child health research project research results and policy formulation on nutrition and...
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Child Health Research ProjectChild Health Research ProjectResearch Results and Policy Research Results and Policy
FormulationFormulationon Nutrition and on Nutrition and MicronutrientsMicronutrients
Selective Presentation of CHR Selective Presentation of CHR ResearchResearch
and Policy Activities in and Policy Activities in Nutrition and Nutrition and MicronutrientsMicronutrientsBreastfeeding/Complementary Breastfeeding/Complementary
FeedingFeeding
Underweight (“PEM”)Underweight (“PEM”)
Vitamin AVitamin A
ZincZinc
Iron/Multiple micronutrientsIron/Multiple micronutrients
Breastfeeding - ImportanceBreastfeeding - Importance Not breastfeeding increases risk of Not breastfeeding increases risk of
death death < 6 mo 6-23 mo - ≈ 2x < 6 mo 6-23 mo - ≈ 2x Diarrhea – 6.1xDiarrhea – 6.1xPneumonia – 2.4xPneumonia – 2.4x
Not exclusively breastfeeding for 4 Not exclusively breastfeeding for 4 mo (compared with partial mo (compared with partial breastfeeding) increases risk of breastfeeding) increases risk of death death Diarrhea – 3.9xDiarrhea – 3.9xPneumonia – 2.4xPneumonia – 2.4x
From WHO Collaborative Study Team, Lancet 2000 and Arifeen From WHO Collaborative Study Team, Lancet 2000 and Arifeen et al., Pediatrics 2001et al., Pediatrics 2001
Research Results with Research Results with IMCI Nutritional CounselingIMCI Nutritional Counseling
Clinic-based intervention in Brazil Clinic-based intervention in Brazil improved diet and weight gainimproved diet and weight gain
Clinic and community intervention in Clinic and community intervention in India increased breastfeeding in 0-3 India increased breastfeeding in 0-3 mo. olds from 14% to 73%mo. olds from 14% to 73%
Clinical and community intervention Clinical and community intervention in Peru reduced stunting by < 70%in Peru reduced stunting by < 70%
From Santos et al, J Nutr 2001 (Brazil), others unpublished)From Santos et al, J Nutr 2001 (Brazil), others unpublished)
Cohort length for age
-1.4
-1.2
-1
-0.8
-0.6
-0.4
-0.2
0
Age (months)
Z-s
core
ControlIntervention
Control -0.48 -0.0041 -0.47 -0.69 -0.94 -1.13 -1.2
Intervention -0.51 -0.0027 -0.24 -0.43 -0.58 -0.68 -0.81
0 3 6 9 12 15 18
Cumulative percent of children with stunting
024681012141618
0 2 4 6 8 15 18
Age in months
% o
f ch
ild
ren
Intervention
Control
Nutrition Policy FormulationNutrition Policy Formulation
WHO recommends exclusive WHO recommends exclusive breastfeeding for first 6 mo. of breastfeeding for first 6 mo. of lifelife
WHO meeting in December 2001 WHO meeting in December 2001 develops Global Strategy for develops Global Strategy for Infant and Young Child Feeding Infant and Young Child Feeding (to protect, promote and support (to protect, promote and support optimal infant and young child optimal infant and young child feeding)feeding)
Underweight (Low Weight for Underweight (Low Weight for Age) Causes and Prevalence in Age) Causes and Prevalence in
Children < 5y Old Children < 5y Old Caused by IUGR, inadequate Caused by IUGR, inadequate
breastfeeding/complementary breastfeeding/complementary feeding feeding and zinc intake and by infectious and zinc intake and by infectious disease morbiditydisease morbidity
Prevalence varies from 5% in middle Prevalence varies from 5% in middle income countries in Latin America to income countries in Latin America to 46% in low income countries of 46% in low income countries of South AsiaSouth Asia
Increased Risk of Morbidity Increased Risk of Morbidity and Mortality for Underweight and Mortality for Underweight
ChildrenChildren Infectious disease morbidity Infectious disease morbidity (< -2z)(< -2z)
DiarrheaDiarrhea - RR - RR 1.251.25
PneumoniaPneumonia
- RR - RR 1.861.86
Mortality (- 1z to -2z; -2z to Mortality (- 1z to -2z; -2z to -3z; < -3z)-3z; < -3z)
DiarrheaDiarrhea - RR 2.3 - RR 2.3 →→
12.512.5
PneumoniaPneumonia
- RR 2.0 - RR 2.0 →→
8.08.0
MalariaMalaria - RR 2.1 - RR 2.1 →→
9.59.5
MeaslesMeasles - RR 1.7 - RR 1.7 →→
5.25.2
Sources: For cause-specific mortality: EIP/WHO using 1999 data. For deaths associated with malnutrition: Caulfield LE, Black RE. Malnutrition and the global burden of disease: underweight and cause-specific mortality. Paper in preparation; NOT FOR CITATION.
