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					Role of Zinc and Vitamin A in Child Health




                         Emorn Wasantwisut
                         Institute of Nutrition
                         Mahidol University
    Millennium Development Goals

    Eradicate extreme poverty         Improve maternal health
1   and hunger                    5
                                      (75% of MMR by 2015)

    Achieve universal primary         Combat HIV/AIDS, malaria,
2   education                     6   and other diseases

    Promote gender equality and       Ensure environmental
3   empower women
                                  7   sustainability

4   Reduce child mortality
                                  8
                                      Develop a global partnership
                                      for development


                                      Millennium Summit, Sep.2000
 Selected major risks to health : Childhood and maternal undernutrition


Risk factor               Measured adverse outcomes (of exposure)


Underweight               Mortality and acute morbidity from infectious
                          diarrhoea, malaria, measles, pneumonia and
                          other infectious diseases.
                          Perinatal conditions from maternal underweight
Iron deficiency           Anaemia, maternal and perinatal causes of death
Vitamin A deficiency      Diarrhoea, malaria, maternal mortality,
                          vitamin A deficiency disease
Zinc deficiency           Diarrhoea, pneumonia, malaria


Source : World Health Report 2002
Summary of selected risk factors

Risk Factor               South - East Asia     West-Pacific

Child/Adult Mortality      Low    High        Very Low Low

• Under weight             26      46           4       16
  (%< 2 SD W/A)
• Iron def                 11.0    10.4       12.5      11.0
  (Mean Hb in g/dl)
• Vitamin A def.           28      18           0        9
  (% VAD+NB)
• Zinc def.                34      73           4        9
  (% inadequate intake)


 World Health Rep:2002
 Leading 10 selected risk factors as percentage causes
        of disease burden measured in DALYs

Developing countries
High mortality countries
       Under weight                           14.9%
       Unsafe sex                             10.2%
       Unsafe water, sanitation and hygiene    5.5%
       Indoor smoke from solid fuels           3.7%
       Zinc deficiency                         3.2%
       Iron deficiency                         3.1%
       Vitamin A deficiency                    3.0%
       Blood pressure                          2.5%
       Tobacco                                 2.0%
       Cholesterol                             1.9%


World Health Rep:2002
    Burden of Disease - Loss of
        healthy life years
                       DALYS (million)
Underweight                 138
Iodine Deficiency           2.5
Iron Deficiency             35
Vitamin A Deficiency        22.5
Zinc Deficiency             28
               Vitamin A Deficiency


                    • Xerophthalmia        blindness
   Childhood
                    • limit growth
                    • Weaken host defenses
                    •     infection &   risk of death
   Women of         •     morbidity & mortality
Reproductive age        during pregnancy and early
                        post partum
                    • disadvantaged newborn
    Vitamin A Supplementation

                                             Prevention
               Treatment
   Age
               at Diagnosis           Dosage         Frequency



< 6 mo                50,000 IU                     6, 10,14 wks with
                                                    DPT/Polio
< 6-11                100,000 IU                    Every 4-6 mo

> 1 yr                200,000 IU                    Every 4-6 mo

Women          200,000 IU                    < 8 wks after
               (? 400,000 IU)                delivery

  Refs : WHO/UNICEF/IVACG 1997, IVACG 2000
  Impact of Vitamin A on child Mortality

                                % Reduction
   Indonesia
     • Aceh                         34
     • Bogor                        45
   Nepal
     • Sarlahi                      30
     • Jumla                        29
   India
     • Tamil Nadu (wkly dose)       54
     • Hyderabad                     6
   Sudan                            +6
   Ghana                            19

Source : Sommer & West 1996
Global Prevalence - Maternal VAD
                                             (In millions)
                                Serum VA       BM-VA        Night-
                              <0.70 umol/L <1.05 umol/L Blindness

Africa                              2.4          5.4            1.1
E. Mediterranean                    1.8          3.8            0.5
S/SE Asia                           2.2          8.8            3.9
W.Pacific                           1.2          2.7            0.5
Americas                            0.4          0.8            0.4


 Ref: K. West, J Nutr 2002; 132: 2857S-2866S
VA and mortality related to pregnancy            12 wks Post partum


