Treatment dosage: Surprising controversy arising from new WHO wasting guidelines?
Natasha Lelijveld Senior Nutritionist at Emergency Nutrition Network (ENN)
Isabel Potani Global Health Research Lead at Ripple Global Health Network
Blessings Likoswe Independent Consultant
What we know: Previous World Health Organization (WHO) guidelines, from 1999 and 2013, stated that the amount of ready-to-use-therapeutic food (RUTF) for wasting treatment should be administered based on the child’s body weight. More recent research has focussed on simplified protocols that provide fixed, reduced doses of RUTF, yet WHO’s 2023 guideline maintains that RUTF dosage should be calculated based on body weight, with only minor dosage reductions.
What this adds: This views piece summarises the arguments that different researchers have put forward regarding whether the 2023 WHO guidelines is appropriate and feasible. We present arguments for dosages being both excessive and insufficient, yet any recommendations must ultimately be considered against the complex realities and practicability at the household level.
As the nutrition sector grapples with additions and amendments in the new WHO guideline on wasting treatment and prevention (WHO, 2023), one topic is attracting a lot of debate: the dosage specifications for RUTF in the treatment of severe wasting, which remain contentious. Much research has focussed on reducing or simplifying RUTF dosage regimes prior to the guideline’s publication and several papers have since been published on this topic. The new WHO guideline contain several updates relating to the dosage of RUTF for severe wasting (Box 1).
Box 1: WHO (2023) wasting treatment and prevention updatesChildren aged 6-59 months with severe wasting and/or nutritional oedema who are enrolled in outpatient care should be given RUTF at a quantity that will provide: 150-185 kcal/kg/day until “anthropometric recovery” and resolution of nutritional oedema. The previous recommendation was to give 150-220 kcal/kg/day (WHO, 1999) OR 150-185 kcal/kg/day until the child is no longer “severely wasted” and does not have nutritional oedema. The quantity can then be reduced to provide 100-130 kcal/kg/day until anthropometric recovery and resolution of nutritional oedema. Anthropometric recovery is defined as weight-for-height z-score ≥ -2 and/or mid-upper arm circumference (MUAC) ≥125mm (depending on the admission criteria used), plus no nutritional oedema for at least two consecutive visits. Severely wasted is defined as weight-for-height z-score < -3 and/or MUAC <115 mm, and/or nutritional oedema in infants and children aged 6-59 months. RUTF dosage must be based on weight and it cannot be determined based on MUAC or simplified to a single dose, regardless of weight. |
In recent years, research into so-called ‘simplified approaches’ has questioned whether RUTF dosage is unnecessarily high. If it is, this could result in excess programme costs and an increased risk of RUTF being misused or wasted (some children struggle to finish all the product provided to them). Researchers have also considered whether the dosage regime needs to be as complex as it currently is. Is it necessary to calculate dosage based on weight? Should the dosage increase in line with weight as children recover? Simplified dosage protocols (such as the ComPAS study) have been trialled, whereby two sachets are provided per day for all children with severe wasting (Bailey et al, 2020). This is approximately 1,000 kcals per day, reducing to one sachet per day (approximately 500 kcal) once children reach moderate wasting status (MUAC ≥115mm and <125mm).
The new guideline is very clear in rebutting some of these innovations. It specifies that RUTF dosage must be allocated based on weight. It articulates that MUAC cannot be used to decide dosage or to measure treatment progression. It outlines that children with severe wasting must be provided with 150-185 kcal/kg/day (which is greater than two sachets per day for heavier/older children, ruling out some simplified dosage programming). This new dosage specification is a slight reduction from the previous guidelines (150-220 kcal/kg/day for severe wasting). The new guideline now also permits a reduction in dosage to 100-130 kcal/kg/day once a child has recovered to moderate status.
Several papers published prior to the release of the new guideline argue that a simplified reduced dosage scheme (such as two sachets for all severe wasting, regardless of weight) is not inferior to standard weight-based dosages. This is true for both recovery and treatment time when compared to standard weight-based dosages (Bailey et al, 2020; Kangas, 2019; Likoswe et al, 2023). One paper published since the release of the new WHO guideline concurs with these previous findings (Bahwere et al, 2024). This study was a secondary data analysis from Afghanistan of a reduced dosage scheme which became necessary due to product stock-outs.
