Efficacy of three feeding regimens for home-based management of children with uncomplicated severe acute malnutrition: a randomised trial in India.
ABSTRACT: To assess the efficacy of ready-to-use therapeutic food (RUTF), centrally produced RUTF (RUTF-C) or locally prepared RUTF (RUTF-L) for home-based management of uncomplicated severe acute malnutrition (SAM) compared with micronutrient-enriched (augmented) energy-dense home-prepared foods (A-HPF, the comparison group).In an individually randomised multicentre trial, we enrolled 906 children aged 6-59?months with uncomplicated SAM. The children enrolled were randomised to receive RUTF-C, RUTF-L or A-HPF. We provided foods, counselling and feeding support until recovery or 16?weeks, whichever was earlier and measured outcomes weekly (treatment phase). We subsequently facilitated access to government nutrition services and measured outcomes once 16?weeks later (sustenance phase). The primary outcome was recovery during treatment phase (weight-for-height ?-2 SD and absence of oedema of feet).Recovery rates with RUTF-L, RUTF-C and A-HPF were 56.9%, 47.5% and 42.8%, respectively. The adjusted OR was 1.71 (95% CI 1.20 to 2.43; p=0.003) for RUTF-L and 1.28 (95% CI 0.90 to 1.82; p=0.164) for RUTF-C compared with A-HPF. Weight gain in the RUTF-L group was higher than in the A-HPF group (adjusted difference 0.90?g/kg/day, 95% CI 0.30 to 1.50; p=0.003). Time to recovery was shorter in both RUTF groups. Morbidity was high and similar across groups. At the end of the study, the proportion of children with weight-for-height Z-score (WHZ) >-2 was similar (adjusted OR 1.12, 95% CI 0.74 to 1.95; p=0.464), higher for moderate malnutrition (WHZ<-2 and ?-3; adjusted OR 1.46, 95% CI 1.02 to 2.08; p=0.039), and lower for those with SAM (adjusted OR 0.58, 95% CI 0.40 to 0.85; p=0.005) in the RUTF-L when compared with the A-HPF group.This first randomised trial comparing options for home management of uncomplicated SAM confirms that RUTF-L is more efficacious than A-HPF at home. Recovery rates were lower than in African studies, despite longer treatment and greater support for feeding.NCT01705769; Pre-results.
Project description:BACKGROUND:Children with uncomplicated severe acute malnutrition (SAM) are treated at home with ready-to-use therapeutic foods (RUTFs). The current RUTF dose is prescribed according to the weight of the child to fulfil 100% of their nutritional needs until discharge. However, there is doubt concerning the dose, as it seems to be shared, resulting in suboptimal cost-efficiency of SAM treatment. We investigated the efficacy of a reduced RUTF dose in community-based treatment of uncomplicated SAM. METHODS AND FINDINGS:We undertook a randomised trial testing the non-inferiority of weight gain velocity of children with SAM receiving (a) a standard RUTF dose for two weeks, followed by a reduced dose thereafter (reduced), compared with (b) a standard RUTF dose throughout the treatment (standard). A mean difference of 0.0 g/kg/day was expected, with a non-inferiority margin fixed at -0.5 g/kg/day. Linear and logistic mixed regression analyses were performed, with study site and team as random effects. Between October 2016 and July 2018, 801 children with uncomplicated SAM aged 6-59 months were enrolled from 10 community health centres in Burkina Faso. At admission, the mean age (± standard deviation [SD]) was 13.4 months (±8.7), 49% were male, and the mean weight was 6.2 kg (±1.3). The mean weight gain velocity from admission to discharge was 3.4 g/kg/day and did not differ between study arms (? 