Predictors of recovery from severe acute malnutrition among 6-59 months children admitted to a hospital.

Background and aim: Severe acute malnutrition is a threat to child survival as mortality rates in children with severe malnutrition are nine times higher. Globally, about 19 million children are severely malnourished. This study looked at children aged 6-59 months admitted to hospital to see how quickly they recovered from severe acute malnutrition as well as what factors predicted their recovery. Methods: The study included 543 systematically chosen children with severe acute malnutrition who were admitted to the stabilization center of a hospital. Data from the patient registry were gathered using a retrospective follow-up study design. In order to find predictors of recovery, the Cox proportional hazard model was applied. Results: From 543 children, 425 (78.27%) were recovered. The median survival time was 8 days. Having grade II edema, grade III edema, and pneumonia were negatively associated with recovery. Similarly, taking ceftriaxone, cloxacillin, and being on a nasogastric tube were associated with poor recovery. Conversely, better recovery rates were linked to exclusive breastfeeding and vitamin A supplementation. Conclusion: Both the recovery rate and the median survival time fell within acceptable bounds. To boost the recovery rate, efforts are needed to lessen comorbidities.

Incidence and predictors of severe acute malnutrition mortality in children aged 6-59 months admitted at Pawe general hospital, Northwest Ethiopia.

BACKGROUND: Severe acute malnutrition (SAM) is defined as a weight-for-height < -3z scores of the median WHO growth standards, or visible severe wasting or the presence of nutritional edema. SAM related mortality rates in under-five children are well documented in Ethiopia but data on their predictors are limited. We aimed to document factors associated with SAM related mortality to inform better inpatient management. METHODS: A facility-based retrospective cohort study was conducted among children admitted due to SAM at Pawe General Hospital, Northwest Ethiopia, from the 1st of January 2015 to the 31st of December 2019. Data from the records of SAM children were extracted using a standardized checklist. Epi-Data version 3.2 was used for data entry, and Stata version 14 was used for analysis. Bi-variable and multivariable Cox regression analyses were conducted to identify predictors of mortality. Variables with P<0.05 were considered significant predictors of mortality. RESULTS: Five-hundred sixty-eight SAM cases were identified of mean age was 27.4 (SD± 16.5) months. The crude death rate was 91/568 (16.02%) and the mean time to death was determined as 13 (±8) days. Independent risk factors for death were: (i) vomiting AHR = 5.1 (1.35-21.1, p = 0.026), (ii) diarrhea AHR = 2.79 (1.46-5.4, p = 0.002), (iii) needing nasogastric therapy AHR = 3.22 (1.65-6.26, p = 0.001), (iv) anemia AHR = 1.89 (1.15-3.2, p = 0.012), and (v) being readmitted with SAM AHR = 1.7 (1.12-2.8, p = 0.037). CONCLUSION: SAM mortality was high in under-five children in our setting. The identified risk factors should inform treatment and prevention strategies. Improved community health education should focus on healthy nutrition and seeking early treatment. Inpatient mortality may be reduced by stricter adherence to treatment guidelines and recognizing early the key risk factors for death.

Risk factors for postdischarge mortality following hospitalization for severe acute malnutrition in Zimbabwe and Zambia.

BACKGROUND: Children discharged from hospital following management of complicated severe acute malnutrition (SAM) have a high risk of mortality, especially HIV-positive children. Few studies have examined mortality in the antiretroviral therapy (ART) era. OBJECTIVES: Our objectives were to ascertain 52-wk mortality in children discharged from hospital for management of complicated SAM, and to identify independent predictors of mortality. METHODS: A prospective cohort study was conducted in children enrolled from 3 hospitals in Zambia and Zimbabwe between July 2016 and March 2018. The primary outcome was mortality at 52 wk. Univariable and multivariable Cox regression models were used to identify independent risk factors for death, and to investigate whether HIV modifies these associations. RESULTS: Of 745 children, median age at enrolment was 17.4 mo (IQR: 12.8, 22.1 mo), 21.7% were HIV-positive, and 64.4% had edema. Seventy children (9.4%; 95% CI: 7.4, 11.7%) died and 26 exited during hospitalization; 649 were followed postdischarge. At discharge, 43.9% had ongoing SAM and only 50.8% of HIV-positive children were receiving ART. Vital status was ascertained for 604 (93.1%), of whom 55 (9.1%; 95% CI: 6.9, 11.7%) died at median 16.6 wk (IQR: 9.4, 21.9 wk). Overall, 20.0% (95% CI: 13.5, 27.9%) and 5.6% (95% CI: 3.8, 7.9%) of HIV-positive and HIV-negative children, respectively, died [adjusted hazard ratio (aHR): 3.83; 95% CI: 2.15, 6.82]. Additional independent risk factors for mortality were ongoing SAM (aHR: 2.28; 95% CI: 1.22, 4.25), cerebral palsy (aHR: 5.60; 95% CI: 2.72, 11.50) and nonedematous SAM (aHR: 2.23; 95% CI: 1.24, 4.01), with no evidence of interaction with HIV status. CONCLUSIONS: HIV-positive children have an almost 4-fold higher mortality than HIV-negative children in the year following hospitalization for complicated SAM. A better understanding of causes of death, an improved continuum of care for HIV and SAM, and targeted interventions to improve convalescence are needed.

