WHO Consultation

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MEETING REPORT

WHO Consultation

on Prevention and Treatment of Wasting in Children

Geneva

17 – 19 December 2019

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WHO Consultation

on Prevention and Treatment of Wasting in Children

Geneva, 17–19 December 2019

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WHO Consultation on Prevention and Treatment of Wasting in Children, Geneva, 17–19 December 2019 ISBN 978-92-4-001224-0 (electronic version)

ISBN 978-92-4-001225-7 (print version)

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This publication contains the report of the WHO Consultation on Prevention and Treatment of Wasting in Children, Geneva, 17–19 December 2019 and does not necessarily represent the decisions or policies of WHO.

Cover design and layout: Sue Hobbs

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WHO COnsultatiOn On PreventiOn and treatment Of Wasting in CHildren, geneva, 17–19 deCember 2019

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3.6 Prevention of wasting 18

3.6.1 Prevention of wasting: definition and scope 18 3.6.2 Cash transfers and social protection: delivering nutrition services

through supply and demand channels 18

3.6.3 Global action plan on wasting: prevention of wasting from a

food systems perspective 19

3.6.4 Taking a multisectoral population perspective: how do we bring

partners together? 20

3.6.5 Experiences in designing a social protection programme:

challenges in implementation and impact on nutrition of

the Ehsaas Programme in Pakistan 21

3.6.6 Review of prevention interventions 21

4. The way forward 23

4.1 Technical framing and risk stratification 23

4.2 Epidemiology 23

4.3 Prevention and treatment 23

5. Proposed guidelines 24

6. Research questions 25

6.1 Technical framing and risk stratification 25

6.1.1 Entry and exit criteria 25

6.1.2 Risk stratification 25

6.1.3 Recovery 25

6.2 Prevention and treatment 26

7. Annexes 27

7.1 Annex 1. Meeting agenda 27

7.2 Annex 2. List of participants 29

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Acknowledgements

This consultation was organized by Zita Weise Prinzo and Jaden Bendabenda, Department of Nutrition for Health and Development, World Health Organization (WHO), together with Nigel Rollins and Pura Solon, Department of Maternal, Newborn, Child and Adolescent Health, under the coordination of Francesco Branca, Director, Department of Nutrition for Health and Development, and Anshu Banerjee, Director, Maternal, Newborn, Child and Adolescent Health.

This consultation was organized in collaboration with Patrizia Fracazzi, Food and Agriculture Organization of the United Nations (FAO); Caroline Wilkinson, Office of the United Nations High Commissioner for Refugees (UNHCR); Saul Guerrero, United Nations Children’s Fund (UNICEF);

and Nicolas Joannic, World Food Programme (WFP).

WHO gratefully acknowledges the technical support provided by Nicki Connell, Eleonor Crook Foundation, and Marie McGrath and Tanya Joannic, Emergency Nutrition Network.

Thanks are due to all the experts who contributed to this consultation. Special thanks are due to Jessica Pullar, United Nations System Standing Committee on Nutrition (UNSCN), for writing the minutes of the meeting. This meeting report was drafted by Jaden Bendabenda and Zita Weise Prinzo, Department of Nutrition for Health and Development.

Financial support

WHO gratefully acknowledges the financial support provided by the Eleanor Crook Foundation for this consultation and the follow-up work, including this report.

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Abbreviations

ABCD Antibiotics for Children with Severe Diarrhoea

AMANHI Alliance for Maternal and Newborn Health Improvement BISP Benazir Income Support Programme

CHAIN Childhood Acute Illness and Nutrition Network CMAM Community-based Management of Acute Malnutrition EMPIC Enhanced Management of Pneumonia in the Community ENN Emergency Nutrition Network

FAO Food and Agriculture Organization of the United Nations HAZ height-for-age Z-score

IMCI Integrated Management of Childhood Illness LAZ length-for-age Z-score

LBW low birth weight

MAMI Management of At Risk Mothers and Infants MUAC mid-upper arm circumference

RUTF ready-to-use therapeutic foods SDG Sustainable Development Goal SGA small for gestational age SNF specialized nutritious foods

UNHCR Office of the United Nations High Commissioner for Refugees UNICEF United Nations Children’s Fund

WASH water, sanitation and hygiene (interventions) WAZ weight-for-age Z-score

WFP World Food Programme WHO World Health Organization WHZ weight-for-height Z-score WLZ weight-for-length Z-score

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1 1. Background

In 2015, the world committed to eliminating all forms of malnutrition by 2030 as one of the Sustainable Development Goals (SDGs). To achieve this objective, the SDGs incorporated the World Health Assembly targets that aim to reduce the proportion of children suffering from wasting to < 5% by 2025 and to < 3% by 2030.

Yet since these targets were adopted, the proportion of children with wasting has remained largely unchanged.¹ In 2019, an estimated 7.3% of all children younger than 5 years (or 50 million children) had wasting.² To achieve the SDG targets on wasting and undernutrition, a major policy shift is needed, with increased efforts to prevent all forms of malnutrition.

The World Health Organization (WHO), in collaboration with the United Nations Children’s Fund (UNICEF), the Office of the United Nations High Commissioner for Refugees (UNHCR), the Food and Agriculture Organization of the United Nations (FAO) and the World Food Programme (WFP) convened a 3-day technical consultation on the prevention and treatment of wasting in children, in Geneva, Switzerland on 17–19 December 2019. Bringing together international experts in the fields of undernutrition and child health, the meeting aimed to review the technical framing of wasting, to discuss how to identify children at highest risk of morbidity and mortality and to identify the key gaps in the guidance on preventing and treating wasting in children.

This report summarizes the key issues discussed at the meeting, including risk stratification, evidence gaps, research questions and recommendations for developing comprehensive global guidelines on preventing and treating child wasting.

2. Objectives of the meeting

The objectives of the meeting were to:

1. develop the basis to update the technical framing of wasting and agree on key questions in preventing and treating wasting;

2. discuss the evidence and gaps in evidence for interventions to prevent and treat wasting;

3. agree on processes to be used to address the gaps and to propose key themes for the global action plan on child wasting.

