Vitamin B12 Status before and after Outpatient Treatment of Severe Acute Malnutrition in Children Aged 6-59 Months: A Sub-Study of a Randomized Controlled Trial in Burkina Faso.

Severe acute malnutrition (SAM) is treated with ready-to-use therapeutic foods (RUTF) containing a vitamin-mineral premix. Yet little is known about micronutrient status in children with SAM before and after treatment. We aimed to investigate vitamin B12 status in children with uncomplicated SAM, aged 6-59 months in Burkina Faso, before and after treatment with a standard or a reduced dose of RUTF. Blood samples were collected at admission and discharge. Serum B12 was determined with microbiological assay and serum methylmalonic acid (MMA) and total homocysteine (tHcy) were analyzed with gas chromatography-tandem mass spectrometry. B12 status was classified using the combined indicator (3cB12). Among 374 children, the median [interquartile range] age was 11.0 [7.7-16.9] months, and 85.8% were breastfed. Marked or severe B12 deficiency, as judged by 3cB12, decreased from 32% to 9% between admission and discharge (p < 0.05). No differences in B12 status following treatment with either standard (n = 194) or reduced (n = 180) doses of RUTF were observed. Breastfed children showed a lower B12 status (3cB12) than non-breastfed ones (-1.10 vs -0.18, p < 0.001 at admission; -0.44 vs 0.19; p < 0.001 at discharge). In conclusion, treatment of SAM with RUTF improved children's B12 status but did not fully correct B12 deficiency.

Predictors of time to recovery and non-response during outpatient treatment of severe acute malnutrition.

BACKGROUND: Every year, over 4 million children are treated for severe acute malnutrition with varying program performance. This study sought to explore the predictors of time to recovery from and non-response to outpatient treatment of SAM. METHODS: Children with weight-for-height z-score (WHZ) <-3 and/or mid-upper arm circumference (MUAC) <115 mm, without medical complications were enrolled in a trial (called MANGO) from outpatient clinics in Burkina Faso. Treatment included a weekly ration of ready-to-use therapeutic foods. Recovery was declared with WHZ ≥-2 and/or MUAC ≥125 mm, for two weeks without illness. Children not recovered by 16 weeks were considered as non-response to treatment. Predictors studied included admission characteristics, morbidity and compliance during treatment and household characteristics. Cox proportional hazard models were fitted and restricted mean time to recovery calculated. Logistic regression was used to analyse non-response to treatment. RESULTS: Fifty-five percent of children recovered and mean time to recovery was eight weeks while 13% ended as non-response to treatment. Independent predictors of longer time to recovery or non-response included low age, being admitted with WHZ <-3, no illness nor anaemia at admission, illness episodes during treatment, skipped or missed visits, low maternal age and not practising open defecation. Eighty-four percent of children had at least one and 59% at least two illness episodes during treatment. This increased treatment duration by 1 to 4 weeks. Thirty-five percent of children missed at least one treatment visit. One missed visit predicted 3 weeks longer and two or more missed visits 5 weeks longer treatment duration. CONCLUSIONS: Both longer time to recovery and higher non-response to treatment seem most strongly associated with illness episodes and missed visits during treatment. This indicates that prevention of illnesses would be key to shortening the treatment duration and that there is a need to seek ways to facilitate adherence.

Availability, use, and consumption practices of ready-to-use therapeutic foods prescribed to children with uncomplicated severe acute malnutrition aged 6-59 months during outpatient treatment in Burkina Faso.

Ready-to-use-therapeutic-foods (RUTF) was designed for the nutritional management of children with uncomplicated severe acute malnutrition (SAM) treated as outpatients. However, to our knowledge, no study has evaluated the availability, use and consumption of RUTF within the beneficiary household in programs and in the context of a reduction in the dose of RUTF. This study, assessed the effect of a reduction in RUTF dose on the availability, use, consumption, and perceptions of caregivers on RUTF prescribed to 516 children treated for SAM, aged 6-59 months in Burkina Faso. Children received a weekly dose of RUTF according to their treatment arm until recovery. Data were collected by structured individual in-depth interviews, with caregivers one month and two months post-admission. Differences between children receiving reduced RUTF (intervention arm) and those receiving standard RUTF (control arm) were assessed by Poisson, logistic, and ordered logistic regression model. RUTF was available for the whole week in 95% in intervention arm compared to about 98% in control arm (p > 0.05). Starting from week 3 onwards, children in intervention arm consumed an average of 9 sachets of RUTF per week compared to 15 sachets in control arm (p < 0.001) and 5% of children in intervention arm reported leftover compared to 11% in control arm (p < 0.05). About 40% of children in intervention arm consumed RUTF at least 3-times per day compared to 82% in control arm (p < 0.001). The amount of RUTF prescribed was perceived as sufficient in 93% by caregivers in intervention arm against 97% in control arm (p > 0.05). In conclusion, reducing the dose of RUTF did not affect the availability of RUTF during treatment but did reduce leftover and the frequency of consumption of RUTF.

