Diagnosis and treatment of growth hormone deficiency in children on the ketogenic diet: A case series.

The ketogenic diet (KD) can have a negative impact on the linear growth and body composition of children. The aims of this study were to review two centers' experience with children who developed height deceleration on the KD and determine if the height deceleration was secondary to growth hormone deficiency (GHD), and if growth hormone therapy (GHT) would be effective and safe (not altering ketosis or seizure frequency). Retrospective chart reviews were performed on patients with KD referred to Endocrinology between 2013 and 2018. Seventeen children were identified. Data reviewed included: demographics, growth velocity, KD ratio, protein/calorie intake, lab results, GH dosage, Tanner stage, and seizure frequency, and endocrine recommendations. Descriptive statistics were performed. Of the 17 children referred to the Endocrine Division, seven children were growth hormone deficient and began GHT. Data were provided for six patients (2 males, 4 females; age 2-7 years at the start of KD) on the KD for >6 years and on GHT for >4 years. Growth for all patients stabilized or increased. IGF-1 z-scores normalized. GHT did not affect seizure frequency or ketosis. GHT in those with GHD can be an appropriate option allowing better growth while still maintaining ketogenic therapy and seizure control. PLAIN LANGUAGE SUMMARY: The KD can be an effective treatment for difficult-to-control epilepsy and some disorders of carbohydrate metabolism. The KD can adversely affect the linear growth (height) of children. This case series reviewed six patients who had slow linear growth. It was found that all six children had growth hormone deficiency, grew better with growth hormone treatments, and that their seizures and ketone levels were not affected.

Equity and Distributional Impact on Stunting of a Nutritional Package Targeting Children Aged 6-36 Months in China: Findings from a Modeling Study.

BACKGROUND: Despite rapid economic development, child stunting remains a persistent problem in China. Stunting prevalence varies greatly across geographical regions and wealth groups. To address child undernutrition, the Ying Yang Bao (YYB) nutritional package has been piloted in China since 2001. OBJECTIVE: We aimed to evaluate the distributional impact of a hypothetical rollout of the YYB nutritional package on child stunting across provinces and wealth groups in China, with a specific focus on equity. METHODS: We used data from China Family Panel Studies and built on extended cost-effectiveness analysis methods. We estimated the distributional impact of a 12-month YYB program targeting children aged 6-36 months across 25 provinces and two wealth groups along three dimensions: the cost of the YYB program; the number of child stunting cases averted by YYB; and the cost per stunting case averted. Children in each province were divided into poverty and non-poverty groups based on the international poverty line of $5.50 per day. We also conducted a range of sensitivity analyses. RESULTS: We showed that 75% coverage of YYB could avert 1.9 million stunting cases among children aged 6-36 months, including 1.3 million stunting cases among children living under the poverty line, at a total cost of ¥5.4-6.2 billion ($1.5-1.8 billion) depending on the type of YYB delivery. The cost per stunting case averted would greatly vary across Chinese provinces and wealth groups, ranging from ¥800 (around $220, Chongqing province) to ¥23,300 (around $6600, Jilin province). In most provinces, the cost per stunting case averted would be lower for children living under the poverty line. CONCLUSIONS: YYB could be a pro-poor nutritional intervention package that brings substantial health benefits to poor and marginalized Chinese children, but with large variations in value for money across provinces and wealth groups. This analysis points to the need for prioritization across provinces and a targeted approach for YYB rollout in China.

Proximal and contextual correlates of childhood stunting in India: A geo-spatial analysis.