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

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

Long-term effects of severe acute malnutrition during childhood on adult cognitive, academic and behavioural development in African fragile countries: The Lwiro cohort study in Democratic Republic of the Congo.

INTRODUCTION: Little is known about the outcomes of subjects with a history of severe acute malnutrition (SAM). We therefore sought to explore the long-term effects of SAM during childhood on human capital in adulthood in terms of education, cognition, self-esteem and health-related disabilities in daily living. METHODOLOGY: We traced 524 adults (median age of 22) in the eastern Democratic Republic of the Congo, who were treated for SAM during childhood at Lwiro hospital between 1988 and 2007 (median age 41 months). We compared them with 407 community controls of comparable age and sex. Our outcomes of interest were education, cognitive function [assessed using the Mini Mental State Examination (MMSE) for literate participants, or its modified version created by Ertan et al. (MMSE-I) for uneducated participants], self-esteem (measured using the Rosenberg Self-Esteem Scale) and health-related social and functional disabilities measured using the World Health Organization Disability Assessment Schedule (WHODAS). For comparison, we used the Chi-squared test along with the Student's t-test for the proportions and means respectively. RESULTS: Compared with the community controls, malnutrition survivors had a lower probability of attaining a high level of education (p < 0.001), of reporting a high academic performance (p = 0.014) or of having high self-esteem (p = 0.003). In addition, malnutrition survivors had an overall mean score in the cognitive test that was lower compared with the community controls [25.6 compared with 27.8, p = 0.001 (MMSE) and 22.8 compared with 26.3, p < 0.001(MMSE-I)] and a lower proportion of subjects with a normal result in this test (78.0% compared with 90.1%, p < 0.001). Lastly, in terms of health-related disabilities, unlike the community controls, malnutrition survivors had less social disability (p = 0.034), but no difference was observed as regards activities of daily living (p = 0.322). CONCLUSION: SAM during childhood exposes survivors to low human capital as regards education, cognition and behaviour in adulthood. Policy-deciders seeking to promote economic growth and to address various psychological and medico-social disorders must take into consideration the fact that appropriate investment in child health as regards SAM is an essential means to achieve this.

Childhood severe acute malnutrition is associated with metabolic changes in adulthood.

BACKGROUNDSevere acute malnutrition (SAM) is a major contributor to global mortality in children under 5 years. Mortality has decreased; however, the long-term cardiometabolic consequences of SAM and its subtypes, severe wasting (SW) and edematous malnutrition (EM), are not well understood. We evaluated the metabolic profiles of adult SAM survivors using targeted metabolomic analyses.METHODSThis cohort study of 122 adult SAM survivors (SW = 69, EM = 53) and 90 age-, sex-, and BMI-matched community participants (CPs) quantified serum metabolites using direct flow injection mass spectrometry combined with reverse-phase liquid chromatography. Univariate and sparse partial least square discriminant analyses (sPLS-DAs) assessed differences in metabolic profiles and identified the most discriminative metabolites.RESULTSSeventy-seven metabolite variables were significant in distinguishing between SAM survivors (28.4 ± 8.8 years, 24.0 ± 6.1 kg/m2) and CPs (28.4 ± 8.9 years, 23.3 ± 4.4 kg/m2) (mean ± SDs) in univariate and sPLS-DA models. Compared with CPs, SAM survivors had less liver fat; higher branched-chain amino acids (BCAAs), urea cycle metabolites, and kynurenine/tryptophan (KT) ratio (P < 0.001); and lower ß-hydroxybutyric acid and acylcarnitine/free carnitine ratio (P < 0.001), which were both associated with hepatic steatosis (P < 0.001). SW and EM survivors had similar metabolic profiles as did stunted and nonstunted SAM survivors.CONCLUSIONAdult SAM survivors have distinct metabolic profiles that suggest reduced ß-oxidation and greater risk of type 2 diabetes (BCAAs, KT ratio, urea cycle metabolites) compared with CPs. This indicates that early childhood SAM exposure has long-term metabolic consequences that may worsen with age and require targeted clinical management.FUNDINGHealth Research Council of New Zealand, Caribbean Public Health Agency, Centre for Global Child Health at the Hospital for Sick Children. DST is an Academic Fellow and a Restracomp Fellow at the Centre for Global Child Health. GBG is a postdoctoral fellow of the Research Foundation Flanders.

