HIV prevalence among children admitted with severe acute malnutrition and associated factors with mother-to-child HIV transmission at Mulago Hospital, Uganda: A mixed methods study.

BACKGROUND: Despite global efforts to eliminate mother-to-child-transmission of HIV (MTCT), many children continue to become infected. We determined the prevalence of HIV among children with severe acute malnutrition (SAM) and that of their mothers, at admission to Mwanamugimu Nutrition Unit, Mulago Hospital, Uganda. We also assessed child factors associated with HIV-infection, and explored factors leading to HIV-infection among a subset of the mother-child dyads that tested positive. METHODOLOGY: We conducted a cross-sectional evaluation within the REDMOTHIV (Reduce mortality in HIV) clinical trial that investigated strategies to reduce mortality among HIV-infected and HIV-exposed children admitted with SAM at the Nutrition Unit. From June 2021 to December 2022, we consecutively tested children aged 1 month to 5 years with SAM for HIV, and the mothers who were available, using rapid antibody testing upon admission to the unit. HIV-antibody positive children under 18 months of age had a confirmatory HIV-DNA PCR test done. In-depth interviews (IDIs) were conducted with mothers of HIV positive dyads, to explore the individual, relationship, social and structural factors associated with MTCT, until data saturation. Quantitative data was analyzed using descriptive statistics and logistic regression in STATAv14, while a content thematic approach was used to analyze qualitative data. RESULTS: Of 797 children tested, 463(58.1%) were male and 630(79.1%) were ≤18months of age; 76 (9.5%) tested positive. Of 709 mothers, median (IQR) age 26 (22, 30) years, 188(26.5%) were HIV positive. Sixty six of the 188 mother-infant pairs with HIV exposure tested positive for HIV, an MTCT rate of 35.1% (66/188). Child age >18 months was marginally associated with HIV-infection (crude OR = 1.87,95% CI: 1.11-3.12, p-value = 0.02; adjusted OR = 1.72, 95% CI: 0.96, 3.09, p-value = 0.068). The IDIs from 16 mothers revealed associated factors with HIV transmission at multiple levels. Individual level factors: inadequate information regarding prevention of MTCT(PMTCT), limited perception of HIV risk, and fear of antiretroviral drugs (ARVs). Relationship level factors: lack of family support and unfaithfulness (infidelity) among sexual partners. Health facility level factors: negative attitude of health workers and missed opportunities for HIV testing. Community level factors: poverty and health service disruptions due to the COVID-19 pandemic. CONCLUSION: In this era of universal antiretroviral therapy for PMTCT, a 10% HIV prevalence among severely malnourished children is substantially high. To eliminate vertical HIV transmission, more efforts are needed to address challenges mothers living with HIV face intrinsically and within their families, communities and at health facilities.

Common mental disorders and associated factors among mothers of children attending severe acute malnutrition treatment in Gedio Zone, Southern Ethiopia, 2022: a cross-sectional study.

BACKGROUND: Common mental disorders describe the physical, mental, and social disturbances that are more prevalent in low and middle-income countries. Mothers are among the more vulnerable groups especially mothers having children with under-nutrition. However, there are limited studies about the magnitude of common mental disorders among mothers of undernourished children in Ethiopia. Therefore, we aimed to assess the magnitude of common mental disorders and associated factors among mothers of children attending severe acute malnutrition treatment in Gedio Zone, Southern Ethiopia. METHODS: A cross-sectional study was employed on 405 systematically selected participants. The outcome variable was assessed by a self-reporting questionnaire (SRQ-20) which was applicable and validated in Ethiopia. Data were entered and analyzed by EPi data version 5 software and SPSS version 25 respectively. Model fitness was checked by Hosmer Lemeshow's test. Logistic regression was employed to identify significant determinants. A p-value < 0.05 was used to declare association and expressed by odds ratio with a 95% CI. RESULT: In this study, the magnitude of common mental disorders was 33.16% (95% CI [28.5-38])). In multivariable analysis, six factors poor social support [AOR: 14.0, 95% CI (5.45, 35.9)], educational status [AOR: 1.95, 95% CI (1.07. 3.55)], cigarette smoking [AOR: 10.9, 95% CI (1.78, 67.01)], mother of a child with another chronic disease [AOR: 3.19, 95% CI (1.13, 8.99)], sexual violence [AOR: 4.14, 95% CI (1.38, 12.4)] and mothers with chronic disease [AOR: 3.44, 95% CI (1.72, 6.86)] were significantly associated with common mental disorders. CONCLUSION: The magnitude of common mental disorders was high. Six factors were significantly associated with common mental disorders; social support, sexual violence, maternal chronic illness, educational status, smoking, and mother of child with other chronic disease. Community awareness regarding the effect of violence, substance use, and social support on mental health should be created by the local stakeholders.

Inflammation and epithelial repair predict mortality, hospital readmission, and growth recovery in complicated severe acute malnutrition.