1 Since 2013, the UNICEF–WHO–World Bank Joint Child Malnutrition Estimates have reported wasting prevalence rates of 8.0% in 2013, 7.5% in 2014, 7.4% in 2015, 7.7% in 2016, 7.5% in 2017 and 7.3% in 2018. From the Global database on child growth and malnutrition: UNICEF–WHO–World Bank joint child malnutrition estimates – levels and trends [website]. Geneva: United Nations Children’s Fund, World Health Organization, International Bank for Reconstruction and Development/The World Bank; 2020 (https://www.who.int/nutgrowthdb/estimates/en/, accessed 20 January 2020).

2 Levels and trends in child malnutrition: key findings of the 2019 edition of the joint child malnutrition estimates.

Geneva: United Nations Children’s Fund, World Health Organization, International Bank for Reconstruction and Development/The World Bank; 2019 (https://apps.who.int/iris/bitstream/handle/10665/331097/WHO-NMH-NHD- 19.20-eng.pdf?ua=1, accessed 20 January 2020).

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2 3. Summary of presentations and discussions

Presentations and discussions from the technical consultation are summarized in the sub- sections below.

3.1 Technical framing of wasting

Nigel Rollins presented a technical framing of wasting in infants and children.

The common understanding is that malnutrition occurs when food intake does not meet the needs for physiological function, growth and the capacity to respond to illness. The current diagnosis of malnutrition is based on anthropometry alone: for severe acute malnutrition, diagnosis is based on weight-for-length/weight-for-height Z-scores (WLZ/WHZ) of < −3 or mid- upper arm circumference (MUAC) < 115 mm or the presence of bipedal pitting oedema; for moderate acute malnutrition, diagnosis is based on WLZ/WHZ of < −2 or MUAC < 125 mm; and for chronic malnutrition (stunting), diagnosis is based on height-for-age/length-for-age Z-scores (HAZ/LAZ) of < −2. Hence, the evidence on the risk of malnutrition-related mortality in children is based on anthropometry.

There are several underlying concepts and assumptions that are commonly accepted.

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■ Severe acute malnutrition is associated with increased mortality and poor developmental outcomes (i.e. health, cognition, growth).

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■ Several physiological and metabolic derangements occur in severe acute malnutrition, such as immune suppression, cell membrane dysfunction, the development of free radicals and oxidative stress, and reductive adaptation.

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■ Severe acute malnutrition is classified as either complicated or uncomplicated, determined by the absence or presence of appetite and medical complications.

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■ Recovery is defined by anthropometry-based criteria (MUAC or weight-for-height).

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■ Moderate acute malnutrition is similar to severe acute malnutrition but associated with lower mortality, less morbidity and fewer long-term developmental risks. There is little evidence regarding possible metabolic or immunological dysfunction associated with moderate acute malnutrition. It is recognized that children with moderate acute malnutrition require appropriate amounts of high-quality protein, energy and micronutrients for recovery of lean tissue. However, it is unclear whether this should be provided using the same therapeutic foods as are provided for children with severe acute malnutrition, but in lesser quantities.

Basing evidence of malnutrition-related child mortality on anthropometry alone has posed challenges and raised questions.

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■ Malnutrition, defined anthropometrically, in patients with HIV, cancer or tuberculosis is not improved simply by increasing the intake of nutritious food.

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■ The mortality risk associated with anthropometric deficit varies by age (i.e. among those aged < 24 months, 24–59 months and > 59 months), by context and by co-morbidities.

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■ Children can suffer repeated episodes of wasting, which suggests that recovery defined only by anthropometry is not sufficient. Anthropometric recovery does not guarantee that metabolic, physiological and cognitive recovery are also achieved, nor that the

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circumstances that led to the child becoming wasted have been resolved – that is, the risk of the child having wasting has not changed.

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■ How do changes along the anthropometry continuum correspond with metabolic changes, immune function, gut function (including the microbiota) and other outcomes while the child is recovering from wasting or deteriorating?

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■ Which individual and population factors are associated with the highest risk of mortality, and how can the children at highest risk be identified?

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■ How can researchers and programme implementers assess functional recovery?

There is need for a technical framing that captures these issues at the individual and population levels as well as risk-stratified approaches for prevention, treatment, follow up, monitoring and research that will facilitate better child outcomes and more effective deployment of resources.

3.1.1 Key discussion point

Programmes should consider taking a risk approach towards the management of wasting; for example, some children with moderate wasting may be at higher risk of mortality than others, and some populations, regions or groups of children are at higher risk than others.

3.2 Pathophysiology of wasting: what we know and do not know

Alan Jackson highlighted three important topics necessary to understanding the pathophysiology of child wasting.

Three separate but related topics of importance in child wasting are (i) the need to understand the nature of the term wasting (ii) the identification and differentiation of the four different pathways to wasting and (iii) the implications of these two points for recovery from wasting.

Child wasting is a state in which there are disproportions in the relative components of the body, usually captured as a deficit of weight relative to height when compared with healthy children who are growing normally. It is the consequence of a lack of tissue formation at an adequate rate or a subsequent loss of the tissue that acts as an energy and nutrient reserve when the needs of the body are not adequately met by dietary intake.

Lack or loss of tissue occurs in different proportions depending on the context, and is quantitatively measured as differences in lean tissue mass (predominantly muscle) and sub- cutaneous adipose tissue mass. There is also a measure of bone rarefaction as nutrients are mobilized to meet the needs of the body, but this is more difficult to capture and characterize.

The primary cause of wasting is insufficient intake of energy and/or nutrients to meet the needs of the body. This may be due to inadequate intake of food, but it is also often a consequence of altered metabolic demands resulting from stress/stressors (which may variously be infection, metabolic, emotional, social). The measurement of weight in relation to height at a single point in time can identify the state of being wasted, but it is not sufficient to identify the underlying wasting processes that have led to that state. The treatment, therefore, must address the underlying process(es) and not simply address being wasted per se.

It is important to differentiate between when wasting represents a failure to acquire the relevant tissues during growth (disproportionate growth) and the active loss of tissues as a consequence of adverse circumstances. Thus, there are four major pathways that lead to wasting, explained below.

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Failure to deposit tissue during growth may result from:

1. being preterm or having poor intrauterine growth, both of which lead to low birth weight (LBW) and relative thinness;

2. poor growth during infancy.

