Individual and combined association analysis of famine exposure and serum uric acid with hypertension in the mid-aged and older adult: a population-based cross-sectional study.

BACKGROUND: Malnutrition in early life may affect health in later life. The associations between malnutrition and serum uric acid (SUA) and hypertension were inconsistent. The present study aimed to investigate the individual and combined association between famine exposure and serum uric acid and hypertension in middle-aged and older Chinese. METHODS: Data were selected from the China Health and Retirement Longitudinal Study (CHARLS) Wave2011. The analytic sample included 9368 individuals aged 45 to 90. Differences between baseline characteristics and famine exposure/SUA level were evaluated using the Chi-square test, t-test, and F-test. Then, the differences in the prevalence of hypertension between characteristic groups was also estimated by the Chi-square and t-test. Finally, multivariable-adjusted logistic regression models examined association of famine exposure and serum uric acid with odds of prevalence of hypertension. RESULTS: A total of 9368 individuals were enrolled in the study, 4366 (46.61%) and 5002 (53.39%) were male and female, respectively. Among males, 459 (10.51%) had been exposed to the Chinese famine during the fetal stage, whereas 1760 (40.31%) and 1645 (37.68%) had been exposed to the famine during childhood and adolescence/adult stage, respectively. Among females, 635 (12.69%) had been exposed to the Chinese famine during the fetal stage, whereas 1988 (39.74%) and 1569 (31.37%) had been exposed to the famine during childhood and adolescence/adult stage, respectively. Regarding the participants with SUA level measurements, 290 (6.64%) reported having Hyperuricemia (HUA) in males and 234 (4.68%) in the females. Furthermore, 1357 (31.08%) reported having hypertension in male and 1619 (32.37%) in the female. In multivariable-adjusted model, famine exposure and serum uric acid were associated with prevalence of hypertension independently in total populations [(1) Model fourd, fatal exposed group vs non-exposed group: 1.25 (95% CI 1.03, 1.52); childhood-exposed group vs non-exposed group:1.60 (95% CI 1.37, 1.87); adolescence/adult exposed group vs non-exposed group: 2.87 (95% CI 2.44, 3.37), P for trend < 0.001; (2) Model four e, high vs normal:1.73 (95% CI 1.44, 2.08)]. When stratified by sex, the results in both males and females were similar to those in the total population. In general, interaction analysis in the multivariable-adjusted model, compared with the combination of normal SUA level and no-exposed famine stage, all groups trended towards higher odds of prevalence of hypertension [the greatest increase in odds, adolescence/adult exposed stage and high SUA level in total participants: OR4.34; 95%CI 3.24, 5.81; P for interaction < 0.001]. When stratified by sex, the results in both males and females were also similar to those in the total population. CONCLUSION: Our data support a strongly positive individual and combined association of famine exposure and serum uric acid with hypertension in middle-aged and elderly Chinese.

Development of a Scale to Measure Infant Eating Behaviour Worldwide.

In order to create a short, internationally valid scale to assess eating behaviour (EB) in young children at risk of undernutrition, we refined 15 phrases describing avidity or food refusal (avoidance). In study one, 149 parents matched phrases in English, Urdu, Cantonese, Indonesian or Greek to videos showing avidity and avoidance; 82-100% showed perfect agreement for the avidity phrases and 73-91% for the avoidant phrases. In study two, 575 parents in the UK, Cyprus and Indonesia (healthy) and in Kenya, Pakistan and Guatemala (healthy and undernourished) rated their 6-24 months old children using the same phrases. Internal consistency (Cronbach's α) was high for avidity (0.88) and moderate for avoidance (0.72). The best-performing 11 items were entered into a principal components analysis and the two scales loaded separately onto 2 factors with Eigen values > 1. The avidity score was positively associated with weight (r = 0.15 p = 0.001) and body mass index (BMI) Z scores (r = 0.16 p = 0.001). Both high and low avoidance were associated with lower weight and BMI Z scores. These scales are internationally valid, relate to nutritional status and can be used to inform causes and treatments of undernutrition worldwide.

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.

Water insecurity potentially undermines dietary diversity of children aged 6-23 months: Evidence from India.