Magnitude of underweight, wasting and stunting among HIV positive children in East Africa: A systematic review and meta-analysis.

BACKGROUND: Malnutrition on the background of HIV (Human Immunodeficiency Virus) infection is a complex medical condition that carries significant morbidity and mortality for affected children, with greater mortality from SAM (Severe Acute Malnutrition) among HIV-positive children than their HIV-negative peers. HIV-induced immune impairment heightened risk of opportunistic infection and can worsen nutritional status of children. HIV infection often leads to nutritional deficiencies through decreased food intake, mal-absorption and increased utilization and excretion of nutrients, which in turn can hasten death. OBJECTIVE: The aim of this systematic review and meta-analysis was to assess the magnitude of underweight, wasting and stunting among HIV positive children in East Africa. METHODS: The authors systematically reviewed and meta-analyzed studies that assessed the prevalence of underweight, wasting and stunting among HIV positive children in East Africa from PubMed, Cochrane Library, Google Scholar, and Gray Literatures using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guideline. The last search date was December 30/2019. The data was extracted in excel sheet considering country, study design, year of publication, prevalence reported. Then the authors transformed the data to STATA 14 for analysis. Heterogeneity across the studies was assessed by the Q and the I2 test. A weighted inverse variance random-effects model was used to estimate the magnitude of underweight, wasting and stunting. The subgroup analysis was done by country, year of publication, and study design. To examine publication bias, a funnel plot and Egger's regression test were used. RESULTS: For the analysis a total of 22 studies with 22074 patients were used. The pooled prevalence of under-weight, wasting, and stunting among HIV positive children in East Africa was found to be 41.63% (95%CI; 35.69-47.57; I2 = 98.7%; p<0.001), 24.65% (95%CI; 18.34-30.95; I2 = 99.2%; p<0.001), and 49.68% (95%CI; 42.59-56.77; I2 = 99.0%; p<0.001) respectively. The prevalence of under-weight among HIV positive children was found to be 49.67% in Ethiopia followed by 42.00 in Rwanda. It was high among cohort studies (44.87%). Based on the year of publication, the prevalence of under-weight among HIV positive children was found to be 40.88% from studies conducted from January 2008-December 2014, while it was 43.68% from studies conducted from 2015-2019. The prevalence of wasting among HIV positive children was found to be 29.7% in Tanzania followed by 24.94% in Ethiopia. Based on the study design, the prevalence of wasting among HIV positive children was found to be high in cohort studies (31.15%). The prevalence of stunting among HIV positive children was found to be 51.63% in Ethiopia, followed by 48.21% in Uganda. CONCLUSIONS: The results presented above provide evidence of a higher prevalence of under nutrition among HIV positive children in East Africa. Despite the country level variations of child under nutrition in East Africa, still it is high in all aspects compared to the studies from other parts of Africa. It is recommended that further systematic review and meta-analysis need to be conducted on magnitude of malnutrition among HIV positive children in Sub-Saharan Africa as a whole.

Length of stay to recover from severe acute malnutrition and associated factors among under-five years children admitted to public hospitals in Aksum, Ethiopia.

BACKGROUND: Severe acute malnutrition is defined by <70% weight for length/height, by visible severe wasting, by the presence of pitting edema, and in children 6 to 59 months of age, mid upper arm circumference <110 mm. Severe acute malnutrition remains to be a worldwide problem, claiming lives of millions of children, especially in sub-Saharan Africa and south Asia. Though the Ethiopian national guideline states the total length of stay in therapeutic feeding units should not be more than four weeks, there is huge difference, varying from 8 to 47 days of stay. Therefore, the objective of this study was to assess length of stay to recover from severe acute malnutrition and associated factors among under five children hospitalized to the public hospitals in Aksum Town. METHODS: Sample size was calculated using STATA version 12.0. A retrospective cohort study was conducted using pretested questionnaire in the public hospitals in Aksum on children aged 0-59 months. Cleaned data was entered to Epi info version 7.1.4 and then exported into SPSS version 21 for analysis. Bivariable and multivariable analyses were performed using Kaplan Meier and Cox regression models. During bivariable analysis, variables with p-value < 0.05 were selected for multivariable analysis to identify independent factors associated with length of stay. RESULTS: A total of 564 participants enrolled to the study. The rate of recovery was 56% with median length of stay of 15 days (95% CI: 14.1, 15.9). The independent predictors of length of stay to recovery were presence of diarrhea at admission (AHR = 0.573, 95% CI: 0.415-0.793), being HIV positive (AHR = 0.391, 95% CI: 0.194-0.788), palmar pallor (AHR = 0.575, 95% CI: 0.416-0.794), presence of other co-morbidities at admission (AHR = 0.415, 95% CI: 0.302-0.570) and not being treated with plumpy nut (AHR = 0.368, 95% CI: 0.262-0.518). CONCLUSIONS: Length of stay is in the acceptable range of the international and national set of standards. Nevertheless, the recovery rate was lower compared to the Sphere standard. Presence of diarrhea, palmar pallor, HIV other co-morbidities and not treated with plumpy nut were found independent protective factors for recovery from sever acute malnutrition.

