µg/L) in 43%, and 62% had tissue iron deficiency (S-TfR > 8.3 mg/L). P-Cob was low (<148 pmol/L) and marginal (148-221 pmol/L) in 3% and 20%, and 16% had high P-MMA (>0.75 µmol/L). Inflammation-corrected S-RBP was low (<0.7 µmol/L) in 21% and P-Fol (<14 nmol/L) in 1%. Age 24-59 months was associated with higher S-FE and P-Fol and lower S-TfR. Breastfeeding beyond infancy was associated with lower iron status and cobalamin status, and malaria was associated with lower cobalamin status and tissue iron deficiency (higher S-TfR) despite iron sequestration in stores (higher S-FE). In conclusion, stunted children have iron, cobalamin, and vitamin A deficiencies. Interventions addressing stunting should target co-existing micronutrient deficiencies.

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.

Background: Despite possible benefits for growth, milk is costly to include in foods for undernourished children. Furthermore, the relative effects of different milk components, milk protein (MP), and whey permeate (WP) are unclear. We aimed to assess the effects of MP and WP in lipid-based nutrient supplement (LNS), and of LNS itself, on linear growth and body composition among stunted children., Methods and Findings: We performed a randomized, double-blind, 2 × 2 factorial trial among 12 to 59 months old stunted children in Uganda. Children were randomized to 4 formulations of LNS with MP or soy protein isolate and WP or maltodextrin (100 g/day for 12 weeks) or no supplementation. Investigators and outcome assessors were blinded; however, participants were only blinded to the ingredients in LNS. Data were analyzed based on intention-to-treat (ITT) using linear mixed-effects models adjusted for age, sex, season, and site. Primary outcomes were change in height and knee-heel length, and secondary outcomes included body composition by bioimpedance analysis (ISRCTN13093195). Between February and September 2020, we enrolled 750 children with a median age of 30 (interquartile range 23 to 41) months, with mean (± standard deviation) height-for-age z-score (HAZ) -3.02 ± 0.74 and 12.7% (95) were breastfed. The 750 children were randomized to LNS (n = 600) with or without MP (n = 299 versus n = 301) and WP (n = 301 versus n = 299), or no supplementation (n = 150); 736 (98.1%), evenly distributed between groups, completed 12-week follow-up. Eleven serious adverse events occurred in 10 (1.3%) children, mainly hospitalization with malaria and anemia, all deemed unrelated to the intervention. Unsupplemented children had 0.06 (95% confidence interval, CI [0.02, 0.10]; p = 0.015) decline in HAZ, accompanied by 0.29 (95% CI [0.20, 0.39]; p < 0.001) kg/m2 increase in fat mass index (FMI), but 0.06 (95% CI [-0.002; 0.12]; p = 0.057) kg/m2 decline in fat-free mass index (FFMI). There were no interactions between MP and WP. The main effects of MP were 0.03 (95% CI [-0.10, 0.16]; p = 0.662) cm in height and 0.2 (95% CI [-0.3, 0.7]; p = 0.389) mm in knee-heel length. The main effects of WP were -0.08 (95% CI [-0.21, 0.05]; p = 220) cm and -0.2 (95% CI [-0.7; 0.3]; p = 403) mm, respectively. Interactions were found between WP and breastfeeding with respect to linear growth (p < 0.02), due to positive effects among breastfed and negative effects among non-breastfed children. Overall, LNS resulted in 0.56 (95% CI [0.42, 0.70]; p < 0.001) cm height increase, corresponding to 0.17 (95% CI [0.13, 0.21]; p < 0.001) HAZ increase, and 0.21 (95% CI [0.14, 0.28]; p < 0.001) kg weight increase, of which 76.5% (95% CI [61.9; 91.1]) was fat-free mass. Using height-adjusted indicators, LNS increased FFMI (0.07 kg/m2, 95% CI [0.0001; 0.13]; p = 0.049), but not FMI (0.01 kg/m2, 95% CI [-0.10, 0.12]; p = 0.800). Main limitations were lack of blinding of caregivers and short study duration., Conclusions: Adding dairy to LNS has no additional effects on linear growth or body composition in stunted children aged 12 to 59 months. However, supplementation with LNS, irrespective of milk, supports linear catch-up growth and accretion of fat-free mass, but not fat mass. If left untreated, children already on a stunting trajectory gain fat at the expense of fat-free mass, thus nutrition programs to treat such children should be considered., Trial Registration: ISRCTN13093195., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: HF and CM have received research grants from Arla Food for Health, HF, BG and CM have received research grants from the Danish Dairy Research Foundation, CM and KFM also received funds from Arla Foods Amba and finally HF, CM, KFM, BG, SF and AB have had research collaboration with Nutriset, a producer of LNS. Other authors declare no financial relationships with any organisations that might have an interest in the submitted work in the previous five years, and declare no other relationships or activities that could appear to have influenced the submitted work, (Copyright: © 2023 Mbabazi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Early growth and body composition may influence the risk of obesity and health in adulthood. Few studies have examined how undernutrition is associated with body composition in early life., Objectives: We assessed stunting and wasting as correlates of body composition in young Kenyan children., Methods: Nested in a randomized controlled nutrition trial, this longitudinal study assessed fat and fat-free mass (FM, FFM) using deuterium dilution technique among children at age 6 and 15 months. This trial was registered at http://controlled-trials.com/ (ISRCTN30012997). Cross-sectional and longitudinal associations between z-score categories of length-for-age (LAZ) or weight-for-length (WLZ) and FM, FFM, fat mass index (FMI), fat-free mass index (FFMI), triceps, and subscapular skinfolds were analyzed by linear mixed models., Results: Among the 499 children enrolled, breastfeeding declined from 99% to 87%, stunting increased from 13% to 32%, and wasting remained at 2% to 3% between 6 and 15 mo. Compared with LAZ >0, stunted children had a 1.12 kg (95% CI: 0.88, 1.36; P < 0.001) lower FFM at 6 mo and increased to 1.59 kg (95% CI: 1.25, 1.94; P < 0.001) at 15 mo, corresponding to differences of 18% and 17%, respectively. When analyzing FFMI, the deficit in FFM tended to be less than proportional to children's height at 6 mo (P ≤ 0.060) but not at 15 mo (P > 0.40). Stunting was associated with 0.28 kg (95% CI: 0.09, 0.47; P = 0.004) lower FM at 6 mo. However, this association was not significant at 15 mo, and stunting was not associated with FMI at any time point. A lower WLZ was generally associated with lower FM, FFM, FMI, and FFMI at 6 and 15 mo. Differences in FFM, but not FM, increased with time, whereas FFMI differences did not change, and FMI differences generally decreased with time., Conclusions: Overall, low LAZ and WLZ among young Kenyan children were associated with reduced lean tissue, which may have long-term health consequences., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: BIA represents an important tool in body composition (BC) assessment, especially in low-income settings in which simple and affordable options are preferred. There is a particular need to measure BC in stunted children, in which cases population-specific BIA estimating equations are lacking., Objectives: We calibrated an equation to estimate body composition from BIA using deuterium dilution ( 2 H) as the criterion method in stunted children., Methods: We measured BC with 2 H and performed BIA in stunted Ugandan children (n = 50). Multiple linear regression models were constructed to predict 2 H-derived FFM from BIA-derived whole-body impedance and other relevant predictors. Model performance was expressed as adjusted R 2 and RMSE. Prediction errors were also calculated., Results: Participants were aged 16-59 mo, of whom 46% were girls, and their median (IQR) height-for-age z-score (HAZ) was -2.58 (-2.92 to -2.37) according to the WHO growth standards. Impedance index (height 2 /impedance measured at 50 kHz) alone explained 89.2% variation in FFM and had an RMSE of 583 g (precision error 6.5%). The final model contained age, sex, impedance index, and height-for-age z-score as predictors and explained 94.5% variation in FFM with an RMSE of 402 g (precision error 4.5%)., Conclusions: We present a BIA calibration equation for a group of stunted children with a relatively low prediction error. This may help evaluate the efficacy of nutritional supplementation in large-scale trials in the same population. J Nutr 20XX;xxx:xx., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