Dietary diversity is a crucial pathway to child nutrition; lack of diversity may deprive children of critical macro and micronutrients. Though water along with hygiene and sanitation is a known driver of child undernutrition, a more direct role of household water in shaping dietary diversity remains unexplored. Existing literature provides a sound theoretical basis to expect that water could affect dietary diversity among young children. Here, we test the proposition that suboptimal household access to water and low regional water availability associate with lower dietary diversity among young children. Using the nationally representative 2015-2016 India Demographic and Health Survey data, we conducted a probit analysis on the sample of 69,841 children aged 6-23 months to predict the probability that a child achieves minimum standards of dietary diversity (MDD). After controlling for relevant socioeconomic and gender-related covariates, we found that children in household with suboptimal household water access were two percentage points less likely to achieve MDD, when compared with those from households with optimal water access. Children in high water availability regions had nine percentage points greater probability of achieving MDD compared with children from low water availability regions, accounting for household water access. As dietary diversity is central to nutrition, establishing the role of water access in shaping early childhood dietary diversity broadens the framework on how household material poverty shapes child malnutrition-independent of sanitation and hygiene pathways. This provides additional window for nutrition planning and intervention wherein water-based strategies can be leveraged in multiple ways.

A double-blind placebo-controlled trial of azithromycin to reduce mortality and improve growth in high-risk young children with non-bloody diarrhoea in low resource settings: the Antibiotics for Children with Diarrhoea (ABCD) trial protocol.

BACKGROUND: Acute diarrhoea is a common cause of illness and death among children in low- to middle-income settings. World Health Organization guidelines for the clinical management of acute watery diarrhoea in children focus on oral rehydration, supplemental zinc and feeding advice. Routine use of antibiotics is not recommended except when diarrhoea is bloody or cholera is suspected. Young children who are undernourished or have a dehydrating diarrhoea are more susceptible to death at 90 days after onset of diarrhoea. Given the mortality risk associated with diarrhoea in children with malnutrition or dehydrating diarrhoea, expanding the use of antibiotics for this subset of children could be an important intervention to reduce diarrhoea-associated mortality and morbidity. We designed the Antibiotics for Childhood Diarrhoea (ABCD) trial to test this intervention. METHODS: ABCD is a double-blind, randomised trial recruiting 11,500 children aged 2-23 months presenting with acute non-bloody diarrhoea who are dehydrated and/or undernourished (i.e. have a high risk for mortality). Enrolled children in Bangladesh, India, Kenya, Malawi, Mali, Pakistan and Tanzania are randomised (1:1) to oral azithromycin 10 mg/kg or placebo once daily for 3 days and followed-up for 180 days. Primary efficacy endpoints are all-cause mortality during the 180 days post-enrolment and change in linear growth 90 days post-enrolment. DISCUSSION: Expanding the treatment of acute watery diarrhoea in high-risk children to include an antibiotic may offer an opportunity to reduce deaths. These benefits may result from direct antimicrobial effects on pathogens or other incompletely understood mechanisms including improved nutrition, alterations in immune responsiveness or improved enteric function. The expansion of indications for antibiotic use raises concerns about the emergence of antimicrobial resistance both within treated children and the communities in which they live. ABCD will monitor antimicrobial resistance. The ABCD trial has important policy implications. If the trial shows significant benefits of azithromycin use, this may provide evidence to support reconsideration of antibiotic indications in the present World Health Organization diarrhoea management guidelines. Conversely, if there is no evidence of benefit, these results will support the current avoidance of antibiotics except in dysentery or cholera, thereby avoiding inappropriate use of antibiotics and reaffirming the current guidelines. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03130114. Registered on April 26 2017.

Drivers of Under-Five Stunting Trend in 14 Low- and Middle-Income Countries since the Turn of the Millennium: A Multilevel Pooled Analysis of 50 Demographic and Health Surveys.

