Purpose of the guideline¹

Severe acute malnutrition affects nearly 20 million preschool-age children, mostly from the World Health Organization (WHO) African Region and South-East Asia Region. Malnutrition is a significant factor in approximately one third of the nearly 8 million deaths in children who are under 5 years of age worldwide (1). WHO established guidelines for the treatment of 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 for key interventions and will also serve to inform revisions of the manual. This guideline does not reflect all WHO recommendations related to the management of 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 Life Course and Undernutrition 2010–2012. This group reviewed the previously published guidelines and indicated the areas of care and specific recommendations that should be revised first in the process of updating all WHO recommendations. Relevant standing recommendations are included adjacent to updated recommendations, to contextualize updated recommendations. Other WHO recommendations will be addressed in future guideline updates.

Guideline development methodology

WHO has developed the present evidence-informed recommendations using the procedures outlined in the WHO handbook for guideline development (3). The steps in this process included: (i) identification of priority questions and outcomes; (ii) retrieval of the evidence; (iii) assessment of the quality of evidence and synthesis of the findings; (iv) formulation of recommendations, including future research priorities; and (v) planning for dissemination, implementation, impact evaluation and updating of the guideline. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was followed to prepare evidence profiles related to preselected topics, based on up-to-date systematic reviews. The WHO Nutrition Guidance Advisory Group – Subgroup on Nutrition in the Life Course and Undernutrition 2010–2012, comprised content experts, methodologists, representatives of potential stakeholders and consumers. These experts, together with external resource people, participated in three WHO technical consultations, held in Geneva, Switzerland, on 2–4 June 2010, 14–16 March 2011 and 1–3 February 2012, to scope questions for the systematic reviews, review and discuss the evidence, draft the recommendations, and vote on their strength, taking into consideration: (i) desirable and undesirable effects of this intervention; (ii) the quality of the available evidence; and (iii) values and preferences related to the intervention in different settings. The cost of options available to health-care workers in different settings was not formally assessed, owing to lack of primary data in the literature or elsewhere. However, cost implications were considered as part of general discussion by the guideline development group, namely the Nutrition Guidance Advisory Group members and the external resource people. Members of the external experts' and stakeholders' panel were identified through a public call for comments and peer reviewed the guideline. Everyone involved in the development of this guideline submitted declarations of interests. All guideline development group members submitted them before each meeting and also made verbal declarations of interest at the beginning of meetings.

Available evidence

The evidence, available for the development of recommendations, was in general of very low quality, as defined in the WHO handbook for guideline development (3). This was due to the limited availability of randomized controlled trials, trials comparing existing WHO recommendations with new treatment options, or trials documenting comparisons of diagnosis and treatment methods identified by the guideline development group as requiring review. Where direct evidence was not available, indirect evidence from different population groups, or different intervention strategies has been noted, if appropriate. The need for future research directly addressing several of the areas of concern was highlighted. Owing to the scarcity of data on the cost of proposed recommendations, it is not possible to directly estimate the financial implications of implementation of these recommendations.

Recommendations

1. Admission and discharge criteria for children who are 6–59 months of age with severe acute malnutrition

   Criteria for identifying children with severe acute malnutrition for treatment

   1.1.

   In order to achieve early identification of children with severe acute malnutrition in the community, trained community health workers and community members should measure the mid-upper arm circumference of infants and children who are 6–59 months of age and examine them for bilateral pitting oedema. Infants and children who are 6–59 months of age and have a mid-upper arm circumference <115 mm, or have any degree of bilateral oedema, should be immediately referred for full assessment at a treatment centre for the management of severe acute malnutrition (strong recommendation, low quality evidence).

   1.2.

   In primary health-care facilities and hospitals, health-care workers should assess the mid-upper arm circumference or the weight-for-height/weight-for-length status of infants and children who are 6–59 months of age and also examine them for bilateral oedema. Infants and children who are 6–59 months of age and have a mid-upper arm circumference <115 mm or a weight-for-height/length <−3 Z-score² of the WHO growth standards (4), or have bilateral oedema, should be immediately admitted to a programme for the management of severe acute malnutrition (strong recommendation, low quality evidence).

   Criteria for inpatient or outpatient care³

   1.3.

   Children who are identified as having severe acute malnutrition should first be assessed with a full clinical examination to confirm whether they have medical complications and whether they have an appetite. Children who have appetite (pass the appetite test) and are clinically well and alert should be treated as outpatients. Children who have medical complications, severe oedema (+++), or poor appetite (fail the appetite test), or present with one or more Integrated Management of Childhood Illness (IMCI) danger signs⁴ should be treated as inpatients (strong recommendation, low quality evidence).

   Criteria for transferring children from inpatient to outpatient care⁵

   1.4.