Severe acute malnutrition (SAM) is the most high-risk form of undernutrition, particularly when children require hospitalization for complications. Complicated SAM is a multisystem disease with high inpatient and postdischarge mortality, especially in children with comorbidities such as HIV; however, the underlying pathogenesis of complicated SAM is poorly understood. Targeted multiplex biomarker analysis in children hospitalized with SAM (n = 264) was conducted on plasma samples, and inflammatory markers were assessed on stool samples taken at recruitment, discharge, and 12 to 24 and 48 weeks after discharge from three hospitals in Zimbabwe and Zambia. Compared with adequately nourished controls (n = 173), we found that at baseline, complicated SAM was characterized by systemic, endothelial, and intestinal inflammation, which was exacerbated by HIV infection. This persisted over 48 weeks despite nutritional recovery and was associated with children's outcomes. Baseline plasma concentrations of vascular endothelial growth factor, glucagon-like peptide-2, and intestinal fatty acid-binding protein were independently associated with lower mortality or hospital readmission over the following 48 weeks. Following principal components analysis of baseline biomarkers, higher scores of a component representing growth factors was associated with greater weight-for-height z score recovery and lower mortality or hospital readmission over the 48 weeks. Conversely, components representing higher gut and systemic inflammation were associated with higher mortality or hospital readmission. These findings highlight the interplay between inflammation, which damages tissues, and growth factors, which mediate endothelial and epithelial regeneration, and support further studies investigating interventions to reduce inflammation and promote epithelial repair as an approach to reducing mortality and improving nutritional recovery.

NUTRITIONAL STATUS AND RISK FACTORS ASSOCIATED WITH SEVERE ACUTE MALNUTRITION AMONG HIV-INFECTED CHILDREN ENROLLED IN THE PAEDIATRIC HIV CLINIC, KORLE BU TEACHING HOSPITAL, ACCRA, GHANA.

Background: Malnutrition remains a common problem among Human Immunodeficiency Virus (HIV)-infected children even while receiving antiretroviral therapy leading to disease progression and reduced survival. Aim: To assess the nutritional status and risk factors associated with severe acute malnutrition (SAM) among HIV-infected children aged 1 to 15 years attending the Paediatric HIV Clinic at Korle Bu Teaching Hospital (KBTH), Accra. Methods: A cross-sectional study was conducted from October 2018 to January 2019 at the Clinic during which 150 participants aged 15 to 179 months were systematically recruited. A structured interview, physical examination, including anthropometric measurements, data extraction from hospital records, and laboratory investigations were conducted. Weight-for- age, weight-for-length/height, length/height-for-age, body mass index Z scores, and mid-upper arm circumference-for-age were obtained. Logistic regression models were used to assess the crude and adjusted odds of the nutritional status on the socio-demographic, clinical, and HIV-related characteristics of the participants at alpha= 0.05. Results: The prevalence of SAM, moderate acute malnutrition and normal nutrition were 4.0% (6/149), 13.4% (20/149) and 80.5% (120/149), respectively, whilst 1.3% (2/149) were overweight and 0.7% (1/149) obese. Stunting and severe stunting were 18.1% (27/149) and 6.7% (10/149) prevalent, respectively. SAM was significantly associated with oral thrush among participants in the adjusted model. The prevalence of mild-, moderate- and severe-anaemia were 23.7% (33/139), 38.8% (54/139) and 1.4% (2/139), respectively. Conclusion: Malnutrition is prevalent among HIV-infected children on antiretroviral therapy at KBTH. SAM is associated with oral thrush.

Lineamientos para la atención integral de niñas y niños menores de diez años con desnutrición severa / Guidelines for the comprehensive care of children under ten years of age with severe malnutrition

Actualmente, 1 de cada 6 niños tiene desnutrición crónica, condición que genera consecuencias preocupantes en el neurodesarrollo y que limitan el progreso del país. En la actualidad la información estadística se enfoca en los primeros 5 años de vida, pero es fundamental realizar intervenciones oportunas en las niñas y niños menores de diez años, ya que en esta etapa se establecen las bases para las funciones cerebrales superiores como la memoria, el lenguaje, el razonamiento lógico, la percepción espacial, la discriminación visual y auditiva. El Sistema Nacional Integrado de Salud, suma esfuerzos para orientar al clínico sobre el abordaje integral de la desnutrición severa, basados en evidencia científica actualizada, siendo vital brindar cuidados cariñosos, intervención oportuna del personal de salud, la familia y comunidad, para evitar o disminuir secuelas o complicaciones

Currently, 1 in 6 children suffer from chronic malnutrition, a condition that has worrying consequences for neurodevelopment and limits the country's progress. Currently the statistical information is focused on the first 5 years of life, but it is essential to make timely interventions in girls and boys under the age of ten, since at this stage the foundations are established for higher brain functions such as memory, language, logical reasoning, spatial perception, visual and auditory discrimination. The National Integrated Health System is working to guide clinicians on the comprehensive approach to severe malnutrition, based on up-to-date scientific evidence, and it is vital to provide loving care and timely intervention by health personnel, family and community, to prevent or reduce sequelae or complications

Feasibility trial for the management of severe acute malnutrition in older children with sickle cell anemia in Nigeria.