BACKGROUND: Understanding the drivers contributing to the decreasing trend in stunting is paramount to meeting the World Health Assembly's global target of 40% stunting reduction by 2025. METHODS: We pooled data from 50 Demographic and Health Surveys since 2000 in 14 countries to examine the relationships between the stunting trend and potential factors at distal, intermediate, and proximal levels. A multilevel pooled trend analysis was used to estimate the association between the change in potential drivers at a country level and stunting probability for an individual child while adjusting for time trends and child-level covariates. A four-level mixed-effects linear probability regression model was fitted, accounting for the clustering of data by sampling clusters, survey-rounds, and countries. RESULTS: Stunting followed a decreasing trend in all countries at an average annual rate of 1.04 percentage points. Among the distal factors assessed, a decrease in the Gini coefficient, an improvement in women's decision-making, and an increase in urbanization were significantly associated with a lower probability of stunting within a country. Improvements in households' access to improved sanitation facilities and drinking water sources, and children's access to basic vaccinations were the important intermediate service-related drivers, whereas improvements in early initiation of breastfeeding and a decrease in the prevalence of low birthweight were the important proximal drivers. CONCLUSIONS: The results reinforce the need for a combination of nutrition-sensitive and -specific interventions to tackle the problem of stunting. The identified drivers help to guide global efforts to further accelerate stunting reduction and monitor progress against chronic childhood undernutrition.

Animal Models of Undernutrition and Enteropathy as Tools for Assessment of Nutritional Intervention.

: Undernutrition is a major public health problem leading to 1 in 5 of all deaths in children under 5 years. Undernutrition leads to growth stunting and/or wasting and is often associated with environmental enteric dysfunction (EED). EED mechanisms leading to growth failure include intestinal hyperpermeability, villus blunting, malabsorption and gut inflammation. As non-invasive methods for investigating gut function in undernourished children are limited, pre-clinical models are relevant to elucidating the pathophysiological processes involved in undernutrition and EED, and to identifying novel therapeutic strategies. In many published models, undernutrition was induced using protein or micronutrient deficient diets, but these experimental models were not associated with EED. Enteropathy models mainly used gastrointestinal injury triggers. These models are presented in this review. We found only a few studies investigating the combination of undernutrition and enteropathy. This highlights the need for further developments to establish an experimental model reproducing the impact of undernutrition and enteropathy on growth, intestinal hyperpermeability and inflammation, that could be suitable for preclinical evaluation of innovative therapeutic intervention.

Nutritional Status of Children with Cerebral Palsy-Findings from Prospective Hospital-Based Surveillance in Vietnam Indicate a Need for Action.

BACKGROUND: Lack of evidence on the burden and risk factors for malnutrition among children with cerebral palsy (CP) in Vietnam limits evidence-based interventions. We aimed to define the nutritional status of children with CP in Vietnam. MATERIALS AND METHODS: The study utilized data from active prospective hospital-based surveillance modelled on the Pediatric Active Enhanced Disease Surveillance system. Children (0-18 years) with CP attending the National Children's Hospital Hanoi, Vietnam between June-November 2017 were included. Data on demographic, clinical and rehabilitation status were collected following detailed neurodevelopmental assessment. Anthropometric measurements were taken. Nutritional status was determined using the World Health Organization guideline. RESULTS: Of 765 children (the mean (SD) age was 2.6 (2.5) years; 35.8% were female), 28.9% (n = 213) were underweight and 29.0% (n = 214) stunted. The odds of underweight were significantly higher among children aged >5 years and/or having a monthly family income of <50 USD. Underweight and/or stunting was high among children with quadriplegia (81%, n = 60 and 84.5%, n = 87) and/or Gross Motor Functional Classification System (GMFCS) level IV-V (62.5%, n = 45 and 67.0%, n = 67). Nearly one-third of intellectually impaired and more than half of hearing-impaired children were underweight and/or stunted. CONCLUSIONS: Poor economic status and increased motor severity increased vulnerability to malnutrition. Our findings will inform nutritional rehabilitation programs among these vulnerable children.

Identifying Dietary Strategies to Improve Nutrient Adequacy among Ethiopian Infants and Young Children Using Linear Modelling.

