Who Reccomendation Malnutrition

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GUIDELINE

UPDATES ON THE MANAGEMENTOF SEVERE ACUTE MALNUTRITION

IN INFANTS AND CHILDREN


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WHO Library Cataloguing-in-Publication Data

Guideline: updates on the management o severe acute malnutrition in inants and children.

1.Malnutrition. 2.Inant nutrition disorders. 3.Child nutrition disorders. 4.Guideline.

I.World Health Organization.

ISBN 978 92 4 150632 8 (NLM classiication: WD 101)

World Health Organization 2013

All rights reserved. Publications o the World Health Organization are available on the WHO web site (www.who.int) or canbe purchased rom WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 7913264; ax: +41 22 791 4857; e-mail: [email protected]).

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Suggested citation

WHO. Guideline: Updates on the management of severe acute malnutrition in infants and children.

Geneva: World Health Organization; 2013.

Cover: Alberto MarchDesign: minimum graphics
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Contents

Acknowledgements v

Financial support v

Abbreviations viExecutive summary 1

Purpose o the guideline 1

Guideline development methodology 1

Available evidence 2

Recommendations 2

Research priorities 8

Scope and purpose 9

Background 10

Recommendations 14 1. Admission and discharge criteria or children who are 659 months o age with

severe acute malnutrition 14

2. Where to manage children with severe acute malnutrition who have oedema 23

3. Use o antibiotics in the management o children with severe acute malnutrition inoutpatient care 26

4. Vitamin A supplementation in the treatment o children with severe acute malnutrition 31

5. Therapeutic eeding approaches in the management o severe acute malnutrition inchildren who are 659 months o age 36

6. Fluid management o children with severe acute malnutrition 46

7. Management o HIV-inected children with severe acute malnutrition 55 8. Identiying and managing inants who are less than 6 months o age with severe

acute malnutrition 60

Dissemination, adaptation and implementation 67

Dissemination 67

Adaptation and implementation 67

Guideline development process 68

Formulation o recommendations, including uture research priorities 69

Advisory groups 69


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v

Acknowledgements

This guideline was coordinated by Zita Weise Prinzo, Department o Nutrition or Health and

Development, and by Dr Nigel Rollins, Department o Maternal, Newborn, Child and Adolescent

Health, with technical input rom Dr Luz Maria De-Regil, Chantal Gegout, Dr Jos Martines, Dr

Juan Pablo Pea-Rosas and Dr Lisa Rogers. Thanks are due to the Guidelines Review CommitteeSecretariat or their support throughout the process. Thanks are also due to Lisa Haintz-Carbonin

rom the World Health Organization (WHO) Office o the Legal Counsel or her support in the

management o conlicts o interest procedures.

WHO grateully acknowledges the technical input o the members o the Nutrition Guidance

Advisory Group (also reerred to as NUGAG) and the external resource people, in particular Dr

Tahmeed Ahmed, Dr Beatrice Amadi, Dr Paluku Bahwere, Dr Andr Briend, Hedwig Deconinck,

Proessor Michael Golden, Proessor Alan Jackson, Dr Marzia Lazzerini and Dr Mark Manary. WHO

is also grateul to the external experts and stakeholders, especially Proessor Ann Ashworth and

Dr Tom Heikens, or their technical advice in peer reviewing the guideline. Special thanks to Juana

Willumsen or taking notes during the guideline development meetings and or her contribution in

drafing the guideline, including reviewing o GRADE tables.

Financial support

WHO acknowledges the inancial suppor t rom the European Commission Directorate General or

Humanitarian Aid and Civil Protection (ECHO), the Government o Luxembourg and the Bill & Melinda

Gates Foundation or this work. Donors do not und speciic guidelines and do not participate in

any decision related to the guideline development process, including the composition o research

questions, membership o the guideline groups, the conduct and interpretation o systematic

reviews, or the ormulation o recommendations.


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vi

Abbreviations

CI conidence interval

eLENA electronic Library o Evidence or Nutrition Actions

FEAST Fluid Expansion as Supportive Therapy (trial)

GRADE Grading o Recommendations Assessment, Development and Evaluation

Hb haemoglobin

IM intramuscular

IMCI Integrated Management o Childhood Illness

IV intravenous

MDG Millennium Development Goal

NCHS National Center or Health Statistics, Centers or Disease Control and Prevention

PICO patient/population, intervention, control, outcomes

SD standard deviation

TB tuberculosis

UNICEF United Nations Childrens Fund

WHO World Health Organization


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Executive summary

Purpose o the guideline1

Severe acute malnutrition affects nearly 20 million preschool-age children, mostly rom the World

Health Organization (WHO) Arican Region and South-East Asia Region. Malnutrition is a signiicantactor in approximately one third o the nearly 8 million deaths in children who are under 5 years

o age worldwide (1). WHO established guidelines or the treatment o severe acute malnutrition

in 1999 and Member States have requested WHO to update their 1999 document Management

of severe malnutrition: a manual for physicians and other senior health workers (2). This guideline

presents the updated evidence and practice or key interventions and will also serve to inorm

revisions o the manual. This guideline does not relect all WHO recommendations related to the

management o children with severe acute malnutrition but only those related to areas that were

prioritized by the guideline development group: the WHO Nutrition Guidance Advisory Group

Subgroup on Nutrition in the Lie Course and Undernutrition 20102012. This group reviewed the

previously published guidelines and indicated the areas o care and speci ic recommendations that

should be revised irst in the process o updating all WHO recommendations. Relevant standingrecommendations are included adjacent to updated recommendations, to contextualize updated

recommendations. Other WHO recommendations will be addressed in uture guideline updates.

Guideline development methodology

WHO has developed the present evidence-inormed recommendations using the procedures

outlined in the WHO handbook for guideline development (3). The steps in this process included:

(i) identiication o priority questions and outcomes; (ii) retrieval o the evidence; (iii) assessment o

the quality o evidence and synthesis o the indings; (iv) ormulation o recommendations, including

uture research priorities; and (v) planning or dissemination, implementation, impact evaluation

and updating o the guideline. The Grading of Recommendations Assessment, Development and

Evaluation (GRADE) methodology was ollowed to prepare evidence proiles related to preselected

topics, based on up-to-date systematic reviews. The WHO Nutrition Guidance Advisory Group

Subgroup on Nutrition in the Lie Course and Undernutrition 20102012, comprised content experts,

methodologists, representatives o potential stakeholders and consumers. These experts, together

with external resource people, participated in three WHO technical consultations, held in Geneva,

1 This publication is a WHO guideline. A WHO guideline is any document, whatever its title, containing WHO recommen-dations about health interventions, whether they be clinical, public health or policy interventions. A recommendationprovides inormation about what policy-makers, health-care providers or patients should do. It implies a choicebetween different interventions that have an impact on health and that have ramiications or the use o resources. A ullguideline is one that provides complete coverage o a health topic or disease. It is expected to include recommendationsin relation to all aspects o the topic (e.g. surveillance, diagnosis, public health and clinical interventions) and to be ullybased on systematic reviews o the evidence or each aspect. All publications containing WHO recommendations are

approved by the WHO Guidelines Review Committee.
http://www.who.int/kms/guidelines_review_committee/en/http://www.who.int/kms/guidelines_review_committee/en/


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GUIDELINE: UPDATES ON THE MANAGEMENT OF SEVERE ACUTE MALNUTRITION IN INFANTS AND CHILDREN

Switzerland, on 24 June 2010, 1416 March 2011 and 13 February 2012, to scope questions or

the systematic reviews, review and discuss the evidence, draf the recommendations, and vote on

their strength, taking into consideration: (i) desirable and undesirable effects o this intervention;

(ii) the quality o the available evidence; and (iii) values and preerences related to the intervention

in different settings. The cost o options available to health-care workers in different settings was

not ormally assessed, owing to lack o primary data in the literature or elsewhere. However, cost

implications were considered as part o general discussion by the guideline development group,

namely the Nutrition Guidance Advisory Group members and the external resource people.