Diarrhoea12%
Other29%
Pneumonia20%
Malaria8%
Measles5%HIV/AIDS
4%
Perinatal22%
Deaths associated with undernutrition
60%
Major causes of death among children under five, global, 2000
Contribution of Contribution of undernutrition undernutrition
to under-five mortality by to under-five mortality by cause, for 2000cause, for 2000
0%
20%
40%
60%
80%
100%
Diarrhoea Malaria Pneumonia Measles All-cause
Proportion of deaths associated with undernutrition All Deaths
Sources: For cause-specific mortality: EIP/WHO using 1999 data. For deaths associated with malnutrition: Caulfield LE, Black RE. Malnutrition and the global burden of disease: underweight and cause-specific mortality. Paper in preparation; NOT FOR CITATION.
Vitamin A Deficiency Prevalence Vitamin A Deficiency Prevalence and Disease Risk in Children < and Disease Risk in Children <
5y Old 5y Old Prevalence varies from 16% in Prevalence varies from 16% in
middle income countries in Latin middle income countries in Latin America to 48% in low income America to 48% in low income countries of Asiacountries of Asia
Infectious disease morbidity Infectious disease morbidity (incidence)(incidence)
MalariaMalaria - RR 1.43 - RR 1.43 MortalityMortality
Diarrhea - RR 1.47 Diarrhea - RR 1.47 Measles - RR 1.35Measles - RR 1.35
Safety of Delivery of Vitamin A Safety of Delivery of Vitamin A with EPIwith EPI
RCT in 9424 mother-infant pairs in RCT in 9424 mother-infant pairs in Ghana, India and PeruGhana, India and Peru
Mothers 200,000 IU vitamin A post-Mothers 200,000 IU vitamin A post-partum, infants 25,000 IU at 6, 10, partum, infants 25,000 IU at 6, 10, 14 weeks with immunizations14 weeks with immunizations
No adverse effectsNo adverse effects Small reduction in vitamin A Small reduction in vitamin A
deficiency deficiency at 6 mo of ageat 6 mo of age
From WHO/CHD Immunization-Linked Vitamin A Supplementation From WHO/CHD Immunization-Linked Vitamin A Supplementation Group, Lancet 1998Group, Lancet 1998
Zinc Deficiency Prevalence in Zinc Deficiency Prevalence in Children < 5y OldChildren < 5y Old
Estimated using FAO food balance Estimated using FAO food balance sheets sheets to determine prevalence of to determine prevalence of inadequate availability of zinc per inadequate availability of zinc per capita to meet capita to meet zinc requirementszinc requirements
Prevalence up to 72% in South Asia Prevalence up to 72% in South Asia (31% global)(31% global)
From International Zinc Consultative GroupFrom International Zinc Consultative Group
Risk of Child Morbidity and Risk of Child Morbidity and Mortality Mortality
with Zinc Deficiencywith Zinc Deficiency Infectious disease morbidity Infectious disease morbidity
(incidence)(incidence)DiarrheaDiarrhea - RR 1.28- RR 1.28PneumoniaPneumonia - RR 1.69- RR 1.69MalariaMalaria - RR 1.56- RR 1.56
Mortality – likely greater risk than for Mortality – likely greater risk than for incidence since also effect on severityincidence since also effect on severity
Published 2/3 ↓ in mortality in 1-9 Published 2/3 ↓ in mortality in 1-9 mo old SGA infants (Sazawal, mo old SGA infants (Sazawal, Pediatrics 2001)Pediatrics 2001)
Process of Priority Setting, Process of Priority Setting, Research Implementation and Research Implementation and Policy Formulation Regarding Policy Formulation Regarding
Zinc DeficiencyZinc Deficiency CHR meeting Nov. 1996 reviewed CHR meeting Nov. 1996 reviewed
evidence and published research evidence and published research prioritiespriorities