Nutrient adequacy of young children's diet and best possible strategies to improve nutrient adequacy were assessed. Data from the Ethiopian National Food Consumption Survey were analysed using Optifood (software for linear programming) to identify nutrient gaps in diets for children (6-8, 9-11 and 12-23 months), and to formulate feasible Food-Based Dietary Recommendations (FBDRs) in four regions which differ in culture and food practices. Alternative interventions including a local complementary food, micronutrient powders (MNPs), Small quantity Lipid-based Nutrient Supplement (Sq-LNS) and combinations of these were modelled in combination with the formulated FBDRs to compare their relative contributions. Risk of inadequate and excess nutrient intakes was simulated using the Estimated Average Requirement cut-point method and the full probability approach. Optimized local diets did not provide adequate zinc in all regions and age groups, iron for infants <12 months of age in all regions, and calcium, niacin, thiamine, folate, vitamin B12 and B6 in some regions and age-groups. The set of regional FBDRs, considerably different for four regions, increased nutrient adequacy but some nutrients remained sub-optimal. Combination of regional FBDRs with daily MNP supplementation for 6-12 months of age and every other day for 12-23 months of age, closed the identified nutrient gaps without leading to a substantial increase in the risk of excess intakes.

Comparison of Skin Structural and Functional Parameters in Well-Nourished and Moderately Undernourished Infants.

BACKGROUND: Little is known about the impact of nutrition on the development of skin structure and function in infants. METHODS: We investigated epidermal, dermal, and subcutis parameters of aged-matched well-nourished and moderately undernourished infants in this single-center, cross-sectional, noninterventional study using noninvasive methods (skin caliper, 20-MHz sonography, transepidermal water loss, skin pH, and corneometry). Plasma fatty acids were determined as an indicator of nutritional differences. 310 infants from different age groups, i.e., 1 week, 4 weeks, and 6, 9, 12, 24, and 36 months were included. Approximately half of each age group was well-nourished (WHO reference values weight-for-height/length Zscore: -0.75 ≤ Z ≤ 0.75) and the other half was moderately undernourished (-3 ≤ Z < -2). RESULTS: Structural maturational differences in the deeper dermis and subcutis regions of the skin and subtle functional changes in the epidermis were observed in moderately undernourished infants without notable clinical symptoms. Reduced skin barrier function or skin hydration were not observed in the undernourished infants, and skin pH shifted to more acidic values in this group. CONCLUSION: These findings reveal a greater impact of moderate undernutrition on the development of the dermis and subcutis and suggest that critical epidermal functions such as skin barrier and pH are mostly maintained.

Determinants of Undernutrition among Young Children Living in Soth Nikum District, Siem Reap, Cambodia.

BACKGROUND: Child undernutrition is of public concern in Cambodia. An understanding of factors influencing child nutritional status is essential to design programs that will reduce undernutrition. Using the UNICEF conceptual framework of causes of malnutrition, our research investigates the relationship between nutritional status of children aged 6⁻23 months and its immediate and underlying determinants. METHODS: Baseline data from a cluster-randomized controlled trial aiming to assess the impact of the promotion of optimal feeding practices combined or not with the provision of local foods among 360 children 6⁻23 months of age were used. Anthropometry and biochemical measurements were performed at baseline. Data on each determinant of undernutrition were collected through interviews and direct observations. RESULTS: Our results show that the degree of satisfaction of proteins and zinc requirements as well as the access to improved water sources and sanitation were positively associated with length-for-age, while having a better health status and a higher degree of satisfaction of energy, protein, zinc, and iron requirements were associated to an improved weight-for-length. Only child health status was associated to ferritin. CONCLUSION: Our results reiterate the importance of improving child diet and health status, but also the access to a healthy environment to ensure an optimal nutritional status.

Effect of a novel supplementary porridge on the nutritional status of infants and young children diagnosed with moderate acute malnutrition in Uganda: a cluster randomised control trial.