0.0 g/kg/day; 95% CI -0.4 to 0.4; p = 0.92) confirming non-inferiority (p = 0.013). However, after two weeks, the weight gain velocity was significantly lower in the reduced dose with a mean of 2.3 g/kg/day compared with 2.7 g/kg/day in the standard dose (? -0.4 g/kg/day; 95% CI -0.8 to -0.02; p = 0.041). The length of stay (LoS) was not different (p = 0.73) between groups with a median of 56 days (interquartile range [IQR] 35-91) in both arms. No differences were found between reduced and standard arm in recovery (52.7% and 55.4%; p = 0.45), referral (19.2% and 20.1%; p = 0.80), defaulter (12.2% and 8.5%; p = 0.088), non-response (12.7% and 12.5%; p = 0.95), and relapse (2.4% and 1.8%; p = 0.69) rates, respectively. However, the reduced RUTF dose had a small 0.2 mm/week (95% CI 0.04 to 0.4; p = 0.015) negative effect on height gain velocity with a mean height gain of 2.6 mm/week with reduced and 2.8 mm/week with standard RUTF dose. The impact was more pronounced in children under 12 months of age (interaction, p = 0.019) who gained 2.8 mm/week with reduced and 3.1 mm/week with standard dose (? -0.4 mm/week; 95% CI -0.6 to -0.2; p < 0.001). Limitations include not blinding participants to the RUTF dose received and excluding all children with negative appetite test. The results are generalisable for relatively food secure contexts with a young SAM population. CONCLUSIONS:Reducing the RUTF dose provided to children with SAM after two weeks of treatment did not reduce overall weight or mid-upper arm circumference (MUAC) gain velocity nor affect recovery or lengthen treatment time. However, it led to a small but significant negative effect on linear growth, especially among the youngest. The potential effect of reducing the RUTF dose in a routine program on treatment outcomes should be evaluated before scaling up. TRIAL REGISTRATION:ISRCTN registry ISRCTN50039021.
Project description:BACKGROUND:In Ethiopia uncomplicated severe acute malnutrition (SAM) is managed at health posts level through the outpatient therapeutic program (OTP). Yet, evidence on the treatment success rate of the program is scarce. This study determines the treatment outcomes and predictors of time-to-recovery among children 6-59?months of age with SAM managed at the health posts level in Shebedino district, Southern Ethiopia. METHODS:This was a prospective cohort study that enrolled 216 children with SAM identified through a campaign conducted in May 2015 and treated over eight weeks at 25 health posts of the district. The average time-to-recovery was estimated using Kaplan-Meier survival curve and the independent predictors of the recovery were determined using multivariable Cox-proportional hazard model. The outputs of the analyses are presented via adjusted hazard ratio with 95% confidence intervals (AHR, CI). RESULTS:At the end of the eight weeks of treatment 79.6% (95% CI: 74.2-85.0%) of cases recovered from SAM with a weight gain rate of 5.4?g/kg/day. The median time-to-recover was 36?days. The analysis indicated, maternal illiteracy (0.54, 0.38-0.78), severe household food insecurity (0.47, 0.28-0.79), walking for more than 1?h to receive the treatment (0.69, 0.50-0.96), diarrhoea co-morbidity (0.63, 0.42-0.91) and practicing sharing of ready to use therapeutic food (RUTF) (0.53, 0.32-0.88) were associated with slower propensity of recovery from SAM. Children who were enrolled with marasmus diagnosis showed lower recovery than children with kwashiorkor (0.30, 0.18-0.51). CONCLUSION:The median time-to-recover was 36?days. Discouraging sharing of RUTF, appropriate management of diarrhoea in SAM cases and improving access to OTP sites can help to improve the treatment outcome for SAM.