BACKGROUND: Globally, India is home to every third child affected by stunting. While numerous studies have examined the correlates of childhood stunting (CS) in India, most of these studies have focused on examining the role of proximal factors, and the role of contextual factors is much less studied. This study presents a comprehensive picture of both proximal and contextual determinants of CS in India, expanding the current evidence base. The present study is guided by the WHO conceptual framework, which outlines the context, causes, and consequences of CS. DATA AND METHODS: The study used exploratory spatial data analysis tools to analyse the spatial pattern and correlates of CS, using data from the fourth round (2015-16) of the National Family Health Survey (NFHS-4) and the 2011 Census of India. RESULTS: The study findings reiterate that CS continues to be high in India, with several hot spot states and districts, and that children from the central and eastern region of the nation, namely, Bihar, Jharkhand, Madhya Pradesh, and Uttar Pradesh are particularly vulnerable. Our analysis has identified six risk factors-maternal short stature, large household size, closely spaced births, prevalence of hypertension among women, household poverty, open defecation, and extreme temperature-and four protective factors-female education, access to improved drinking water, dietary diversity among children, and iron and folic acid (IFA) supplementation during pregnancy. CONCLUSIONS: The study highlights the need for investing in pre-conception care, addressing both demand- and supply-side barriers to increase the coverage of nutrition-specific interventions, implementing programmes to promote the intake of healthy foods from an early age, providing contraceptive counselling and services to unmarried and married adolescents and young women and men, and universalizing quality primary and secondary education that is inclusive and equitable to avert the burden of childhood stunting in India.

The impact of food fortification on stunting in Zimbabwe: does gender of the household head matter?

BACKGROUND: High prevalence of stunting in children under 5 years poses a major threat to child development in developing countries. It is associated with micronutrient deficiency arising from poor diets fed to children under 5 years. Food fortification is amongst the interventions focused at reducing the incidence of stunting in children under 5 years. METHODS: Using a large-scale household data from Zimbabwe, we investigated the gender-based importance of household adoption of food fortification on the proportion of stunted children in the household. We employed propensity score matching to mitigate self-selection bias associated with household adoption of food fortification. RESULTS: We offer three major findings. Firstly, we find statistically weak evidence that female headed households are more likely to adopt food fortification than their male counterparts. Secondly, food fortification reduces the proportion of stunted children in the household. Finally, in comparison to non-adopters, female headed households that adopt food fortification are more able to reduce the proportion of stunted children in their households than their male counterparts. CONCLUSION: The results highlight the need for policy makers to actively promote food fortification, as such interventions are likely to contribute to the reduction of stunting and to involve men in fortification interventions to improve on their knowledge and appreciation of fortified foods and the associated benefits.

Metabolome and microbiome alterations related to short-term feeding of a micronutrient-fortified, high-quality legume protein-based food product to stunted school age children: A randomized controlled pilot trial.

BACKGROUND & AIMS: Stunting in children is a comorbid condition in undernutrition that may be ameliorated by the provision of high-quality foods that provide protein and micronutrients. Addressing this problem in lower social economic environments requires, in part, affordable and scalable food-based solutions with efficacious food products. Towards this end, biochemical/metabolic indicators for fast-throughput screening of foods and their components are desired. A highly acceptable and economical micronutrient-fortified food product with different levels of legume protein was provided to stunted Indian children for one month, to determine change in their linear growth and explore associated biochemical, metabolomic and microbiome indicators. METHODS: A randomized controlled pilot trial was conducted with 100 stunted children (6-10 years of age) to elucidate metabolic and microbiome-based biomarkers associated with linear growth. They were randomized into 4 groups receiving 6, 8, 10 or 12 g of legume-based protein for one month. Anthropometry, blood biochemistry, aminoacidomics, acylcarnitomics and fecal microbiome were measured before and after feeding. RESULTS: No significant differences were observed between groups in height, height-for-age Z-score (HAZ) or BMI-for-age Z-score (BAZ); however, 38 serum metabolites were altered significantly (Bonferroni adjusted P < 0.1) in response to the interventions. IGF-1 (Insulin like Growth Factor-1) was positively (ρ > 0.2, P = 0.02), while serine and ornithine (ρ < -0.2, P = 0.08) were negatively associated with change in height. Leucine, isoleucine and valine positively correlated (P = 0.011, 0.023 and 0.007 respectively) with change in BAZ. Three Operational Taxonomic Units belonging to Bacteroidetes and Firmicutes (VIP score > 1.5) were significantly correlated with change in height. CONCLUSIONS: In this pilot trial, a number of fasting serum metabolomic and fecal microbiome signatures were associated with linear growth after a short-term dietary intervention. The alterations of these markers should be validated in long-term dietary intervention trials as potential screening indicators towards the development of food products that favor growth. This trial was registered at www.ctri.nic.in as CTRI/2016/12/007564.