BACKGROUND: Moderate acute malnutrition (MAM) and anaemia are prevalent among infants and young children (IYC) in Uganda. A lack of consensus regarding the most effective strategy for managing MAM among IYC resulted in the present study comparing the effect of malted sorghum-based porridge (MSBP) (an active malt, extruded maize and soy sorghum supplementary porridge developed for the purpose of the present study) as an intervention versus an extruded maize and soy micronutrient fortified blend (CSB+) as a control and current standard care. Outcome measures were anthropometric status and haemoglobin levels. METHODS: The study comprised a double-blind cluster randomised control trial with eight to 10 conveniently sampled consenting mother-IYC pairs per cluster who were randomly assigned to the intervention (n = 110) or control (n = 110) for 3 months. Weekly anthropometric measurements were taken. Haemoglobin levels were measured at baseline and end line. Mean length-for-age, weight-for-age, length-for-weight and mean haemoglobin levels of the treatment and control groups were compared using an independent t-test. The Z-test was used to compare proportions of the outcome indicators between the treatment and control groups. RESULTS: Difference in mean weight-for-age Z-scores in the treatment group improved compared to control (P = 0.010). The change in mean haemoglobin levels was lower in the treatment versus the control group (P = 0.010). The proportion of IYC recovering from MAM between treatment and control did not differ significantly (P = 0.055). CONCLUSIONS: Recovery rates after supplementation with MSBP versus CSB+ resulted in similar weight-for-length and haemoglobin levels. Therefore, MSBP has the potential for being scaled up in the management of IYC with MAM in Uganda.

A multicenter, randomized controlled comparison of three renutrition strategies for the management of moderate acute malnutrition among children aged from 6 to 24 months (the MALINEA project).

BACKGROUND: The aim of this open-label, randomized controlled trial conducted in four African countries (Madagascar, Niger, Central African Republic, and Senegal) is to compare three strategies of renutrition for moderate acute malnutrition (MAM) in children based on modulation of the gut microbiota with enriched flours alone, enriched flours with prebiotics or enriched flours coupled with antibiotic treatment. METHODS: To be included, children aged between 6 months and 2 years are preselected based on mid-upper-arm circumference (MUAC) and are included based on a weight-for-height Z-score (WHZ) between - 3 and - 2 standard deviations (SD). As per current protocols, children receive renutrition treatment for 12 weeks and are assessed weekly to determine improvement. The primary endpoint is recovery, defined by a WHZ ≥ - 1.5 SD after 12 weeks of treatment. Data collected include clinical and socioeconomic characteristics, side effects, compliance and tolerance to interventions. Metagenomic analysis of gut microbiota is conducted at inclusion, 3 months, and 6 months. The cognitive development of children is evaluated in Senegal using only the Developmental Milestones Checklist II (DMC II) questionnaire at inclusion and at 3, 6, and 9 months. The data will be correlated with renutrition efficacy and metagenomic data. DISCUSSION: This study will provide new insights for the treatment of MAM, as well as original data on the modulation of gut microbiota during the renutrition process to support (or not) the microbiota hypothesis of malnutrition. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03474276 Last update 28 May 2018.

Biomarkers of Systemic Inflammation and Growth in Early Infancy are Associated with Stunting in Young Tanzanian Children.

Stunting can afflict up to one-third of children in resource-constrained countries. We hypothesized that low-grade systemic inflammation (defined as elevations in serum C-reactive protein or alpha-1-acid glycoprotein) in infancy suppresses the growth hormone⁻insulin-like growth factor (IGF) axis and is associated with subsequent stunting. Blood samples of 590 children from periurban Dar es Salaam, Tanzania, were obtained at 6 weeks and 6 months of age as part of a randomized controlled trial. Primary outcomes were stunting, underweight, and wasting (defined as length-for-age, weight-for-age and weight-for-length z-scores < -2) between randomization and endline (18 months after randomization). Cox proportional hazards models were constructed to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of time to first stunting, underweight, and wasting as outcomes, with measures of systemic inflammation, insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) as exposures, adjusting for numerous demographic and clinical variables. The incidences of subsequent stunting, underweight, and wasting were 26%, 20%, and 18%, respectively. In multivariate analyses, systemic inflammation at 6 weeks of age was significantly associated with stunting (HR: 2.14, 95% CI: 1.23, 3.72; p = 0.002). Children with higher levels of IGF-1 at 6 weeks were less likely to become stunted (HR: 0.58, 95% CI: 0.37, 0.93; p for trend = 0.019); a similar trend was noted in children with higher levels of IGF-1 at 6 months of age (HR: 0.50, 95% CI: 0.22, 1.12; p for trend = 0.07). Systemic inflammation occurs as early as 6 weeks of age and is associated with the risk of future stunting among Tanzanian children.