Children with sickle cell anemia (SCA) living in Nigeria are at an increased risk of malnutrition, which contributes to increased morbidity and mortality. However, evidence-based guidelines for managing malnutrition in children with SCA are lacking. To address this gap, we conducted a multicenter, randomized controlled feasibility trial to assess the feasibility and safety of treating children with SCA aged from 5 to 12 years and having uncomplicated severe acute malnutrition (body mass index z score of <-3.0). Children with SCA and uncomplicated severe acute malnutrition were randomly allocated to receive supplemental ready-to-use therapeutic food (RUTF) with or without moderate-dose hydroxyurea therapy (20 mg/kg per day). Over a 6-month enrollment period, 3190 children aged from 5 to 12 years with SCA were evaluated for eligibility, and 110 of 111 children who were eligible were enrolled. During the 12-week trial, no participants withdrew or missed visits. One participant died of unrelated causes. Adherence was high for hydroxyurea (94%, based on pill counts) and RUTF (100%, based on the number of empty sachets returned). No refeeding syndrome event or hydroxyurea-related myelosuppression occurred. At the end of the trial, the mean change in body mass index z score was 0.49 (standard deviation = 0.53), and 39% of participants improved their body mass index z score to ≥-3.0. Our findings demonstrate the feasibility, safety, and potential of outpatient treatment for uncomplicated severe acute malnutrition in children with SCA aged from 5 to 12 years in a low-resource setting. However, RUTF sharing with household and community members potentially confounded the response to malnutrition treatment. This trial was registered at clinicaltrials.gov as #NCT03634488.

A Systematic Review on the Optimal Dose and Duration of Ready-to-Use Therapeutic Food (RUTF) for 6-59-Month-Old Children with Severe Wasting or Oedema.

The World Health Organisation (WHO) recommends that severe wasting and/or oedema should be treated with ready-to-use therapeutic food (RUTF) at a dose of 150-220 kcal/kg/day for 6-8 weeks. Emerging evidence suggests that variations of RUTF dosing regimens from the WHO recommendation are not inferior. We aimed to assess the comparative efficacy and effectiveness of different RUTF doses and durations in comparison with the current WHO RUTF dose recommendation for treating severe wasting and/or oedema among 6-59-month-old children. A systematic literature search identified three studies for inclusion, and the outcomes of interest included anthropometric recovery, anthropometric measures and indices, non-response, time to recovery, readmission, sustained recovery, and mortality. The study was registered with PROSPERO, CRD 42021276757. Only three studies were eligible for analysis. There was an overall high risk of bias for two of the studies and some concerns for the third study. Overall, there were no differences between the reduced and standard RUTF dose groups in all outcomes of interest. Despite the finding of no differences between reduced and standard-dose RUTF, the studies are too few to conclusively declare that reduced RUTF dose was more efficacious than standard RUTF.

RUTF (ready-to-use-therapeutic-food): eficácia e segurança no tratamento de crianças com desnutrição grave / RUTF (Ready-to-use-therapeutic-food): efficacy and safety in the treatment of children with severe malnutrition