Project description:Background:Community-based treatment of severe acute malnutrition (SAM) has proven to be safe and cost-effective, although identifying additional factors that can increase recovery and decrease treatment failure may improve program effectiveness. We examine the association of dietary diversity and clinical and program treatment outcomes among children treated for uncomplicated SAM in Niger. Methods:Two thousand four hundred twelve children were enrolled in a randomized trial of routine amoxicillin in the treatment of uncomplicated SAM from 2012 to 2014. All children received ready to use therapeutic food (RUTF) and standard clinical care. Child dietary diversity was assessed using a 7-day food frequency questionnaire and 8-food group diet diversity score. We assessed the association of dietary diversity at admission with nutritional recovery, hospitalization, and death at program discharge and 12 weeks, and weight and height gain. Results:Food groups most commonly consumed by children in seven days preceding SAM treatment were cereals, roots and tubers (N =?2364, 99.5%) and vitamin A rich fruits and vegetables (N =?2253, 94.8%). Egg (N =?472, 19.9%) and dairy (N =?659, 27.7%) consumption was low. Mean (SD) diet diversity score was significantly lower in the lean vs. non-lean season [2.7 (1.1) vs. 2.9 (1.0)]. There was no evidence that dietary diversity increased nutritional recovery at discharge (RR: 1.02, 95% CI: 1.00, 1.04) or 12 weeks (RR: 0.98, 95%CI: 0.94, 1.02). No significant association was found with risk of hospitalization or death, or weight and height gain. Egg consumption was protective against death at discharge (RR: 0.53, 95% CI: 0.39, 0.70) and 12 weeks (RR: 0.66, 95% CI: 0.45, 0.96). Vitamin A rich fruits and vegetable consumption was associated with greater risk of mortality in children at discharge (RR: 1.30, 95% CI: 1.08, 1.56) and 12 weeks (RR: 1.19, 95% CI: 1.03, 1.36). Conclusions:We did not find evidence that dietary diversity influenced nutrition recovery or response to treatment for children with uncomplicated SAM in Niger. It is feasible consumption of nutrient-dense foods like eggs may be important for recovery from SAM. There is need for continued research to further elucidate drivers of nutritional recovery from acute malnutrition in different settings. Trial registration:Trial registration number: ClinicalTrials.gov NCT01613547. Registered May 26, 2012.
Project description:BACKGROUND:The prevalence of anaemia and iron deficiency (ID) among children with severe acute malnutrition (SAM) and their correction during nutritional rehabilitation are not well documented. This study assessed anaemia and ID prevalence and their predictors at start of SAM treatment, and the efficacy of their treatment and effect on gut health of two novel Ready-To-Use Therapeutic foods (RUTF) prepared from soybean, maize and sorghum (SMS) with (MSMS-RUTF) or without added milk (FSMS-RUTF) compared to those of the standard formulation prepared from peanut and milk (PM-RUTF). METHODS:This was a 3-arms parallel groups, simple randomised, controlled non-inferiority trial in 6-59?months old Central Malawian children with SAM. Anaemia was defined using altitude- and ethnicity-adjusted haemoglobin. Iron status was defined using soluble transferrin receptor (sTfR) and body iron stores (BIS). We used Pearson's chi-square test, t-test for paired or unpaired data, Kruskal-Wallis test for between-arm differences as appropriate and logistic regression to identify independent predictors of anaemia or iron deficiency anaemia (IDA). RESULTS:The sample size was 389. At admission, the prevalence [%(95%CI)] of anaemia was 48.9(41.4-56.5)% while that of ID and IDA were 55.7(48.6-62.5)% and 34.3(28.2-41.0)% when using sTfR criterion and 29.1(24.4-34.4)% and 28.9(23.7-34.9)% when using BIS criterion, respectively. At discharge, nutrition rehabilitation with SMS-RUTF was associated with the lowest prevalence of anaemia [12.0(6.9-20.3)% for FSMS-RUTF, 18.2(11.9-26.8)% for MSMS-RUTF and 24.5(15.8-35.9)% for PM-RUTF; p =?0.023] and IDA [7.9(3.4-17.3)% for FSMS-RUTF, 10.9(4.8-22.6)% for MSMS-RUTF and 20.5(10.7-35.5)% for PM-RUTF; p =?0.028]. SMS-RUTF was also associated with the highest increase in BIS [Change in BIS (95%CI)] among the iron deplete at admission [6.2 (3.7; 8.6), 3.2 (0.8; 5.6), 2.2 (0.2; 4.3) for the same study arms; Anova p =?0.045]. Compared to P-RUTF, FSMS-RUTF had the highest adjusted recovery rate [OR (95%CI?=?0.3 (0.2-0.5) with p <?0.001 for FSMS-RUTF and 0.6 (0.3-1.0) with p =?0.068 for MSMS-RUTF]. No effect of iron content on risk of iron overload or gut inflammation was observed. CONCLUSIONS:Anaemia and ID are common among children with SAM. FSMS-RUTF is more efficacious in treating anaemia and correcting BIS among this group than PM-RUTF. TRIAL REGISTRATION:This study was registered on 15 April 2015 ( PACTR201505001101224 ).