Short Malnourished Children and Fat Accumulation With Food Supplementation.

BACKGROUND: In moderate acute malnutrition programs, it is common practice to not measure mid-upper arm circumference (MUAC) of children whose length is <67 cm. This is based on expert opinion that supplementation of shorter children with low MUAC and weight-for-height z score ≥-2 may increase risk of excessive fat accumulation. Our aim was to assess if shorter children gain more fat than taller children when treated for moderate acute malnutrition diagnosed by low MUAC alone. METHODS: In this observational study, we included children aged 6 to 23 months with a MUAC between 115 and 125 mm and a weight-for-height z score ≥-2. On the basis of length at admission, children were categorized as short if <67 cm and long if ≥67 cm. Linear mixed-effects models were used to assess body composition on the basis of deuterium dilution and skinfold thickness. RESULTS: After 12 weeks of supplementation, there was no difference in change in fat mass index (-0.038 kg/m2, 95% confidence interval [CI]: -0.257 to 0.181, P = .74) or fat-free mass index (0.061 kg/m2, 95% CI: -0.150 to 0.271, P = .57) in short versus long. In absolute terms, the short children gained both less fat-free mass (-230 g, 95% CI: -355 to -106, P < .001) and fat mass (-97 g, 95% CI: -205 to 10, P = .076). There was no difference in changes in absolute subscapular and triceps skinfold thickness and z scores (P > .5). CONCLUSIONS: Short children with low MUAC do not gain excessive fat during supplementation. With these data, we support a recommendation for policy change to include all children ≥6 months with low MUAC in supplementary feeding programs, regardless of length. The use of length as a criterion for measuring MUAC to determine treatment eligibility should be discontinued in policy and practice.

Critical Windows for the Programming Effects of Early-Life Nutrition on Skeletal Muscle Mass.

Skeletal myogenesis begins in the embryo with proliferation and differentiation of muscle progenitor cells that ultimately fuse to form multinucleated myofibers. After midgestation, muscle growth occurs through hypertrophy of these myofibers. The most rapid growth phase occurs in the perinatal period, resulting in the expansion of muscle mass from 25% of lean mass at birth to 40-45% at maturity. These 2 phases of muscle growth are regulated by distinct molecular mechanisms engaged by extracellular cues and intracellular signaling pathways and regulatory networks they activate. Nutrients influence muscle growth by both providing the necessary substrates and eliciting extracellular cues which regulate the signal transduction pathways that control the anabolic processes of the fibers. The uniquely large capacity of immature myofibers for hypertrophy is enabled by a heightened capacity and sensitivity of protein synthesis to feeding-induced changes in plasma insulin and amino acids, and the ability to expand their myonuclear population through proliferation of muscle precursor cells (satellite cells). With maturation, satellite cells become quiescent, limiting myonuclear accretion, and the capacity of the muscles for protein anabolism progressively diminishes. Therefore, the early developmental phases represent critical windows for muscle growth which, if disrupted, result in muscle mass deficits that are unlikely to be entirely recoverable.

Improved Information and Educational Messages on Outer Packaging of Micronutrient Powders Distributed in Indonesia Increase Caregiver Knowledge and Adherence to Recommended Use.

The objective of this study was to examine the influence of improved information and educational messages on outer packaging of a micronutrient powder (MNP), locally known as “Taburia”, on knowledge and adherence to recommended use. A community-based cluster randomized controlled trial was conducted among 1149 caregivers and their children aged 6⁻36 months. Caregiver⁻child dyads were randomized by their villages to receive 30 sachets of Taburia with the: (i) original outer packaging; (ii) improved outer packaging; or (iii) improved outer packaging combined with cooking demonstrations. Adherence to Taburia use was assessed through caregiver interviews and observation of unused sachets during home visits; “high” adherence was defined as consuming 13⁻17 sachets in the previous month. Data collection included surveys and focus groups discussions. The majority of caregivers (>80%) preferred the improved packaging because it was more attractive and contained more comprehensive information. Caregivers who received the improved packaging had better knowledge regarding the recommended use of Taburia (p < 0.001) and higher adherence with the prescribed use of Taburia (43% with “high” adherence) (p < 0.001) than those who received the original packaging (29% with “high” adherence). Caregivers who participated in cooking demonstrations generally had better knowledge regarding the benefits of Taburia and recommended use, but this did not lead to higher adherence to recommended use. “Underconsumption” of Taburia (≤7 sachets) was much less prevalent than “overconsumption” (≥23 sachets), and original packaging users were more likely to consume Taburia daily instead of every two days as recommended. We conclude that the design of the outer packaging and comprehensiveness of information provided are important influencers of recommended MNP use by caregivers.