The correction of failure to deposit tissue during growth may or may not be responsive to the simple provision of additional food, and it can be very difficult to correct, especially if the disruption occurs during a sensitive period of growth.

Active loss of tissue may occur:

3. as a result of inadequate food availability – that is, a limitation of energy and/or nutrients – during which the needs of the body are met by selectively drawing on tissue reserves, leading to different degrees of muscle loss, lean or adipose tissue loss, and bone rarefaction.

Provision of food of adequate quality and quantity is expected to lead to rapid correction of this state, with recovery of weight and body composition;

4. as the metabolic response to any stress or stressor (e.g. infection, emotional, social), which has a series of effects including loss of appetite, altered digestion and absorption, increased loss of endogenous nutrients (through urine and stool), altered demands for energy and nutrients, and altered delivery of energy and nutrients to tissues. This state requires correction with adequate food. There is also the need to remove or ameliorate the effect of the stressor if the response to improved food availability and utilization is to have the best effect.

In general, the objective of correcting the wasted state is to return body weight and composition to that which is expected for a child of similar height and/or maturation. Most individuals with wasting have experienced varying degrees of limitation of food and exposure to one or another stressor. The pattern of tissue mobilization and loss varies with the context, and the pattern of nutrients required to correct these losses has to match the needs for correcting the mobilized tissue(s). This requires an assessment of the process that has led to the wasted state.

It is possible to determine the underlying basis of the process of wasting only from a reliable history, which would include secure longitudinal measurements of growth. This is useful to identify the different pathways of wasting and the variable pattern of tissue loss, which any interventions for wasting must aim to fully address. A cause for poor response to interventions needs to be determined, and alternative patterns of causation must be taken into account.

When the diet that is provided only poorly matches the need for correction of tissue deficits, the likelihood of obesity developing is enhanced. Thus, simply giving more food to correct wasting without ensuring there is adequate attention to the quality of the food provided leads to significant (but reversible) increases in adiposity and obesity.

3.2.1 Key discussion point

Anthropometric status is critical, but should not be the only measure for determining risk and recovery. There are enormously complex biological systems that influence wasting; for example, there are more than 40 essential nutrients that could be deficient in a child who has wasting, and these nutrients’ interactions with the microbiome are currently not considered in the treatment of wasting.

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5 3.3 Epidemiology of wasting

3.3.1 Regional trends over time and by age: data limitations and findings

Elaine Borghi and Elisa Dominguez discussed regional trends in wasting and the limitations of modelling.

The data used to generate regional estimates of wasting are aggregated from national nutrition surveys and do not capture seasonal fluctuations in wasting. The data also fail to consistently capture context-specific shocks, crises and livelihood factors.

There are efforts to produce harmonized datasets that would allow for regional and global modelling. However, current modelling cannot disaggregate data by sex or allow for compar- isons across years or seasons. A pilot exercise conducted to compare wasting by region and age demonstrated the difficulty of producing trends for wasting. More information is needed from the countries submitting data to understand variations in the prevalence of wasting and contextual details.

Trends in wasting may vary significantly depending on the survey methodology used; therefore, caution is needed when interpreting the results (e.g. by considering the season and that high- population countries, such as India, represented during specific time periods can skew results).

Until methods are implemented that can ensure seasonality and shocks are accounted for, and data on the incidence of wasting are available, it is not recommended that the UNICEF–WHO–

World Bank Joint Child Malnutrition Estimates are used to present information about trends in wasting because smoothing across surveys may misrepresent the real trends.

Currently, there are large gaps in the data for infants aged < 6 months and children aged 5–10 years. There is a need to invest in collecting data for these age groups.

3.3.2 Patterns of wasting by WHZ and MUAC

Michael Golden discussed patterns of wasting and the implications of using only MUAC or only WHZ or both for diagnosis.

There are differences across countries and regions between children diagnosed with wasting based on MUAC and those diagnosed based on WHZ, although the risk of mortality is similar among children identified by the two indicators. The differences in the performance of the two indicators may be due to underlying morphological differences across regions (e.g. between the African and South-East Asia regions); however, these morphological differences are not fully defined. As such, wasting data from East Africa may not be appropriate for determining the situation in South-East Asia, where body shape and diagnoses are quite different.

While both indicators are important individually, historic community cohorts show that having a diagnosis based on either MUAC or WHZ is associated with a higher risk of mortality. However, programmes using only one indicator (MUAC only or WHZ only) have a risk of missing more than 30% of children with severe wasting. In some countries, such as India, the proportion missed could be as high as 50% for MUAC-only programmes and 13% for WHZ-only programmes.

In the general population, the mortality risk is expected to decrease as children grow older.

However, data from historic community cohorts suggest that older children (> 2 years) with wasting have the same mortality risk as younger children. These children are unlikely to be identified by MUAC-only screening.

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The interaction between stunting and wasting needs to be explored further. A meta-analysis of individual data in 10 prospective studies from developing countries by McDonald et al. in 2013 included children aged 0–60 months.¹ Infants aged <6 months dominate mortality statistics because of the risks of being, for example, premature or small for gestational age (SGA) or having congenital defects. The analysis by McDonald et al. showed that in children aged 6–60 months, wasting without stunting was associated with a hazard ratio for mortality of 7.2, whereas having both wasting and stunting was associated with a slightly lower risk of mortality (hazard ratio 5.8). However, when Schwinger et al. stratified by age group, this interaction was no longer evident in children aged 6–60 months.²

Admission data show definite seasonality in the incidence of wasting, and children with moderate wasting appear to recover anthropometrically when the family food situation changes (e.g. with harvest or other interventions). In a randomized controlled trial conducted in the Democratic Republic of the Congo, children from families that were provided US$ 1 per day showed a lower rate of wasting relapse after 6 months of follow-up compared with families who did not receive a financial subsidy.³ This finding suggests that economic interventions at the population and household levels reduce the risk of wasting, and perhaps it also explains why providing ready-to-use supplementary foods or ready-to-use therapeutic foods (RUTF) without additional improvement in economic status have only a modest impact on moderate wasting. There is a need to move away from interventions designed for emergency response being applied in developmental contexts without integrating them into existing programmes aimed at improving family outcomes.

3.3.3 Interactions between wasting and stunting: retrospective cohort data from Gambia Sophie Moore discussed longitudinal cohort data from Gambia on the interactions between wasting and stunting, as well as the effects of seasonality.