Members o the external experts and stakeholders panel were identiied through a public call or

comments and peer reviewed the guideline. Everyone involved in the development o this guideline

submitted declarations o interests. All guideline development group members submitted them

beore each meeting and also made verbal declarations o interest at the beginning o meetings.

Available evidence

The evidence, available or the development o recommendations, was in general o very lowquality, as deined in the WHO handbook for guideline development(3). This was due to the limited

availability o randomized controlled trials, trials comparing existing WHO recommendations with

new treatment options, or trials documenting comparisons o diagnosis and treatment methods

identiied by the guideline development group as requiring review. Where direct evidence was not

available, indirect evidence rom different population groups, or different intervention strategies has

been noted, i appropriate. The need or uture research directly addressing several o the areas o

concern was highlighted. Owing to the scarcity o data on the cost o proposed recommendations,

it is not possible to directly estimate the inancial implications o implementation o these

recommendations.

Recommendations

1. Admission and discharge criteria or children who are 659 months o age with severe

acute malnutrition

Criteria or identiying children with severe acute malnutrition or treatment

1.1 In order to achieve early identiication o children with severe acute malnutrition in

the community, trained community health workers and community members should

measure the mid-upper arm circumerence o inants and children who are 659 months

o age and examine them or bilateral pitting oedema. Inants and children who are 659

months o age and have a mid-upper arm circumerence


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Criteria or inpatient or outpatient care1

1.3 Children who are identiied as having severe acute malnutrition should irst be assessed

with a ull clinical examination to conirm whether they have medical complications and

whether they have an appetite. Children who have appetite (pass the appetite test) andare clinically well and alert should be treated as outpatients. Children who have medical

complications, severe oedema (+++), or poor appetite (ail the appetite test), or present

with one or more Integrated Management o Childhood Illness (IMCI) danger signs2should

be treated as inpatients (strong recommendation, low quality evidence).

Criteria or transerring children rom inpatient to outpatient care3

1.4 Children with severe acute malnutrition who are admitted to hospital can be transerred

to outpatient care when their medical complications, including oedema, are resolving

and they have a good appetite, and are clinically well and alert. The decision to transer

children rom inpatient to outpatient care should be determined by their clinical condition

and not on the basis o speciic anthropometric outcomes such as a speciic mid-upperarm circumerence or weight-or-height/length (strong recommendation, low quality

evidence).

Criteria or discharging children rom treatment

1.5. a. Children with severe acute malnutrition should only be discharged rom treatment

when their:

weight-or-height/length is 2 Z-score and they have had no oedema or at least

2 weeks, or

mid-upper-arm circumerence is 125 mm and they have had no oedema or at

least 2 weeks.

b. The anthropometric indicator that is used to conirm severe acute malnutrition should

also be used to assess whether a child has reached nutritional recovery, i.e. i mid-

upper arm circumerence is used to identiy that a child has severe acute malnutrition,

then mid-upper arm circumerence should be used to assess and conirm nutritional

recovery. Similarly, i weight-or-height is used to identiy that a child has severe acute

malnutrition, then weight-or-height should be used to assess and conirm nutritional

recovery.

c. Children admitted with only bilateral pitting oedema should be discharged rom

treatment based on whichever anthropometric indicator, mid-upper arm circumerence

or weight-or-height is routinely used in programmes.

d. Percentage weight gain should not be used as a discharge criterion

(strong recommendation, low quality evidence).

Follow-up o inants and children afer discharge rom treatment orsevere acute malnutrition

1.6. Children with severe acute malnutrition who are discharged rom treatment programmes

should be periodically monitored to avoid a relapse (strong recommendation, low

quality evidence).

EXECUTIVE SUMMARY

1 Necessar y resources and serv ices need to be in place i children are reerred to outpatient care.2 Danger signs: unable to drink or breasteed; vomits every thing; has had convulsions (more than one or prolonged

>15 min); lethargic or unconscious; convulsing now.3 Necessar y resources and serv ices need to be in place i children are reerred to outpatient care.


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2. Where to manage children with severe acute malnutrition who have oedema

2.1 Children with severe acute malnutrition who have severe bilateral oedema (+++),1even i

they present with no medical complications and have appetite, should be admitted or

inpatient care (strong recommendation, ver y low quality evidence).

3. Use o antibiotics in the management o children with severe acute malnutrition in

outpatient care

3.1 Children with uncomplicated severe acute malnutrition, not requiring to be admitted

and who are managed as outpatients, should be given a course o oral antibiotic such as

amoxicillin (conditional recommendation, low quality evidence).

3.2 Children who are undernourished but who do nothave severe acute malnutrition should

not routinely receive antibiotics unless they show signs o clinical inection (strong

recommendation, low quality evidence).

4. Vitamin A supplementation in the treatment o children with severe acute malnutrition

4.1 Children with severe acute malnutrition should receive the daily recommended nutrient

intake o vitamin A throughout the treatment period. Children with severe acute mal-

nutrition should be provided with about 5000 IU vitamin A daily, either as an integral part

o therapeutic oods or as part o a multi-micronutrient ormulation (strong recommen-

dation, low quality evidence).

4.2 Children with severe acute malnutrition do not require a high dose o vitamin A as a

supplement i they are receiving F-75, F-1002 or ready-to-use therapeutic ood that

complies with WHO speciications (and thereore already contains sufficient vitamin A),

or vitamin A is part o other daily supplements (strong recommendation, low quality

evidence).

4.3. Children with severe acute malnutrition should be given a high dose o vitamin A (50 000 IU,100 000 IU or 200 000 IU, depending on age) on admission, only i they are given therapeutic

oods that are not ortiied as recommended in WHO speciications and vitamin A is not

part o other daily supplements (strong recommendation, low quality evidence).

5. Therapeutic eeding approaches in the management o severe acute malnutrition in

children who are 659 months o age

5.1 Children with severe acute malnutrition who present with either acute or persistent

diarrhoea, can be given ready-to-use therapeutic ood in the same way as children

without diarrhoea, whether they are being managed as inpatients or outpatients (strong

recommendation, very low quality evidence).

5.2 In inpatient settings, where ready-to-use therapeutic food is provided as the therapeutic foodin the rehabilitation phase (following F-75 in the stabilization phase)

Once children are stabilized, have appetite and reduced oedema and are thereore ready

to move into the rehabilitation phase, they should transition rom F-75 to ready-to-use

therapeutic ood over 23 days, as tolerated. The recommended energy intake during this

1 + Mild: both eet; ++ moderate: both eet, plus lower legs, hands, or lower arms; +++ severe: generalized oedemaincluding both eet, legs, hands, arms and ace. Source: Module 2. Principles o care. In: WHO training course on themanagement of severe malnutrition. Geneva: World Health Organization; 2002 (updated 2009).

2 F-75 and F-100 are ormula diets used or the management o children with severe acute malnutrition in inpatient care.F-75 (75 kcal or 315 kJ/100 mL) is used during the initial phase o treatment, while F-100 (100 kcal or 420kJ/100 mL) is

used during the rehabilitation phase.


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period is 100135 kcal/kg/day. The optimal approach or achieving this is not known and

may depend on the number and skills o staff available to supervise eeding and monitor

the children during rehabilitation (strong recommendation, very low quality evidence).

Two options or transitioning children rom F-75 to ready-to use therapeutic ood are

suggested:

a. start eeding by giving ready-to-use therapeutic ood as prescribed or the transition

phase. Let the child drink water reely. I the child does not take the prescribed amount

o ready-to-use therapeutic ood, then top up the eed with F-75. Increase the amount

o ready-to-use therapeutic ood over 23 days until the child takes the ull requirement

o ready-to-use therapeutic ood, or

b. give the child the prescribed amount o ready-to-use therapeutic ood or the

transition phase. Let the child drink water reely. I the child does not take at least hal

the prescribed amount o ready-to-use therapeutic ood in the irst 12 h, then stop

giving the ready-to-use therapeutic ood and give F-75 again. Retry the same approach

afer another 12 days until the child takes the appropriate amount o ready-to-usetherapeutic ood to meet energy needs.