Predictors of inpatient mortality among children hospitalized for severe acute malnutrition: a systematic review and meta-analysis.

BACKGROUND: Malnutrition underlies 45% of under-5 deaths globally. Severe acute malnutrition (SAM) is the most serious form of undernutrition, characterized by wasting with or without edema. Mortality remains high (10%-40%) among children requiring hospitalization for complicated SAM. OBJECTIVES: We aimed to systematically document the factors independently associated with inpatient mortality in children with SAM. METHODS: Embase, Ovid MEDINE, the Cochrane Library, and clinicaltrials.gov were searched for articles published between January 2000 and January 2020, using a prespecified protocol. Eligible studies included children aged ≤59 mo hospitalized with SAM and used multivariable analysis to assess the baseline factors independently associated with inpatient mortality. Random-effects meta-analysis, stratified by the stated measure of effect, was used where >20% of studies included the same factor in analyses. RESULTS: Twenty-eight of 1432 studies fulfilled inclusion criteria: 19 studies included all children with SAM and 9 included specific subgroups of children with SAM. All 19 main studies were from 8 countries across Africa, with a median of 400 children/study. The mean inpatient mortality was 15.7% (95% CI: 10.4%, 21.0%) and HIV prevalence ranged from 2.1% to 51%. Nine factors were included in the meta-analysis, stratified by HR and OR. HIV infection (HR: 4.32; 95% CI: 2.31, 8.08), weight-for-height z score (WHZ) (OR: 0.44; 95% CI: 0.24, 0.80), diarrhea (HR: 2.84; 95% CI: 1.40, 5.75), pneumonia (HR: 1.89; 95% CI: 1.19, 3.02), presence of shock (HR: 3.67; 95% CI: 2.24, 6.03), and lack of appetite (HR: 2.16; 95% CI: 1.48, 3.16) were associated with increased mortality, whereas child age and sex were not. The association between edema and mortality was difficult to ascertain from the available studies. CONCLUSIONS: HIV infection, diarrhea, pneumonia, shock, lack of appetite, and lower WHZ are independent predictors of inpatient mortality in children with SAM. These factors may help to risk-stratify children being hospitalized with complicated SAM.This systematic review/meta-analysis protocol was registered at www.crd.york.ac.uk/prospero as CRD42019152267.

Recovery rate and its predictors among children with severe acute malnutrition in Addis Ababa, Ethiopia: A retrospective cohort study.

INTRODUCTION: Malnutrition is a public health problem in under-five children in several parts of the world even after decades of the implementation of management protocols. An estimated 17 million children under the age of five years are living with severe acute malnutrition and the majorities are found in Asia and Africa, including Ethiopia. OBJECTIVE: The main objective of this study was to determine the recovery rate and its predictors among under-five children who were admitted to St. Paul's Hospital Millennium Medical College from 2012 to 2019. METHODS: An institution based retrospective cohort study was employed at St. Paul's Hospital Millennium Medical College from May 20, 2019 to June 28, 2019. Data were collected by reviewing children's' medical records using a structured checklist. A total of 534 charts were selected using a simple random sampling method and 515 of them were used for the final analysis. Ep-info version 7 software was used for data entry and STATA Version 15 for analysis. The Kaplan Meier failure estimate with Log-rank test was used to determine the survival estimates. Bi-variable and multivariable Cox proportional hazards regression model were fitted to identify predictors of mortality. Finally, variables with p-values less than 0.05 in the multivariable Cox regression were considered as independent predictors. The proportional hazards assumption was checked using the Schoenfeld residuals test and the final model fitness was checked using the Cox-Snail residual test. RESULT: In this study, a total of 515 subjects were followed for 8672 child-days and 79% of the subjects recovered from SAM with the median time of 17 days. The incidence density rate of recovery was 46 per 1000 child-days. Tuberculosis (AHR(Adjusted Hazard Ratio) 0.44 & 95% CI: 0.32, 0.62), pale conjunctiva (AHR,0.67 & 95% CI: 0.52, 0.88), IV fluid infusion (AHR, 0.71 & 95 CI: 0.51, 0.98), feeding F100 (AHR, 1.63 & 95% CI:1.04,2.54), Vitamin A supplementation (AHR, 1.3 & 95% CI:1.07, 1.59) and bottle feeding (AHR, 0.79 & 95CI%: 0.64-0.98) were the independent predictors of time to recovery from SAM. CONCLUSION: In conclusion, the recovery rate was relatively higher than the Sphere standard and the national SAM management protocol. Co-morbidities and the treatments given were the main determinants of recovery of children. Co-morbidities must be managed as early as possible and the treatments given during the SAM management process need to be given with precaution.