The Emergency Nutrition Network (ENN) commissioned a study to investigate the interaction between wasting and stunting, the age-related differences in prevalence of wasting and prevalence of stunting, and the seasonality of the two conditions in children aged 0–2 years in Gambia.

Longitudinal data from more than 5000 children (collected by the Medical Research Council Unit The Gambia) showed that wasting peaked at 1 year of age; boys were at greatest risk; and wasting was more common if the child had stunting and vice versa (i.e. being stunted or having wasting increased the odds of having both conditions 3 months later). However, there was no difference between the prevalence of moderate wasting and the prevalence of severe wasting, and clinical outcomes were not reported. Infants with wasting during the first rainy season were more likely to suffer wasting during the second rainy season (i.e. recovery from seasonal wasting was not sustained). Infants born at the beginning of the rainy season did not catch up

1 McDonald CM, Olofin I, Flaxman S, Fawzi WW, Spiegelman D, Caulfield LE, et al. The effect of multiple anthropometric deficits on child mortality: meta-analysis of individual data in 10 prospective studies from developing countries.

Am J Clin Nutr. 2013;97:896–901. doi:10.3945/ajcn.112.047639.

2 Schwinger C, Golden MH, Grellety E, Roberfroid D, Guesdon B. Severe acute malnutrition and mortality in children in the community: comparison of indicators in a multicountry pooled analysis. PLOS ONE. 2019;14(8):e0219745.

doi:10.1371/journal.pone.0219745.

3 Grellety E, Babakazo P, Bangana A, Mwamba G, Lezama I, Zagre NM, et al. Effects of unconditional cash transfers on the outcome of treatment for severe acute malnutrition (SAM): a cluster-randomised trial in the Democratic Republic of the Congo. BMC Med. 2017;15:87. doi:10.1186/s12916-017-0848-y.

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during the first 6 months of life compared with infants born at other times of year, and this had a lasting impact.

3.3.4 Wasting, stunting and mortality

André Briend discussed the relationships between wasting, stunting and mortality.

A study by McDonald et al. in 2013 that included 10 different cohorts of children aged 0–60 months suggested that children who have both wasting and stunting are at higher risk of mortality than children who have wasting only.¹ In 2019, this finding was challenged by an analysis of this interaction by Schwinger et al. that showed no increased risk of mortality in children with both wasting and stunting, but the analysis was limited to children aged 6–60 months.² Further analysis of the dataset used by McDonald et al., with the addition of one cohort, showed that in children aged 6–60 months, severe anthropometric deficits are associated with nearly half of the total number of deaths (Briend, unpublished). This analysis also showed that children with both wasting and stunting had the highest risk of mortality, which is consistent with the initial findings from McDonald et al., but different from the findings of Schwinger et al. The lack of increased risk of mortality in children with both wasting and stunting reported by Schwinger et al. may be due to the need to have a large sample size to show an interaction effect. Also, this interaction may vary by setting. The Schwinger et al. study included only three of the 11 cohorts examined in the analysis by Briend (unpublished). The Briend analysis also suggested that addressing wasting and stunting together would lead to the largest reduction in mortality.

In this pooled analysis a low weight-for-age Z-score (WAZ), which reflects both wasting and stunting, showed the highest population attributable fraction (37%), suggesting the importance of WAZ as a screening indicator in children aged 6–60 months. Many deaths associated with low WAZ will not be prevented by programmes targeted only at children with low WHZ or low HAZ.

Duration of follow-up may have a strong effect on the sensitivity and specificity of different nutritional indices (as assessed by receiver operating characteristic curves), which was suggested by a study in 1986 in Bangladesh that looked at the relationship between MUAC and mortality.³ This effect was confirmed by a reanalysis of three more recent cohorts that suggested the sensitivity and specificity of MUAC, WHZ and, to a lesser extent, WAZ in predicting death was significantly increased when used over 1 month compared with at 3- to 6-month intervals. This effect is presumably due to the transient nature of wasting. In addition, with monthly screening, very few deaths in children aged 6–60 months with WHZ < −3 or WAZ < −3 would be missed by MUAC, even with a MUAC cut-off point of < 115 mm. This suggests that frequent screening using MUAC, with screening possibly conducted by families, would significantly increase case detection and may have an impact on the delivery of interventions to reduce wasting.

1 McDonald CM, Olofin I, Flaxman S, Fawzi WW, Spiegelman D, Caulfield LE, et al. The effect of multiple anthropometric deficits on child mortality: meta-analysis of individual data in 10 prospective studies from developing countries.

Am J Clin Nutr. 2013;97:896–901. doi:10.3945/ajcn.112.047639.

2 Schwinger C, Golden MH, Grellety E, Roberfroid D, Guesdon B. Severe acute malnutrition and mortality in children in the community: comparison of indicators in a multicountry pooled analysis. PLOS ONE. 2019;14(8):e0219745.

doi:10.1371/journal.pone.0219745.

3 Briend A, Dykewicz C, Graven K, Mazumder RN, Wojtyniak B, Bennish M. Usefulness of nutritional indices and classifications in predicting death of malnourished children. Br Med J. 1986;293:373–5. doi:10.1136/

bmj.293.6543.373.

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3.3.5 Key discussion points

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■ Data quality needs to be improved within countries to enable monitoring of trends in different age groups (including infants aged < 6 months and school-aged children), and contextual information should be collected (e.g. about season, crisis, disasters). In parallel, work to determine the incidence of wasting should be intensified.

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■ WHZ and MUAC do not always identify the same children with wasting, but the mortality risk is similar regardless of whether the child is identified by MUAC or WHZ. The number of children identified by each criterion varies depending on the context.

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■ Wasting in older children poses a similar risk of mortality as it does among younger children, and it may be missed with MUAC-only screening that uses 115 mm as a cut-off value (most MUAC-only programmes use a higher MUAC cut-off of 120 mm or, more frequently, 125 mm).

The mortality risk in older children needs attention because current guidelines and programmes focus on children younger than 5 years.

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■ The seasonality of wasting suggests that many children with moderate wasting recover anthropometrically without medical intervention when the family situation improves (e.g.

postharvest). However, the recovery is not necessarily sustained, as the same children may suffer a repeat wasting episode in the following lean season. Programmes aimed at improving families’ socioeconomic status are integral to strategies for preventing and treating moderate wasting. The effect of season is not only limited to food availability but also includes other factors, such as infections.