In nutrition research, sample size calculations for continuous outcomes are important for the planning phase of many randomized trials and could also be relevant for some observational studies such as cohort and cross-sectional studies. However, only little literature dedicated to this topic exists within nutritional science. This article reviews the most common methods for sample size calculations in nutrition research. Approximate formulas are used for explaining concepts and requirements and for working through examples from the literature. Sample size calculations for the various study designs, which are covered, may all be seen as extensions of the sample size calculation for the basic two-group comparison through the application of suitable scaling factors and, possibly, modification of the significance level. The latter is needed for sample size calculations for multi-group designs and designs involving multiple primary outcomes. Like cluster-randomized designs, these types of study designs may be more challenging than standard sample size calculations. In such non-standard scenarios, there may be a need for consulting a biostatistician. Finally, it should be stressed that there may be many ways to plan a study. The final sample size calculation provided for a grant applicant, study protocol, or publication will often not only depend on considerations and input information as described in this article but will also involve restrictions in terms of logistics and/or resources., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Aim: The effect of different protein sources on the appetite-related hormones in children is largely unknown. We investigated the effect of milk protein versus blends of milk and rapeseed protein on plasma leptin and adiponectin in children., Methods: We included 88 Danish 7- to 8-year-old children randomised to receive 35 g protein/day for 4 weeks in 2018 as either milk protein or blends of milk and rapeseed protein (ratio 54:46 or 30:70). Outcomes included absolute and fat mass-adjusted adiponectin and leptin measured at baseline, Weeks 1 and 4., Results: There was no difference in changes in absolute and fat mass-adjusted adiponectin and leptin after 1 or 4 weeks between the three groups (p ≥ 0.100). Leptin increased within all groups (p ≤ 0.046). Combining the three groups, leptin and fat mass-adjusted leptin increased by 23% (95% CI 11;35) and 17% (6.4;29) during the intervention respectively (both p ≤ 0.001). Adiponectin variables did not change during the intervention period., Conclusion: There were no differences between milk protein and blends of milk and rapeseed protein on absolute and fat mass-adjusted leptin and adiponectin in healthy children with a habitual intake of milk. However, leptin increased within all three groups. Future studies should further investigate effect on appetite-related hormones of rapeseed protein alone., (© 2022 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