Project description:Community-based Management of Acute Malnutrition using ready-to-use therapeutic food (RUTF) has revolutionised the treatment of severe acute malnutrition (SAM). However, 25% milk content in standard peanut-based RUTF (P-RUTF) makes it too expensive. The effectiveness of milk-free RUTF has not been reported hitherto. This non-blinded, parallel group, cluster randomised, controlled, equivalence trial that compares the effectiveness of a milk-free soy-maize-sorghum-based RUTF (SMS-RUTF) with P-RUTF in treatment of children with SAM, closes the gap. A statistician randomly assigned health centres (HC) either to the SMS-RUTF (n?=?12; 824 enrolled) or P-RUTF (n?=?12; 1103 enrolled) arms. All SAM children admitted at the participating HCs were enrolled. All the outcomes were measured at individual level. Recovery rate was the primary outcome. The recovery rates for SMS-RUTF and P-RUTF were 53.3% and 60.8% for the intention-to-treat (ITT) analysis and 77.9% and 81.8% for per protocol (PP) analyses, respectively. The corresponding adjusted risk difference (ARD) and 95% confidence interval, were -7.6% (-14.9, 0.6%) and -3.5% (-9,6., 2.7%) for ITT (P?=?0.034) and PP analyses (P?=?0.257), respectively. An unanticipated interaction (interaction P?<?0.001 for ITT analyses and 0.0683 for PP analyses) between the study arm and age group was observed. The ARDs were -10.0 (-17.7 to -2.3)% for ITT (P?=?0.013) and -4.7 (-10.0 to 0.7) for PP (P?=?0.083) analyses for the <24 months age group and 2.1 (-10.3,14.6)% for ITT (P?=?0.726) and -0.6 (-16.1, 14.5) for PP (P?=?0.939) for the ?24 months age group. In conclusion, the study did not confirm our hypothesis of equivalence between SMS-RUTF and P-RUTF in SAM management.
Project description:Background:Goals of treating childhood severe acute malnutrition (SAM), in addition to anthropometric recovery and preventing short-term mortality, include reducing the risks of subsequent serious infections. How quickly and how much the risk of serious illness changes during rehabilitation are unknown but could inform improving the design and scope of interventions. Objective:The aim of this study was to investigate changes in the risk of life-threatening events (LTEs) in relation to anthropometric recovery from SAM. Design:This was a secondary analysis of a clinical trial including 1778 HIV-uninfected Kenyan children aged 2-59 mo with complicated SAM, enrolled after the inpatient stabilization phase of treatment, and followed for 12 mo. The main outcome was LTEs, defined as infections requiring rehospitalization or causing death. We examined anthropometric variables measured at months 1, 3, and 6 after enrollment in relation to LTEs occurring during the 6 mo after each of these time points. Results:Over 12 mo, there were 823 LTEs (257 fatal), predominantly severe pneumonia and diarrhea. At months 1, 3, and 6, 557 (34%), 764 (49%), and 842 (56%) children had a weight-for-height or -length z score (WHZ) ≥-2, respectively, which, compared with a WHZ <-3, was associated with lower risks of subsequent LTEs [adjusted HRs (95% CIs): 0.50 (0.40, 0.64), 0.30 (0.23, 0.39), and 0.23 (0.16, 0.32), respectively]. However, children with a WHZ ≥-2 at 1, 3, and 6 mo still had 39 (95% CI: 32, 47), 26 (95% CI: 22, 32), and 15 (95% CI: 12, 20) LTEs/100 child-years of observation during the following 6 mo. WHZ at study enrollment predicted subsequent WHZ but not the risk of LTEs. Changes in height-for-age z score did not predict LTEs. Conclusions:Anthropometric response was associated with a rapid and substantial reduction in risk of LTEs. However, reduction in susceptibility lagged behind anthropometric improvement. Disease events, together with anthropometric assessment, may provide a clearer picture of the effectiveness of interventions. Robust protocols for detecting and treating poor anthropometric recovery and addressing broader vulnerabilities that complicated SAM indicates may save lives. This trial was registered at www.clinicaltrials.gov as NCT00934492.