5.3 In inpatient settings where F-100 is provided as the therapeutic food in the rehabilitation

phase

Children who have been admitted with complicated severe acute malnutrition and are

achieving rapid weight gain on F-100 should be changed to ready-to-use therapeutic ood

and observed to ensure that they accept the diet beore being transerred to an outpatient

programme (strong recommendation, ver y low quality evidence).

6. Fluid management o children with severe acute malnutrition

6.1 Children with severe acute malnutrition who present with some dehydration or severe

dehydration but who are not shockedshould be rehydrated slowly, either orally or by naso-gastric tube, using oral rehydration solution or malnourished children (510 mL/kg/h up

to a maximum o 12 h) (strong recommendation, low quality evidence).

6.2 Full-strength, standard WHO low-osmolarity oral rehydration solution (75 mmol/L o

sodium) should not be used or oral or nasogastric rehydration in children with severe

acute malnutrition who present with some dehydration or severe dehydration. Give either

ReSoMal or hal-strength standard WHO low-osmolarity oral rehydration solution with

added potassium and glucose, unless the child has cholera or prouse watery diarrhoea

(strong recommendation, low quality evidence).

Dissolve one sachet of standard WHO low-osmolarity oral rehydration solution in 2 L water

(instead of 1 L). Add 1 level scoop of commercially available combined minerals and vitaminsmix1or 40 ml of mineral mix solution (5), and add and dissolve 50 g of sugar. In some countries,

sachets are available that are designed to make 500 mL of standard WHO low-osmolarity

oral rehydration solution. In this situation, dilution can be revised to add 1 L.

6.3 ReSoMal2 (or locally prepared ReSoMal using standard WHO low-osmolarity oral

rehydration solution) should not be given i children are suspected o having cholera

EXECUTIVE SUMMARY

1 A speciic electrolyte micronutr ient product ormulated according to WHO speciications or use in the management ochildren with severe acute malnutrition.

2 ReSoMal (short or rehydration solution or severely malnourished children) is the generic name or a powder or thepreparation o an oral rehydration solution exclusively or oral or nasogastric rehydration o people suffering romsevere acute malnutrition. It must be used exclusively under medical supervision in inpatient care, and must not be

given or ree use to the mother or caregiver.


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or have prouse watery diarrhoea.1 Such children should be given standard WHO low-

osmolarity oral rehydration solution that is normally made, i.e. not urther diluted (strong

recommendation, low quality evidence).

6.4 Children with severe acute malnutrition and signs o shock or severe dehydration and whocannot be rehydrated orally or by nasogastric tube should be treated with intravenous

luids, either:

a. hal-strength Darrows solution with 5% dextrose, or

b. Ringers lactate solution with 5% dextrose.

I neither is available, 0.45% saline + 5% dextrose should be used (conditional recommen-

dation, very low quality evidence).

7. Management o HIV-inected children with severe acute malnutrition

7.1 Children with severe acute malnutrition who are HIV inected and who qualiy or lielong

antiretroviral therapy should be started on antiretroviral drug treatment as soon aspossible afer stabilization o metabolic complications and sepsis. This would be indicated

by return o appetite and resolution o severe oedema. HIV-inected children with severe

acute malnutrition should be given the same antiretroviral drug treatment regimens, in

the same doses, as children with HIV who do not have severe acute malnutrition. HIV-

inected children with severe acute malnutrition who are started on antiretroviral drug

treatment should be monitored closely (inpatient and outpatient) in the irst 68 weeks

ollowing initiation o antiretroviral therapy, to identiy early metabolic complications and

opportunistic inections (strong recommendation, ver y low quality evidence).

7.2 Children with severe acute malnutrition who are HIV inected should be managed with the

same therapeutic eeding approaches as children with severe acute malnutrition who are

not HIV inected (strong recommendation, ver y low quality evidence).7.3 HIV-inected children with severe acute malnutrition should receive a high dose o vitamin

A on admission (50 000 IU to 200 000 IU depending on age) and zinc or management o

diarrhoea, as indicated or other children with severe acute malnutrition, unless they are

already receiving F-75, F-100 or ready-to-use therapeutic ood, which contain adequate

vitamin A and zinc i they are ortiied ollowing the WHO speciications (strong recom-

mendation, very low quality evidence).

7.4 HIV-inected children with severe acute malnutrition in whom persistent diarrhoea does

not resolve with standard management should be investigated to exclude carbohydrate

intolerance and inective causes, which may require different management, such as

modiication o luid and eed intake, or antibiotics (strong recommendation, very low

quality evidence).

8. Identiying and managing inants who are less than 6 months o age with severe acute

malnutrition

8.1 Inants who are less than 6 months o age with severe acute malnutrition and any o the

ollowing complicating actors should be admitted or inpatient care:

a. any serious clinical condition or medical complication as outlined or inants who are

6 months o age or older with severe acute malnutrition;

b. recent weight loss or ailure to gain weight;

1

Three or more loose or watery stools in a day, or more than 14 days.


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c. ineffective eeding (attachment, positioning and suckling) directly observed or

1520 min, ideally in a supervised separated area;

d. any pitting oedema;

e. any medical or social issue needing more detailed assessment or intensive support

(e.g. disability, depression o the caregiver, or other adverse social circumstances)

(strong recommendation, ver y low quality evidence).

8.2 Inants who are less than 6 months o age with severe acute malnutrition should receive the

same general medical care1as inants with severe acute malnutrition who are 6 months

o age or older:

a. inants with severe acute malnutrition who are admitted or inpatient care should be

given parenteral antibiotics to treat possible sepsis and appropriate treatment or

other medical complications such as tuberculosis, HIV, surgical conditions or disability;

b. inants with severe acute malnutrition who are not admitted should receive a courseo broad-spectrum oral antibiotic, such as amoxicillin, in an appropriately weight-

adjusted dose


8.3 Feeding approaches or inants who are less than 6 months o age with severe acute

malnutrition should prioritize establishing, or re-establishing, effective exclusive breast-

eeding by the mother or other caregiver (strong recommendation, very low quality

evidence).

8.4 Inants who are less than 6 months o age with severe acute malnutrition and who are

admitted:

a. should be breasted where possible and the mothers or emale caregivers should besupported to breasteed the inants. I an inant is not breasted, support should be

given to the mother or emale caregiver to re-lactate. I this is not possible, wet nursing2

should be encouraged;

b. should also be provided a supplementary eed:

supplementary suckling approaches should, where easible, be prioritized;

or inants with severe acute malnutrition but no oedema, expressed breast milk

should be given, and, where this is not possible, commercial (generic) inant ormula

or F-75 or diluted F-1003may be given, either alone or as the supplementary eed

together with breast milk;

or inants with severe acute malnutrition and oedema, inant ormula or F-75should be given as a supplement to breast milk;

c. should not be given undiluted F-100 at any time (owing to the high renal solute load

and risk o hypernatraemic dehydration);

d. i there is no realistic prospect o being breasted, should be given appropriate and

adequate replacement eeds such as commercial (generic) inant ormula, with relevant

support to enable sae preparation and use, including at home when discharged.

EXECUTIVE SUMMARY

1 Recommendations regarding vitamin A, zinc and other micronutrients were not reviewed in this guideline process.2 All potential wet-nurses should be tested or HIV.3

Prepared F-100 should be urther diluted by adding 30% water.