Another new publication argues that, in the new guideline, WHO have overestimated therapeutic energy requirements in their calculations of the new dosage recommendation (Sachdev & Kurpad, 2024). Instead of the WHO-recommended energy intake of 150-185 kcal/kg/day, the authors’ alternative calculations suggest that only 105-120 kcal/kg/day are required to treat children with severe wasting. If this is true, they suggest that there could be adverse consequences from caloric overfeeding in the new guideline. They also argue that there are gaps in practical guidance, such as when and how to transition to home-based diets, and what the maximal duration of therapeutic feeding should be. As such, there are multiple arguments that the new WHO guideline has dosage recommendations that are still too high.
While recovery rate and treatment length appear to be unaffected by reduced and simplified dosage schemes, the Afghanistan paper and another paper from Mali (Potani et al, 2024) do state that weight gain and MUAC gain velocities are slightly higher with higher dosage regimes. Reduced dosage studies have also noted a potential negative impact on linear growth which could exacerbate stunting (Kangas et al, 2019). The new paper from Mali argues that even the slight reduction in dosage permitted by the new 2023 guideline, compared to previous guidelines, will affect growth velocity. So, this is an argument that the dosage recommended in the new WHO guideline is in fact too low for certain outcomes! But if these arguments largely centre around the speed of weight gain, is faster weight gain actually better?
Is faster weight gain better?
Treatment of severe wasting does aim for quick catch-up growth to decrease the short-term mortality risk. However, when we consider long-term health, the optimal rate of weight gain for children treated for severe wasting is not currently known.
A paper in Jamaica found that high inpatient rehabilitation weight gain (exceeding 13 g/kg/day) was associated with adult adiposity in young, normal-weight adult severe wasting survivors (Thompson et al, 2023). Previous WHO guidelines recommended gaining ≥10 g/kg/day for inpatients. The new WHO guideline states that RUTF dosage of 150-185 kcal/kg/day should be provided for a target weight gain of 5-10 g/kg/day. This is lower than the previous recommended target and within the limits associated with long-term cardiometabolic risks (according to the analysis from Jamaica). It has been argued that a lower recommended weight gain of 3-4 g/kg/day is more realistic. This may be advisable based on average weight gains in recovered children across recent community management of acute malnutrition (CMAM) programmes (Sachdev & Kurpad, 2024).
In a more recent cohort of survivors in Malawi, faster weight gain (averaging 5.3 g/kg/day, ranging from -3 to 27 g/kg/day) was associated with lower mortality and stunting risk (Lelijveld et al, 2023). However, a larger waist-to-hip ratio was also observed, which could be indicative of future dyslipidaemia. This suggests a complex pattern of risks and benefits associated with faster treatment weight gain.
The bigger picture
Besides this issue of specific dosage, is it even helpful to focus on energy intake to this level of detail if we consider the huge variation in individual living conditions? Home environments, availability of family food, cultures of sharing, infectious disease burden, and other health risk exposures all play important roles in wasting pathogenesis. Focusing on small changes in dosage may be distracting from much harder (and potentially more impactful) issues that need to be tackled. Reducing relapse, improving coverage, health system strengthening, and improving home diets are just some of these challenges.
The large focus on RUTF and the lack of focus on the use of home foods to treat severe and moderate wasting where possible was highlighted in a recent opinion paper regarding the new guidelines (Rohloff et al, 2024). The paper by Sachdev and Kurpad also states:
“The current WHO Guideline is silent about the transitioning process from the product-based intervention (RUTF) to the home diets…surely, the intent of the Guideline is not to continue the RUTF product indefinitely in such subjects, which apart from being impractical, is a sure recipe for developing later cardiometabolic risk factors”
This raises another question in relation to the guideline: when should treatment be stopped? Some children are discharged as ‘non-responders’ after 12 weeks of treatment, but they may in fact be benefitting from treatment and simply require longer to reach set discharge criteria. Distinguishing these children from those who are truly not responding to treatment is a part of ongoing work by the Wasting and Stunting Technical Interest Group.
Other concerns that are worth considering in relation to dosage regimes are the issues of RUTF stock-outs and low treatment coverage. Many contexts at present are already implementing the simplified, reduced dosage regime, such as in Gaza, where the context required very rapid initiation and scale-up of CMAM programming. Prior to the besiegement of Gaza in 2023, CMAM programming was not widespread. Significant programme infrastructure, equipment, and human resources had to be built from the beginning, while also responding to the large, life-threatening burden of child malnourishment. In this context, MUAC-only, simplified dosage regimes became the most feasible option.