The "ComPAS Trial" combined treatment model for acute malnutrition: study protocol for the economic evaluation.

BACKGROUND: Acute malnutrition is currently divided into severe (SAM) and moderate (MAM) based on level of wasting. SAM and MAM currently have separate treatment protocols and products, managed by separate international agencies. For SAM, the dose of treatment is allocated by the child's weight. A combined and simplified protocol for SAM and MAM, with a standardised dose of ready-to-use therapeutic food (RUTF), is being trialled for non-inferior recovery rates and may be more cost-effective than the current standard protocols for treating SAM and MAM. METHOD: This is the protocol for the economic evaluation of the ComPAS trial, a cluster-randomised controlled, non-inferiority trial that compares a novel combined protocol for treating uncomplicated acute malnutrition compared to the current standard protocol in South Sudan and Kenya. We will calculate the total economic costs of both protocols from a societal perspective, using accounting data, interviews and survey questionnaires. The incremental cost of implementing the combined protocol will be estimated, and all costs and outcomes will be presented as a cost-consequence analysis. Incremental cost-effectiveness ratio will be calculated for primary and secondary outcome, if statistically significant. DISCUSSION: We hypothesise that implementing the combined protocol will be cost-effective due to streamlined logistics at clinic level, reduced length of treatment, especially for MAM, and reduced dosages of RUTF. The findings of this economic evaluation will be important for policymakers, especially given the hypothesised non-inferiority of the main health outcomes. The publication of this protocol aims to improve rigour of conduct and transparency of data collection and analysis. It is also intended to promote inclusion of economic evaluation in other nutrition intervention studies, especially for MAM, and improve comparability with other studies. TRIAL REGISTRATION: ISRCTN 30393230 , date: 16/03/2017.

Combined Protocol for Acute Malnutrition Study (ComPAS) in rural South Sudan and urban Kenya: study protocol for a randomized controlled trial.

BACKGROUND: Acute malnutrition is a continuum condition, but severe and moderate forms are treated separately, with different protocols and therapeutic products, managed by separate United Nations agencies. The Combined Protocol for Acute Malnutrition Study (ComPAS) aims to simplify and unify the treatment of uncomplicated severe and moderate acute malnutrition (SAM and MAM) for children 6-59 months into one protocol in order to improve the global coverage, quality, continuity of care and cost-effectiveness of acute malnutrition treatment in resource-constrained settings. METHODS/DESIGN: This study is a multi-site, cluster randomized non-inferiority trial with 12 clusters in Kenya and 12 clusters in South Sudan. Participants are 3600 children aged 6-59 months with uncomplicated acute malnutrition. This study will evaluate the impact of a simplified and combined protocol for the treatment of SAM and MAM compared to the standard protocol, which is the national treatment protocol in each country. We will assess recovery rate as a primary outcome and coverage, defaulting, death, length of stay, average weekly weight gain and average weekly mid-upper arm circumference (MUAC) gain as secondary outcomes. Recovery rate is defined across both treatment arms as MUAC ≥125 mm and no oedema for two consecutive visits. Per-protocol and intention-to-treat analyses will be conducted. DISCUSSION: If the combined protocol is shown to be non-inferior to the standard protocol, updating guidelines to use the combined protocol would eliminate the need for separate products, resources and procedures for MAM treatment. This would likely be more cost-effective, increase availability of services, enable earlier case finding and treatment before deterioration of MAM into SAM, promote better continuity of care and improve community perceptions of the programme. TRIAL REGISTRATION: ISRCTN, ISRCTN30393230 . Registered on 16 March 2017.