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., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Linear catch-up growth after treatment of severe acute malnutrition (SAM) is low, and little is known about the association between ponderal and subsequent linear growth., Objective: The study assessed the association of weight-for-height z -score (WHZ) gain with subsequent linear growth during SAM treatment and examined its modifiers., Methods: This was a prospective study, nested in a trial (ISRCTN16454889), among 6-59-mo-old children treated for SAM in Uganda. Weight, total length (TL), and knee-heel length (KHL) were measured at admission, weekly during inpatient therapeutic care (ITC), at discharge, and fortnightly during outpatient therapeutic care (OTC) for 8 wk. Linear regression was used to assess the association between WHZ gain during ITC and linear growth during OTC., Results: Of 400 children, 327 were discharged to OTC and 290 were followed up for 8 wk. Mean WHZ gains were 0.45 in ITC and 1.24 in OTC, whereas mean height-for-age z -score (HAZ) declined by 0.41 during ITC and increased by 0.14 during OTC. WHZ gain during ITC was positively associated with HAZ, TL, and KHL gains during OTC [regression coefficients (β) (95% CI): 0.12 (0.09, 0.15) z -score; 3.1 (2.4, 3.8) mm and 0.5 (0.1, 0.7) mm, respectively]. The regression coefficients were highest for the middle tertile of WHZ gain with respect to HAZ and TL. Admission diarrhea and low plasma citrulline reduced the association between WHZ gain during ITC and HAZ and TL gain during OTC ( P  < 0.001). In contrast, pneumonia ( P  = 0.051) and elevated plasma C-reactive protein ( P  < 0.001) increased the association with TL gain, but reduced the association with KHL gain ( P  < 0.001)., Conclusions: Among children admitted with SAM, considerable WHZ gain during ITC was followed by very modest linear catch-up growth during OTC, with no indication of a WHZ gain threshold, above which linear growth was higher. To optimize linear growth in these children, early treatment of infections and conditions affecting the gut may be necessary., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Serum insulin-like growth factor 1 (sIGF-1) is an important growth factor in childhood. However, studies on sIGF-1 among children from low-income countries are few, and the role of body composition is unknown., Objectives: To assess the associations of anthropometry, body composition, inflammation, and breastfeeding with sIGF-1 among children with moderate acute malnutrition (MAM)., Methods: A cross-sectional study based on admission data from 6- to 23-mo-old children with MAM participating in a nutrition intervention trial (Treatfood) in Burkina Faso. Linear regression analysis was used to identify correlates of sIGF-1., Results: Among 1546 children, the median (IQR) sIGF-1 was 12 (8.2-18.3) ng/mL. sIGF-1 was highest at 6 mo, with a nadir ∼10-11 mo, and higher in girls than boys. Length-for-age z score (LAZ), weight-for-length z score (WLZ), and midupper arm circumference were positively associated with sIGF-1 (P ≤ 0.001). Fat-free mass (FFM) was also positively associated, as sIGF-1 increased 1.5 (95% CI: 0.5, 2.5) ng/mL for each 1-kg increase in FFM. However, the association disappeared after adjustment for height. Elevated serum C-reactive protein and α1-acid glycoprotein were negatively associated with sIGF-1 (P ≤ 0.001), as was fever (P < 0.001) but not a positive malaria test per se (P = 0.15). Children never breastfed had lower sIGF-1 (-5.1; 95% CI: -9.8, -0.3)., Conclusions: LAZ and WLZ were positively and inflammation negatively associated with sIGF-1. As all children were moderately malnourished and many had inflammation, this probably explains the very low median sIGF-1. The association of FFM with sIGF-1 was fully explained by height. There was a marked age pattern, with a nadir in late infancy, confirming findings from smaller studies from well-nourished populations. There is a need for prospective studies to disentangle the role of sIGF-1 in growth and health. This trial was registered at https://www.isrctn.com as ISRCTN42569496., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Weight gain is routinely monitored to assess hydration and growth during treatment of children with complicated severe acute malnutrition (SAM). However, changes in weight and mid-upper arm circumference (MUAC) gain velocities over time are scarcely described. We assessed weight and MUAC gain velocities in 6-59 mo-old children with complicated SAM by treatment phase and edema status., Methods: This was a prospective study, nested in a randomized/probiotic trial ( ISRCTN16454889 ). Weight and MUAC gain velocities were assessed by treatment phase and edema at admission using linear mixed-effects models., Results: Among 400 children enrolled, the median (IQR) age was 15.0 (11.2;19.2) months, 58% were males, and 65% presented with edema. During inpatient therapeutic care (ITC), children with edema vs no edema at admission had negative weight gain velocity in the stabilization phase [differences at day 3 and 4 were - 11.26 (95% CI: - 20.73; - 1.79) g/kg/d and - 13.09 (95% CI: - 23.15; - 3.02) g/kg/d, respectively]. This gradually changed into positive weight gain velocity in transition and eventually peaked at 12 g/kg/d early in the rehabilitation phase, with no difference by edema status (P > 0.9). During outpatient therapeutic care (OTC), overall, weight gain velocity showed a decreasing trend over time (from 5 to 2 g/kg/d), [difference between edema and non-edema groups at week 2 was 2.1 (95% CI: 1.0;3.2) g/kg/d]. MUAC gain velocity results mirrored those of weight gain velocity [differences were - 2.30 (95% CI: - 3.6; - 0.97) mm/week at week 1 in ITC and 0.65 (95% CI: - 0.07;1.37) mm/week at week 2 in OTC]., Conclusions: Weight and MUAC gain velocities among Ugandan children with complicated SAM showed an increasing trend during transition and early in the rehabilitation phase, and a decreasing trend thereafter, but, overall, catch-up growth was prolonged. Further research to establish specific cut-offs to assess weight and MUAC gain velocities during different periods of rehabilitation is needed.