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In addition:

e. assessment o the physical and mental health status o mothers or caregivers should

be promoted and relevant treatment or support provided


8.5. Inants who are less than 6 months o age and have been admitted to inpatient care can

be transerred to outpatient care when:

a. all clinical conditions or medical complications, including oedema, are resolved, and

b. the inant has good appetite, is clinically well and alert, and

c. weight gain on either exclusive breasteeding or replacement eeding is satisactory,

e.g. above the median o the WHO growth velocity standards or more than 5 g/kg/day

or at least 3 successive days, and

d. the inant has been checked or immunizations and other routine interventions, and

e. the mother or caregiver is linked with needed community-based ollow-up and

support


8.6 Inants who are less than 6 months o age can be discharged rom all care when they are

breasteeding effectively or eeding well with replacement eeds, and

a. have adequate weight gain, and

b. have a weight-or-length 2 Z-score


8.7 For inants who are less than 6 months o age with severe acute malnutrition and who donot require inpatient care (Recommendation 8.1), or whose caregivers decline admission

or assessment and treatment:

a. counselling and support or optimal inant and young child eeding should be provided,

based on general recommendations or eeding inants and young children, including

or low-birth-weight inants;

b. weight gain o the inant should be monitored weekly to observe changes;

c. i the inant does not gain weight, or loses weight while the mother or caregiver is

receiving support or breasteeding, then he or she should be reerred to inpatient

care;

d. assessment o the physical and mental health status o mothers or caregivers shouldbe promoted and relevant treatment or support provided


Research priorities

Guideline group members and stakeholders identiied several research priorities to improve the

body o evidence at the basic, clinical, epidemiological and operational levels on the management

o severe acute malnutrition in inants and children. Major research gaps were identiied in each o

the sections covered. SeeAnnex 7or a compiled list.


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Scope and purpose

This guideline provides global, evidence-inormed recommendations on a number o speciic issues

related to the management o severe acute malnutrition in inants and children. In conjunction

with other World Health Organization (WHO) recommendations,1 it provides evidence-inormed

guidance on the care o inants and children with severe malnutrition, including in the context oHIV.

The guideline will help Member States and their partners in their efforts to make inormed decisions

on the appropriate nutrition actions or severely malnourished children, and contribute to achieving

the Millennium Development Goals (MDGs), particularly reduction in child mortality (MDG 4). It will

also support Member States in their efforts to achieve global targets on the maternal, inant and

young child nutrition comprehensive implementation plan, especially global target 1, which entails

achieving 40% reduction by 2025 o the global number o children under 5 years who are stunted

and global target 6, which aims to reduce and maintain childhood wasting to less than 5%. (6).

The guideline is intended or a wide audience, including policy-makers, their expert advisers, and

technical and programme staff in organizations involved in the design, implementation and scaling-

up o nutrition actions or public health. The guideline will orm the basis or a revised manual onthe management o severe malnutrition or physicians and other senior health workers), a training

course on the management o severe malnutrition and other training materials.

This document presents the key recommendation and a summary o the supporting evidence.

1 This guideline does not relec t all WHO recommendations related to the management o children with severe acutemalnutrition but only those related to areas o care that were prioritized by the guideline development group advisingWHO or this guideline. Relevant standing recommendations are included adjacent to updated recommendations, to

contextualize updated recommendations.


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Background

It is estimated that 19 million preschool-age children, mostly rom the WHO Arican Region and

South-East Asia Region, are suffering rom severe wasting (7). Childhood undernutrition is a major

global health problem, contributing to childhood morbidity, mortality, impaired intellectual

development, suboptimal adult work capacity, and increased risk o diseases in adulthood (7). Othe 7.6 million deaths annually among children who are under 5 years o age (1), approximately

35% are due to nutrition-related actors and 4.4% o deaths have been shown to be speciically

attributable to severe wasting (7). Severe acute malnutrition remains a major cause o child mortality

worldwide. While pneumonia and diarrhoea are ofen the inal steps in the pathway, severe wasting

is estimated to account or around 400 000 child deaths each year (7). For this reason, the improved

management o severe acute malnutrition is an integral part o the World Health Resolution on Infant

and Young Child Nutrition(WHA 63.23), to improve child survival and to reduce the global burden o

disease.

In 2006, WHO released new growth standards or children aged 05 years (8). These represent the

standards on which all WHO deinitions and estimates o malnutrition, including moderate and

severe acute malnutrition, and obesity are now based. In children who are 659 months o age,severe acute malnutrition is deined as weight-or-height less than 3 Z-score1 o the median o

the WHO growth standards, or clinical signs o bilateral oedema o nutritional origin, despite other

measures being above speciied cut-off values (9). Since publication o the WHO Management of

severe malnutrition: a manual for physicians and other senior health workers (2), a joint statement by

the World Health Organization, World Food Programme, United Nations Standing Committee on

Nutrition and United Nations Childrens Fund (UNICEF) in 2007 (10)acknowledged the easibility o

community health workers or volunteers identiying children affected by severe acute malnutrition,

using simple coloured plastic strips that are designed to measure mid-upper arm circumerence.

In children who are 659 months o age, a mid-upper arm circumerence less than 115 mm also

indicates severe acute malnutrition, allowing early identiication o affected children within the

community beore the onset o complications.Major challenges remain to implementation o effective use o growth monitoring in primary

health-care settings, to identiy the most at-risk inants and children who need medical and

nutritional interventions to prevent serious morbidity and mortality. The importance o this is

highlighted by the strong epidemiological evidence that low weight-or-height, weight-or-length

or mid-upper arm circumerence are highly associated with a 520-old increased risk o mortality

(11). At the same time, it is necessary to examine the implications o very low anthropometry in

different epidemiological settings, especially South East Asia, and to establish the equivalent

anthropometric thresholds or older children and adolescents.

1 A Z-score (or standard deviation score) is the deviation o the value or an individual rom the median value o thereerence population, divided by the standard deviation or the reerence population. We reer herein to the median o

the WHO growth standards.


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Malnutrition in children typically develops during the period rom 6 to 18 months o age, when growth

velocity and brain development are especially high. Young children are particularly susceptible

to malnutrition i complementary oods are o low nutrient density and have low bioavailability

o micronutrients. In addition, childrens nutritional status will be urther compromised i

complementary oods are introduced too early or too late, or are contaminated.

The nutritional status o children can also be affected by chronic inections such as HIV. It is

estimated that over 2 million children worldwide are living with HIV, 90% o them in sub-Saharan

Arica (12). In a report describing children admitted to hospital in southern Arica, the prevalence o

HIV in children with severe acute malnutrition was 29% and these children were more likely to die

than malnourished children who were not inected with HIV (13). Higher HIV prevalence, i.e. up to

50%, has been reported among children with severe acute malnutrition (14).

Children with severe acute malnutrition have prooundly disturbed physiology and metabolism,

such that i intensive reeeding is initiated beore metabolic and electrolyte imbalances have

been corrected, mortality rates are high. For this reason, WHO developed clinical guidance (2) on

the management o the child with severe acute malnutrition. This guidance was updated in partthrough subsequent WHO publications on the outpatient management(10)and inpatient treatment

o children with severe acute malnutrition (15, 16). Outpatient treatment o uncomplicated severe

acute malnutrition is increasingly provided, using ready-to-use therapeutic oods (10). These are

high-energy, ortiied, ready-to-eat oods that have a nutrient content/100 kcal similar to that o

F-100, the therapeutic diet used to treat children with severe acute malnutrition in hospital settings.

Unlike F-100, however, ready-to-use therapeutic oods are not water based, meaning that bacteria

are less likely to grow in them. These oods can thereore be used saely at home or in hospital

without rerigeration and even in areas where hygiene conditions are not optimal. Ready-to-use

therapeutic ood can be consumed easily by children rom the age o 6 months and have been

shown to be effective in treating children with severe acute malnutrition in communities or in

hospital afer the stabilization phase. The technology to produce ready-to-use therapeutic ood

is simple and can be transerred to any country with minimal industrial inrastructure, while still

complying with the Recommended international code of hygienic practice for foods for infants and

childreno the Codex Alimentarius Standard CAC/RCP 21-1979 (17).

These signiicant advances have not been matched by research and development in other key areas

o clinical management o children with severe acute malnutrition. Furthermore, the HIV epidemic

has produced a number o new research questions related to the basic science and clinical

management o undernutrition in children inected with HIV. While some o the basic principles and

lessons or managing children without HIV can be extended to HIV-inected children, there is little

empirical evidence to guide management o this speciic population.

Increasingly, severe acute malnutrition is being documented among inants who are less than

6 months o age. However, there are ew data describing to what extent the pathophysiology inthis population is the same as that in older children and how to approach therapeutic eeding,

including the support and/or supplementation o breasteeding. The lack o epidemiological and

intervention data in young inants is common also or children who are older than 5 years. WHO

has commissioned systematic reviews and convened a guideline development group to ormulate

guidelines or this important age group.