Complementary feeding practices and associated factors of dietary diversity among uncomplicated severe acute malnourished children aged 6-23 months in Burkina Faso.

Nutritional treatment of children with uncomplicated severe acute malnutrition (SAM) is based on ready-to-use therapeutic foods (RUTF). With treatment provided at community level, children could have access to other foods, and a reduction in the dose of RUTF could further increase dietary diversity during treatment. We assessed the dietary diversity score (DDS), the minimum dietary diversity (MDD), the minimum meal frequency (MMF) and the minimum acceptable diet (MAD) of 459 infants and young children aged 6-23 months being treated for SAM with different doses of RUTF. We also investigated the factors associated with DDS. Dietary intake was estimated using a single 24-h multipass dietary recall, 1 month after starting treatment, from December 2016 to August 2018. The DDS was calculated on the basis of eight food groups. Differences between children receiving the reduced RUTF and the standard RUTF dose and factors associated with DDS were assessed by Poisson and logistic regression models. RUTF dose was not associated with DDS (4.07 ± 1.25 for reduced RUTF and 4.01 ± 1.26 for standard RUTF; P = 0.77). Food groups most consumed by children were grains, roots or tubers (96%) and legumes and nuts (72%). Eggs consumption was low (3%). DDS was positively associated with child's age, mother's education, household wealth index, urban residence and rainy season. The present findings show that children with SAM consumed a variety of foods during treatment in addition to the RUTF ration prescribed to them. Reducing the dose of RUTF during SAM treatment did not impact DDS.

Economic evaluation of a reduced dosage of ready-to-use therapeutic foods to treat uncomplicated severe acute malnourished children aged 6-59 months in Burkina Faso.

Ready-to-use therapeutic foods (RUTF) used to treat children with severe acute malnutrition (SAM) are costly, and the prescribed dosage has not been optimized. The MANGO trial, implemented by Action Contre la Faim in Burkina Faso, proved the non-inferiority of a reduced RUTF dosage in community-based treatment of uncomplicated SAM. We performed a cost-minimization analysis to assess the economic impact of transitioning from the standard to the reduced RUTF dose. We used a decision-analytic model to simulate a cohort of 399 children/arm, aged 6-59 months and receiving SAM treatment. We adopted a societal perspective: direct medical costs (drugs, materials and staff time), non-medical costs (caregiver expenses) and indirect costs (productivity loss) in 2017 international US dollar were included. Data were collected through interviews with 35 caregivers and 20 informants selected through deliberate sampling and the review trial financial documents. The overall treatment cost for 399 children/arm was $36,550 with the standard and $30,411 with the reduced dose, leading to $6,140 (16.8%) in cost savings ($15.43 saved/child treated). The cost/consultation was $11.6 and $9.6 in the standard and reduced arms, respectively, with RUTF accounting for 56.2% and 47.0% of the total. The savings/child treated was $11.4 in a scenario simulating the Burkinabè routine SAM treatment outside clinical trial settings. The reduced RUTF dose tested in the MANGO trial resulted in significant cost savings for SAM treatment. These results are useful for decision makers to estimate potential economic gains from an optimized SAM treatment protocol in Burkina Faso and similar contexts.

Adequacy of Nutrient Intakes of Severely and Acutely Malnourished Children Treated with Different Doses of Ready-To-Use Therapeutic Food in Burkina Faso.

BACKGROUND: Ready-to-use therapeutic foods (RUTF) are designed to cover the daily nutrient requirements of children with severe acute malnutrition (SAM). However, with the transfer of uncomplicated SAM care from the hospital environment to the community level, children will be able to consume complementary and family foods (CFF) in addition to RUTF, and this might decrease the quantity of RUTF needed for recovery. OBJECTIVES: Using an individually randomized clinical trial, we investigated the effects of a reduced RUTF dose on the daily energy and macronutrient intakes, the proportion of energy coming from CFF, and the mean probability of adequacy (MPA) of intake in 11 micronutrients of 516 children aged 6-59 mo who were treated for SAM in Burkina Faso. METHODS: The data were collected using a single 24-h multipass dietary recall, 1 mo after starting treatment, from December 2016 to August 2018, repeated on a subsample of 66 children. Differences between children receiving the reduced RUTF (intervention arm) and those receiving standard RUTF (control arm) were assessed by linear mixed models. RESULTS: Daily energy intake was lower (P < 0.01) in the intervention arm (mean ± SD 1321 ± 339 kcal) than in the control arm (1467 ± 319 kcal). CFF contributed to 40% of the daily energy intake in the intervention and 35% in the control arm. The MPA for 11 micronutrients was 0.89 ± 0.1 in the intervention arm and 0.95 ± 0.07 in the control arm (P = 0.06). CONCLUSIONS: Reducing the dose of RUTF during SAM treatment had a negative impact on daily energy intake of the children. Despite this, children covered their recommended energy intake. The energy intake coming from CFF was similar between arms, suggesting that children's feeding practices did not change due to the reduction in RUTF in this context. This trial was registered at the IRSCTN registry as ISRCTN50039021.