Pooled analyses of existing studies Pooled analyses of existing studies conducted – 1997-8conducted – 1997-8
Research undertaken – 1997-presentResearch undertaken – 1997-present Recommendations made – 1998-Recommendations made – 1998-
presentpresent
Zinc in Therapy of Persistent Zinc in Therapy of Persistent DiarrheaDiarrhea
5 published trials: 29% ↓ in 5 published trials: 29% ↓ in duration, 40% ↓ in treatment duration, 40% ↓ in treatment failure or deathfailure or death
WHO recommends zinc be used WHO recommends zinc be used in treatment of persistent in treatment of persistent diarrheadiarrhea
From Zinc Investigators’ Collaborative Group, Am J Clin Nutr From Zinc Investigators’ Collaborative Group, Am J Clin Nutr 20002000
Zinc in Therapy of Acute Zinc in Therapy of Acute DiarrheaDiarrhea
7 published trials: 22% ↓ in 7 published trials: 22% ↓ in duration, plus reduction in stool duration, plus reduction in stool outputoutput
4 of 6 additional trials show 4 of 6 additional trials show similar benefitsimilar benefit
Controlled trial (12,000 child-Controlled trial (12,000 child-years) shows 19% ↓ diarrhea years) shows 19% ↓ diarrhea hospitalization, 51% ↓ in mortality hospitalization, 51% ↓ in mortality and 62% ↓ in antibiotic useand 62% ↓ in antibiotic use
Zinc in Therapy of Acute Zinc in Therapy of Acute Diarrhea: Diarrhea:
Policy and Needed ResearchPolicy and Needed Research WHO meeting in May 2001 concludes WHO meeting in May 2001 concludes
that zinc supplementation is efficacious that zinc supplementation is efficacious in reducing severity and duration in reducing severity and duration
Effectiveness studies needed to assess Effectiveness studies needed to assess strategies for delivering zinc strategies for delivering zinc supplementation to children with supplementation to children with diarrheadiarrhea
Initiating 5-site study of acceptability Initiating 5-site study of acceptability and 2-site study of effectiveness and and 2-site study of effectiveness and impactimpact
Zinc Supplements in Zinc Supplements in Prevention of Prevention of
Morbidity (Incidence)Morbidity (Incidence) 9 trials with diarrhea outcome: 22% 9 trials with diarrhea outcome: 22%
↓↓ 4 trials with pneumonia outcome: 4 trials with pneumonia outcome:
41% ↓41% ↓ 2 trials with malaria (clinic visits) 2 trials with malaria (clinic visits)
outcome: 36% ↓outcome: 36% ↓ 3 mortality impact trails underway in 3 mortality impact trails underway in
India, Nepal, ZanzibarIndia, Nepal, Zanzibar From Zinc Investigators’ Collaborative Group, J Pediatrics 1999From Zinc Investigators’ Collaborative Group, J Pediatrics 1999
Alternatives for Increasing Alternatives for Increasing Zinc IntakeZinc Intake
Supplements – dispersible tablet with Supplements – dispersible tablet with zinc or zinc/iron highly acceptable zinc or zinc/iron highly acceptable and costs 1 U.S. cent or lessand costs 1 U.S. cent or less
““Sprinkle” with multiple Sprinkle” with multiple micronutrients micronutrients
Fully fortified (i.e. RDA) sachet of Fully fortified (i.e. RDA) sachet of food food
Fortified staple foods, e.g. maize flour Fortified staple foods, e.g. maize flour in Mexico in Mexico
Iron Deficiency Prevalence and Iron Deficiency Prevalence and
Disease RiskDisease Risk Prevalence of anemia in Prevalence of anemia in
children up to 63% in South children up to 63% in South Asia and 50% thought to be IDA; Asia and 50% thought to be IDA; estimates of risk per gram estimates of risk per gram decrease in hemoglobindecrease in hemoglobin