Lastly, the epidemiological and clinical implications o the WHO child growth standards and the

populations that will be deined as having severe acute malnutrition need to be examined. While

increased mortality has been reported among children with severe acute malnutrition in several

Arican countries and Bangladesh, the burden o disease based on the revised growth standards

has not been estimated, especially in India and other settings in South Asia.

BACKGROUND


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Given developments in treatment options or severely malnourished children and the increasing

prevalence o HIV as an adjunct to undernutrition, certain aspects o the existing guidelines on the

management and treatment o severe acute malnutrition needed updating and revision. Following

the review (18)o the existing recommendations (2, 9, 10), WHO identiied the eight ollowing major

areas where revision o guidelines was needed:

1. Admission and discharge criteria or children who are 659 months o age with severe acute

malnutrition

Admission cut-off values or the respective screening indicators

Discharge cut-off values or the different admission indicators

Admission criteria or inpatient care and outpatient care

Transition rom inpatient care to outpatient care afer stabilization

2. Where to manage children with severe acute malnutrition who have oedema

Which children with severe acute malnutrition who also have oedema should be managed inhospital compared to at home?

3. Use o antibiotics in the management o children with severe acute malnutrition in outpatient

care

Do children with uncomplicated severe acute malnutrition need to be treated with antibiotics

and, i so, then which antibiotic should be used?

4. Vitamin A supplementation in the treatment o children with severe acute malnutrition

What is the effectiveness and saety o giving high-dose vitamin A supplementation to

children with severe acute malnutrition when they are receiving a WHO-recommended

therapeutic diet containing vitamin A?

How does the timing o high-dose vitamin A supplementation (i.e. at the beginning, afer

stabilization or afer rehabilitation) affect the effectiveness and saety o the management o

children with severe acute malnutrition?

5. Therapeutic eeding approaches in the management o severe acute malnutrition in children

who are 659 months o age

Does ready-to-use therapeutic ood given to children with severe acute malnutrition as

outpatients increase the incidence o acute diarrhoea or worsen acute diarrhoea i already

present?

Do children with severe acute malnutrition and acute diarrhoea who are managed as

outpatients require modiication o therapeutic eeding approaches? Does ready-to-use therapeutic ood given to children with severe acute malnutrition in

the rehabilitation phase, as either inpatients or outpatients, increase the prevalence o

diarrhoea or worsen diarrhoea i already present, in comparison to F-100?

Can ready-to-use therapeutic ood be given saely to children with severe acute malnutrition

who have persistent diarrhoea?

What is the most appropriate transition eeding approach or changing rom F-75 to F-100,

or rom F-75 to ready-to-use therapeutic ood, or children with severe acute malnutrition

who are managed in hospital?


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6. Fluid management o children with severe acute malnutrition

What is the most effective and saest luid-management approach or children with severe

acute malnutrition diagnosed with dehydration but without shock?

What is the most effective and saest luid-management approach or children with severe

acute malnutrition with shock?

7. Management o HIV-inected children with severe acute malnutrition

What is the optimal timing or initiating and dosing o antiretroviral drug treatment?

What are the optimal eeding regimens or HIV-inected children with severe acute malnutri-

tion and do these differ rom those or uninected children with severe acute malnutrition?

What is the value (effectiveness and saety) o vitamin A supplementation?

What are the most effective therapeutic strategies or managing diarrhoea?

8. Identiying and managing inants who are less than 6 months o age with severe acutemalnutrition

What are the criteria or deining severe acute malnutrition in inants who are less than 6

months o age?

What are the criteria or hospital admission o inants who are less than 6 months o age with

severe acute malnutrition?

What are the essential interventions, especially eeding approaches, or inants who are less

than 6 months o age with severe acute malnutrition?

What are the criteria or transerring inants who are less than 6 months o age and have

been treated in hospital or severe acute malnutrition to outpatient care, or discharging

them rom treatment?

BACKGROUND


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Recommendations

1. Admission and discharge criteria or children who are659 months o age with severe acute malnutrition

Preamble

Severe malnutrition in children who are 659 months o age was deined in previous publications(2)

as weight-or-height (or length) less than 3 Z-score, or less than 70% o the median National Center

or Health Statistics (NHCS)/WHO reerence values, or the presence o oedematous malnutrition.

The manual recommended admitting children with severe acute malnutrition to hospital or initial

treatment and rehabilitation, and to continue treatment as outpatients (transer to a nutritional

rehabilitation centre) when children have completed the initial phase o the treatment, have no

complications, and are eating satisactorily and gaining weight (2). Since ready-to-use therapeutic

ood became available in the 1990s, reports have demonstrated that most children with severe

acute malnutrition can be treated saely without admission to hospital (19). Consequently, in 2007

a joint United Nations statement endorsed outpatient care o children who are 659 months o

age with severe acute malnutrition and who present with no medical complications and with

good appetite (10). The same statement also endorsed the use o mid-upper arm circumerence

measurements as an independent criterion or screening.

The transition rom the NCHS growth reerence to the WHO growth standards in 2006 (4)prompted

the revision o cut-off values or indicators o severe acute malnutrition. A 2009 joint United Nations

statement endorsed a low mid-upper arm circumerence less than 115 mm as a criterion or

diagnosing severe acute malnutrition in children, in light o the high predictive value or mortality

(9). Mid-upper arm circumerence is measured using simple arm bands that are marked in millimetre

graduations and are sometimes colour coded. These armbands can be used and interpreted by

health-care workers who receive appropriate training. The statement also noted the programmatic

advantage o using a single mid-upper arm circumerence cut-off value to identiy children with

severe acute malnutrition in this age group (9). However, mid-upper arm circumerence and weight-

or-height indicators do not always correlate when used to identiy children with severe acute

malnutrition(2022). About 40% o children who are classiied as having severe acute malnutrition

using one o these indicators are similarly classiied using the other indicator (8). The agreement

between these criteria varies considerably between settings and geographic location (9, 23).

Comparison o the sensitivityspeciicity curves (receiver operating characteristic curves) in

community studies shows that mid-upper arm circumerence is better at identiying children with

a high risk o death (24).

The 1999 recommendations included discharging children rom hospital care when they achieved a

weight-or-height 1 Z-score or 90% o the median NCHS/WHO reerence values (2). The 2009 joint


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United Nations statement proposed using a single discharge criterion o 15% (or 20%, depending on

the local context) weight gain over oedema-ree weight on enrolment, or children admitted based

on weight-or-height or mid-upper arm circumerence, as well as absence o oedema or 2 weeks (9).

Data rom children treated or severe acute malnutrition in outpatient care in Malawi and Ethiopia

have suggested that 15% weight gain would result in 50% o children with severe acute malnutrition

meeting or exceeding 80% o the median weight-or-height o the NCHS reerence (25). However,

while some programmes adopted this approach, there was concern about its validity as an indicator

o nutritional recovery, and in many settings only the mid-upper arm circumerence cut-off value

o 125 mm was applied (26). The discharge cut-off value or mid-upper arm circumerence o 125

mm was based on historical cohort studies rom Bangladesh, Malawi and Uganda that suggested

that mortality risk at this cut-off value did not exceed 1/10 000 per day (25). The saety o using

changes in mid-upper arm circumerence as an indicator o progress o recovery during nutritional

rehabilitation, and a single cut-off value to indicate recovery, has not been validated.

