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From Santos et al, J Nutr 2001 (Brazil), others unpublished)From Santos et al, J Nutr 2001 (Brazil), others unpublished)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?