Effects of a nutrient-dense formula compared with a post-discharge formula on post-discharge growth of preterm very low birth weight infants with extrauterine growth retardation: a multicentre randomised study in China.

BACKGROUND: Post-discharge optimal growth and nutritional intake have beneficial effects for neurodevelopment in preterm very low birth weight infants (VLBWIs) with extrauterine growth retardation (EUGR). The present study aimed to compare the effects of a nutrient-dense formula (NDF) to a post-discharge formula (PDF) on post-discharge growth of preterm VLBWIs with EUGR. METHODS: Forty-eight preterm VLBWIs with EUGR at discharge were randomised to receive NDF (100 kcal per 100 mL; 2.6 g protein per 100 mL) or PDF (74 kcal per 100 mL; 1.95 g protein per 100 mL) for 1-6 months until body weight reached the 50th percentile on growth charts with corrected age. Volume, nutrient intake, anthropometry and biochemistry data were collected. RESULTS: Volume intake was lower in the NDF group than the PDF group during the first 2 months of feeding (P = 0.039 and 0.018, respectively).There were no significant differences in volume intake during months 2-6 of feeding. Energy, protein, carbohydrate and fat intake were higher in the NDF group during months 1-6 of feeding. There were no significant differences in weight, length, and head circumference Z-scores during months 1-6 between the two groups. The △length Z-score from discharge to month 6 was significantly higher in the NDF group than the PDF group (P = 0.043). No differences existed between the two groups with respect to biochemistry. CONCLUSIONS: After discharge, preterm VLBWIs with EUGR fed a NDF gain anthropometric parameter Z-scores similar to those for a PDF within 6 months of follow-up. A NDF leading to gain in length requires further follow-up.

Low-molecular-weight chitosan relieves enterotoxigenic Escherichia coli-induced growth retardation in weaned pigs.

The objective of the present study was to evaluate the effects of low-molecular-weight chitosan (LMWC) on the growth performance, immune responses and intestinal health of weaned pigs challenged by enterotoxigenic Escherichia coli (ETEC). A total of 32 weaned pigs were randomly allocated to four treatments: non-challenged (fed with basal diet), ETEC-challenged (fed with basal diet) and ETEC-challenged plus 50 or 100 mg/kg LMWC supplementation, respectively. After 11 days feeding, the non-challenged pigs were infused with sterilised Luria-Bertani culture, while the remaining pigs were infused with 2.6 × 1011 colony-forming units of ETEC. At 3 days post-challenge, all pigs were administered d-xylose at 0.1 g/kg body weight. One hour later, blood samples were obtained, and the pigs then euthanised to collect intestinal samples. Data showed that only 100 mg/kg LMWC supplementation attenuated (P < 0.05) the average daily gain reduction caused by ETEC. Furthermore, besides the decreased (P < 0.05) serum tumour necrosis factor-α and immunoglobulin (Ig) G concentrations detected in ETEC-challenged pigs supplemented with LMWC at 50 or 100 mg/kg, the higher dose (100 mg/kg) also decreased (P < 0.05) the serum IgM concentration and increased (P < 0.05) the villus height and villus height-to-crypt depth ratio in both the jejunum and ileum, and the sucrase activity in the ileal mucosa. Moreover, LMWC supplementation (50 or 100 mg/kg) in ETEC-challenged pigs elevated (P < 0.05) the mRNA levels of jejunal mucosal peptide transporter 1 and ileal mucosal peptide transporter 1, divalent metal transporter 1 and zinc transporter 1, and decreased (P < 0.05) the ileal and caecal E. coli abundances, while 100 mg/kg LMWC additionally elevated (P < 0.05) the ileal Bacillus abundance, and caecal and colonic Bifidobacterium abundances. These results suggest that LMWC helps alleviate ETEC-induced growth retardation in weaned pigs, which could be associated with the inhibition of the immune responses and improved intestinal health.