In light o these experiences, WHO, with support rom the guideline development group aimed to

provide guidance on the ollowing:

Admission and discharge criteria or children who are 659 months o age with severe acute

malnutrition:

Admission cut-off values or the respective screening indicators

Discharge cut-off values or the different admission indicators

Admission criteria or inpatient care and outpatient care

Transition rom inpatient care to outpatient care afer stabilization

Summary o the evidence

A systematic review was conducted to examine admission and discharge criteria or severeacute malnutrition in children who are 659 months o age (27). The search identiied 11 relevant

epidemiological studies. Three o the 11 studies used cut-off values or admission that did not

correspond to the WHO deinition o severe acute malnutrition, namely mid-upper arm circumerence


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(mid-upper arm circumerence initially 114 mm) was 47 25 days, which was longer than or the less

malnourished children (initial mid-upper arm circumerence between 115 mm and 119 mm) who

were discharged on average afer 33 16 days. These observations provide indirect evidence that

15% weight gain is not an appropriate discharge criterion, because it results in the more severely

malnourished children getting the shortest duration o treatment and being discharged when still

malnourished. In this study, the mortality risks up until the end o treatment when using 15% weight

gain versus mid-upper arm circumerence 124 mm as a discharge criterion were comparable and

were 1.5 %. The second study in Guinea-Bissau used a mid-upper arm circumerence 130 mm as

a discharge criterion but did not separate outcomes or children who were admitted with severe

acute malnutrition rom those with moderate acute malnutrition (29).

No published data were ound that reported the inal outcome status o children with severe acute

malnutrition ollowing discharge rom treatment programmes, e.g. relapse rates; subsequent

mortality when discharged was based on a mid-upper arm circumerence measurement compared

to other indicators such as weight-or-height Z-score, mid-upper arm circumerence-or-age Z-score,

or mid-upper arm circumerence-or-height Z-score.

The overall quality o evidence was rated as low or the relationship between anthropometry and

mortality risk on admission. There was no evidence available inorming the relationship between

anthropometry and the risk o mortality post discharge. The quality o evidence or other important

outcomes, including time to recovery, growth and daily weight gain was rated very low or low, owing

to methodological and reporting issues. A Grading o Recommendations Assessment, Development

and Evaluation (GRADE) summary o the evidence was not developed, as the published data were

epidemiological reports rather than comparative studies.

Only one o the studies reported outcomes in children identiied, monitored or discharged based

on mid-upper arm circumerence and also by weight-or-height, and this was carried out among

hospitalized children. Few o the studies addressed the precision and accuracy o anthropometric

measurements, which may affect reliability. The act that most o the studies were done in Malawi,where the majority o cases are oedematous and the prevalence o HIV inection is high, may affect

the external validity (30, 3438). No studies were retrieved reporting on a number o important

outcomes, i.e. costs, adverse effects and population coverage.

Discussion

The guideline group noted that the development o ready-to-use therapeutic ood has made

outpatient management o children with severe acute malnutrition more easible and saer.

Active community screening makes it possible to identiy and treat these children early as

outpatients. It also allows children to be appropriately managed while avoiding the risk and

problems o inpatient care, such as nosocomial inections, patient transport and costs anddisruptions to amilies. Screening in the community has been acilitated by the easibility o

using mid-upper arm circumerence to identiy severely malnourished children.

Depending on the age group, and excluding consideration o oedematous malnutrition,

anthropometric assessments based on weight-or-height using the WHO growth standards

(8)are likely to identiy a larger population with severe acute malnutrition than NCHS growth

reerence values. This has a major implication or countries in South and South-East Asia,

where large numbers o inants and young children would be deined as having severe acute

malnutrition, using the WHO growth standards.

The guideline group noted that while weight-or-height and mid-upper arm circumerence are

good methods to assess wasting, both require training and methodical implementation to

RECOMMENDATIONS #1


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achieve reliable assessments. Even afer training, signiicant variation has been noted in health-

care workers measurements and classiication during standardization tests.

The guideline group agreed that children with severe acute malnutrition identiied using weight-

or-height do not consistently have a mid-upper arm circumerence


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The guideline group noted that the decision to transer children rom inpatient care to outpatient

care (i.e. discharge rom hospital) afer the initial phase o stabilization should be guided

primarily by the childrens clinical condition, including appetite and response to treatment, and

also social circumstances.

The guideline group noted that percentage weight gain should no longer be used as a criterion

or discharge rom treatment.

The guideline group noted that correlations o anthropometric indicators with risk o death and

response to treatment are urgently needed to inorm clinical recommendations and guidelines

or managing severe acute malnutrition in inants less than 6 months old and in children 5 years

and older, especially in the context o HIV.

Relevant standing recommendations

The recommendations below were conirmed as current in the context o existing WHO

recommendations included in WHO Management of severe malnutrition: a manual for physiciansand other senior health workers, 1999 (2); joint United Nations statement on Community-based

management of severe acute malnutrition, 2007 (10); WHO child growth standards and the identification

of severe acute malnutrition in infants and children: a joint statement by the World Health Organization

and the United Nations Childrens Fund, 2009 (9); and WHO Integrated management of childhood

illness: caring for newborns and children in the community, 2011 (IMCI)(41), noting in particular that:

in children who are 659 months o age, severe acute malnutrition is deined as:

weight-or-height 3 Z-score, or

mid-upper-arm circumerence


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age and have a mid-upper arm circumerence


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Similarly, i weight-or-height is used to identiy that a child has severe acute malnutrition,

then weight-or-height should be used to assess and conirm nutritional recovery.

c. Children admitted with only bilateral pitting oedema should be discharged rom treatment

based on whichever anthropometric indicator, mid-upper arm circumerence or weight-or-height is routinely used in programmes.

d. Percentage weight gain should not be used as a discharge criterion.

strong recommendation, low quality evidence

Follow-up o inants and children afer discharge rom treatment or severe acutemalnutrition

1.6 Children with severe acute malnutrition who are discharged rom treatment programmes

should be periodically monitored to avoid a relapse.


Rationale

The guideline development group noted that the quality o evidence was low or the relationship

between anthropometry and mortality risk on admission and very low/low or the relationship

between anthropometr y and time to recovery, growth and weight gain. However, the guideline group

agreed that the recommendation should be strong. The group recognized that the associations

between anthropometric outcomes and high mortality risks originated largely rom observational or

population-based studies rather randomized trials. Other evidence inorming the recommendations

was also based on programmatic experience and this characteristically downgrades the quality o

evidence. However, it was elt that examining these issues through randomized trials would be very

difficult and possibly unethical. The guideline group also considered that there is high biological

plausibility or the associations between poor anthropometry and mortality. The beneits o

identiying and treating children with severe acute malnutrition through screening with mid-upper

arm circumerence were determined to ar outweigh the possible disadvantage o overdiagnosing

malnutrition and causing children to be urther assessed. The recommendations were considered

to be easible and sustainable in low-resource settings, even though there were no cost data

available. As has been reported in a limited number o settings, community screening does increase

the rate o identiication o children with severe acute malnutrition. This will result in increased

costs to the health system as treatment, either as inpatients or in the community. However, it is also

likely that earlier identiication will enable children to be successully treated at home without the

costs o hospitalization or complications associated with later presentation, or through nosocomial

inection. Community-based management will also probably reduce transportation costs to the

amily and time away rom home. The guideline group viewed the other recommendations in asimilar way and that their overall beneits ar outweighed any potential harm. However, there are

several important research questions that need to be addressed to give greater certainty to these

recommendations.

Implications or uture research

Discussion with guideline development group members and stakeholders highlighted the limited

evidence available in themes related to the priority areas listed next.

To reine cut-off values o mid-upper arm circumerence to identiy severe acute malnutrition in

children who are 611 months, 1223 months and 2459 months o age, through assessment o

treatment outcomes.

RECOMMENDATIONS #1


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To test strategies to improve active community screening and routine health-acility screening,

and investigate barriers to service access and uptake, to enhance treatment coverage.

Other issues (no specific order) To evaluate the validity o mid-upper-arm circumerence values versus weight-or-height Z-score

as discharge criteria or end o treatment (in relation to response to treatment, relapse and

mortality) and determine the appropriate cut-off values.

To assess the sensitivity and speciicity o mid-upper-arm circumerence measurements at the

lower and higher age ranges o children who are 659 months o age, controlled or stunting and

the presence o oedema.

To establish mid-upper-arm circumerence thresholds to identiy severe acute malnutrition in

inants who are less than 6 months o age and children who are 5 years o age and older.

To assess the response to treatment according to initial anthropometric criteria and clinical and

biochemical characteristics.

To assess the correlation o anthropometric indicators with risk o death and response to

treatment o severe acute malnutrition in inants who are less than 6 months o age and children

who are 5 years o age and older, especially in the context o high and low HIV prevalence.