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Malnutrition continues to be a major cause of mortality and morbidity among children in resource limited settings. Children with severe acute malnutrition (SAM) experience severe thymus atrophy, possibly reflecting poor immune function. This immune dysfunction is responsible for the severe infections they experience which lead to mortality. Since their immune dysfunction is not fully understood and there has been a lapse in research in this field, more research is needed. Knowing the correlates of thymus size may help clinicians identify those with more severe atrophy who might have more severe immune impairment. We aimed to describe thymus size and its correlates at admission among children hospitalized with SAM., Methods: This cross-sectional study involved children 6-59 months admitted with complicated SAM in Mulago National Referral Hospital. Well-nourished children from same communities were used as a community reference group for thymus size. At admission, thymus size was measured by ultrasound scan. Demographic, clinical and laboratory variables were identified at admission. A linear regression model was used to determine correlates of thymus size among children with SAM., Results: Among 388 children with SAM, the mean age was 17±8.5 months and 58% were boys. The mean thymus size was 3.14 (95% CI 2.9; 3.4) cm 2 lower than that of the 27 healthy community reference children (1.06 vs 4.2 cm 2 , p<0.001) when controlled for age. Thymus size positively correlated with current breastfeeding (0.14, 95% CI 0.01, 0.26), anthropometric measurements at admission (weight, length, mid-upper-arm circumference, weight-for-height Z scores and length-for-age Z scores) and suspected tuberculosis (0.12, 95% CI 0.01; 0.22). Thymus size negatively correlated with > 2 weeks duration of sickness (-0.10; 95% CI -0.19; -0.01)., Conclusion: The thymus is indeed a barometer for nutrition since all anthropometric measurements and breastfeeding were associated with bigger thymus. The immune benefits of breastfeeding among children with SAM is underscored. Children with longer duration of illness had a smaller thymus gland indicating that infections have a role in the cause or consequence of thymus atrophy.

Severe acute malnutrition (SAM) is a major challenge in low-income countries and gut microbiota (GM) dysbiosis may play a role in its etiology. Here, we determined the GM evolution during rehabilitation from SAM and the impact of probiotics ( Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12) supplementation. The GM (16S rRNA gene amplicon sequencing) of children admitted to hospital with SAM showed distinct composition over admission (e.g. Klebsiella spp., and Enterobacteriaceae spp.), discharge (e.g. Clostridiaceae spp., Veilonella dispar ) and follow-up (e.g. Lactobacillus ruminis, Blautia spp., Faecalibacterium prausnitzii ), reaching similar β- and α-diversity as healthy individuals. Children with diarrhea had reduced distribution of Bacteroidaceae, Lachnospiraceae, increased Enterobacteriaceae and Moraxellaceae, and lower α-diversity. Children suffering from edematous SAM had diminished proportion of Prevotellaceae, Lachnospiraceae, Ruminoccaceae and a higher α-diversity when compared to non-edematous SAM. Supplementation of probiotics did not influence β-diversity upon discharge or follow-up, but it increased ( p < .05) the number of observed species [SE: > 4.5]. Children where the probiotic species were detected had lower cumulative incidence ( p < .001) of diarrhea during the follow-up period compared to children receiving placebo and children receiving probiotics, but where the probiotics were not detected. The GM of children with non-edematous and edematous SAM differ in composition, which might have implications for future GM targeted treatments. Probiotics treatment reduced the cumulative incidence of diarrhea during the outpatient phase, with the strongest effect in children where the administered probiotics could be detected in the GM.