Presence of Giardia lamblia in stools of six- to 18-month old asymptomatic Malawians is associated with children's growth failure.

AIM: Despite high pathogen burden and malnutrition in low-income settings, knowledge on relationship between asymptomatic viral or parasitic infections, nutrition and growth is insufficient. We studied these relationships in a cohort of six-month-old Malawian infants. METHODS: As part of a nutrient supplementation trial for 12 months, we documented disease symptoms of 840 participant daily and anthropometric measurements every three months. Stool specimens were collected every six months and analysed for Giardia lamblia, Cryptosporidium species and enterovirus, rotavirus, norovirus, parechovirus and rhinovirus using polymerase chain reaction (PCR). The prevalence of the microbes was compared to the children's linear growth and the dietary. RESULTS: The prevalence of the microbes was similar in every intervention group. All age groups combined, children negative for G. lamblia had a mean standard deviation (SD) of -0.01 (0.49) change in length-for-age Z-score (LAZ), compared to -0.12 (0.045) among G. lamblia positive children (difference -0.10, 95% CI -0.21 to -0.00, p = 0.047). The LAZ change difference was also statistically significant (p = 0.042) at age of 18-21 months but not at the other time points. CONCLUSION: Asymptomatic G. lamblia infection was mainly associated with growth reduction in certain three-month periods. The result refers to the chronic nature of G. lamblia infection.

Decreased plasma l-arginine levels in organic acidurias (MMA and PA) and decreased plasma branched-chain amino acid levels in urea cycle disorders as a potential cause of growth retardation: Options for treatment.

BACKGROUND AND AIM: Patients with methylmalonic acidemia (MMA) and propionic acidemia (PA) and urea cycle disorders (UCD), treated with a protein restricted diet, are prone to growth failure. To obtain optimal growth and thereby efficacious protein incorporation, a diet containing the essential and functional amino acids for growth is necessary. Optimal growth will result in improved protein tolerance and possibly a decrease in the number of decompensations. It thus needs to be determined if amino acid deficiencies are associated with the growth retardation in these patient groups. We studied the correlations between plasma L-arginine levels, plasma branched chain amino acids (BCAA: L-isoleucine, L-leucine and L-valine) levels (amino acids known to influence growth), and height in MMA/PA and UCD patients. METHODS: We analyzed data from longitudinal visits made in stable metabolic periods by patients registered at the European Registry and Network for Intoxication Type Metabolic Diseases (E-IMD, Chafea no. 2010 12 01). RESULTS: In total, 263 MMA/PA and 311 UCD patients were included, all aged below 18 years of age. In patients with MMA and PA, height z-score was positively associated with patients' natural-protein-to-energy prescription ratio and their plasma L-valine and L-arginine levels, while negatively associated with the amount of synthetic protein prescription and their age at visit. In all UCDs combined, height z-score was positively associated with the natural-protein-to-energy prescription ratio. In those with carbamylphosphate synthetase 1 deficiency (CPS1-D), those with male ornithine transcarbamylase deficiency (OTC-D), and those in the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome subgroup, height z-score was positively associated with patients' plasma L-leucine levels. In those with argininosuccinate synthetase deficiency (ASS-D) and argininosuccinate lyase deficiency (ASL-D), height was positively associated with patients' plasma L-valine levels. CONCLUSION: Plasma L-arginine and L-valine levels in MMA/PA patients and plasma L-leucine and L-valine levels in UCD patients, as well as the protein-to-energy prescription ratio in both groups were positively associated with height. Optimization of these plasma amino acid levels is essential to support normal growth and increase protein tolerance in these disorders. Consequently this could improve the protein-to-energy intake ratio.