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2. Where to manage children with severe acute malnutritionwho have oedema

Preamble

The standard recommendation or the management o severe acute malnutrition has been

inpatient care during the stabilization phase and the irst part o the rehabilitation phase, and then

transer to a nutrition rehabilitation centre (when they exist) or the rest o the rehabilitation phase

(42). However, inpatient treatment is resource intensive (43), disrupts the amily and places children

at risk o nosocomial inections. Reports o children with severe acute malnutrition being effectively

treated at home (34, 35, 44)have prompted categorization o severe acute malnutrition as being

with or without medical complications (43, 45). Cases are uncomplicated i there are no signs o

severe clinical illness and the child has a good appetite. Using this classiication, WHO, UNICEF

and the World Food Programme recommend treating children with uncomplicated severe acute

malnutrition as outpatients whenever possible (10). Children with severe acute malnutrition whohave severe bilateral oedema (+++) have an increased risk o mortality compared to children with

severe acute malnutrition but with lesser degrees o oedema. For this reason, it is unclear whether

the severity o oedema, in the absence o other complications and with adequate appetite, should

independently inluence where to treat children with severe acute malnutrition.

The guideline development group aimed to review the evidence and provide guidance on the

ollowing question:

Which children with severe acute malnutrition who also have oedema should be managed in

hospital compared to at home?


A systematic review examined the evidence on the effectiveness o managing children who are more

than 6 months o age with uncomplicated oedematous malnutrition grade +/++, 1 in ambulatory

settings (46). No randomized controlled trials comparing the outcomes achieved in inpatient and

outpatient care or this speciic group were identiied. However, eight reports were ound that

described outcomes o children with severe acute malnutrition who had bilateral oedema and who

were treated as outpatients. The data were rom case-series that did not have control groups and

so comparisons were not thereore possible.

Among uncomplicated cases o oedematous malnourished children, recovery rates exceeded 88%

and case-atality rates remained below 4%. Oedema classiication varied among the studies and in

some studies it was not clear whether children with severe oedema were excluded rom outpatient

treatment. These outcomes are consistent with those recommended in the Sphere guidelines(47)

and the Prudhon index or case-atality rates (48). However, complicated cases were associated

with high case-atality rates during the irst 4 days o inpatient stabilization, especially in the context

o HIV inection (49). The weight gain o children with oedema who were treated as outpatients was

reported in only two studies and the time to nutritional recovery was prolonged and did not meet

the minimum Sphere standards (47). Authors suggested that this was due to sharing o ready-to-use

therapeutic ood at home or absence o ood supplementation in the home-based treatment group

(51). Methods to assess weight gain were not, however, uniorm across the studies. No association

was reported between the severity o oedema and the likelihood o nutritional recovery or not.

RECOMMENDATIONS #2

1 + Mild: both eet; ++ moderate: both eet, plus lower legs, hands, or lower arms; +++ severe: generalized oedema

including both eet, legs, hands, arms and ace. Source: Module 2. Principles o care, in re (50).
http://www.sphereproject.org/resources/?search=1&keywords=&language=English&category=22&subcat-22=23&subcat-29=0&subcat-31=0&subcat-35=0&subcat-49=0http://www.sphereproject.org/resources/?search=1&keywords=&language=English&category=22&subcat-22=23&subcat-29=0&subcat-31=0&subcat-35=0&subcat-49=0


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The quality o the evidence was rated as very low, as the absence o a control group in the reports

o outpatient treatment o children with severe acute malnutrition and oedema make it difficult

to make conclusions about the effectiveness and saety o outpatient treatment or children with

oedema +/++. As a result, no GRADE table or this evidence base was developed.

Discussion

The guideline development group considered that the systematic review supported the general

principle that severely malnourished children with oedema, but no other medical complications,

can be effectively and saely treated as outpatients.

It was also noted that the severity o oedema reported in children is inluenced by the

amiliarity o the staff with seeing oedematous cases. Inexperienced staff have been observed

to overestimate the extent o oedema.

While data were not available to comment on the severity o oedema and the saety and effective-

ness o managing children with severe malnutrition and oedema at home, the association oincreased mortality risk with more severe oedema (independent o site o care) was noted by

the guideline group.

The guideline group considered that evidence rom inpatient settings supported managing

children with severe malnutrition who have oedema +++ as inpatients and those with oedema

+/++ as outpatients.

The guideline group noted, however, that caution is required in interpretation o these results,

as there are limitations in the quality o the design o the included studies.


The recommendations were conirmed as current in the context o existing WHO recommendations

included in the WHO Management of severe malnutrition: a manual for physicians and other senior

health workers, 1999 (2)and Joint United Nations statement on Community-based management of

severe acute malnutrition, 2007 (10), noting in particular that:

inants and children who have only + or ++ bilateral pitting oedema but present with medical

complications or have no appetite should be admitted or inpatient care;

inants above 6 months o age and children who have + or ++ bilateral pitting oedema but who

have no medical complications and have appetite should be managed as outpatients;

children with bilateral pitting oedema who are admitted or inpatient care should transition

rom the stabilization to the transition phase when appetite returns and oedema is reducing.

Recommendations

2.1 Children with severe acute malnutrition who have severe bilateral oedema +++,1even i they

present with no medical complications and have appetite, should be admitted or inpatient

care.

strong recommendation, ver y low quality evidence


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Rationale

The guideline group noted that the quality o evidence was very low but was in consensus that

the recommendation should be strong. The recommendation essentially makes explicit what ispresently implicit in existing WHO recommendations. The recommendation is thereore not new

but clariies where children with severe bilateral oedema should be treated, i.e. in hospital. The

recommendation prioritizes the saety o children with this complication. The recommendation

is easible, as, in previous guidelines, all children with severe acute malnutrition were admitted.

Hence, this recommendation places no additional cost burden on health systems than previously.

Implications or uture research

Discussion with guideline development group members and stakeholders highlighted the limited

evidence available in themes related to the priority areas listed next.

What is the predictive value o different degrees o oedema (+, ++ or +++) on recovery o childrenwith severe acute malnutrition managed as inpatients or outpatients?

RECOMMENDATIONS #2

1 Mild: both eet; ++ moderate: both eet, plus lower legs, hands, or lower arms; +++ severe: generalized oedema includingboth eet, legs, hands, arms and ace (50).


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3. Use o antibiotics in the management o children withsevere acute malnutrition in outpatient care

Preamble

Epidemiological and clinical studies have documented the high prevalence o pneumonia,

bacteraemia and urinary tract inections in children with severe acute malnutrition, which ofen

may not be symptomatic.

The WHO Management of severe malnutrition: a manual for physicians and other senior health

workers, 1999 recommended that all children with severe acute malnutrition should be admitted

to hospital and treated with a course o antibiotics (2). I clinical complications were present, then

parenteral antibiotics were recommended, depending on local resistance patterns and availability.

For children without obvious clinical sepsis, oral antibiotics were recommended. Because severe

acute malnutrition suppresses the immune response, it is hard to detect inection.

The availability o ready-to-use-therapeutic oods now allows large numbers o children who have

severe acute malnutrition and are over 6 months o age, but who do not have medical complications,

to be treated as outpatients. These children were previously treated in hospital because ready-to-

use therapeutic oods that could be saely used in the community were not available. The 2007

joint United Nations statement on Community-based management of severe acute malnutrition

(10)recommends that, in addition to the provision o ready-to-use therapeutic ood, children with

severe acute malnutrition receive a short course o basic oral medication to treat inections.

In 2007, however, the evidence to support the use o oral antibiotics in children without signs o

clinical sepsis was limited. The emergence o successul outpatient management o children who

have severe acute malnutrition but do not demonstrate clinical complications, has raised the

question o whether these children would beneit rom a course o oral antibiotics as par t o routinemanagement in line with WHOs 1999 recommendation or treatment in hospitals (2).