Severe acute malnutrition in children admitted in an Intensive Therapeutic and Feeding Centre of South Kivu, Eastern Democratic Republic of Congo: Why do our patients die?

BACKGROUND: Severe acute malnutrition (SAM) remains a serious public health concern in low- and middle-income countries. Little is known about treatment outcomes of child inpatients in Intensive Therapeutic and Feeding Units. This study aimed to assess treatment outcomes of SAM and identify factors associated with mortality among children treated at Saint Joseph Nutritional Center, South Kivu, Eastern Democratic Republic of Congo. METHODS: A retrospective hospital-based cross-sectional study was conducted on medical records of 633 severely malnourished children followed as inpatients at Saint Joseph Nutritional Center from July 2017 to December 2018. Data were entered, thoroughly cleaned and analyzed in SPSS version 25. Univariable and multivariable logistic regression model were fitted to identify factors associated with mortality. RESULTS: Among 633 patients admitted with SAM, 13.1% were lost to follow-up and 9.2% died while in hospital. Children with late referral to the health facility (> 14 days) after the onset of main external malnutrition signs had 2.03 times higher odds of death than those referred less than 14 days [AOR = 2.03 at 95%CI (1.12, 3.68)]. The odds of death was 1.91 times higher for children with MUAC < 115 mm than for those with MUAC ≥ 115 mm [AOR = 1.91 at 95% CI (1.05, 3.50)]. Children infected with HIV were 3.90 times more likely to die compared to their counterparts [AOR = 3.90 at 95% CI (2.80, 9.41)]. CONCLUSION: Particular emphasis should be placed on partnering with communities to improve information on malnutrition signs and on critical importance of early referral to the health system. While HIV incidence in DRC is still low (0.21%), its impact on mortality among severely malnourished children is increased due to the limited access to HIV testing and antiretroviral therapy.

Predictors of in-hospital mortality among under-five children with severe acute malnutrition in South-Western Uganda.

BACKGROUND: Severe acute malnutrition (SAM) affects about 13 million under-five children (U5), with an estimated one million dying every year. In this study we aimed at determining the in hospital mortality and its associated factors among U5s admitted with SAM. METHODS: This was a prospective cohort study of children 6 months to 5 years with SAM admitted at Mbarara Regional Referral Hospital (MRRH) between June and August 2015. Care-takers were interviewed to collect socio-demographic and clinical information. Children under-went physical examination and had blood drawn for HIV, serum glucose, malaria, full blood count, culture and serum electrolytes investigation. Children were managed according to WHO treatment guidelines for SAM. All participants were followed up for a maximum period of 30 days. The proportion of U5 deaths within the first 48 hours and during the entire admission period was calculated. Using Poisson regression analysis, predictors of in-hospital mortality were analyzed with STATA/IC 11.0. RESULTS: We enrolled 122 children, median age of 15 months [IQR:11-24], 58.2% males, 90% immunized, 81% ill for more than 2 weeks before admission, 71% from lower health facilities and majority with unknown HIV status(76%). Overall, 13 (10.7%) children died in hospital. Seven (5.7%) died within the first 48 hours. Intravenous (IV) fluid administration significantly predicted in-hospital mortality (adjusted IRR: 7.2, 95%CI: 2.14-24.08, p = 0.001). CONCLUSION: The in-hospital mortality in U5s with SAM was lower than that previously reported in central Uganda. Intravenous fluid administration significantly predicted overall in-hospital mortality. While Administration of intravenous fluids is still the main stay of managing severely malnourished children with shock, more research needs to be conducted in order to review the parameters presently used to assess children for shock with a view of diagnosing and managing shock in these children when it is still early. Adequate guidance on use of IV fluids in management of severely malnourished children should be prioritized during continuous medical education for healthcare workers and in the treatment guidelines.