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■ Frequent screening (e.g. with family-based MUAC measurement) improves case detection.

The practicality of measuring and the diagnostic value of WAZ in identifying children younger than 5 years who are at risk of mortality needs to be re-examined and there is a need to determine the specific age group for which WAZ has diagnostic value. Other ways of improving screening without adding extra burdens to health systems need to be explored (e.g. using mobile technology).

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■ The nature of the interaction between stunting and wasting on mortality risk needs further analysis. However, when considering universal health coverage, we need to advocate for these two conditions together as they can affect the same children, although the processes may be different.

3.3.6 Individual patient profiles

This section summarizes the evidence from individual child data on the association of wasting with infections such as diarrhoea and pneumonia, the possible risk of post-discharge mortality associated with wasting, and longitudinal data demonstrating the incidence of and risk factors for wasting in different populations.

3.3.6.1 Diarrhoea and wasting

Jonathon Simon presented results of a crude analysis of data from the Antibiotics for Children with Severe Diarrhoea (ABCD) trial, which was conducted from May 2017 to January 2020 at seven study sites.

The ABCD trial (https://clinicaltrials.gov/ct2/show/NCT03130114) aims to evaluate the efficacy of delivering a short course of antibiotic (azithromycin for 3 days) to young children aged < 2 years

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at high risk of diarrhoea. The study evaluates the ability of the intervention to reduce mortality within 180 days of an acute diarrhoeal episode and improve nutritional status (as measured by MUAC, WHZ and HAZ) during the first 90 days of follow-up in children aged 2–23 months. The study included children with moderate wasting and stunting, but excluded children with severe wasting.

A crude analysis of the data showed no difference in mortality by enrolment anthropometry (i.e. the mortality rate was similar in the study population over 180 days, regardless of whether the children had moderate wasting at enrolment or not). The number of deaths was low, which contributed to the lack of detected difference, and was attributed to the quality of case management and provision of primary health care to the children.

3.3.6.2 Pneumonia and wasting

Yasir Bin Nisar summarized recent data on associations between pneumonia outcomes and wasting.

In 2014, WHO initiated the Pneumonia REsearch Partnership to Assess WHO REcommendations (PREPARE)¹ project, which collated information from 41 datasets. These datasets were assembled through retrospective identification of primary data on childhood pneumonia from low- and middle-income countries in in Africa, Asia and Latin America as well as high-income countries (Australia and the United States of America). Study sites were considered for inclusion in the WHO PREPARE study group if they included data from control arms of vaccine trials, community-based cohorts, and hospital-based studies with clinical and epidemiological data collected. Potential study sites were identified from a list of contributors to a systematic review of global burden of hospital admissions for severe acute lower respiratory infections in children.

Researchers from these study sites agreed to provide their datasets which contributed to the 41 unique databases for the WHO PREPARE study group. Pooled analysis of these datasets showed that in children aged 2–59 months with any degree of severity of signs of pneumonia, the presence of wasting increased the severity of and mortality risk due to pneumonia.

Additionally, the preliminary results of a WHO-coordinated cluster randomized controlled trial which investigated whether children aged 2–59 months with chest indrawing pneumonia can be treated effectively and safely with oral antibiotics by community health workers (the Enhanced Management of Pneumonia in the Community, or EMPIC, study),² showed that MUAC influenced treatment outcomes: the treatment failure rate was 1.7 times higher and mortality was 9 times higher in children with MUAC of 115–125 mm compared to those with MUAC > 125 mm.

3.3.6.3 The Childhood Acute Illness and Nutrition Network

James Berkley described preliminary results from the Childhood Acute Illness and Nutrition (CHAIN) Network study.

Anthropometry is a marker of inpatient mortality risk, but does not necessarily identify specific mechanisms that can be used to guide treatment. Working with existing data as well

1 The WHO established the PREPARE study group with the aim of better understanding the clinical diagnostic criteria for childhood pneumonia.

2 EMPIC Study Group. Community case management of chest indrawing pneumonia in children aged 2 to 59 months by community health workers: study protocol for a multi-country cluster randomized open label non-inferiority trial. Int J Clin Trials 2020;7(2):131–41. doi: 10.18203/2349-3259.ijct20201719.

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as by conducting a cohort study, the CHAIN Network aims to identify and prioritize effective interventions for acute illnesses in children with wasting through understanding mechanisms and risk groups (see https://chainnetwork.org/).

Preliminary results suggest that in children aged 2–13 months who are admitted to hospital with acute illness, those with severe wasting (defined by MUAC < 115 mm) had an almost 20% total risk of death (from the time of admission to 6 months after discharge). A number of deaths in children with severe wasting occurred immediately after discharge despite strict and thorough checks before discharge. Thus, despite anthropometric recovery, these children may still have abnormal physiology including metabolic and immunological dysfunctions.

Planned analyses will examine how illness severity, comorbidities, financial status, health services and access to care influence outcomes across severely, moderately and non-wasted children younger than 2 years who are admitted to hospital with acute illness; additionally, a systems biology analysis of physiological, metabolic and immune mechanisms related to mortality risk will also be conducted.

3.3.6.4 Critical warning signs

Robert Bandsma highlighted some of the danger signs for children with wasting as assessed in the F75 trial.

WHO has defined danger signs for paediatric populations, such as respiratory distress, hypo- glycaemia, lethargy, severe diarrhoea and oedema. These signs are usually assessed upon admission and used to triage and assign treatment. However, it is unclear which signs are most relevant in children with severe wasting. More importantly, mortality risk is expected to improve in response to medical treatment. Whether these signs have prognostic value later during hospitalization has not been studied.

Unpublished data from a trial using reformulated F75 milk to treat severe acute malnutrition (https://clinicaltrials.gov/ct2/show/NCT02246296) indicate that when using clinical danger signs at admission, the discriminating power for mortality of the model was 77%. Simply counting the number of clinical danger signs on any given day during admission provided a predictive power of 86%. Having three or more danger signs on any given day was significantly associated with mortality during hospitalization. This means that daily monitoring of specific danger signs improves the predictive power of inpatient mortality among children with severe acute malnutrition.