Background: Milk intake stimulates linear growth and improves cognition in children from low-income countries. These effects may be mediated through insulin-like growth factor-1 (IGF-1)., Objective: The objective was to assess the effect of milk supplement on circulating IGF-1 and to assess IGF-1 as a correlate of growth and cognition in children., Methods: Secondary data on blood spot IGF-1 from a randomized, double-blind, controlled trial in 6-9-y-old children from rural Ghana were analyzed. Intervention groups received porridge with non-energy-balanced supplements: 8.8 g milk protein/d, 100 kcal/d (Milk8); 4.4 g milk and 4.4 g rice protein/d, 100 kcal/d (Milk/rice); 4.4 g milk protein/d, 48 kcal/d (Milk4); or a control (no protein, 10 kcal/d). IGF-1, length, body composition, and Cambridge Neuropsychological Test Automated Battery (CANTAB) were measured at 3.5 or 8.5 mo. Linear regressions were used to assess the effect of milk interventions on IGF-1 and IGF-1 as a correlate of growth and cognition., Results: The increase in IGF-1 was 15.3 (95% CI: 3.3, 27.3) ng/mL higher in children receiving Milk8 compared with the control. The IGF-1 increases in the isonitrogenous, isoenergetic Milk/rice or the Milk4 groups were not different from the control (P ≥ 0.49). The increase in IGF-1 was associated with improvements in 4 out of 5 CANTAB domains. The strongest associations included reductions in "mean correct latency" from Pattern Recognition Memory and "pre-extradimensional (pre-ED) shift errors" from Intra/Extradimensional Set Shift (P ≤ 0.005). In addition, change in IGF-1 was positively associated with changes in height, weight, and fat-free mass (P ≤ 0.001)., Conclusions: Intake of skimmed milk powder corresponding to one, but not half a glass of milk on school days stimulates IGF-1 in 6-9-y-old Ghanian children. IGF-1 seems to mediate the effect of milk intake on growth and cognition. The association between IGF-1 and cognition in relation to milk intake is novel and opens possibilities for dietary interventions to improve cognition., (Copyright © The Author(s) 2020.)

Cow's milk and dairy products intake increase linear growth in children and result in increased adult stature. This is supported by observational and intervention studies mainly from low- and middle-income countries. However, recent reviews primarily based on studies from well-nourished populations question the relation. The probable effects seem to be mediated by insulin-like growth factor-1 and insulin and to be more pronounced during periods of high growth velocity. Several components of cow's milk are suggested to stimulate growth: a high protein quality, bioavailable minerals that are important for growth, and perhaps lactose. Higher adult stature is associated with both positive and negative health effects. Growth stimulation is important in populations with undernutrition, but in well-nourished populations, it might not be important. A high intake of cow's milk and thereby a high protein intake early in life can increase the risk of later overweight and obesity, while a high protein intake later in childhood seems to be associated with a lower BMI later in childhood. A high dairy intake can limit the diversity of the diet and result in iron deficiency. Therefore, milk intake should not exceed 500 mL/day in young children. Most products for the treatment of undernutrition include dairy protein because of the well-documented effects on growth and recovery. However, as dairy is an expensive ingredient, the amount needed and the effects of alternative plant-based protein sources are considered., (© 2020 Nestlé Nutrition Institute, Switzerland/S. Karger AG, Basel.)

Objective: Children with severe acute malnutrition (SAM) may have impaired intestinal function, which can result in malabsorption, diarrhoea, and poor growth. This study evaluated the gut function of children with SAM using fecal and blood biomarkers and assessed their correlates., Methods: A cross-sectional study, nested in a randomized trial (www.isrctn.com, ISRCTN 16454889), was conducted at Mulago hospital, Uganda among subgroups of 400 children with complicated SAM and 30 community controls. Gut function was evaluated by 5 biomarkers: plasma citrulline, fecal myeloperoxidase and fecal neopterin, bacterially derived 16S rRNA gene and internal transcribed Spacer region (ITS) specific for Candida spp. in blood., Results: Compared with controls, children with SAM had lower median plasma citrulline (5.14 vs 27.4 μmol/L, P < 0.001), higher median fecal myeloperoxidase (18083 vs 7482 ng/mL, P = 0.001), and fecal neopterin (541 vs 210 nmol/L, P < 0.001). A higher blood concentration of 16S rRNA gene copy numbers was observed among children with SAM (95 vs 28 copies/μl, P = 0.05), whereas there was no difference in the blood concentration of Candida-specific ITS fragment.Among those with SAM, plasma citrulline was lower in children with edema, diarrhoea, dermatosis, and plasma C-reactive protein (CRP) >10 mg/L. Fecal neopterin was positively correlated with symptoms of fever and cough whereas it was negatively correlated with mid-upper arm circumference (MUAC), weight-for-height z score (WHZ), edema, and dermatosis., Conclusions: Children with complicated SAM seem to have impaired gut function characterized by reduced enterocyte mass, intestinal inflammation, and increased bacterial translocation.