Vitamin A and iron status of children before and after treatment of uncomplicated severe acute malnutrition.

BACKGROUND & AIMS: Treatment of children with uncomplicated severe acute malnutrition (SAM) is based on ready-to-use therapeutic foods (RUTF) and aims for quick regain of lost body tissues while providing sufficient micronutrients to restore diminished body stores. Little evidence exists on the success of the treatment to establish normal micronutrient status. We aimed to assess the changes in vitamin A and iron status of children treated for SAM with RUTF, and explore the effect of a reduced RUTF dose. METHODS: We collected blood samples from children 6-59 months old with SAM included in a randomised trial at admission to and discharge from treatment and analysed haemoglobin (Hb) and serum concentrations of retinol binding protein (RBP), ferritin (SF), soluble transferrin receptor (sTfR), C-reactive protein (CRP) and α1-acid glycoprotein (AGP). SF, sTfR and RBP were adjusted for inflammation (CRP and AGP) prior to analysis using internal regression coefficients. Vitamin A deficiency (VAD) was defined as RBP < 0.7 µmol/l, anaemia as Hb < 110 g/l, storage iron deficiency (sID) as SF < 12 µg/l, tissue iron deficiency (tID) as sTfR > 8.3 mg/l and iron deficiency anaemia (IDA) as both anaemia and sID. Linear and logistic mixed models were fitted including research team and study site as random effects and adjusting for sex, age and outcome at admission. RESULTS: Children included in the study (n = 801) were on average 13 months of age at admission to treatment and the median treatment duration was 56 days [IQR: 35; 91] in both arms. Vitamin A and iron status markers did not differ between trial arms at admission or at discharge. Only Hb was 1.7 g/l lower (95% CI -0.3, 3.7; p = 0.088) in the reduced dose arm compared to the standard dose, at recovery. Mean concentrations of all biomarkers improved from admission to discharge: Hb increased by 12% or 11.6 g/l (95% CI 10.2, 13.0), RBP increased by 13% or 0.12 µmol/l (95% CI 0.09, 0.15), SF increased by 36% or 4.4 µg/l (95% CI 3.1, 5.7) and sTfR decreased by 16% or 1.5 mg/l (95% CI 1.0, 1.9). However, at discharge, micronutrient deficiencies were still common, as 9% had VAD, 55% had anaemia, 35% had sID, 41% had tID and 21% had IDA. CONCLUSION: Reduced dose of RUTF did not result in poorer vitamin A and iron status of children. Only haemoglobin seemed slightly lower at recovery among children treated with the reduced dose. While improvement was observed, the vitamin A and iron status remained sub-optimal among children treated successfully for SAM with RUTF. There is a need to reconsider RUTF fortification levels or test other potential strategies in order to fully restore the micronutrient status of children treated for SAM.

Body composition during outpatient treatment of severe acute malnutrition: Results from a randomised trial testing different doses of ready-to-use therapeutic foods.

BACKGROUND & AIMS: Treatment of children with uncomplicated severe acute malnutrition (SAM) is based on ready-to-use therapeutic foods (RUTF) prescribed based on body weight and administered at home. Treatment performance is typically monitored through weight gain. We previously reported that a reduced dose of RUTF resulted in weight gain velocity similar to standard dose. Here we investigate the change in body composition of children treated for SAM and compare it to community controls, and describe the effect of a reduced RUTF dose on body composition at recovery. METHODS: Body composition was measured via bio-electrical impedance analysis at admission and recovery among a sub-group of children with SAM participating in a clinical trial and receiving a reduced or a standard dose of RUTF. Non-malnourished children were measured to represent community controls. Linear mixed regression models were fitted. RESULTS: We obtained body composition data from 452 children at admission, 259 at recovery and 97 community controls. During SAM treatment the average weight increased by 1.20 kg of which 0.55 kg (45%) was fat-free mass (FFM) and 0.67 kg (55%) was fat mass (FM). At recovery, children treated for SAM had 1.27 kg lower weight, 0.38 kg lower FFM, and 0.90 kg lower FM compared to community controls. However, their fat-free mass index (FFMI) was not different from community controls (Δ0.2 kg/m2; 95% CI -0.1, 0.4). No differences were observed in FFM, FM or fat mass index (FMI) between the study arms at recovery. However, FFMI was 0.35 kg/m2 higher at recovery with the reduced compared to standard dose (p = 0.007) due to slightly lower height (Δ0.22 cm; p = 0.25) and higher FFM (Δ0.11 kg; p = 0.078) in the reduced dose group. CONCLUSIONS: Almost half of the weight gain during SAM treatment was FFM. Compared to community controls, children recovered from SAM had a lower FM while their height-adjusted FFM was similar. There was no evidence of a differential effect of a reduced RUTF dose on the tissue accretion of treated children when compared to standard treatment.

Impact of reduced dose of ready-to-use therapeutic foods in children with uncomplicated severe acute malnutrition: A randomised non-inferiority trial in Burkina Faso.

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 (Δ 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 (Δ -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 (Δ -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.