Unpublished data from the same F75 trial indicate that mortality during hospitalization for children with severe acute malnutrition is associated with disturbances in energy homeostasis, including mitochondrial function. Inflammation may also be a predictor of mortality in these children. Some children with severe wasting have poor phagocytosis, revealing a compromised immune system, and immune and metabolic functions are not fully corrected even after clinical stabilization. Measuring biomarkers (e.g. C-reactive protein or intestinal markers) at discharge shows that some children may still be in an inflammatory state.¹ It is unclear whether children with moderate wasting experience the same disruptions.

1 Njunge JM, Gwela A, Kibinge NK, Ngari M, Nyamako L, et al. Biomarkers of post-discharge mortality among children with complicated severe acute malnutrition. Sci Rep. 2019;9:5981. doi:10.1038/s41598-019-42436-y.

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3.3.6.5 Analyses of early growth failure: meta-analysis of data from individual participants

Andrew Mertens presented remotely on a meta-analysis of the results of 31 studies that included more than 9000 children.

The Bill & Melinda Gates Foundation’s Knowledge Integration Project¹ has assembled a database of information from individual participants in 189 studies of child growth and development.

The aims of assembling these data are to use them to find out whether there are key ages when growth failure is highest and how key ages may vary by region and time of year; whether there are characteristics that can be used to identify children who are at the highest risk of growth failure; and whether early growth failure during the first 6 months of life has longer term consequences only in some children, or whether all children simply recover.

A meta-analysis of 31 studies involving more than 9000 children, conducted in 15 low- and middle-income countries in Eastern Europe, Latin America, South Asia and sub-Saharan Africa between 1969 and 2014, revealed high rates of wasting and stunting in infants younger than 6 months. The highest prevalence of wasting occurred at birth (pooled prevalence of 12%), with a second peak at around the age of 12 months (pooled prevalence of 7%). However, the highest incidence of wasting occurred at birth and right after birth, with 15% of children becoming wasted during the first 3 months of life, while no more than 7% became wasted in the first 6 months of life. Concurrent wasting and stunting increased with age and was highest in study populations in South Asia; by the age of 12 months, more than 50% of children with wasting were also stunted.

Most children recovered from wasting episodes within 90 days (although it was unclear what interventions were provided), and only 9% of infants with wasting at birth still had wasting at 3 months. Even though these children seemed to recover, they never completely caught up with their peers, and this group had a higher cumulative incidence of wasting, higher level of persistent wasting, and more concurrent wasting and stunting after 6 months. There was also high seasonality of wasting corresponding with higher rainfall in all regions.

However, these data were not balanced geographically, the children were measured at different ages and frequencies across studies, and there were few MUAC measurements.

3.3.6.6 Key discussion points

■

■ The incidence of wasting has two distinct peaks: at or shortly after birth and at 12 months of age. Characteristics of the child, parents and household strongly associated with wasting (e.g. maternal anthropometry and education and child’s size at birth) are not easily modifiable, but could be useful for screening children who are at high risk of growth failure.

■

■ There was consensus that anthropometric recovery alone is inadequate, and that functional recovery is needed. The key questions are which indicators are useful in deciding when to discharge children from the hospital and when they can exit outpatient care. The focus should be on functional recovery – that is, the child’s ability to stay healthy and grow well.

The development of a frailty score that depends on organ failure and inflammatory markers may be a useful approach to guide hospital discharge, but what could be done for children who have a low score? Keeping them in hospital for longer also increases their risk for nosocomial infections and mortality, as well as social disruptions.

1 https://kiglobalhealth.org/, accessed 10 July 2020.

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■

■ A frailty score may best apply at the individual level. At the population level, there is need for a resilience index aimed at identifying individual, household, and population-level risk factors. Developing these indices or scores requires further research.

3.4 Wasting in infants younger than 6 months

3.4.1 Data from the Alliance for Maternal and Newborn Health Improvement study

Sunil Sazawal described an analysis of data from 3000 children in the Alliance for Maternal and Newborn Health Improvement (AMANHI) study.¹

The AMANHI study is an analysis of data from 3000 children recruited from pregnancy and newborn cohorts in East Africa and South Asia, with follow up from birth to age 3 years. The analyses were conducted to understand the underlying causes of and factors influencing wasting. Preliminary results show that in utero growth affects postnatal growth patterns, and children born at LBW (either SGA or preterm) constituted a significant proportion of infants who later experienced growth failure, accounting for 13% of preterm infants, 32% of LBW infants and 49% of SGA infants. The analyses also showed that mean WHZ remained relatively flat, with the highest prevalence of wasting at birth and 12 months, while the prevalence of stunting increased at 12 months. SGA infants achieved rapid catch-up growth and followed a similar trajectory to that of full-term babies, but they did not achieve equivalence at 12 months. A similar pattern was observed in LBW infants, who achieved some catch-up growth during their first 3 months.

3.4.2 The Women Improving Nutrition through Group-based Strategies trial

Rajiv Bahl presented data from the Women Improving Nutrition through Group-based Strategies (WINGS) study conducted in India.²

The objective of the study, which was conducted in periurban and low to mid-low socioeconomic neighbourhoods in Delhi, India, is to determine the effect of an integrated package of health, nutrition, WASH (water, sanitation and hygiene) and psychosocial interventions on improving birth weight and length, and stunting at 24 months. Three study arms reflect the timing of the interventions: (i) during only the preconceptual and periconceptual periods (ii) during pregnancy and early childhood (up to the first 1000 days) and (iii) throughout the preconceptual and periconceptual periods, pregnancy and into early childhood (> 1000 days).

For children who have already reached 12 months of age, their mean WLZ increased during their first few months but then returned to almost their birth WLZ at 12 months. The prevalence of wasting was high at birth (8.7%) and then declined before peaking at age 11–12 months (8%).

When stratified by gestational age and birth weight, LBW infants born at term had the highest prevalence of wasting at 12 months despite catch-up growth occurring from age 0 to 4 months;

preterm LBW infants had the second highest prevalence of wasting at 12 months. Preterm normal birth-weight infants showed similar WLZ trajectories as term infants. About half of the children with wasting at 6 or 12 months of age had been LBW, which shows the importance of addressing LBW to prevent wasting.