Contexto O Ministério da Saúde, por meio da Portaria GM/MS nº 28, de 20 de janeiro de 2023, declarou a Emergência em Saúde Pública de Importância Nacional (ESPIN) em decorrência de desassistência à população Yanomami. Desde então, entre 19 crianças indígenas de seis meses e cinco anos de idade com desnutrição grave que foram atendidas pela Casa de Apoio à Saúde Indígena (Casai) de Boa Vista/RR, 15 (78%) ganharam peso e estão evoluindo de quadros graves para moderados de desnutrição, a partir dos protocolos e diretrizes do Ministério da Saúde. No Brasil, a recomendação do Ministério da Saúde para o tratamento da desnutrição grave inclui esquemas para alimentação utilizando preparado alimentar inicial ­ F-75 (75 kcal e 0,9g de proteína/100ml) e o preparado alimentar para crescimento rápido - F-100 (100 kcal e 2,9g de proteína/100ml). O guia de prática clínica (GPC) da Organização Mundial da Saúde (OMS) refere que a maioria das crianças de seis meses ou mais com desnutrição aguda grave, sem complicações médicas, pode ser tratada com segurança por meio de alimentos terapêuticos prontos para uso (Ready-to-use-therapeutic-food - RUTF), sem necessidade de internação em unidade de saúde. Pergunta Qual é a segurança e eficácia de RUTF, no curto e longo prazo, para o tratamento de crianças menores de cinco anos com desnutrição grave? Métodos Após realização de protocolo de pesquisa, cinco bases da literatura eletrônica foram acessadas em março de 2023 para identificar estudos que pudessem oferecer resposta à pergunta de investigação. Utilizando atalhos de revisão rápida, foram realizados os processos de seleção de estudos, extração de dados e avaliação da qualidade metodológica das RS incluídas com a ferramenta AMSTAR 2. Resultados Duas revisões sistemáticas (RS) foram incluídas, sendo avaliadas como de confiança baixa e moderada. Uma RS realizou metanálises, indicando que não houve diferença entre os grupos RUTF e F-100 para ganho de peso e mortalidade. A maioria dos estudos primários, 3 de 5 ensaios clínicos randomizados (ECR) citados nas RS mostram que não houve diferença entre os grupos RUTF e F-100 quanto à altura, circunferência do braço e desnutrição aguda. Dois estudos primários incluídos nas RS indicam que o tratamento com RUFT apresenta os seguintes resultados positivos: maior probabilidade de atingir o escore Z de peso para altura; menor probabilidade de recaída e de recidiva; melhora no ganho de peso e redução do tempo de recuperação. Ressalta-se que um destes ECR apresenta conflito de interesses. Nenhuma RS analisou desfechos acerca da segurança do uso de RUTF. Dois GPC da Organização Mundial da Saúde foram selecionados mediante busca manual. Um GPC recomenda que o RUTF pode ser utilizado para crianças com desnutrição aguda grave que apresentam diarreia aguda ou persistente da mesma forma que crianças sem diarreia, quer sejam tratadas como pacientes internados ou ambulatoriais. O outro GPC recomenda que para tratamento ambulatorial de crianças com desnutrição aguda grave seja utilizado o RUTF padrão (com pelo menos 50% de proteína proveniente de laticínios). Considerações finais Esta revisão rápida aponta que há poucos estudos sobre o tema. As evidências são insuficientes para afirmar quais intervenções (RUTF ou F-100) são mais eficazes. As recomendações dos GPC também são baseadas em evidências escassas. Portanto, não há evidências que sustentem o uso do RUTF em detrimento da F-100, pois não há comprovação de maior eficácia e nenhum estudo abordou a segurança a longo prazo do uso de RUTF.

Context: The Ministry of Health, through Ordinance GM/MS No. 28, of January 20, 2023, declared a Public Health Emergency of National Importance (ESPIN) due to lack of assistance to the Yanomami population. Since then, among 19 indigenous children aged between six months and five years old with severe malnutrition who were assisted by the Casa de Apoio à Saúde Indígena (Casai) in Boa Vista/RR, 15 (78%) have gained weight and are evolving from serious conditions. for moderate malnutrition, based on the protocols and guidelines of the Ministry of Health. In Brazil, the recommendation of the Ministry of Health for the treatment of severe malnutrition includes feeding schemes using initial food preparation - F-75 (75 kcal and 0.9g of protein/100ml) and food preparation for rapid growth - F-100 (100 kcal and 2.9g of protein/100ml). The clinical practice guide (CPG) of the World Health Organization (WHO) states that most children aged six months or more with severe acute malnutrition, without medical complications, can be safely treated with ready-to-use therapeutic foods ( Ready-to-use-therapeutic-food - RUTF), without the need for hospitalization in a health unit. Question: What is the safety and efficacy of RUTF, in the short and long term, for the treatment of children under five with severe malnutrition? Methods: After carrying out a research protocol, five electronic literature databases were accessed in March 2023 to identify studies that could answer the research question. Using rapid review shortcuts, the processes of study selection, data extraction and methodological quality assessment of the SR included with the AMSTAR 2 tool were carried out. Results: Two systematic reviews (SR) were included, being assessed as having low and moderate confidence. An SR performed meta-analyses, indicating that there was no difference between the RUTF and F-100 groups for weight gain and mortality. Most of the primary studies, 3 out of 5 randomized clinical trials (RCTs) cited in the SR show that there was no difference between the RUTF and F-100 groups in terms of height, arm circumference and acute malnutrition. Two primary studies included in the SR indicate that treatment with RUFT has the following positive outcomes: increased likelihood of achieving weight-for-height Z-score; lower probability of relapse and recurrence; improvement in weight gain and reduced recovery time. It should be noted that one of these RCTs has a conflict of interest. No SR analyzed outcomes regarding the safety of using RUTF. Two World Health Organization CPGs were selected by manual search. A CPG recommends that RUTF can be used for children with severe acute malnutrition who have acute or persistent diarrhea in the same way as children without diarrhea, whether they are treated as inpatients or outpatients. The other CPG recommends that standard RUTF be used for outpatient treatment of children with severe acute malnutrition (with at least 50% protein from dairy products). Final considerations: This quick review points out that there are few studies on the subject. There is insufficient evidence to state which interventions (RUTF or F-100) are most effective. The CPGs recommendations are also based on sparse evidence. Therefore, there is no evidence to support the use of RUTF over F-100, as there is no evidence of greater efficacy and no study has addressed the long-term safety of using RUTF.