Objective: To assess predictors of diarrhea and dehydration and to investigate the role of diarrhea in mortality among children with complicated severe acute malnutrition., Study Design: A prospective cohort study, nested in a probiotic trial, was conducted in children with complicated severe acute malnutrition. Children were treated according to World Health Organization and national guidelines, and diarrhea and dehydration were assessed daily. Multiple linear and log-linear Poisson regression models were used to identify predictors of days with diarrhea and dehydration, respectively, and multiple logistic regression was used to assess their role in mortality., Results: Among 400 children enrolled, the median (IQR) age was 15.0 months (11.2-19.2 months), 58% were boys, and 61% had caregiver-reported diarrhea at admission. During hospitalization, the median (range) number of days with diarrhea was 5 (0-31), the median duration of hospitalization was 17 days (1-69 days), and 39 (10%) died. Of 592 diarrhea episodes monitored, 237 were admission episodes and 355 were hospital acquired. During hospitalization, young age was associated with days with diarrhea, and young age and HIV infection were associated with dehydration. Both days with diarrhea and dehydration predicted duration of hospitalization as well as mortality. The odds of mortality increased by a factor of 1.4 (95% CI, 1.2-1.6) per day of diarrhea and 3.5 (95% CI, 2.2-6.0) per unit increase in dehydration score., Conclusions: Diarrhea is a strong predictor of mortality among children with complicated severe acute malnutrition. Improved management of diarrhea and prevention of hospital-acquired diarrhea may be critical to decreasing mortality., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background : Children with severe acute malnutrition (SAM) are prone to infections due to immune dysfunction including severe thymus atrophy which recovers during nutritional rehabilitation. Aim : To investigate predictors of thymus size recovery, including probiotics during nutritional rehabilitation of children admitted with complicated SAM. Methods : In this prospective study nested in a randomized controlled trial, children 6-59 months admitted with SAM received standard care and either probiotics or placebo during hospitalization until 8 weeks post-discharge. Thymus size was measured using ultrasound at admission, discharge, 8 weeks post-discharge and among 27 community controls. Predictors of thymus size recovery were assessed using linear regression. Results : Among 388 children with SAM, mean (SD) thymus size was 1.06 cm2 (0.41), 1.24 cm2 (0.48), 2.85 cm2 (1.07) and 4.2 cm2 (0.93) at admission, discharge, follow-up and in the healthy controls respectively (p < 0.05).Probiotics did not affect thymus recovery. During both inpatient therapeutic care (ITC) and outpatient therapeutic care (OTC), thymus recovery correlated positively with anthropometry but negatively with caregiver-perceived illness severity and Haemoglobin <8 g/dl. Negative predictors of thymus recovery during ITC included grade 3 oedema (β -0.13, 95%CI -0.25; -0.01), dermatosis (β -0.21, 95%CI -0.41; -0.01), C-reactive protein (CRP) >15mg/L (β -0.13, 95%CI -0.25; -0.02) and neutrophils (β -0.01, 95%CI -0.02; -0.002). During OTC, HIV negatively predicted thymus recovery. Conclusion : Children with SAM failed to regain thymus size at 8 weeks post-discharge. Probiotics did not predict thymus recovery during nutritional rehabilitation. More research is needed to find interventions which can accelerate immune recovery. Abbreviations : ART, Antiretroviral therapy; BB-12, Bifidobacterium animalis subsp. Lactis; CRP, C-reactive protein; ITC, inpatient therapeutic care; LGG, Lactobacillus rhamnosus ; MNU, Mwanamugimu Nutrition Unit; MUAC, mid-upper arm circumference; OTC, outpatient therapeutic care; PCR, Polymerised chain reaction; RUTF, ready-to-use therapeutic food; SAM, severe acute malnutrition; VAS, visual analogue score; WHO, World Health Organization; WHZ, weight-for-height score.