1 The Alliance for Maternal and Newborn Health Improvement (AMANHI) [website]. Geneva: World Health Organization;

2020 (https://www.who.int/life-course/news/events/amanhi/en/, accessed 20 January 2020).

2 Women Improving Nutrition through Group-based Strategies (WINGS) [website]. Washington (DC): International Food Policy Research Institute; 2020 (https://www.ifpri.org/project/women-improving-nutrition-through-group- based-strategies-wings, accessed 20 January 2020).

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3.4.3 Managing nutritionally at-risk mothers and infants younger than 6 months

Marko Kerac outlined the urgent need to scale up interventions using tools such as the Management of At Risk Mothers and Infants (MAMI) approach.

There is a need to bridge gaps between the current reality and the urgent need to scale up interventions to achieve the 2030 SDGs by focusing on: the link between undernutrition and future obesity, overweight and risk of noncommunicable diseases; public health versus clinical perspectives; and translating internal discussions to external messages.

There are four critical opportunities for addressing wasting in infants: (i) in utero, and through (ii) infant and child nutrition (iii) optimal treatment and (iv) optimal coverage of interventions.

We need to communicate simply and think deeply about the different causes of wasting in children, as well as about how to clearly communicate the different criteria, cut-off points and categories for different age groups and in different contexts. Even for children who are above the cut-off points, patterns show that important information – for example, that an infant may be small but otherwise healthy – needs to be conveyed clearly, otherwise there is the risk that a carer, family member or health care worker may become needlessly concerned and decide to make the high-risk switch from breastfeeding to bottle feeding.

Breastfeeding is a core intervention for ensuring infant health and nutrition, but it is often inadequately supported and sometimes it is actively undermined. Opportunities for support are often missed or poorly utilized, for example, during visits for growth monitoring and vaccination.

The MAMI tool is a checklist-based care pathway that aims to support the identification and management of vulnerable infant–mother dyads. The MAMI approach draws lessons from the Community-based Management of Acute Malnutrition (known as CMAM) model, the Integrated Management of Childhood Illness (or IMCI) model and the latest WHO guidance on severe acute malnutrition. It includes support for mothers and carers as well as infants, and facilitates the use of individually tailored interventions.

3.4.4 Young infants with growth failure during the first 6 months of life: guidance and research

Nigel Rollins presented an overview of a meeting held in January 2019 to address growth failure in children.

In WHO’s 2013 Guideline: updates on the management of severe acute malnutrition in infants and children, several recommendations were supported only by low-quality or very low–quality evidence.¹ In January 2019, WHO convened a meeting to assess the issue of growth failure in infants aged < 6 months and to identify a research agenda to improve screening and identification of these infants, improve management and prevent growth failure. There is a lack of long-term data about health, catch-up growth and other outcomes, such as child development, in children who previously had wasting, which poses a challenge to interpreting growth patterns during the first 6 months of life.

Presentations at the meeting highlighted major differences in postnatal growth trajectories according to gestational or birth weight phenotypes (e.g. LBW, preterm SGA). LBW and SGA infants contribute significantly to the population of infants with postnatal growth failure (wasting). In some analyses, LBW infants achieved weight gain (across Z-score lines) with breastfeeding only and without nutritional supplements.

1 Guideline: updates on the management of severe acute malnutrition in infants and children. Geneva: World Health Organization; 2013 (https://apps.who.int/iris/handle/10665/95584, accessed 20 January 2020).

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Programmes need to elevate the importance of growth failure, establish systems to consistently capture birth weight and consider implementing increased follow-up. Interpretation of postnatal growth must include birth weight and, ideally, consideration of prenatal growth and all relevant events during the gestational period.

More than 300 research questions were proposed during the meeting, and these were narrowed down to the following research priorities for investigation:

■

■ the short- and long-term consequences of growth patterns during an infant’s first 6 months for SGA, preterm and LBW infants, to enable development of a new framework for integrating knowledge generated by different types of studies on multiple outcomes (e.g. mortality, growth, development) at the individual and population levels;

■

■ for screening and identification, it is important to determine the minimum package that identifies young infants at risk, while accounting for different levels of health system capacity. Which simple anthropometric criteria (e.g. WAZ, LAZ, MUAC) would be most useful for identifying children at risk of negative outcomes?

■

■ the efficacy, effectiveness and safety of using non–breast milk supplements for growth failure for children aged 4–6 months (with and without additional interventions, including azithromycin) and the provision of psychosocial support and intensive lactation support;

■

■ the impact of intensive counselling and lactation support on breastfeeding among mothers of infants with growth faltering, addressing whether targeted, intensive delivery of such counselling reduces barriers and morbidity; and to determine how such counselling and lactation support can best be targeted to different groups and different contexts.

3.4.5 Key discussion points

■

■ About half of infants with wasting at 6 or 12 months have LBW, and this shows the importance of addressing LBW in prevention efforts, particularly in contexts with a high incidence of wasting, such as South-East Asia.

■

■ The impact of maternal malnutrition on the quality of breast milk is not fully known, and there is evidence to suggest that breast milk may be deficient in certain micronutrients in certain populations. The WINGS and CHAIN studies have extensive data on maternal weight and its impact on breastfeeding that can be used to assess this relationship. There is also research being funded by the Bill & Melinda Gates Foundation that will explore nutritional products for pregnant women that aim to prevent LBW infants; these data will be available in the next few years.

■

■ The prevalence of LBW varies greatly depending on the context, for example, the prevalence is lower in southern and eastern Africa compared with South-East Asia.

3.5 Treatment of wasting

3.5.1 Guidance on treatment interventions

Zita Weise Prinzo summarized WHO’s publications on wasting and highlighted gaps in guidance on treating wasting.

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WHO’s guideline for the management of severe acute wasting¹ provides guidance on eight main topics: admission and discharge criteria; where to manage children with severe acute malnutrition and oedema; the use of antibiotics; the use of vitamin A supplementation;

therapeutic feeding approaches; fluid management with and without shock; management of HIV; and identifying and managing infants younger than 6 months. As a result of new evidence, some of the recommendations require updating, and additional guidance is needed for emerging challenges in the management of severe wasting (see Section 5).