Ready-to-Use Therapeutic Foods Fail to Improve Vitamin A and Iron Status Meaningfully during Treatment for Severe Acute Malnutrition in 6-59-Month-old Cambodian Children.

Severe acute malnutrition (SAM) remains a global health concern. Studies on the impact of ready-to-use therapeutic foods (RUTFs) on micronutrient status during SAM treatment are almost nonexistent. The objective was to investigate the impact of RUTFs on the iron and vitamin A status of 6-59-month-old children receiving SAM treatment. Biomarkers of vitamin A status (retinol-binding protein, RBP), iron status (ferritin and soluble transferrin receptor, sTfR), and inflammation (C-reactive protein, CRP, and alpha-1 acid glycoprotein, AGP) were collected at admission and discharge (week 8) during an RUTF effectiveness trial. Vitamin A deficiency was defined as RBP <0.70 µmol/L, low body iron as body iron (BI) <0 mg/kg and deficient iron stores as ferritin <12 µg/L. Data were available for 110 and 75 children at admission and discharge, respectively. There was no significant difference in haemoglobin, ferritin, sTfR, BI or RBP concentrations between admission and discharge. At discharge, BI was 0.2 mg/kg lower, and there was a tendency towards a slightly lower RBP concentration, but the prevalence of vitamin A deficiency was low at admission and discharge (6% and 3%, respectively). The small impact of both RUTFs on improving vitamin A and iron status during SAM treatment calls for further research on the bioavailability of micronutrients to enhance the effectiveness of SAM treatment on micronutrient status.

Increased vs. Standard Dose of Iron in Ready-to-Use Therapeutic Foods for the Treatment of Severe Acute Malnutrition in a Community Setting: A Systematic Review and Meta-Analysis.

The optimal dose of iron in ready-to-use therapeutic foods (RUTF) used to treat uncomplicated severe acute malnutrition (SAM) in community settings is not well established. The objective of this systematic review was to assess if an increased iron dose in RUTF, compared with the standard iron dose in the World Health Organization (WHO)-recommended peanut-based RUTF, improved outcomes in children aged six months or older. We searched multiple electronic databases and only included randomized controlled trials. We pooled the data in a meta-analysis to obtain relative risk (RR) and reported it with a 95% confidence interval (CI). Three studies, one each from Zambia, the Democratic Republic of Congo, and Malawi, were included. In all studies, the RUTF used in the intervention group was milk-free soya-maize-sorghum-based RUTF. The pooled results showed that, compared to the control group, a high iron content in RUTF may lead to increase in hemoglobin concentration (mean difference 0.33 g/dL, 95% CI: 0.02, 0.64, two studies, certainty of evidence: low) and a decrease in any anemia (RR 0.66, 95% CI: 0.48, 0.91, two studies, certainty of evidence: low), but also decrease recovery rates (RR 0.91, 95% CI: 0.84, 0.99, three studies, certainty of evidence: low) and increase mortality (RR 1.30, 95% CI: 0.87, 1.95, three studies, certainty of evidence: moderate). However, the CIs were imprecise for the latter outcome. Future studies with large sample sizes are needed to confirm the beneficial versus harmful effects of high iron content in RUTF in treating uncomplicated SAM in children aged 6-59 months in community settings.

Post-discharge morbidity and mortality in children admitted with severe anaemia and other health conditions in malaria-endemic settings in Africa: a systematic review and meta-analysis.