The study aimed at assessing stunting, wasting and breast-feeding as correlates of body composition in Cambodian children. As part of a nutrition trial (ISRCTN19918531), fat mass (FM) and fat-free mass (FFM) were measured using 2H dilution at 6 and 15 months of age. Of 419 infants enrolled, 98 % were breastfed, 15 % stunted and 4 % wasted at 6 months. At 15 months, 78 % were breastfed, 24 % stunted and 11 % wasted. Those not breastfed had lower FMI at 6 months but not at 15 months. Stunted children had lower FM at 6 months and lower FFM at 6 and 15 months compared with children with length-for-age z ≥0. Stunting was not associated with height-adjusted indexes fat mass index (FMI) or fat-free mass index (FFMI). Wasted children had lower FM, FFM, FMI and FFMI at 6 and 15 months compared with children with weight-for-length z (WLZ) ≥0. Generally, FFM and FFMI deficits increased with age, whereas FM and FMI deficits decreased, reflecting interactions between age and WLZ. For example, the FFM deficits were -0·99 (95 % CI -1·26, -0·72) kg at 6 months and -1·44 (95 % CI -1·69; -1·19) kg at 15 months (interaction, P&lt;0·05), while the FMI deficits were -2·12 (95 % CI -2·53, -1·72) kg/m2 at 6 months and -1·32 (95 % CI -1·77, -0·87) kg/m2 at 15 months (interaction, P&lt;0·05). This indicates that undernourished children preserve body fat at the detriment of fat-free tissue, which may have long-term consequences for health and working capacity.

Background: Cow's milk is a core ingredient in foods for prevention and treatment of undernutrition in children. It promotes growth, but there is limited knowledge of which components in milk have growth-stimulating effects., Objective: To discuss the growth-stimulating effects of milk in undernourished children with emphasis on protein, lactose, and minerals., Methods: We reviewed literature on dairy and growth in undernourished children., Results: Cow's milk has a specific stimulating effect on linear growth, even in well-nourished children, and it may stimulate weight gain and muscle accretion in wasted children. Dairy protein has high protein quality scores with no major differences between whey protein concentrate and dried skimmed milk. Lactose has potential growth-stimulating effects, and the high content of potassium, phosphorus, magnesium, and zinc in milk is also likely to stimulate growth. Furthermore, a high dairy content reduces the amount of antinutrients from plant protein., Conclusions: Dairy protein, lactose, and bioavailable minerals all have potential growth-stimulating effects, which make cow's milk an important ingredient in foods for undernourished children. Different dairy ingredients vary with regard to protein amount and quality, content of lactose, and minerals, and thereby growth stimulating effects. This should be taken into consideration when deciding which dairy ingredient to use. Challenges include the relatively high cost of dairy. Therefore, future studies should include cost-effectiveness analysis and assessment of the desirable content of each growth-promoting milk component.

Background: We determined the predictors of mortality among children admitted with severe acute malnutrition (SAM)., Methods: This was a prospective study nested in a randomized trial among 6-59-month-old children admitted with SAM. Socio-demographic and medical history data were collected using questionnaires and clinical examination, anthropometry and laboratory tests were performed. They were monitored daily until discharge or death during hospitalization while receiving care according to national guidelines. Predictors of death were assessed using Cox regression., Results: Of 400 children, 9.8% (n = 39) died during hospitalization. Predictors of mortality included diarrhoea at admission [hazard ratio [HR] 2.19, 95% confidence interval (CI): 1.06; 4.51], lack of appetite [HR 4.50, 95% CI: 1.76; 11.50], suspected sepsis [HR 2.23, 95% CI: 1.18; 4.24] and skin ulcers [HR 4.23, 95% CI: 1.26; 4.17]. Chest indrawing [HR 5.0, 95% CI: 1.53; 16.3], oxygen saturation below 94% [HR 3.92, 95% CI: 1.42; 10.83] and confirmed HIV infection [HR 3.62, 95% CI: 1.69; 7.77] also predicted higher mortality., Conclusion: Infections were major contributors to mortality. This underscores the need for improved prevention and management of these infections among children with severe malnutrition.

Background: World Health Organization now recommends the transition from F-75 to ready-to-use therapeutic foods (RUTF) in the management of severe acute malnutrition (SAM). We described the transition from F-75 to RUTF and identified correlates of failed transition., Methods: We conducted an observational study among children aged 6-59 months treated for SAM at Mulago hospital, Kampala, Uganda. Therapeutic feeding during transition phase was provided by first offering half of the energy requirements from RUTF and the other half from F-75 and then increasing gradually to RUTF as only energy source. The child was considered to have successfully transitioned to RUTF if child was able to gradually consume up to 135 kcal/kg/day of RUTF in the transition phase on first attempt. Failed transition to RUTF included children who failed the acceptance test or those who had progressively reduced RUTF intake during the subsequent days. Failure also included those who developed profuse diarrhoea or vomiting when RUTF was ingested., Results: Among 341 of 400 children that reached the transition period, 65% successfully transitioned from F-75 to RUTF on first attempt while 35% failed. The median (IQR) duration of the transition period was 4 (3-8) days. The age of the child, mid-upper arm circumference, weight-for-height z-score and weight at transition negatively predicted failure. Each month increase in age reflected a 4% lower likelihood of failure (OR 0.96 (95% CI 0.93; 0.99). Children with HIV (OR 2.73, 95% CI 1.27; 5.85) and those rated as severely ill by caregiver (OR 1.16, 95% CI: 1.02; 1.32) were more likely to fail. At the beginning of the rehabilitation phase, the majority (95%) of the children eventually accepted RUTF while only 5% completed rehabilitation in hospital on F-100., Conclusion: Transition from F-75 to RUTF for hospitalized children with SAM by gradual increase of RUTF was possible on first attempt in 65% of cases. Younger children, severely wasted, HIV infected and those with severe illness as rated by the caregiver were more likely to fail to transit from F-75 to RUTF on first attempt.