Other WHO publications that address aspects of the management of severe wasting include:

■

■ Pocket book of hospital care for children (2013);²

■

■ joint statement by WHO, UNICEF and WFP on the community-based management of acute malnutrition (2007);³

■

■ WHO/UNICEF guide for physicians and health workers on case management of severe wasting in infants, children, adolescents and adults (under peer review);

■

■ Training course on child growth assessment: counselling on growth and feeding (2008);⁴

■

■ training course on the inpatient management of severe acute malnutrition (in press);

■

■ Technical note: supplementary foods for the management of moderate acute malnutrition in infants and children 6–59 months of age (2012).⁵

Currently, there is no WHO guideline on the comprehensive management of moderate wasting in children. The following WHO documents contain some information on caring for children with moderate wasting:

■

■ Technical note: supplementary foods for the management of moderate acute malnutrition in infants and children 6–59 months of age (2012);⁵

■

■ Essential nutrition actions: mainstreaming nutrition through the life-course (2019);⁶ a com- pendium of nutrition interventions recommended by WHO to promote healthy growth and prevent premature death, such as ensuring access to balanced diets that meet nutrient requirements, promoting exclusive breastfeeding and improving complementary feeding practices, caring for LBW infants, and caring for women during pregnancy and in the post- partum period;

1 Guideline: updates on the management of severe acute malnutrition in infants and children. Geneva: World Health Organization; 2013 (https://apps.who.int/iris/handle/10665/95584, accessed 20 January 2020).

2 Pocket book of hospital care for children: guidelines for the management of common childhood illnesses, second edition. Geneva: World Health Organization; 2013 (https://apps.who.int/iris/handle/10665/81170, accessed 20 January 2020).

3 Community-based management of severe acute malnutrition: a joint statement by the World Health Organization, the World Food Programme, the United Nations System Standing Committee on Nutrition and the United Nations Children’s Fund. Geneva: World Health Organization, World Food Programme, United Nations Standing Committee on Nutrition, United Nations Children’s Fund; 2007 (https://apps.who.int/iris/handle/10665/44295, accessed 20 January 2020).

4 Training course on child growth assessment: counselling on growth and feeding. Geneva: World Health Organization;

2008 (https://www.who.int/childgrowth/training/module_d_counselling.pdf?ua=1, accessed 20 January 2020).

5 Technical note: supplementary foods for the management of moderate acute malnutrition in infants and children 6–59 months of age. Geneva: World Health Organization; 2012 (https://apps.who.int/iris/handle/10665/75836, accessed 20 January 2020).

6 Essential nutrition actions: mainstreaming nutrition through the life-course. Geneva: World Health Organization;

2019 (https://apps.who.int/iris/handle/10665/326261, accessed 21 January 2020).

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■

■ Global nutrition targets 2025: wasting policy brief (2014);¹

■

■ Guideline: assessing and managing children at primary health-care facilities to prevent overweight and obesity in the context of the double burden of malnutrition (2017);² this recommends against routinely providing specially formulated supplementary foods to infants and children with moderate wasting who present to primary health care facilities (i.e. as a default intervention for all cases). The guideline highlights special cases in which the provision of supplementary foods may be permissible, such as in settings where there is a high prevalence of wasting or food insecurity;

■

■ WHO recommendations on antenatal care for a positive pregnancy experience (2016);³ this recommends that undernourished populations be provided with nutrition education and counselling to encourage an increase in daily energy and nutrient intake to reduce the risk of LBW infants. In food-insecure populations, food supplementation for pregnant women is necessary to reduce the risk of stillbirths and SGA neonates.

Currently, there are gaps in guidance for the treatment of wasting including knowledge about:

■

■ which children with wasting are at greatest risk of dying, how best to identify and treat these children in different contexts, how to define recovery and when to discharge children from programmes, with appropriate follow-up to prevent relapse and mortality;

■

■ the impact of dietary and medical interventions on short- and long-term outcomes, such as growth, development, body composition, functional and metabolic outcomes, and how to measure this impact to monitor and evaluate interventions;

■

■ the diagnostic and treatment options for infants younger than 6 months;

■

■ the optimal inpatient treatment for children with severe wasting.

3.5.2 Operationalization of WHO guidelines for treating severe wasting

Saul Guerrero Oteyza summarized efforts being made by countries to adapt WHO guidelines to their particular contexts.

There has been a general shift towards a more decentralized public health approach to the management of severe wasting, and this has implications for scalability and integration of approaches into national primary care and community health services. The number of children with wasting who access treatment has steadily increased over time. However, two out of three children aged 6–59 months with severe wasting still do not have access to treatment. This low treatment coverage reflects challenges in financing and treatment policy and practice across different regions and contexts.

Currently, more than 70 countries have national guidelines for the treatment of severe wasting, with the majority based on WHO’s normative guidelines. Implementation of the guidelines, however, is not consistent across regions and there are notable adaptations. For example, in Ecuador and Haiti, the national guidelines include the use of a single product for both moderate

1 Global nutrition targets 2025: wasting policy brief. Geneva: World Health Organization; 2014 (https://apps.who.int/

iris/handle/10665/149023, accessed 21 January 2020).

2 Guideline: assessing and managing children at primary health-care facilities to prevent overweight and obesity in the context of the double burden of malnutrition. Geneva: World Health Organization; 2017 (https://apps.who.int/

iris/handle/10665/259133, accessed 21 January 2020).

3 WHO recommendations on antenatal care for a positive pregnancy experience. Geneva: World Health Organization;

2016 (https://apps.who.int/iris/bitstream/handle/10665/250796/9789241549912-eng.pdf?sequence=1, accessed 21 January 2020).

WHO Consultation

MEETING REPORT

WHO Consultation

on Prevention and Treatment of Wasting in Children

Geneva

17 – 19 December 2019

WHO Consultation

on Prevention and Treatment of Wasting in Children

Geneva, 17–19 December 2019

iii

Contents

iv

v

Acknowledgements

Financial support

vi

Abbreviations

1

1. Background

2. Objectives of the meeting

2

3. Summary of presentations and discussions

3.1 Technical framing of wasting

3

3.2 Pathophysiology of wasting: what we know and do not know

4

5

3.3 Epidemiology of wasting

6

7

8

9

10

11

12

3.4 Wasting in infants younger than 6 months

13

14

3.5 Treatment of wasting

15

16