BACKGROUND: Severe anaemia is associated with high in-hospital mortality among young children. In malaria-endemic areas, surviving children also remain at increased risk of mortality for several months after hospital discharge. We aimed to compare the risks of morbidity and mortality among children discharged from hospital after recovery from severe anaemia versus other health conditions in malaria-endemic settings in Africa. METHODS: Following PRISMA guidelines, we searched PubMed, Scopus, Web of Science, and Cochrane Central from inception to Nov 30, 2021, without language restrictions, for prospective or retrospective cohort studies and randomised controlled trials that followed up children younger than 15 years for defined periods after hospital discharge in malaria-endemic countries in Africa. We excluded the intervention groups in trials and studies or subgroups involving children with sickle cell anaemia, malignancies, or surgery or trauma, or those reporting follow-up data that were combined with the in-hospital period. Two independent reviewers extracted the data and assessed the quality and risk of bias using the Newcastle Ottawa Scale or the Cochrane Collaboration's tool. The coprimary outcomes were all-cause death and all-cause readmissions 6 months after discharge. This study is registered with PROSPERO, CRD42017079282. FINDINGS: Of 2930 articles identified in our search, 27 studies were included. For children who were recently discharged following hospital admission with severe anaemia, all-cause mortality by 6 months was higher than during the in-hospital period (n=5 studies; Mantel-Haenszel odds ratio 1·72, 95% CI 1·22-2·44; p=0·0020; I2=51·5%) and more than two times higher than children previously admitted without severe anaemia (n=4 studies; relative risk [RR] 2·69, 95% CI 1·59-4·53; p<0·0001; I2=69·2%). Readmissions within 6 months of discharge were also more common in children admitted with severe anaemia than in children admitted with other conditions (n=1 study; RR 3·05, 1·12-8·35; p<0·0001). Children admitted with severe acute malnutrition (regardless of severe anaemia) also had a higher 6-month mortality after discharge than those admitted for other reasons (n=2 studies; RR=3·12, 2·02-4·68; p<0·0001; I2=54·7%). Other predictors of mortality after discharge included discharge against medical advice, HIV, bacteraemia, and hypoxia. INTERPRETATION: In malaria-endemic settings in Africa, children admitted to hospital with severe anaemia and severe acute malnutrition are at increased risk of mortality in the first 6 months after discharge compared with children admitted with other health conditions. Improved strategies are needed for the management of these high-risk groups during the period after discharge. FUNDING: Research Council of Norway and US Centers for Disease Control and Prevention.

Optimal iron content in ready-to-use therapeutic foods for the treatment of severe acute malnutrition in the community settings: a protocol for the systematic review and meta-analysis.

INTRODUCTION: The current standard of care for children with severe acute malnutrition (SAM) involves using ready-to-use therapeutic food (RUTF) to promote growth; however, the precise formulation to achieve optimal recovery remains unclear. Emerging research suggests that alternative RUTF formulations may be more effective in correcting SAM-related complications such as anaemia and iron deficiency. This systematic review commissioned by the WHO aims to synthesise the most recent research on the iron content in RUTF and related products in the community-based treatment of uncomplicated severe malnutrition in children aged 6 months and older. METHODS AND ANALYSIS: We will search multiple electronic databases. We will include randomised controlled trials and non-randomised studies with a control arm. The intervention group will be infants who received RUTF treatments other than the current recommended guidelines set forth by the WHO. The comparison group is children receiving RUTF containing iron at the current WHO-recommended level of 1.9 mg/100 kcal (10-14 mg/100 g). The primary outcomes of interest include blood haemoglobin concentration, any anaemia, severe anaemia, iron-deficiency anaemia, recovery from SAM and any adverse outcomes. We will use meta-analysis to pool findings if sufficient homogeneity exists among included studies. The risk of bias in studies will be evaluated using the Cochrane risk of bias-2. We will use the Grading of Recommendations Assessment, Development, and Evaluation(GRADE) approach to examine the overall certainty of evidence. ETHICS AND DISSEMINATION: This is a systematic review and will not involve direct contact with human subjects. The findings of this review will be published in a peer-reviewed journal and will guide the WHO's recommendation on the optimal iron content in RUTFs for the treatment of SAM in children aged 6-59 months.

Low linoleic acid foods with added DHA given to Malawian children with severe acute malnutrition improve cognition: a randomized, triple-blinded, controlled clinical trial.

BACKGROUND: There is concern that the PUFA composition of ready-to-use therapeutic food (RUTF) for the treatment of severe acute malnutrition (SAM) is suboptimal for neurocognitive recovery. OBJECTIVES: We tested the hypothesis that RUTF made with reduced amounts of linoleic acid, achieved using high-oleic (HO) peanuts without added DHA (HO-RUTF) or with added DHA (DHA-HO-RUTF), improves cognition when compared with standard RUTF (S-RUTF). METHODS: A triple-blind, randomized, controlled clinical feeding trial was conducted among children with uncomplicated SAM in Malawi with 3 types of RUTF: DHA-HO-RUTF, HO-RUTF, and S-RUTF. The primary outcomes, measured in a subset of subjects, were the Malawi Developmental Assessment Tool (MDAT) global z-score and a modified Willatts problem-solving assessment (PSA) intention score for 3 standardized problems, measured 6 mo and immediately after completing RUTF therapy, respectively. MDAT domain z-scores, plasma fatty acid content, anthropometry, and eye tracking were secondary outcomes. Comparisons were made between the novel PUFA RUTFs and S-RUTF. RESULTS: Among the 2565 SAM children enrolled, mean global MDAT z-scores were -0.69 ± 1.19 and -0.88 ± 1.27 for children receiving DHA-HO-RUTF and S-RUTF, respectively (difference 0.19, 95% CI: 0.01, 0.38). Children receiving DHA-HO-RUTF had higher gross motor and social domain z-scores than those receiving S-RUTF. The PSA problem 3 scores did not differ by dietary group (OR: 0.92, 95% CI: 0.67, 1.26 for DHA-HO-RUTF). After 4 wk of treatment, plasma phospholipid EPA and α-linolenic acid were greater in children consuming DHA-HO-RUTF or HO-RUTF when compared with S-RUTF (for all 4 comparisons P values < 0.001), but only plasma DHA was greater in DHA-HO-RUTF than S-RUTF (P < 0.001). CONCLUSIONS: Treatment of uncomplicated SAM with DHA-HO-RUTF resulted in an improved MDAT score, conferring a cognitive benefit 6 mo after completing diet therapy. This treatment should be explored in operational settings. This trial was registered at clinicaltrials.gov as NCT03094247.