   Children with severe acute malnutrition who are admitted to hospital can be transferred 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 transfer children from inpatient to outpatient care should be determined by their clinical condition and not on the basis of specific anthropometric outcomes such as a specific mid-upper arm circumference or weight-for-height/length (strong recommendation, low quality evidence).

   Criteria for discharging children from treatment

   1.5.

   1. Children with severe acute malnutrition should only be discharged from treatment when their:

      —

      weight-for-height/length is ≥−2 Z-score and they have had no oedema for at least 2 weeks, or

      —

      mid-upper-arm circumference is ≥125 mm and they have had no oedema for at least 2 weeks.

   2. The anthropometric indicator that is used to confirm severe acute malnutrition should also be used to assess whether a child has reached nutritional recovery, i.e. if mid-upper arm circumference is used to identify that a child has severe acute malnutrition, then mid-upper arm circumference should be used to assess and confirm nutritional recovery. Similarly, if weight-for-height is used to identify that a child has severe acute malnutrition, then weight-for-height should be used to assess and confirm nutritional recovery.
   3. Children admitted with only bilateral pitting oedema should be discharged from treatment based on whichever anthropometric indicator, mid-upper arm circumference or weight-for-height is routinely used in programmes.
   4. Percentage weight gain should not be used as a discharge criterion

   (strong recommendation, low quality evidence).

   Follow-up of infants and children after discharge from treatment for severe acute malnutrition

   1.6.

   Children with severe acute malnutrition who are discharged from treatment programmes should be periodically monitored to avoid a relapse (strong recommendation, low quality evidence).

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

   2.1.

   Children with severe acute malnutrition who have severe bilateral oedema (+++),⁶ even if they present with no medical complications and have appetite, should be admitted for inpatient care (strong recommendation, very low quality evidence).

3. Use of antibiotics in the management of 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 of 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 of clinical infection (strong recommendation, low quality evidence).

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

   4.1.

   Children with severe acute malnutrition should receive the daily recommended nutrient intake of vitamin A throughout the treatment period. Children with severe acute malnutrition should be provided with about 5000 IU vitamin A daily, either as an integral part of therapeutic foods or as part of a multi-micronutrient formulation (strong recommendation, low quality evidence).

   4.2.

   Children with severe acute malnutrition do not require a high dose of vitamin A as a supplement if they are receiving F-75, F-100⁷ or ready-to-use therapeutic food that complies with WHO specifications (and therefore already contains sufficient vitamin A), or vitamin A is part of other daily supplements (strong recommendation, low quality evidence).

   4.3.

   Children with severe acute malnutrition should be given a high dose of vitamin A (50 000 IU, 100 000 IU or 200 000 IU, depending on age) on admission, only if they are given therapeutic foods that are not fortified as recommended in WHO specifications and vitamin A is not part of other daily supplements (strong recommendation, low quality evidence).

5. Therapeutic feeding approaches in the management of severe acute malnutrition in children who are 6–59 months of age

   5.1.

   Children with severe acute malnutrition who present with either acute or persistent diarrhoea, can be given ready-to-use therapeutic food 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 food in the rehabilitation phase (following F-75 in the stabilization phase)

   Once children are stabilized, have appetite and reduced oedema and are therefore ready to move into the rehabilitation phase, they should transition from F-75 to ready-to-use therapeutic food over 2–3 days, as tolerated. The recommended energy intake during this period is 100–135 kcal/kg/day. The optimal approach for achieving this is not known and may depend on the number and skills of staff available to supervise feeding and monitor the children during rehabilitation (strong recommendation, very low quality evidence). Two options for transitioning children from F-75 to ready-to use therapeutic food are suggested:

   1. start feeding by giving ready-to-use therapeutic food as prescribed for the transition phase. Let the child drink water freely. If the child does not take the prescribed amount of ready-to-use therapeutic food, then top up the feed with F-75. Increase the amount of ready-to-use therapeutic food over 2–3 days until the child takes the full requirement of ready-to-use therapeutic food, or
   2. give the child the prescribed amount of ready-to-use therapeutic food for the transition phase. Let the child drink water freely. If the child does not take at least half the prescribed amount of ready-to-use therapeutic food in the first 12 h, then stop giving the ready-to-use therapeutic food and give F-75 again. Retry the same approach after another 1–2 days until the child takes the appropriate amount of ready-to-use therapeutic food 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 food and observed to ensure that they accept the diet before being transferred to an outpatient programme (strong recommendation, very low quality evidence).

6. Fluid management of children with severe acute malnutrition

   6.1.

