The document discusses the vicious cycle of diarrhea and malnutrition. It summarizes that underweight, stunting and wasting in children are risk factors for diarrhea mortality. Deficiencies in vitamin A and zinc increase the risk of diarrhea mortality, and zinc deficiency increases the risk of diarrhea incidence. Trials show that vitamin A and zinc supplementation can significantly reduce diarrhea mortality and incidence in children, demonstrating the substantial disease burden attributable to these nutritional risk factors.

1. The Vicious Cycle of Diarrhea and
Malnutrition: Nutritional Risk Factors
Robert E. Black, MD, MPH
Edgar Berman Professor and Chair
Department of International Health

2. Potential Conflicts of Interest
• Robert Black has documented that he has
no financial relationships to disclose or
Conflicts of Interest to resolve.
• He has documented that his presentation
will not involve discussion of unapproved,
off-label, experimental or investigational
drugs.

3. Outline of Presentation
• Vicious Cycle of Diarrhea and Malnutrition
• Underweight, stunting and wasting
• Vitamin A deficiency
• Zinc deficiency

4. Undernutrition and Infection Vicious Cycle

5. Nutritional Status by
Anthropometric Measures
and Childhood Mortality Risk

6. 178 Million Children Under 5 Suffer from Stunting
Prevalence of
Stunting
No Data
<20%
20-29.9%
30-39.9%
≥40%

7. Datasets Included in the Analyses of
Anthropometric Measures and Child Mortality
Bangladesh, Ghana, Guinea
Bissau, India, Indonesia,
Nepal, Peru, Philippines,
Senegal, Sudan

8. Increased Risk of Child Mortality with Mild Stunting (-2 to < -1z)
Versus Adequate Height-For-Age (WHO 2006)

9. Increased Risk of Child Mortality with Moderate Stunting
(-3 to < -2z) Versus Adequate Height-For-Age (WHO 2006)

10. Increased Risk of Child Mortality with Severe Stunting (< -3z)
Versus Adequate Height-For-Age (WHO 2006)

11. Risk of Child Mortality by Anthropometric
Measures Using the WHO Standard
< -3z -3 to < -2z -2 to < -1z
(95% CI) (95% CI) (95% CI)
Weight-for-age 10.8 (6.7-17.4) 3.0 (2.1-4.3) 1.7 (1.2-2.4)
Height-for-age 5.7 (4.0-8.1) 2.4 (1.7-3.4) 1.5 (1.1-2.1)
Weight-for-height 13.4 (7.8-19.8) 3.4 (2.4-4.9) 1.7 (1.2-2.3)

12. Risk of Child Diarrhea Mortality by Anthropometric
Measures Using the WHO Standard
< -3z -3 to < -2z -2 to < -1z
(95% CI) (95% CI) (95% CI)
Weight-for-age 11.6 (8.6-15.5) 2.9 (2.0-4.0) 1.7 (1.2-2.4)
Height-for-age 6.3 (4.6-8.7) 2.4 (1.7-3.3) 1.7 (1.2-2.3)
Weight-for-height 12.3 (9.2-16.6) 3.4 (2.5-4.6) 1.6 (1.2-2.1)

13. Vitamin A
Intervention Effects
as Estimate of Risk

14. Distribution of Global Vitamin A Deficiency
Vitamin A deficient

15. Vitamin A Supplementation Trials:
~165,000 Children;
~23% Reduction in Preschool Child Mortality
Black bars: p<0.05
White bars: NS
Beaton et al. 1992

16. Effect of Vitamin A Supplementation
on Child Diarrhea Deaths
Imdad et al. BMC Public Health 2011

17. Relative Risk of Diarrhea Mortality
Due to Vitamin A Deficiency
• Inverse of risk reduction in trials
- RR: 1.4 (95% CI 1.2-1.7)
• Applied to populations at risk of vitamin A
deficiency such as those where trials were
done

18. Zinc Intervention Effects
as Estimate of Risk

19. National Risk of Zinc Deficiency Based on
Prevalence of Stunting Among Children Under 5
and Absorbable Zinc Content of the Food
Supply
Category of Zinc deficiency % at Risk of inadequate zinc intake Stunting
High  25  20%
Intermediate >15 <25 >10 <20%
Low 15 10%
International Zinc Nutrition Consultative Group, Food Nutr Bull, 2004

20. Trial of Zinc Supplementation in India:
Effects on Diarrhea Incidence
• Age group: 6-35 months
• Dose of zinc: 10 mg/d
• In children 6-11 months old, no effect on
diarrhea
• In children 12-35 months old, diarrhea
incidence reduced by 35% in boys and 19%
in girls
Sazawal, Black, Bhan et al. AJCN 1997

21. Trials Evaluating the Preventive Effects of Zinc
Supplementation on Diarrhea
• Countries: Bangladesh (4), Burkina Faso, Chile (2),
China (2), Ecuador (3), Ethiopia (2), the Gambia,
Guatemala, India (6), Jamaica, Mexico (4), Peru (3),
S Africa, USA, Vietnam
• Age groups: 1-60 mo
• Dose of zinc: ≈10mg/d (range 3.5-20 mg/d) or 20-70
mg once per week
• Zinc vs. placebo or some trials gave selected
vitamins and/or minerals to both groups
• 33 comparisons involving 16,665 children
Brown et al. Food Nutr Bull 2009

22. Effect of Preventive Zinc Supplementation
on Incidence of Diarrhea
Meta-analysis of 33 comparisons*
Overall Incidence Log RR = 0.80 (0.71 – 0.90)
Mean Initial Age
highly associated with magnitude of the
effect of Zn supplementation (p<.0001)
Analysis by sub-population
> 12 mo Incidence Log RR = 0.73 (0.61- 0.87)
* There was significant heterogeneity among studies (p<.0001)
Brown et al. Food Nutr Bull 2009

23. Preventive Effect of Zinc
Supplementation on Child Mortality
Tielsch et al., Lancet 2007

24. Preventive Effect of Zinc Supplementation on
Mortality in Children 12-47 Months of Age
Tielsch et al., Lancet 2007

25. Relative Risk of Diarrhea Morbidity and Mortality
Due to Zinc Deficiency in Children < 5 y Old
• Inverse of risk reduction in trials
- RR for diarrhea incidence: 1.3 (95% CI 1.2-1.6)
- RR for diarrhea mortality: 1.2 (95% CI 0.95-1.6)
• Applied to populations at risk of zinc
deficiency such as those where trials were
done

26. Conclusions
• Underweight, stunting and wasting are risk
factors for diarrhea mortality
• Deficiencies of vitamin A and zinc are risk
factors for diarrhea mortality and zinc for
diarrhea incidence
• A substantial disease burden in children can
be attributed to these risk factors