Changes in growth, anaemia, and iron deficiency among children aged 6-23 months in two districts in Nepal that were part of the post-pilot scale-up of an integrated infant and young child feeding and micronutrient powder intervention.

There is limited research on integrated infant and young child feeding (IYCF) and micronutrient powders (MNPs) programmes operating at scale, despite widespread implementation. This study uses cross-sectional baseline (n = 2,542) and endline (n = 2,578) surveys representative of children 6-23 months in two districts in Nepal that were part of a post-pilot scale-up of a IYCF-MNP programme. Multivariable log-binomial regression models were used to estimate prevalence ratios (PRs) for stunting (length-for-age z-score <-2), wasting (weight-for-length z-score <-2), underweight (weight-for-age z-score <-2), anaemia (altitude-adjusted haemoglobin <110 µg/L), moderate or severe anaemia (altitude-adjusted haemoglobin <100 g/L), iron deficiency (inflammation-adjusted ferritin <12 µg/L), and iron deficiency anaemia (iron deficiency + anaemia [IDA]) at endline versus baseline and also to compare children in the endline survey based on frequency of mothers' interactions with female community health volunteers (FCHVs; >1× per month or monthly vs. <1× per month) and MNP coverage (1 or ≥2 distributions vs. none among children 12-23 months). Endline children were significantly less likely to be stunted than baseline children in both districts (multivariable-adjusted PR [95% CI]: 0.77 [0.69, 0.85], P < 0.001 and 0.82 [0.75, 0.91], P < 0.001 in Kapilvastu and Achham, respectively); however, only Achham had significantly lower prevalences of underweight, moderate/severe anaemia, iron deficiency, and IDA at endline. At endline, 53.5% and 71.4% of children had tried MNP in Kapilvastu and Achham districts, respectively, consuming an average of 24 sachets from the last distribution. Frequent maternal-FCHV interactions were associated with a reduced risk of stunting and underweight at endline, whereas repeat MNP coverage was associated with reduced risk of anaemia and IDA. Future research using experimental designs should verify the potential of integrated IYCF-MNP programmes to improve children's nutritional status.

Renal Calculus in Floating-Harbor Syndrome: A Case Report.

Floating-Harbor syndrome is a rare condition marked by short stature and delayed bone age, characteristic facial features, and speech impairment. Floating-Harbor syndrome commonly results from a sporadic genetic mutation. Renal abnormalities have rarely been encountered. We report the first patient with Floating-Harbor syndrome who spontaneously passed a renal calculus consisting of calcium oxalate monohydrate and calcium oxalate dihydrate. A renal ultrasound showed echotexture within the renal pyramids, hydronephrosis, and a cyst. Pediatric nurse practitioners should be alert to the unique features associated with Floating-Harbor syndrome and be prepared to monitor and treat the renal abnormalities that may accompany this uncommon condition.

Micronutrient-rich food consumption, intra-household food allocation and child stunting in rural Nigeria.

OBJECTIVE: Children from rural households are often deprived of adequate micronutrient intakes either from food or supplementation. The present study examines: (i) the determinants of households' micronutrient-rich food consumption; and (ii) the combined effect of vitamin A supplementation and micronutrient-rich food consumption on child stunting in households with different food allocation patterns. DESIGN: Cross-sectional study. Households' micronutrient-rich food consumption frequency and vitamin A supplementation were used as a proxy measure for child micronutrient intakes. Intra-household food allocation patterns were assessed from caregivers' perception of the disparity in food distribution within the household. Descriptive statistics and logistic regression were employed in analysing the study's objectives. SETTING: Rural communities in Kwara State, Nigeria.ParticipantsIncluded 419 children aged 6-59 months and 413 households. RESULTS: Owning small livestock and a refrigerator, knowledge of micronutrient-rich foods and higher parental education had strong associations with households' micronutrient-rich food consumption. Children from households that consumed micronutrient-rich foods and received more diverse diets were less likely to experience stunting. The combined effect of micronutrient-rich food consumption and vitamin A supplementation was stronger on the likelihood of stunting reduction than the separate effect of each. CONCLUSIONS: Assets ownership, human capital and knowledge of micronutrient-rich foods improve consumption of micronutrient-rich foods among the study population. Micronutrient supplementation to children with poor access to micronutrient-rich foods may not substantially enhance child growth unless reinforced through consumption of micronutrient-rich foods. Fruit and vegetable gardening, livestock holdings and nutrition education to parents should be integral parts of community nutrition programming.