   Children with severe acute malnutrition who present with some dehydration or severe dehydration but who are not shocked should be rehydrated slowly, either orally or by nasogastric tube, using oral rehydration solution for malnourished children (5–10 mL/kg/h up to a maximum of 12 h) (strong recommendation, low quality evidence).

   6.2.

   Full-strength, standard WHO low-osmolarity oral rehydration solution (75 mmol/L of sodium) should not be used for oral or nasogastric rehydration in children with severe acute malnutrition who present with some dehydration or severe dehydration. Give either ReSoMal or half-strength standard WHO low-osmolarity oral rehydration solution with added potassium and glucose, unless the child has cholera or profuse 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 vitamins mix⁸ or 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.

   ReSoMal⁹ (or locally prepared ReSoMal using standard WHO low-osmolarity oral rehydration solution) should not be given if children are suspected of having cholera or have profuse watery diarrhoea.¹⁰ Such children should be given standard WHO low-osmolarity oral rehydration solution that is normally made, i.e. not further diluted (strong recommendation, low quality evidence).

   6.4.

   Children with severe acute malnutrition and signs of shock or severe dehydration and who cannot be rehydrated orally or by nasogastric tube should be treated with intravenous fluids, either:

   1. half-strength Darrow's solution with 5% dextrose, or
   2. Ringer's lactate solution with 5% dextrose.

   If neither is available, 0.45% saline + 5% dextrose should be used (conditional recommendation, very low quality evidence).

7. Management of HIV-infected children with severe acute malnutrition

   7.1.

   Children with severe acute malnutrition who are HIV infected and who qualify for lifelong antiretroviral therapy should be started on antiretroviral drug treatment as soon as possible after stabilization of metabolic complications and sepsis. This would be indicated by return of appetite and resolution of severe oedema. HIV-infected 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-infected children with severe acute malnutrition who are started on antiretroviral drug treatment should be monitored closely (inpatient and outpatient) in the first 6–8 weeks following initiation of antiretroviral therapy, to identify early metabolic complications and opportunistic infections (strong recommendation, very low quality evidence).

   7.2.

   Children with severe acute malnutrition who are HIV infected should be managed with the same therapeutic feeding approaches as children with severe acute malnutrition who are not HIV infected (strong recommendation, very low quality evidence).

   7.3.

   HIV-infected children with severe acute malnutrition should receive a high dose of vitamin A on admission (50 000 IU to 200 000 IU depending on age) and zinc for management of diarrhoea, as indicated for other children with severe acute malnutrition, unless they are already receiving F-75, F-100 or ready-to-use therapeutic food, which contain adequate vitamin A and zinc if they are fortified following the WHO specifications (strong recommendation, very low quality evidence).

   7.4.

   HIV-infected children with severe acute malnutrition in whom persistent diarrhoea does not resolve with standard management should be investigated to exclude carbohydrate intolerance and infective causes, which may require different management, such as modification of fluid and feed intake, or antibiotics (strong recommendation, very low quality evidence).

8. Identifying and managing infants who are less than 6 months of age with severe acute malnutrition

   8.1.

   Infants who are less than 6 months of age with severe acute malnutrition and any of the following complicating factors should be admitted for inpatient care:

   1. any serious clinical condition or medical complication as outlined for infants who are 6 months of age or older with severe acute malnutrition;
   2. recent weight loss or failure to gain weight;
   3. ineffective feeding (attachment, positioning and suckling) directly observed for 15–20 min, ideally in a supervised separated area;
   4. any pitting oedema;
   5. any medical or social issue needing more detailed assessment or intensive support (e.g. disability, depression of the caregiver, or other adverse social circumstances)

   (strong recommendation, very low quality evidence).

   8.2.

   Infants who are less than 6 months of age with severe acute malnutrition should receive the same general medical care¹¹ as infants with severe acute malnutrition who are 6 months of age or older:

   1. infants with severe acute malnutrition who are admitted for inpatient care should be given parenteral antibiotics to treat possible sepsis and appropriate treatment for other medical complications such as tuberculosis, HIV, surgical conditions or disability;
   2. infants with severe acute malnutrition who are not admitted should receive a course of broad-spectrum oral antibiotic, such as amoxicillin, in an appropriately weight-adjusted dose

   (strong recommendation, very low quality evidence).

   8.3.

   Feeding approaches for infants who are less than 6 months of age with severe acute malnutrition should prioritize establishing, or re-establishing, effective exclusive breastfeeding by the mother or other caregiver (strong recommendation, very low quality evidence).

   8.4.