AF of maternal mortality – 20%AF of maternal mortality – 20% AF of early neonatal mortality – AF of early neonatal mortality –
22%22% AF of mental retardation – 18%AF of mental retardation – 18%
Meta-analyses of Effects of Meta-analyses of Effects of Oral Iron Supplements in Oral Iron Supplements in
Infectious Disease MorbidityInfectious Disease Morbidity 50% ↑ clinical malaria and other 50% ↑ clinical malaria and other
infectious diseases in malarious areas infectious diseases in malarious areas (Oppenheimer, J Nutrition 2001)(Oppenheimer, J Nutrition 2001)
17%↑ 17%↑ P. falciparumP. falciparum infection; non sig. infection; non sig. 9% ↑ clinical malaria (Shankar, 9% ↑ clinical malaria (Shankar, submitted)submitted)
11% ↑ diarrhea, no difference in other 11% ↑ diarrhea, no difference in other morbidity (Gera, submitted)morbidity (Gera, submitted)
Effects of Multiple Effects of Multiple Micronutrients vs. Zinc Micronutrients vs. Zinc Supplementation in PeruSupplementation in Peru
RCT compared daily zinc (10 mg) RCT compared daily zinc (10 mg) or multiple micronutrients with or multiple micronutrients with placebo in 6-24 mo old infantsplacebo in 6-24 mo old infants
Supplement for 6 mo, home visits Supplement for 6 mo, home visits by workers 5 d/wk to give by workers 5 d/wk to give supplement and record morbiditysupplement and record morbidity
Effects of Multiple Micronutrients Effects of Multiple Micronutrients (MN) vs. Zinc, Iron or Zinc/Iron (MN) vs. Zinc, Iron or Zinc/Iron Supplementation on Diarrhea of Supplementation on Diarrhea of Moderate Severity in BangladeshModerate Severity in Bangladesh
RCT compared weekly zinc (20 RCT compared weekly zinc (20 mg), iron, zinc/iron, or MN with mg), iron, zinc/iron, or MN with placebo in 6-11 mo old infantsplacebo in 6-11 mo old infants
Infants < -1z W/A: diarrhea Infants < -1z W/A: diarrhea reduced 19% by zinc and 17% by reduced 19% by zinc and 17% by zinc/iron (borderline sig.) and zinc/iron (borderline sig.) and increased 10% by MN (not sig.)increased 10% by MN (not sig.)
All infants: diarrhea same in All infants: diarrhea same in zinc, iron or zinc/iron, but zinc, iron or zinc/iron, but increased by 18% in MN (sig.)increased by 18% in MN (sig.)
Continuing Challenges/Research Continuing Challenges/Research QuestionsQuestions
Can we successfully implement Can we successfully implement programs to improve BF/CF and programs to improve BF/CF and thus enhance nutritional status?thus enhance nutritional status?
Can we devise sustainable means Can we devise sustainable means to improve nutrition/micronutrient to improve nutrition/micronutrient status where dietary approaches status where dietary approaches are not sufficient?are not sufficient?
What are the positive and negative What are the positive and negative interactions of micronutrients interactions of micronutrients provided in supplements? provided in supplements?
Continuing Challenges/Research Continuing Challenges/Research QuestionsQuestions
How should programs be How should programs be implemented to use zinc for implemented to use zinc for treatment of diarrhea?treatment of diarrhea?
How can zinc and iron deficiencies be How can zinc and iron deficiencies be prevented?prevented?
What are the What are the nutritional/micronutrient effects in nutritional/micronutrient effects in malaria, TB, HIV/AIDS?malaria, TB, HIV/AIDS?