Mitigated Impact of Provision of Local Foods Combined with Nutrition Education and Counseling on Young Child Nutritional Status in Cambodia.

BACKGROUND: In Cambodia, stunting and wasting affect, respectively, 32% and 10% of children 0⁻59 months while 55% are anemic. Our research aims to assess the efficiency of two local foods combined with nutritional education and counseling (CEN) activities as compared to CEN alone on improving child nutritional status and dietary intake. METHODS: A cluster-randomized controlled trial was conducted in Soth Nikum area over a six-month period among children 6⁻23 months (n = 360) assigned to receive either moringa +CEN, cricket +CEN or CEN alone. Anthropometric measurements were performed and hemoglobin and ferritin levels assessed. RESULTS: Overall, no significant increase in the mean length/height-for-age z-score was observed, although a small increase of the weight-for-length/height was noted in intervention groups. Hemoglobin and ferritin mean values increased in all groups. The degree of satisfaction of energy, proteins, iron, and zinc requirements improved in all groups, but to a greater extent in the intervention groups and more children were healthy. CONCLUSION: Our research shows no significant impact of the provision of two local foods combined with CEN on the improvement of child nutritional status as compared to CEN alone. However, children consuming them better fulfilled their energy, iron, and zinc requirements and were healthier.

The modification of the ketogenic diet mitigates its stunting effects in rodents.

The high-fat and low-carbohydrate ketogenic diet (HFKD) is extensively studied within the fields of numerous diseases, including cancer and neurological disorders. Since most studies incorporate animal models, ensuring the quality of ketogenic rodent diets is important, both in the context of laboratory animal welfare as well as for the accuracy of the obtained results. In this study we implemented a modification to a commonly used ketogenic rodent chow by replacing non-resorbable cellulose with wheat bran. We assessed the effects of month-long treatment with either the unmodified or the modified HFKD on the growth and development of young male rats. Daily body weight, functional performance, and brain morphometric parameters were assessed to evaluate the influence of both applied diets on rodent development. Our results revealed that the unmodified ketogenic chow induced strong side effects that included weakness, emaciation, and brain undergrowth concomitant to growth inhibition. However, application of the ketogenic chow supplemented with wheat bran suppressed these adverse side effects, which was associated with the restoration of insulin-like growth factor 1 and a decrease in corticosterone levels. We have also shown that the advantageous results of the modified HFKD are not species- or sex-specific. Our data indicate that the proposed HFKD modification even allows for its application in young animals, without causing detrimental side effects.

Nutrition Interventions in the Lives Saved Tool (LiST).

The Lives Saved Tool (LiST) was initially developed in 2003 to estimate the impact of increasing coverage of efficacious interventions on under-5 mortality. Over time, the model has been expanded to include more outcomes (neonatal mortality, maternal mortality, stillbirths) and interventions. The model has also added risk factors, such as stunting and wasting, and over time has attempted to capture a full range of nutrition and nutrition-related interventions (e.g., antenatal supplementation, breastfeeding promotion, child supplemental feeding, acute malnutrition treatment), practices (e.g., age-appropriate breastfeeding), and outcomes (e.g., stunting, wasting, birth outcomes, maternal anemia). This article reviews the overall nutrition-related structure, assumptions, and outputs that are currently available in LiST. This review focuses on the new assumptions and structure that have been added to the model as part of the current effort to expand and improve the nutrition modeling capability of LiST. It presents the full set of linkages in the model that relate to nutrition outcomes, as well as the research literature used to support those linkages.