Objectives: The aim of the study was the development and validation of a simple stool diary for caretakers collecting data on stool frequency and consistency among young children in a low-income country., Methods: Focus group studies evaluated how diarrhea was understood by caregivers (content validity). The sensitivity, reliability, and correlations between dehydration and diary scores (construct validity) were tested in a clinical trial., Results: Caregivers recognized and understood the concept and severity of diarrhea. Stool frequency and liquid consistency decreased in children admitted with diarrhea (P < 0.0001 for both), confirming good sensitivity of the diary. High reliability was obtained after a few days of training. The caregiver intracorrelation coefficients were 0.66 (0.55-0.77) and 0.75 (0.66-0.84) after 2 and 7 days of training, respectively, and subjective staff evaluation of caregiver scores showed that ≤6% of caregivers had low scoring abilities after 3 days. The degree of dehydration (4-point score) was correlated with both increasing stool frequency and liquid stool consistency (+0.2 points [0.07-0.3], P = 0.0018 for 6 or more diarrheal stools, compared to 3 or more diarrheal stools per day, and +0.5 points (0.3-0.6), P < 0.0001 for diarrheal episodes with 3 or more watery stools/day compared with episodes with 3 or more "watery + abnormally loose + loose" stools per day)., Conclusions: The diary showed high validity, good reliability, and high sensitivity. After 3 days of training, caregivers with mainly no or limited education could report stool consistency with good reliability. Stool consistency, which correlated strongly with dehydration, may be considered an important marker of diarrhea severity in future research.

Objectives: The aim of the study was to assess the effect of probiotics on diarrhea during in- and outpatient treatment of children with severe acute malnutrition (SAM)., Methods: A randomized, double-blind, placebo-controlled study was conducted involving 400 children admitted with SAM. Patients received 1 daily dose of a blend of Bifidobacterium animalis subsp lactis and Lactobacillus rhamnosus (10 billion colony-forming units, 50:50) or placebo during hospitalization followed by an 8- to 12-week outpatient treatment period, depending on patients' recovery rate. All outcomes were reported for in- and outpatient treatment separately. The primary outcome was number of days with diarrhea during hospitalization. Secondary outcomes included other diarrhea outcomes, pneumonia, weight gain, and recovery., Results: There was no difference in number of days with diarrhea between the probiotic (n = 200) and placebo (n = 200) groups during inpatient treatment (adjusted difference +0.2 days, 95% confidence interval -0.8 to 1.2, P = 0.69); however, during outpatient treatment, probiotics reduced days with diarrhea (adjusted difference -2.2 days 95% confidence interval -3.5 to -0.3, P = 0.025). There were no effects of probiotics on diarrhea incidence and severity or pneumonia, weight gain or recovery during in- or outpatient treatment. Twenty-six patients died in the probiotic versus 20 in the placebo group (P = 0.38)., Conclusions: Bifidobacterium animalis subsp lactis and Lactobacillus rhamnosus had no effect on diarrhea in children with SAM during hospitalization, but reduced the number of days with diarrhea in outpatient treatment by 26%. Probiotics may have a role in follow-up of hospitalized children with SAM or in community-based treatment of malnourished children, but further studies are needed to confirm this.

Background: Lactose is an important energy source in young mammals, and in fully breast-fed human infants, it constitutes around 40% of the total daily energy intake. The role of lactose in feeding of undernourished infants and young children is not well described., Objective: A narrative review of the potential positive and negative effects of lactose in the treatment of undernourished children., Methods: Searches were conducted using PUBMED and Web of Science up to July 2015. Relevant references in the retrieved articles were included., Results: Lactose may exhibit several health benefits in young children, including a prebiotic effect on the gut microbiota and a positive effect on mineral absorption. Studies in piglets suggest there might also be a stimulating effect on growth, relative to other carbohydrates. Lactose intolerance is a potential concern for undernourished children. Most undernourished children seem to tolerate the currently recommended (low lactose level) therapeutic foods well. However, a subgroup of severely undernourished children with secondary lactase deficiency due to severe diarrhea or severe enteropathy may benefit from products with even more restricted lactose content. At limited extra costs, lactose or lactose-containing milk ingredients may have beneficial effects if added to food products for undernourished children., Conclusions: Lactose may be an overlooked beneficial nutrient for young and undernourished children. Research is needed to define the balance between beneficial and detrimental effects of lactose in undernourished children at different ages and with different degrees of diarrhea and intestinal integrity., (© The Author(s) 2016.)