Factors associated with mortality in children under five years old hospitalized for Severe Acute Malnutrition in Limpopo province, South Africa, 2014-2018: A cross-sectional analytic study.

BACKGROUND: In South Africa, 30.9% of children under five years with Severe Acute Malnutrition (SAM) died in 2018. We aimed to identify factors associated with mortality among children under five years hospitalized with SAM in Limpopo province, South Africa. METHODS: We conducted a cross-sectional study including children under five years admitted with SAM from 2014 to 2018 in public hospitals of Limpopo province. We extracted socio-demographic and clinical data from hospital records. We used logistic regression to identify factors associated with mortality. FINDINGS: We included 956 children, 50.2% (480/956) male and 49.8% (476/956) female. The median age was 13 months (inter quartile range: 9-19 months). The overall SAM mortality over the study period was 25.9% (248/956). The most common complications were diarrhea, 63.8% (610/956), and lower respiratory tract infections (LRTIs), 42.4% (405/956). Factors associated with mortality included herbal medication use (adjusted Odds Ratio (aOR): 2.2, 95% Confidence Interval (CI): 1.4-3.5, p = 0.001), poor appetite (aOR: 2.7, 95% CI: 1.4-5.2, p = 0.003), Mid-upper circumference (MUAC) <11.5 cm (aOR: 3.0, 95% CI: 1.9-4.7, p<0.001), lower respiratory tract infections (LRTIs) (aOR: 1.6, 95% CI: 1.2-2.0, p<0.001), anemia (aOR: 2.5, 95% CI: 1.1-5.3, p = 0.021), hypoglycemia (aOR: 12.4, 95% CI: 7.1-21.8, p<0.001) and human immunodeficiency virus (HIV) infection (aOR: 2.3, 95% CI: 1.6-3.3, p<0.001). INTERPRETATION: Herbal medication use, poor appetite, LRTIs, anemia, hypoglycemia, and HIV infection were associated with mortality among children with SAM. These factors should guide management of children with SAM.

Socio-demographic and Household-Level Risk Factors for Severe Acute Malnutrition in Pre-school Children in North-Western Nigeria.

BACKGROUND: Severe acute malnutrition (SAM) is associated with significant morbidity and mortality and is disproportionately distributed mainly in developing countries. In Nigeria, the prevalence of SAM in the North-Western region of the country is significantly higher than the national average. In this study, we identified risk factors for SAM in North-Western Nigeria. Identifying such risk factors would be helpful in developing local preventive strategies and providing insights for broader SAM control programs in other high-burden country settings. METHODS: We performed post hoc data analysis, comparing baseline socio-demographic and household-level risk factors in a cohort of 1011 children aged between 6 and 59 months who either had SAM or were well-nourished children. We defined nutritional status using the World Health Organization (WHO) reference standards and investigated the association between SAM and our identified risk factors using multivariable logistic regression model. RESULTS: Children aged between 12 and 23 months [adjusted odds ratio (AOR) 2.95, 95% confidence interval (CI) 1.99-4.38], household who reared domestic animals (AOR 1.94, 95% CI 1.40-2.69) and those from polygamous households (AOR 1.91, 95% CI 1.33-2.74) had significantly increased odds of developing SAM. Parental education and being on the household diet reduced the odds of having SAM. CONCLUSIONS: Our findings suggest the need to develop optimal complementary feeding nutrition programs and promote adult and general education in our community. Cultural and feeding practices in local polygamous households also need further investigation to understand the association between polygamy with SAM.

Risk factors for mortality and management of children with complicated severe acute malnutrition at a tertiary referral hospital in Malawi.