Evaluation of Nutrition Interventions in Children in Conflict Zones: A Narrative Review.

Food and nutrition insecurity becomes increasingly worse in areas affected by armed conflict. Children affected by conflict, or in war-torn settings, face a disproportionate burden of malnutrition and poor health outcomes. As noted by humanitarian response reviews, there is a need for a stronger evidence-based response to humanitarian crises. To achieve this, we systematically searched and evaluated existing nutrition interventions carried out in conflict settings that assessed their impact on children's nutrition status. To evaluate the impact of nutrition interventions on children's nutrition and growth status, we identified published literature through EMBASE, PubMed, and Global Health by using a combination of relevant text words and Medical Subject Heading terms. Studies for this review must have included children (aged ≤18 y), been conducted in conflict or postconflict settings, and assessed a nutrition intervention that measured ≥1 outcome for nutrition status (i.e., stunting, wasting, or underweight). Eleven studies met the inclusion and exclusion criteria for this review. Five different nutrition interventions were identified and showed modest results in decreasing the prevalence of stunting, wasting, underweight, reduction in severe or moderate acute malnutrition or both, mortality, anemia, and diarrhea. Overall, nutrition interventions in conflict settings were associated with improved children's nutrition or growth status. Emergency nutrition programs should continue to follow recent recommendations to expand coverage and access (beyond refugee camps to rural areas) and ensure that aid and nutrition interventions are distributed equitably in all conflict-affected populations.

Effects of protein or amino-acid supplementation on the physical growth of young children in low-income countries.

Child growth stunting is common in low-income countries, possibly due to insufficient protein intakes. Most previous studies have concluded that children's protein intakes are adequate in relation to estimated requirements, but these studies did not consider issues of protein digestibility and effects of infection on dietary protein utilization. Using an alternative approach to assess the possible role of protein inadequacy in children's growth restriction, the results of 18 intervention trials in which supplementary protein or amino acids were provided to children ages 6-35 months and growth outcomes were reviewed. Eight studies conducted in hospitalized children recovering from acute malnutrition found that the recommended protein intake levels for healthy children supported normal growth rates, but higher intakes were needed for accelerated rates of "catch-up" growth. Ten community-based studies did not demonstrate a consistent benefit of supplemental protein on children's growth. However, weaknesses in the study designs limit the conclusions that can be drawn from these studies, and additional appropriately designed trials are needed to answer this question definitively. Recommendations for optimizing future study designs are provided herein.

Home- and community-based growth monitoring to reduce early life growth faltering: an open-label, cluster-randomized controlled trial.

Background: Despite the continued high prevalence of faltering growth, height monitoring remains limited in many low- and middle-income countries.Objective: The objective of this study was to test whether providing parents with information on their child's height can improve children's height and developmental outcomes.Design: Villages in Chipata District, Zambia (n = 127), were randomly assigned with equal probability to 1 of 3 groups: home-based growth monitoring (HBGM), community-based growth monitoring including nutritional supplementation for children with stunted growth (CBGM+NS), and control. Primary study outcomes were individual height-for-age z score (HAZ) and overall child development assessed with the International Fetal and Newborn Growth Consortium for the 21st Century Neurodevelopment Assessment tool. Secondary outcomes were weight-for-age z score (WAZ), protein consumption, breastfeeding, and general dietary diversity.Results: We enrolled a total of 547 children with a median age of 13 mo at baseline. Estimated mean difference (ß) in HAZ was 0.127 (95% CI: -0.107, 0.361) for HBGM and -0.152 (95% CI: -0.341, 0.036) for CBGM+NS. HBGM had no impact on child development [ß: -0.017 (95% CI: -0.133, 0.098)]; CBGM+NS reduced overall child development scores by -0.118 SD (95% CI: -0.230, -0.006 SD). Both interventions had larger positive effects among children with stunted growth at baseline, with estimated interaction effects of 0.503 (95% CI: 0.160, 0.846) and 0.582 (95% CI: 0.134, 1.030) for CBGM+NS and HBGM, respectively. HBGM increased mean WAZ [ß = 0.183 (95% CI: 0.037, 0.328)]. Both interventions improved parental reports of children's protein intake.Conclusions: The results from this trial suggest that growth monitoring has a limited effect on children's height and development, despite improvements in self-reported feeding practices. HBGM had modest positive effects on children with stunted growth. Given its relatively low cost, this intervention may be a cost-effective tool for increasing parental efforts toward reducing children's physical growth deficits. This trial was registered at clinicaltrials.gov as NCT02242539.

