TY - JOUR

T1 - Impact of reduced dose of ready-to-use therapeutic foods in children with uncomplicated severe acute malnutrition

T2 - A randomised non-inferiority trial in Burkina Faso

AU - Kangas, Suvi T

AU - Salpéteur, Cécile

AU - Nikièma, Victor

AU - Talley, Leisel

AU - Ritz, Christian

AU - Friis, Henrik

AU - Briend, André

AU - Kæstel, Pernille

N1 - CURIS 2019 NEXS 272

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pmed.1002887

DO - 10.1371/journal.pmed.1002887

M3 - Journal article

C2 - 31454351

VL - 16

JO - P L o S Medicine (Online)

JF - P L o S Medicine (Online)

SN - 1549-1277

IS - 8

M1 - e1002887

ER -