BACKGROUND: Severe acute malnutrition (SAM) is a major cause of childhood mortality in resource-limited settings. The relationship between clinical factors and adherence to the 'WHO 10 Steps' and mortality in children with SAM is not fully understood. METHODS: Data from an ongoing prospective observational cohort study assessing admission characteristics, management patterns and clinical outcome in children aged 6-36 months admitted to a tertiary hospital in Malawi from September 2018 to September 2019 were analysed. Data clerks independently collected data from patients' charts. Demographics, clinical and nutritional status, identification of SAM and adherence to the 'WHO 10 Steps' were summarised. Their relationship to in-hospital mortality was assessed using multivariable logistic regression. RESULTS: Of the 6752 patients admitted, 9.7% had SAM. Mortality was significantly higher in those with SAM (10.1% vs 3.8%, p < 0.001). Compared with independent assessment anthropometrics, clinicians appropriately documented SAM on admission in 39.5%. The following factors were independently associated with mortality: kwashiorkor [adjusted odds ratio (aOR) 5.14, 95% confidence interval (CI) 1.27-20.78], shock (aOR 18.54, 95% CI 3.87-88.90), HIV-positive (aOR 5.32, 95% CI 1.76-16.09), SAM documented on admission (aOR 2.41, 95% CI 1.11-5.22), documentation of blood glucose within 24 hrs (aOR 3.97, 95% CI 1.90-8.33) and IV fluids given without documented shock (aOR 3.13, 95% CI 1.16-8.44). CONCLUSION: HIV infection remains an important predictor of mortality in children with SAM. IV fluids should be avoided in those without shock. Early identification of SAM by the clinical team represents a focus of future quality improvement interventions at this facility.

Treatment of severe acute malnutrition with oat or standard ready-to-use therapeutic food: a triple-blind, randomised controlled clinical trial.

OBJECTIVE: We hypothesised that an alternative RUTF (ready-to-use therapeutic food) made with oats (oat-RUTF) would be non-inferior to standard RUTF (s-RUTF). DESIGN: This was a randomised, triple-blind, controlled, clinical non-inferiority trial comparing oat-RUTF to s-RUTF in rural Sierra Leone. Children aged 6-59 months with severe acute malnutrition (SAM) were randomised to oat-RUTF or s-RUTF. s-RUTF was composed of milk powder, sugar, peanut paste and vegetable oil, with a hydrogenated vegetable oil additive. Oat-RUTF contained oats and no hydrogenated vegetable oil additives. The primary outcome was graduation, an increase in anthropometric measurements such that the child was not acutely malnourished. Secondary outcomes were rates of growth, time to graduation and presence of adverse events. Intention to treat analyses was used. RESULTS: Of the 1406 children were enrolled, graduation was attained in 404/721 (56%) children receiving oat-RUTF and 311/685 (45%) receiving s-RUTF (difference 10.6%, 95% CI 5.4% to 15.8%). Death, hospitalisation or remaining with SAM was seen in 87/721 (12%) receiving oat-RUTF and in 125/685 (18%) receiving s-RUTF (difference 6.2%, 95% CI 2.3 to 10.0, p=0.001). Time to graduation was less for children receiving oat RUTF; 3.9±1.8 versus 4.5±1.8 visits, respectively (p<0.001). Rates of weight in the oat-RUTF group were greater than in the s-RUTF group; 3.4±2.7 versus 2.5±2.3 g/kg/d, p<0.001. CONCLUSION: Oat-RUTF is superior to s-RUTF in the treatment of SAM in Sierra Leone. We speculate that might be because of beneficial bioactive components or the absence of hydrogenated vegetable oil in oat-RUTF. TRIAL REGISTRATION NUMBER: NCT03407326.

The effect of acute malnutrition on enteric pathogens, moderate-to-severe diarrhoea, and associated mortality in the Global Enteric Multicenter Study cohort: a post-hoc analysis.

BACKGROUND: Host vulnerabilities associated with acute malnutrition could facilitate the ability of specific enteric pathogens to cause diarrhoea and associated mortality. Using data from the Global Enteric Multicenter Study, we assessed whether acute malnutrition modifies the association between common enteric pathogens and moderate-to-severe diarrhoea, and whether associations between enteric pathogens and death were modified by acute malnutrition. METHODS: Children with moderate-to-severe diarrhoea and age-matched and community-matched controls were included in this post-hoc analysis if their mid-upper arm circumference had been measured and if they were older than 6 months of age. Acute malnutrition was defined as mid-upper arm circumference below 12·5 cm, capturing both severe acute malnutrition (<11·5 cm) and moderate acute malnutrition (≥11·5 cm and <12·5 cm). We tested whether acute malnutrition modified associations between enteric pathogens and moderate-to-severe diarrhoea in conditional logistic regression models. Among children with moderate-to-severe diarrhoea, Cox proportional hazards regression evaluated the modifying effect of acute malnutrition on the relationship between pathogens and 60-day fatality rate. FINDINGS: The age, site, and co-infection adjusted odds ratios (aORs) for moderate-to-severe diarrhoea associated with typical enteropathogenic Escherichia coli among children aged 6-11 months was 2·08 (95% CI 1·14-3·79) in children with acute malnutrition, and 0·97 (0·77-1·23) in children with better nutritional status, compared with healthy controls. Enterotoxigenic E coli producing heat-stable toxin among children aged 12-23 months also had a stronger association with moderate-to-severe diarrhoea in children with acute malnutrition (aOR 7·60 [2·63-21·95]) than among similarly aged children with better nutritional status (aOR 2·39 [1·76-3·25]). Results for Shigella spp, norovirus, and sapovirus suggested they had a stronger association with moderate-to-severe diarrhoea than other pathogens among children with better nutritional status, although Shigella spp remained associated with moderate-to-severe diarrhoea in both nutritional groups. 92 (64%) of 144 children with moderate-to-severe diarrhoea who died had acute malnutrition. Pathogen-specific 60-day fatality rates for all pathogens were higher among children with acute malnutrition, but no individual pathogen had a significantly larger increase in its relative association with mortality. INTERPRETATION: Acute malnutrition might strengthen associations between specific pathogens and moderate-to-severe diarrhoea. However, the strong link between acute malnutrition and mortality during moderate-to-severe diarrhoea in children is not limited to specific infections, and affects a broad spectrum of enteric pathogens. Interventions addressing acute malnutrition could be an effective way to lower the mortality of both childhood malnutrition and diarrhoea. FUNDING: The Bill & Melinda Gates Foundation.