Project description:Childhood malnutrition is a major public health concern, as it is associated with significant short- and long-term morbidity and mortality. The objective of this review was to comprehensively review the evidence for the management of severe acute malnutrition (SAM) and moderate acute malnutrition (MAM) according to the current World Health Organization (WHO) protocol using facility- and community-based approaches, as well as the effectiveness of ready-to-use therapeutic food (RUTF), ready-to-use supplementary food (RUSF), prophylactic antibiotic use, and vitamin A supplementation. We searched relevant electronic databases until 11 February 2019, and performed a meta-analysis. This review summarizes findings from a total of 42 studies (48 papers), including 35,017 children. Limited data show some benefit of integrated community-based screening, identification, and management of SAM and MAM on improving recovery rate. Facility-based screening and management of uncomplicated SAM has no effect on recovery and mortality, while the effect of therapeutic milk F100 for SAM is comparable to RUTF for weight gain and mortality. Local food and whey RUSF are comparable to standard RUSF for recovery rate and weight gain in MAM, while standard RUSF has additional benefits to CSB. Prophylactic antibiotic administration in uncomplicated SAM improves recovery rate and probably improves weight gain and reduces mortality. Limited data suggest that high-dose vitamin A supplementation is comparable with low-dose vitamin A supplementation for weight gain and mortality among children with SAM.
Project description:Severe acute malnutrition (SAM) affects almost all organs and has been associated with reduced intestinal absorption of medicines. However, very limited information is available on the pharmacokinetic properties of antimalarial drugs in this vulnerable population. We assessed artemether-lumefantrine (AL) clinical efficacy in children with SAM compared to those without.Children under 5 years of age with uncomplicated P. falciparum malaria were enrolled between November 2013 and January 2015 in Mali and Niger, one third with uncomplicated SAM and two thirds without. AL was administered under direct observation with a fat intake consisting of ready-to-use therapeutic food (RUTF - Plumpy'Nut®) in SAM children, twice daily during 3 days. Children were followed for 42 days, with PCR-corrected adequate clinical and parasitological response (ACPR) at day 28 as the primary outcome. Lumefantrine concentrations were assessed in a subset of participants at different time points, including systematic measurements on day 7.A total of 399 children (360 in Mali and 39 in Niger) were enrolled. Children with SAM were younger than their non-SAM counterparts (mean 17 vs. 28 months, P?<?0.0001). PCR-corrected ACPR was 100 % (95 % CI, 96.8-100 %) in SAM at both day 28 and 42, versus 98.8 % (96.4-99.7 %) at day 28 and 98.3 % (95.6-99.4 %) at day 42 in non-SAM (P?=?0.236 and 0.168, respectively). Compared to younger children, children older than 21 months experienced more reinfections and SAM was associated with a greater risk of reinfection until day 28 (adjusted hazard ratio?=?2.10 (1.04-4.22), P?=?0.038). Day 7 lumefantrine concentrations were significantly lower in SAM than non-SAM (median 251 vs. 365 ng/mL, P?=?0.049).This study shows comparable therapeutic efficacy of AL in children without SAM and in those with SAM when given in combination with RUTF, but a higher risk of reinfection in older children suffering from SAM. This could be associated with poorer exposure to the antimalarials as documented by a lower lumefantrine concentration on day 7.ClinicalTrials.gov: NCT01958905 , registration date: October 7, 2013.
