Title

Title

Malnutrition-associated inpatient and post-discharge child deaths Tickell KD, Walson JL, Denno DM Inpatient management of malnutrition Prevention Food systems Treatment Nutrient deficiency Malnutrition & complications Infection WASH Severe acute malnutrition with complications (SAM-C)

Severe Acute Malnutrition: 3 SD WFH, MUAC <115 mm, Bilateral edema With medical complications or no appetite Without complications Inpatient treatment Outpatient treatment SAM-C case fatality Severe Acute Malnutrition: 3 SD WFH, MUAC <115 mm, Bilateral edema With medical complications or no appetite Without complications Inpatient treatment Outpatient treatment WHO indicates <10% 1 Sub-Saharan centers of excellence: 15 25% 2,3,4 Blantyre, Malawi: 42% at 1 year 5 Importance of SAM-C guidelines Directly attributable to SAM-C 6 12.2% of diarrhea deaths 12.3% of measles deaths 8.7% of pneumonia deaths Opportunity We estimate that 100,000/year child deaths averted if 10% target reached Highly accessible population rapid impact

is possible Methods 1) Ancestry tracing guideline 2013 WHO update 2003 & 1999 WHO SAM guideline 1981 WHO PEM guideline Text books: F. Savage-King (1992) Nutrition in Developing Countries M. King (1969) Medical Care in Developing Countries Results: Only 1/4 based on RCT evidence Randomized control trials Observational directly related Indirectly related

RCT / observational Expert opinion / no evidence Areas of guidance Feeding & fluids Infection management Discharge & follow-up care Feeding & fluids King (1969) WHO PEM (1981) Savage King (1992)

WHO (1999) WHO (2003) WHO (2013) Shock/Severe dehydration: IV HS Darrows or Ringers + 5% Dextrose Monitor every 5-10 mins if on IV ReSoMal, unless cholera Cholera: standard ORS Transfusion: unimproved shock/anemia No transfusions after 24 hrs F75 -> RUTF: stabilized F100->rapid wgt gain RUTF for diarrhea

<6 mo: breastfeed or relactate Low dose vit A RCT High dose vit A: measles, eye signs Observational No Fe until rehabilitation Indirect Folic acid, Zn, Cu Feeding & fluids King (1969) WHO PEM (1981)

Savage King (1992) WHO (1999) WHO (2003) WHO (2013) Shock/Severe dehydration: IV HS Darrows or Ringers + 5% Dextrose Monitor every 5-10 mins if on IV ReSoMal, unless cholera Cholera: standard ORS Transfusion: unimproved shock/anemia

No transfusions after 24 hrs F75 -> RUTF: stabilized F100->rapid wgt gain RUTF for diarrhea <6 mo: breastfeed or relactate Low dose vit A RCT High dose vit A: measles, eye signs Observational No Fe until rehabilitation Indirect Folic acid, Zn, Cu Infection King

(1969) WHO PEM (1981) Savage King (1992) WHO (1999) WHO (2003) WHO (2013) Conscious & hypoglycemic: IV + oral dose glucose Unconcious & hypoglycemic: IV + oral dose

Ampicillin & gentamicin on admission < 6mo same ABX as older Zn for diarrhea Measles vaccine if not immunized HIV+ no difference for feeding HIV+ no difference for zn & vit A HIV+ & <24 months: ART for life RCT HIV+ & >24 months: ART based on CD4 Observational Indirect ART when stable if HIV+ Infection King (1969)

WHO PEM (1981) Savage King (1992) WHO (1999) WHO (2003) WHO (2013) Conscious & hypoglycemic: IV + oral dose glucose Unconcious & hypoglycemic: IV + oral dose Ampicillin & gentamicin on admission < 6mo same ABX as older Zn for diarrhea Measles vaccine if not immunized HIV+ no difference for feeding HIV+ no difference for zn & vit A HIV+ & <24 months: ART for life RCT HIV+ & >24 months: ART based on CD4 Observational Indirect ART when stable if HIV+ Discharge & follow-up care King (1969) WHO PEM (1981)

Savage King (1992) WHO (1999) WHO (2003) WHO (2013) Provide emotional and sensory support Hospital d/c: no complications, alert, appetite not anthropometry Assess progress using the anthropometric measure which qualified the child for admission

< 6mo: hospital d/c W gain > 5g/kg/day Do not use %weight gain If edema only complication normal anthropmetirc used for F/U RCT Observational Indirect Follow-up care d/c: WHZ >-2 & no edema x 2 weeks WHO 2013 update: Major research gaps were identified in each of the sections covered. Two key populations:7 No randomized controlled trials in HIV-infected children with SAM were identified that directly addressed any of the prioritized questions. No studies were found in the peer-reviewed literature that reported outcomes when WHO therapeutic feeding recommendationsare applied

to SAM infants who are less than 6 months of age. Weak evidence & high mortality 42% of SAM inpatients die within 1 year o 62% of HIV+ children died o 67% of infants died Post-discharge mortality o 44% of deaths Data from Kerac, et al 2014 5 Queen Elizabeth hospital: the biggest and one of the best (The Guardian 2005) Timing of deaths No data on causes of death

SAM-C Guidelines Useful clinical tool & synthesis of evidence/opinion Evidence Weak or non-existent for most elements Systematic search of trials registries Limited potential for impact Underlying cause: We dont know why these children die Beyond SAM-C No guidelines for MAM No guidelines for stunting

34% of diarrhea deaths attributable to MAM 45% of diarrhea deaths attributable to stunting 32% of pneumonia deaths attributable to MAM6 43% of pneumonia deaths attributable to stunting6 Next steps: The CHAIN network Kenya Jay Berkley

Director Malawi Pakistan Judd Walson Co-director Bangladesh Donna Denno Investigator Uganda Kirk Tickell Coordinator Opportunities for intervention

Hospital & post-discharge Intervene on modifiable pathways to death References 1: WHO. Guidelines for the Inpatient Management of Severely Malnourished Children. Geneva: WHO, 2003. 2: Personal communication between Kirk Tickell and Jay Berkley (12/8/14) 3: Fergusson, P. "HIV Prevalence and Mortality Among Children Undergoing Treatment for Severe Acute Malnutrition in Sub-Saharan Africa: a Systematic Review and Meta-analysis. R Soc Tropl Med (2009) 103, 541 548 4: Personal communication between Donna Denno and Maurice Kelly (6/6/14) 5: Kerac, MH. Et al. "Follow-Up of Post-Discharge Growth and Mortality After Treatment for Severe Acute Malnutrition (FuSAM Study): a Prospective Cohort Study." PLOS One 9.6 (2014): E96030. 7: Black RE, et al. (2013) Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet, Aug 3; 382: 427-51. 7: WHO. Updates on the Management of Severe Acute Malnutrition in Infants and Children. Geneva: WHO, 2013.

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