Supplementary Feeding of Moderately Wasted Children in Sierra Leone Reduces Severe Acute Malnutrition and Death When Compared with Nutrition Counseling: A Retrospective Cohort Study.

BACKGROUND: There is uncertainty about whether children with moderate wasting should receive supplementary feeding. OBJECTIVES: We examined whether supplementary feeding compared with counseling alone in children with moderate wasting prevented progression to severe acute malnutrition (SAM) or death. METHODS: This was a retrospective, dual-cohort study in which 1791 children with moderate wasting were drawn from 2 prior randomized controlled trials that took place in the same location in rural Sierra Leone. A total of 1077 children received supplementary feeding, whereas 714 children received counseling alone. Children in both cohorts were followed for ≥24 wk from enrollment. The primary outcome was time to SAM or death using Kaplan-Meier analysis. Secondary outcomes included time to death as well as proportions of children with healthy midupper arm circumference (MUAC), moderate wasting, SAM, or death at 6, 12, and 24 wk from enrollment. RESULTS: Children who received supplementary feeding were less likely to develop SAM or die across the entire follow-up period (HR: 0.53; 95% CI: 0.44, 0.65; P < 0.001). Time to event for death alone also revealed a lower risk for children who received supplementary feeding (HR: 0.52; 95% CI: 0.28, 0.94; P = 0.03). Children who received supplementary feeding were more likely to have a healthy MUAC at 6 wk (RR: 2.0; 95% CI: 1.7, 2.2) and 12 wk (RR: 1.3; 95% CI: 1.2, 1.5), were less likely to develop SAM at 6 (RR: 0.7; 95% CI: 0.6, 0.9), 12 (RR: 0.5; 95% CI: 0.3, 0.8), and 24 wk (RR: 0.2; 95% CI: 0.1, 0.5), and had higher rates of gain in weight and MUAC at 6 and 12 wk. CONCLUSIONS: Supplementary feeding of children with moderate wasting reduces risk of SAM and death across 24 wk of follow-up.

Topical emollient therapy with sunflower seed oil alters the skin microbiota of young children with severe acute malnutrition in Bangladesh: A randomised, controlled study.

BACKGROUND: Topical emollient therapy with sunflower seed oil (SSO) reduces risk of sepsis and mortality in very preterm infants in low- or middle-income countries (LMICs). Proposed mechanisms include modulation of skin and possibly gut barrier function. The skin and gut microbiota play important roles in regulating barrier function, but the effects of emollient therapy on these microbiotas are poorly understood. METHODS: We characterised microbiota structure and diversity with 16S rRNA gene amplicon sequence data and ecological statistics in 20 children with severe acute malnutrition (SAM) aged 2-24 months, at four skin sites and in stool, during a randomised, controlled trial of emollient therapy with SSO in Bangladesh. Microbes associated with therapy were identified with tree-based sparse discriminant analysis. RESULTS: The skin microbiota of Bangladeshi children with SAM was highly diverse and displayed significant variation in structure as a function of physical distance between sites. Microbiota structure differed between the study groups (P = 0.005), was more diverse in emollient-treated subjects-including on the forehead which did not receive direct treatment-and changed with each day (P = 0.005) at all skin sites. Overall, Prevotellaceae were the most differentially affected by emollient treatment; several genera within this family became more abundant in the emollient group than in the controls across several skin sites. Gut microbiota structure was associated with sample day (P = 0.045) and subject age (P = 0.045), but was not significantly affected by emollient treatment (P = 0.060). CONCLUSIONS: Emollient therapy altered the skin microbiota in a consistent and temporally coherent manner. We speculate that therapy with SSO enhances skin barrier function in part through alterations in the microbiota, and through systemic mechanisms. Strategies to strengthen skin and gut barrier function in populations at risk, such as children in LMICs like Bangladesh, might include deliberate manipulation of their skin microbiota. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02616289.

Effect of topical applications of sunflower seed oil on systemic fatty acid levels in under-two children under rehabilitation for severe acute malnutrition in Bangladesh: a randomized controlled trial.