Bangladesh Environmental Enteric Dysfunction (BEED) study: protocol for a community-based intervention study to validate non-invasive biomarkers of environmental enteric dysfunction.

INTRODUCTION: Environmental enteric dysfunction (EED) is a subacute inflammatory condition of the small intestinal mucosa with unclear aetiology that may account for more than 40% of all cases of stunting. Currently, there are no universally accepted protocols for the diagnosis, treatment and ultimately prevention of EED. The Bangladesh Environmental Enteric Dysfunction (BEED) study is designed to validate non-invasive biomarkers of EED with small intestinal biopsy, better understand disease pathogenesis and identify potential therapeutic targets for interventions designed to control EED and stunting. METHODS AND ANALYSIS: The BEED study is a community-based intervention where participants are recruited from three cohorts: stunted children aged 12-18 months (length for age Z-score (LAZ) <-2), at risk of stunting children aged 12-18 months (LAZ <-1 to -2) and malnourished adults aged 18-45 years (body mass index <18.5 kg/m2). After screening, participants eligible for study provide faecal, urine and plasma specimens to quantify the levels of candidate EED biomarkers before and after receiving a nutritional intervention. Participants who fail to respond to nutritional therapy are considered as the candidates for upper gastrointestinal endoscopy with biopsy. Histopathological scoring for EED will be performed on biopsies obtained from several locations within the proximal small intestine. Candidate EED biomarkers will be correlated with nutritional status, the results of histochemical and immunohistochemical analyses of epithelial and lamina propria cell populations, plus assessments of microbial community structure. ETHICS AND DISSEMINATION: Ethics approval was obtained in all participating institutes. Results of this study will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov ID: NCT02812615. Registered on 21 June 2016.

Results with Complementary Food Using Local Food Ingredients.

Appropriate complementary food is a must for optimum growth of infants and children. The food should be diverse and be given in sufficient quantities 2-4 times a day depending upon age. Poverty, food insecurity, and lack of awareness regarding the choice of nutritious food ingredients are deterrents to optimum complementary feeding. In Bangladesh, 77% of children do not receive appropriate complementary food and, hence, the high prevalence of childhood malnutrition. We developed ready-to-use complementary foods (RUCFs) using locally available food ingredients, rice/lentil and chickpea, which conform to standard specifications. These foods were found to be acceptable by children and their mothers compared to the Pushti packet, the cereal-based supplement used in the erstwhile National Nutrition Program of Bangladesh. In a cluster-randomized community-based trial in rural Bangladesh among more than 5,000 children, the efficacy of rice/lentil- and chickpea-based RUCFs was compared with another commonly used supplementary food called wheat-soy blend++ (WSB++) and a commercial product called Plumpy'doz. Deceleration in length for age was significantly lower (by 0.02-0.04/month) in the rice/lentil, Plumpy'doz, and chickpea groups compared to the control group at 18 months of age. Weight-for-length z-score decline was lower only in Plumpy'doz and chickpea groups. WSB++ was not different from the control group. In children who received chickpea RUCF or Plumpy'doz, the prevalence of stunting was 5-6% lower at 18 months. These foods can be used to prevent or treat malnutrition among children, particularly those from food-insecure households.