The choice o antibiotic, or either inpatient or outpatient management, should consider patterns

o antibiotic resistance, which vary between countries (52, 53); high rates o resistance to second-

line antibiotics such as chloramphenicol, gentamicin and cephalosporins have been reported (52),

while sensitivity to ciproloxacin remains generally high. In vitro resistance, however, does not

necessarily relect clinical efficacy.

The guideline development group aimed to update guidance on the ollowing question:

Do children with uncomplicated severe acute malnutrition need to be treated with antibiotics

and, i so, then which antibiotic should be used?


A systematic review was conducted to examine the clinical saety and efficacy o antibiotic inter-

ventions among children with uncomplicated severe acute malnutrition (54).

One study reported outcomes in hospitalized children with severe acute malnutrition who all

received antibiotics. In a randomized controlled trial (20022003), there were no signiicant

differences in any o the efficacy outcomes among Sudanese children with severe acute malnutrition

(complicated and uncomplicated) who were treated with either 5 days o oral amoxicillin or 2 days

o intramuscular (IM) cefriaxone (55). Given that the study population was restr icted to hospitalized

children and there was no control group, this study did not provide direct evidence on the saety

and efficacy o antibiotics in children with uncomplicated severe acute malnutrition.


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Two studies provided evidence on the efficacy o antibiotics in children managed as outpatients.

In a retrospective analysis o children in Malawi with uncomplicated severe acute malnutrition

managed as outpatients, outcomes in one cohort who received 7 days o oral amoxicillin in addition

to ready-to-use therapeutic ood were compared with those o a cohort who received ready-to-use

therapeutic ood only. At 12 weeks ollow-up, mortality rates were less than 5% in both cohorts

and rates o nutritional recovery were similar (56). However, these two cohorts o children were

quite different at baseline and thereore the results are difficult to interpret.

In a prospective, randomized, double-blind trial in southern Malawi, children with uncomplicated

severe acute malnutrition managed as outpatients were randomized to receive either 1 week o

amoxicillin 8090 mg/kg/day, cedinir 14 mg/kg /day or placebo(57). The rate o nutritional recovery

o children who received antibiotics was signiicantly better than that o those who received placebo

(amoxicillin 89.0%, cedinir 91.4%, placebo 85.1%, P < 0.0002). This result was consistent among

both children with bilateral oedema (amoxicillin 91.6%, cedinir 92.9%, placebo 88.3%, P< 0.007)

and those with severe wasting (amoxicillin78.9%, cedinir 85.1%, placebo 73.7%, P< 0.03). Mortality

rates were signiicantly lower in the groups that received antibiotics (amoxicillin 4.63%, cedinir

3.86%, placebo 7.48%, P< 0.002). When analysed by type o malnutrition, mortality was reduced in

children who had bilateral oedema (amoxicillin 3.49%, cedinir 3.56%, placebo 7.48%, P< 0.0006).

However, the study was not speciically powered to undertake the latter analysis.

One beore-and-afer study o ampicillin and gentamicin as second-line antibiotics was also identi-

ied. The design o the study was such that it was not possible to estimate the relative effect o the

introduction o the antibiotic regimen independently o an algorithm or managing hypoglycaemia

that was introduced in parallel (58).

No studies o cefriaxone, ciproloxacin or co-trimoxazole as a irst-line treatment or children with

severe acute malnutrition were identiied.

The overall quality o this evidence was rated as low, owing to methodological and reporting bias.

SeeAnnex 1, Table 1or details o the GRADE assessment o the evidence.

Discussion

The guideline group considered that the use o broad-spectrum antibiotics such as amoxicillin

or children with severe acute malnutrition is supported by epidemiological data demonstrating

a high prevalence o inections in these children, including children with uncomplicated severe

acute malnutrition receiving outpatient management.

It is possible that providing antibiotics will result in some adverse events such as diarrhoea, skin

reactions and hypersensitivities. However, it is unlikely that the requency o such complications

will be signiicantly more than in well-nourished children.

However, it was noted that the one randomized trial that speciically examined outcomes in this

population was in a setting where the pattern o severe acute malnutrition is predominantly

oedematous and HIV is also prevalent.

Increased antimicrobial resistance is a potential consequence o prescribing broad-spectrum

antibiotics or the outpatient treatment o children with severe acute malnutrition.

However, children with severe acute malnutrition are at high risk o mortality higher or

example, than inants with ast breathing, where antibiotics are also currently recommended.

The reported reduction in mortality in children with uncomplicated severe acute malnutri-

tion treated with antibiotics as outpatients (7.48% to 4.63%) is signiicant and the guideline

group thought it was justiied to recommend this intervention to this population, even at the

risk o increasing antimicrobial resistance in the community.

RECOMMENDATIONS #3


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Community-level antimicrobial resistance is not a certain consequence o providing

antibiotics to children as part o outpatient care but will depend on actors that include the

prevalence o uncomplicated severe acute malnutrition, the quality o health-care worker

counselling and adherence to medications at home.

Antimicrobial resistance o community-acquired inections may be already present and the

consequence o antibiotic use or other reasons.

Research is needed to examine these issues.

It was noted that small bowel bacterial overgrowth is common in children with severe acute

malnutrition and affects intestinal unction.

The mechanism by which oral antibiotics may beneit children with uncomplicated severe

malnutrition is unclear but may include reducing excessive prolieration o small bowel lora,

translocation o gut bacteria into the bloodstream, or modiication o the microbiome.

The cost o providing oral antibiotics to all children with uncomplicated severe acute mal-

nutrition as outpatients would be about US$0.45 to US$0.60 per child or 5 days treatment (59).WHO guidelines previously recommended that all children with severe acute malnutrition

should be admitted and all children given appropriate antibiotics (2). Hence, while guidelines

have changed to provide treatment or these children in outpatient care, treating all children

with antibiotics has been the standard o care. While the budget to pay or antibiotics may be

different between hospital and primary health-care acilities, the total cost to the national

health authority would theoretically not be different. It is likely that all children in hospital are

indeed given antibiotics and hence this cost is real. Reports rom programmes indicate that

the introduction o community-based screening has increased the identiication o children

with severe acute malnutrition both those requiring hospital care and those that can be

managed as outpatients. The unds required or antibiotics have thereore increased because

o community-based screening improving coverage and service uptake. Managing children as

outpatients is likely to be cheaper than hospital care, even i oral antibiotics are included as part

o standard care. No cost analysis o these approaches was available.

While providing antibiotics would increase the transaction time between health-care workers

and mothers/caregivers o children, and highlights the importance o reliable supply-chain

management, the potential reduction in mortality justiies these opportunity costs.

WHO endorses the principle that antimicrobials should only be given to patients when

inection is present. In the context o severe acute malnutrition, uncomplicated should not be

understood to mean that inection is not present. Rather uncomplicated implies the absence

o symptoms or inection and that the child can be otherwise managed as an outpatient.

The guideline group noted that research is urgently needed to examine outcomes in populations

where wasting predominates, such as in South-East Asia, and where HIV is less common.


The recommendations were conirmed as current in the context o existing WHO recommendations

included in the WHO Management of severe malnutrition: a manual for physicians and other senior

health workers, 1999 (2), noting in particular that:

children admitted with severe acute malnutrition and complications such as septic shock,

hypoglycaemia, hypothermia, skin inections, or respiratory or urinary tract inections, or who

appear lethargic or sickly, should be given parenteral (IM or intravenous [IV]) antibiotics;

children admitted with severe acute malnutrition and with no apparent signs o inection andno complications should be given an oral antibiotic.


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Recommendations

3.1 Children with uncomplicated severe acute malnutrition, not requiring to be admitted and who

are managed as outpatients, should be given a course o oral antibiotic such as amoxicillin. conditional recommendation, low quality evidence

3.2 Children who are undernourished but who do not have severe acute malnutrition should not

routinely receive antibiotics unless they show signs o clinical inection.


Rationale

The guideline group noted that the quality o evidence regarding the efficacy o antibiotics in children

with uncomplicated severe acute malnutrition was low and agreed that the irst recommendation

should thereore be conditional. However, the guideline group acknowledged that there is an

extensive evidence base highlighting the adverse consequences o indiscriminate use o antibiotics,

including antibio

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