BACKGROUND: Children with severe acute malnutrition (SAM) have inadequate levels of fatty acids (FAs) and limited capacity for enteral nutritional rehabilitation. We hypothesized that topical high-linoleate sunflower seed oil (SSO) would be effective adjunctive treatment for children with SAM. METHODS: This study tested a prespecified secondary endpoint of a randomized, controlled, unblinded clinical trial with 212 children with SAM aged 2 to 24 months in two strata (2 to < 6 months, 6 to 24 months in a 1:2 ratio) at Dhaka Hospital of icddr,b, Bangladesh between January 2016 and December 2017. All children received standard-of-care management of SAM. Children randomized to the emollient group also received whole-body applications of 3 g/kg SSO three times daily for 10 days. We applied difference-in-difference analysis and unsupervised clustering analysis using t-distributed stochastic neighbor embedding (t-SNE) to visualize changes in FA levels in blood from day 0 to day 10 of children with SAM treated with emollient compared to no-emollient. RESULTS: Emollient therapy led to systematically higher increases in 26 of 29 FAs over time compared to the control. These effects were driven primarily by changes in younger subjects (27 of 29 FAs). Several FAs, especially those most abundant in SSO showed high-magnitude but non-significant incremental increases from day 0 to day 10 in the emollient group vs. the no-emollient group; for linoleic acid, a 237 µg/mL increase was attributable to enteral feeding and an incremental 98 µg/mL increase (41%) was due to emollient therapy. Behenic acid (22:0), gamma-linolenic acid (18:3n6), and eicosapentaenoic acid (20:5n3) were significantly increased in the younger age stratum; minimal changes were seen in the older children. CONCLUSIONS: SSO therapy for SAM augmented the impact of enteral feeding in increasing levels of several FAs in young children. Further research is warranted into optimizing this novel approach for nutritional rehabilitation of children with SAM, especially those < 6 months. TRIAL REGISTRATION: ClinicalTrials.gov : NCT02616289 .

Metabolomic changes in severe acute malnutrition suggest hepatic oxidative stress: a secondary analysis.

Severe acute malnutrition (SAM), due to poor energy and/or protein intake, is associated with poor growth, depressed immune function, and long-term impacts on metabolic function. As the liver is a major metabolic organ and malnutrition poses metabolic stress, we hypothesize that SAM will be associated with alterations in the hepatic metabolome reflective of oxidative stress, gluconeogenesis, and ketogenesis. Thus, the purpose of this secondary analysis was to understand how SAM alters hepatic metabolism using a piglet model. Weanling piglets were feed either a reference (REF) or protein-energy deficient diet (MAL) for 5 weeks. After dietary treatment MAL piglets were severely underweight (weight-for-age Z-score of -3.29, Welch's t test, P = .0007), moderately wasted (weight-for-length Z-score of-2.49, Welch's t test, P = .003), and tended toward higher hepatic triglyceride content (Welch's t test, P = .07). Hematologic and blood biochemical measurements were assessed at baseline and after dietary treatment. The hepatic metabolome was investigated using 1H-NMR spectroscopy. Hepatic concentrations of betaine, cysteine, and glutathione tended to be lower in MAL (Welch's t test with FDR correction, P < .1), while inosine, lactate, and methionine sulfoxide concentrations were higher in MAL (inosine: P = .0448, lactate: P = .0258, methionine sulfoxide: P = .0337). These changes suggest that SAM is associated with elevated hepatic oxidative stress, increased gluconeogenesis, and alterations in 1-carbon metabolism.

Amino acid-enriched plant-based RUTF treatment was not inferior to peanut-milk RUTF treatment in restoring plasma amino acid levels among patients with oedematous or non-oedematous malnutrition.

Ready-to-use therapeutic food (RUTF) with adequate quality protein is used to treat children with oedematous and non-oedematous severe acute malnutrition (SAM). The plasma amino acid (AA) profile reflects the protein nutritional status; hence, its assessment during SAM treatment is useful in evaluating AA delivery from RUTFs. The objective was to evaluate the plasma AAs during the treatment of oedematous and non-oedematous SAM in community-based management of acute malnutrition (CMAM) using amino acid-enriched plant-based RUTFs with 10% milk (MSMS-RUTF) or without milk (FSMS-RUTF) compared to peanut milk RUTF (PM-RUTF). Plasma AA was measured in a non-blinded, 3-arm, parallel-group, simple randomized controlled trial conducted in Malawi. The RUTFs used for SAM were FSMS-RUTF, MSMS-RUTF or PM-RUTF. A non-inferiority hypothesis was tested to compare plasma AA levels from patients treated with FSMS-RUTF or MSMS-RUTF with those from patients treated with PM-RUTF at discharge. For both types of SAM, FSMS-RUTF and MSMS-RUTF treatments were non-inferior to the PM-RUTF treatment in restoration of the EAA and cystine except that for FSMS-RUTF, methionine and tryptophan partially satisfied the non-inferiority criteria in the oedematous group. Amino-acid-enriched milk-free plant-source-protein RUTF has the potential to restore all the EAA, but it is possible that enrichment with amino acids may require more methionine and tryptophan for oedematous children.