Edematous severe acute malnutrition is characterized by hypomethylation of DNA.

Edematous severe acute childhood malnutrition (edematous SAM or ESAM), which includes kwashiorkor, presents with more overt multi-organ dysfunction than non-edematous SAM (NESAM). Reduced concentrations and methyl-flux of methionine in 1-carbon metabolism have been reported in acute, but not recovered, ESAM, suggesting downstream DNA methylation changes could be relevant to differences in SAM pathogenesis. Here, we assess genome-wide DNA methylation in buccal cells of 309 SAM children using the 450 K microarray. Relative to NESAM, ESAM is characterized by multiple significantly hypomethylated loci, which is not observed among SAM-recovered adults. Gene expression and methylation show both positive and negative correlation, suggesting a complex transcriptional response to SAM. Hypomethylated loci link to disorders of nutrition and metabolism, including fatty liver and diabetes, and appear to be influenced by genetic variation. Our epigenetic findings provide a potential molecular link to reported aberrant 1-carbon metabolism in ESAM and support consideration of methyl-group supplementation in ESAM.

Factors associated with child survival in children admitted to outpatient therapeutic program at public health institutions in Afar Regional State, Ethiopia: a prospective cohort study.

INTRODUCTION: About 20 million children suffer from severe acute malnutrition each year. The World Health Organization recommends the outpatient therapeutic program as a standard treatment protocol for the management of uncomplicated severe acute malnutrition and for children who are transferred from inpatient cares after recovery. This study aimed to assess the treatment outcome of severe acute malnutrition and determinants of survival in children admitted to outpatient therapeutic program at public health institutions, Afar Regional State. METHODS: Institution-based prospective cohort study was conducted on 286 children aged 6-59 months admitted to the outpatient therapeutic program, from April to September 2017, at selected public health institutions in Afar Regional State. For the comparison of time to recovery among the different groups of children on the outpatient therapeutic program, Kaplan-Meir curve was used and significance test for these differences was assessed by the log-rank test. Then, a proportional hazard in the Cox model was used to identify independent predictors of survival. p value < 0.05 was considered significant. RESULTS: Of 286 children, 238 (83.2%; 95% CI (79, 88)), 18 (6.3%), 14 (4.9%), 8 (2.8%), and 8 (2.8%) cases were cured, defaulters, non-responder, died, and transfer to inpatient care, respectively. The overall mean rate of weight gain was 10.5(± 3.45) g/kg/day, and mean length of stay was 44.15(± 8.77) days. The recovery rate of children whose mothers travel less than 2 h to the health institution was about three times (AHR, 2.91; 95% CI (2.18, 3.88)) higher than children whose mothers travel 2 h and above. Compared with children who received vitamin A supplementation, children who lack supplementation were less likely (AHR, 0.39; 95% CI (0.25, 0.59)) to be cured. Moreover, the rate of recovery from outpatient therapeutic program among children who received antibiotics was about 1.4 times (AHR, 1.38; 95% CI (1.01, 1.89)) higher compared with children who did not receive of antibiotics. CONCLUSION: This study showed that nearly eight children in every ten had recovered from severe acute malnutrition. Therefore, considering the distance of health facility from children's residence, improving vitamin A supplementation and antibiotics are vital in improving the rate of recovery. Further research is also required to identify and address barriers to the provision of antibiotics and vitamin A supplementation.