The requirement in the 2023 guideline (“dosage must be determined based on weight”) could have huge implications for treatment coverage. While national governments can make their own decisions about what to implement within their contexts, the new guideline can be prohibitive. It discourages MUAC-only programming, necessitates access to weighing scales and batteries, and requires a certain level of literacy from health workers. Should the WHO guideline recognise that in certain contexts (like Gaza) the requirement for following weight-based dosage might compromise achieving higher coverage, compared to a logistically simpler MUAC-only approach? How important is following the weight-based dosage regime if feasibility and coverage might be negatively affected in complex scenarios?
Gaza also faces the challenge of importing supplies. The reduced dosage allows existing supplies to be rationed across more children. The recent paper from Afghanistan (Bahwere et al, 2024) describes the decision to reduce RUTF dosage to mitigate an impending period with RUTF out of stock. This was as a result of high caseload and financial constraints. Presently, there is a high incidence of stock-outs in many parts of the world. Is it acceptable to reduce dosages to make stocks last longer when it is known that no more stock will be arriving? More fundamentally, how can we better prevent stock-outs? The issue of stock-outs is a challenging one, and we feature a separate article related to this subject in this issue.
The debate on the appropriate dosage regime for RUTF will no doubt continue, and hopefully new evidence will be generated to help settle the issue for future guidelines. Further evidence is required to strike a balance between optimal recovery times versus longer-term health risks. But the bigger picture of higher coverage, long-term health, family diets, and preventing relapse must not be forgotten. Implementation guidance which is set to follow the release of the 2023 WHO guideline will hopefully stimulate further attention to these overshadowed issues. In addressing these issues, we can encourage national governments to implement programmes that are appropriate for their contexts.
For more information, please contact Natasha Lelijveld at natasha@ennonline.net
References
Bahwere P, Funnell G, Qarizada AN et al (2024) Effectiveness of a nonweight-based daily dosage of ready-to-use therapeutic food in children suffering from uncomplicated severe acute malnutrition: A nonrandomized, noninferiority analysis of programme data in Afghanistan. Maternal & Child Nutrition, 20, 3, e13641
Bailey J, Opondo C, Lelijveld N et al (2020) A simplified, combined protocol versus standard treatment for acute malnutrition in children 6-59 months (ComPAS trial): A cluster-randomized controlled non-inferiority trial in Kenya and South Sudan. PLOS Medicine, 17, 7, e1003192
Kangas ST, Salpéteur C, Nikièma V et al (2019) 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. PLOS Medicine 16, 8, e1002887
Lelijveld N, Cox S, Anujuo K et al (2023) Post-malnutrition growth and its associations with child survival and non-communicable disease risk: A secondary analysis of the Malawi ‘ChroSAM’cohort. Public Health Nutrition, 26, 8, 1658-1670
Likoswe BH, Chimera-Khombe B, Patson N et al (2023) A systematic review on the optimal dose and duration of ready-to-use therapeutic food (RUTF) for 6–59-month-old children with severe wasting or oedema. Nutrients, 15, 7, 1750
Potani I, Tausanovitch Z, Ritz C et al (2024) The relationship between energy provided and growth during severe wasting treatment. Maternal & Child Nutrition, 20, 4, e13693
Rohloff P, Gupta S, López Canu W et al (2024) New WHO guideline on the prevention and management of acute malnutrition in infants and young children: Remaining challenges. BMJ Paediatrics Open, 8, 1, e002471
Sachdev HS & Kurpad AV (2024) The recent WHO guideline on acute malnutrition overestimates therapeutic energy requirement. The Lancet Regional Health Southeast Asia, 25, 100419
Thompson D, McKenzie K, Opondo C et al (2023) Faster rehabilitation weight gain during childhood is associated with risk of non-communicable disease in adult survivors of severe acute malnutrition. PLOS Global Public Health 3, 12, e0002698
World Health Organization (2023) WHO guideline on the prevention and management of wasting and nutritional oedema (acute malnutrition) in infants and children under 5 years. app.magicapp.org
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Natasha Lelijveld, Isabel Potani and Blessings Likoswe (2024). Treatment dosage: Surprising controversy arising from new WHO wasting guidelines? Field Exchange 74. https://doi.org/10.71744/t4xa-tp88