   Infants who are less than 6 months of age with severe acute malnutrition and who are admitted:

   1. should be breastfed where possible and the mothers or female caregivers should be supported to breastfeed the infants. If an infant is not breastfed, support should be given to the mother or female caregiver to re-lactate. If this is not possible, wet nursing¹² should be encouraged;
   2. should also be provided a supplementary feed:

      —

      supplementary suckling approaches should, where feasible, be prioritized;

      —

      for infants with severe acute malnutrition but no oedema, expressed breast milk should be given, and, where this is not possible, commercial (generic) infant formula or F-75 or diluted F-100¹³ may be given, either alone or as the supplementary feed together with breast milk;

      —

      for infants with severe acute malnutrition and oedema, infant formula or F-75 should be given as a supplement to breast milk;

   3. should not be given undiluted F-100 at any time (owing to the high renal solute load and risk of hypernatraemic dehydration);
   4. if there is no realistic prospect of being breastfed, should be given appropriate and adequate replacement feeds such as commercial (generic) infant formula, with relevant support to enable safe preparation and use, including at home when discharged.
      In addition:
   5. assessment of the physical and mental health status of mothers or caregivers should be promoted and relevant treatment or support provided

   (strong recommendation, very low quality evidence).

   8.5.

   Infants who are less than 6 months of age and have been admitted to inpatient care can be transferred to outpatient care when:

   1. all clinical conditions or medical complications, including oedema, are resolved, and
   2. the infant has good appetite, is clinically well and alert, and
   3. weight gain on either exclusive breastfeeding or replacement feeding is satisfactory, e.g. above the median of the WHO growth velocity standards or more than 5 g/kg/day for at least 3 successive days, and
   4. the infant has been checked for immunizations and other routine interventions, and
   5. the mother or caregiver is linked with needed community-based follow-up and support

   (strong recommendation, very low quality evidence).

   8.6.

   Infants who are less than 6 months of age can be discharged from all care when they are breastfeeding effectively or feeding well with replacement feeds, and

   1. have adequate weight gain, and
   2. have a weight-for-length ≥−2 Z-score

   (strong recommendation, very low quality evidence).

   8.7.

   For infants who are less than 6 months of age with severe acute malnutrition and who do not require inpatient care (Recommendation 8.1), or whose caregivers decline admission for assessment and treatment:

   1. counselling and support for optimal infant and young child feeding should be provided, based on general recommendations for feeding infants and young children, including for low-birth-weight infants;
   2. weight gain of the infant should be monitored weekly to observe changes;
   3. if the infant does not gain weight, or loses weight while the mother or caregiver is receiving support for breastfeeding, then he or she should be referred to inpatient care;
   4. assessment of the physical and mental health status of mothers or caregivers should be promoted and relevant treatment or support provided

   (strong recommendation, very low quality evidence).

Research priorities

Guideline group members and stakeholders identified several research priorities to improve the body of evidence at the basic, clinical, epidemiological and operational levels on the management of severe acute malnutrition in infants and children. Major research gaps were identified in each of the sections covered. See Annex 7 for a compiled list.

Footnotes

1

This publication is a WHO guideline. A WHO guideline is any document, whatever its title, containing WHO recommendations about health interventions, whether they be clinical, public health or policy interventions. A recommendation provides information about what policy-makers, health-care providers or patients should do. It implies a choice between different interventions that have an impact on health and that have ramifications for the use of resources. A full guideline is one that provides complete coverage of a health topic or disease. It is expected to include recommendations in relation to all aspects of the topic (e.g. surveillance, diagnosis, public health and clinical interventions) and to be fully based on systematic reviews of the evidence for each aspect. All publications containing WHO recommendations are approved by the WHO Guidelines Review Committee.

2

A Z-score equates to one standard deviation.

3

Necessary resources and services need to be in place if children are referred to outpatient care.

4

Danger signs: unable to drink or breastfeed; vomits everything; has had convulsions (more than one or prolonged >15 min); lethargic or unconscious; convulsing now.

5

Necessary resources and services need to be in place if children are referred to outpatient care.

6

+ Mild: both feet; ++ moderate: both feet, plus lower legs, hands, or lower arms; +++ severe: generalized oedema including both feet, legs, hands, arms and face. Source: Module 2. WHO training course on the management of severe malnutrition. Geneva: World Health Organization; 2002 (updated 2009) Principles of care.

7

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

8

A specific electrolyte–micronutrient product formulated according to WHO specifications for use in the management of children with severe acute malnutrition.

9

ReSoMal (short for rehydration solution for severely malnourished children) is the generic name for a powder for the preparation of an oral rehydration solution exclusively for oral or nasogastric rehydration of people suffering from severe acute malnutrition. It must be used exclusively under medical supervision in inpatient care, and must not be given for free use to the mother or caregiver.

10

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

11

Recommendations regarding vitamin A, zinc and other micronutrients were not reviewed in this guideline process.

12

All potential wet-nurses should be tested for HIV.

13

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