Project description:Ready-to-use therapeutic foods (RUTFs) are an important component of effective outpatient treatment of severe wasting. However, their effectiveness in the population-based prevention of moderate and severe wasting has not been evaluated.To evaluate the effect of a 3-month distribution of RUTF on the nutritional status, mortality, and morbidity of children aged 6 to 60 months in Niger.A cluster randomized trial of 12 villages in Maradi, Niger. Six villages were randomized to intervention and 6 to no intervention. All children in the study villages aged 6 to 60 months were eligible for recruitment.Children with weight-for-height 80% or more of the National Center for Health Statistics reference median in the 6 intervention villages received a monthly distribution of 1 packet per day of RUTF (92 g [500 kcal/d]) from August to October 2006. Children in the 6 nonintervention villages received no preventive supplementation. Active surveillance for conditions requiring medical or nutritional treatment was conducted monthly in all 12 study villages from August 2006 to March 2007.Changes in weight-for-height z score (WHZ) according to the World Health Organization Child Growth Standards and incidence of wasting (WHZ <-2) over 8 months of follow-up.The number of children with height and weight measurements in August, October, December, and February was 3166, 3110, 2936, and 3026, respectively. The WHZ difference between the intervention and nonintervention groups was -0.10 z (95% confidence interval [CI], -0.23 to 0.03) at baseline and 0.12 z (95% CI, 0.02 to 0.21) after 8 months of follow-up. The adjusted effect of the intervention on WHZ from baseline to the end of follow-up was thus 0.22 z (95% CI, 0.13 to 0.30). The absolute rate of wasting and severe wasting, respectively, was 0.17 events per child-year (140 events/841 child-years) and 0.03 events per child-year (29 events/943 child-years) in the intervention villages, compared with 0.26 events per child-year (233 events/895 child-years) and 0.07 events per child-year (71 events/1029 child-years) in the nonintervention villages. The intervention thus resulted in a 36% (95% CI, 17% to 50%; P < .001) reduction in the incidence of wasting and a 58% (95% CI, 43% to 68%; P < .001) reduction in the incidence of severe wasting. There was no reduction in mortality, with a mortality rate of 0.007 deaths per child-year (7 deaths/986 child-years) in the intervention villages and 0.016 deaths per child-year (18 deaths/1099 child-years) in the nonintervention villages (adjusted hazard ratio, 0.51; 95% CI, 0.25 to 1.05).Short-term supplementation of nonmalnourished children with RUTF reduced the decline in WHZ and the incidence of wasting and severe wasting over 8 months.clinicaltrials.gov Identifier: NCT00682708.
Project description:BACKGROUND:Ready-to-use therapeutic food (RUTF) is used to treat children suffering from severe acute malnutrition (SAM). Standard RUTF uses milk as the primary protein source, which makes the product expensive, and given the high worldwide SAM burden, having a less expensive effective alternative is a public health priority. OBJECTIVE:The objective of this study was to evaluate whether newly developed amino acid-enriched milk-free RUTF (FSMS-RUTF) or amino acid-enriched low-milk RUTF (MSMS-RUTF) treatment could replenish plasma amino acids to levels comparable to those following standard peanut-milk RUTF (PM-RUTF) treatment and to improve understanding of the effects of treatment on anthropometric measurements. A secondary analysis was performed to test the noninferiority hypothesis of plasma essential amino acid (EAA) levels. METHODS:Plasma EAA levels were measured in a nonblinded, 3-arm, parallel-group simple randomized controlled trial conducted in Malawi to examine the efficacy of FSMS-RUTF, MSMS-RUTF and PM-RUTF in the treatment of SAM in 2 groups of children aged 6-23 and 24-59 months (mo). Sample size calculations were performed based on the previous our study. A noninferiority margin was set at -25% of the PM-RUTF arm at discharge. RESULTS:The relative values of the differences (95% CI) in plasma EAA levels between PM-RUTF treatment and FSMS-RUTF and MSMS-RUTF treatments at discharge were -7.9% (-18.6, 2.8) and 9.8% (0.2, 19.5), respectively, in children aged 6-23 mo, while in those aged 24-59 mo, the difference values were 17.8% (1.6, 34.1) and 13.6% (-2.8, 29.9), respectively. CONCLUSION:At discharge, the plasma EAA concentrations in 6-59-mo-old SAM children treated with FSMS-RUTF and MSMS-RUTF were not less than those of children treated with PM-RUTF. These findings indicate that treatment with either of the 3 RUTFs was associated with adequate protein synthesis and that all the formulations provided sufficient functional metabolites of plasma amino acids to support nutritional recovery from SAM.