                    Placebo      VA          b -carotene   VA or b- C


# Pregnancies        7,241      7,747         7,201         14,948

# Deaths                 51       33             26             59

Mortality           704         426            361             395
(per 100,000 pregnancies)

RR                       1.0     0.60          0.51             0.56
(95%CI)                        (0.37-0.97)   (0.30-0.86)    (0.37-0.84)


Refs : West et al 1999
Clinical signs of severe zinc deficiency

 • Reduced appetite, taste acuity
 • Reduced growth velocity
 • Skin lesions
 •  Diarrhea, other infections
 • Delayed sexual maturation, reduced fertility
  Mean (± SD) daily per capita absorbable zinc as
  percent of requirement, and estimated percent
   of population at risk of low intake, by region
      A bsorbable z inc as % of EA R             % of population at risk of low intake
175                                              50
150
                                                 40
125
100                                              30
75
                                                 20
50
25                                               10

 0       r m     r d  a   c r ia ia fr      ld    0
       Eu A Eu Me hin Pa Ca As As S A     or             r m    r d  a   c r ia ia fr      ld
      W N E r/E     C W & S E S          W             Eu A Eu Me hin Pa Ca As As S A    or
                              S                       W N E r/E    C W & S E S          W
             A f        Am                                                   S
           N          L.                                     Af        Am
                                                           N         L.
 Prevalence of growth stunting
• Percentage of pre-school children with
  height-for-age < -2 SD with respect to
  international reference data (data already
  available for most countries)

• Based on prior observations that stunted
  (but not non-stunted) children respond to
  zinc supplementation with increased
  linear growth
2002
                                                                   Effect size - height




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                                                                                                                change in height, by mean initial
                                                                                                                Mean + 95% C.I. for effect size of
 Risk of zinc deficiency, based on
absorbable zinc in food supply and
  prevalence of growth-stunting


                                Low


                                Inter-
                                mediate


                                High
Preventive Effect of Zinc Supplementation
 on Diarrheal Prevalence in Continuous
         Supplementation Trials
  B.Faso
    India
  Mexico
     PNG
    Peru
 Vietnam
 Ethiopia
Guatemala
 Jamaica

  Pooled
           0   0.25 0.5 0.75 1 1.25 1.5 1.75   2
                     Odds Ratio and 95% CI
        Effect of Zinc Supplementation on Duration
           of Acute Diarrhoea/Time to Recovery
       *India, 1988
*Bangladesh, 1999
       *India, 2000
      *Brazil, 2000
       *India, 2001
   Indonesia, 1998
        India, 1995
 Bangladesh, 1997
        India, 2001
        India, 2001
       Nepal, 2001
 Bangladesh, 2001

          Pooled

                                     1
                      *Difference in mean and 95% CI
                       Relative Hazards and 95% CI
     Efficacy of Zinc in Therapy
       of Severe Pneumonia*
• Bangladeshi children <2y old with severe
  pneumonia
• 270 randomized to 20mg zinc/d or placebo
  along with standard antibiotics
  (amp./gent.)
• Zinc group had shorter duration of severe
  pneumonia (RH 0.81; 0.67, 0.99) and of
  chest indrawing, elevated RR and hypoxia

   * Brooks et al, submitted
Effect of Zinc Supplementation on
        Malaria in Children

               Reduction in Clinic
   Location    Visits for Malaria
The Gambia       32% (p=0.09)
Papua New        38% (p<0.05)
Guinea
Combined        36% (CI 9-55%,
                   p<0.05)
    Trial of Zinc or Vitamin/Iron
  Supplementation in SGA Infants
             on Mortality
Group       Children Deaths Mortality
                            Hazards
Zinc          581       5    0.32 (0.12,
                                0.89)
No Zinc       573      15     p = 0.028
Vit./Iron     570       9     0.83 (0.34,
                                  2.0)
No.
              584      11      p = 0.677
Vit./Iron
    Effective Child Survival Interventions
                                        Cause of Under 5 death

                       Diarrhea       Pneumonia   Measles   Malaria..
Prevention

• Exc.BF 6 mo
  & Cont.BF 6-11 mo
• Comp. feeding
 ………
• Zinc
                                                                ?
• Vitamin A                                         ?           ?

  Source : Jones et al. Lancet 2003
    Effective Child Survival Interventions
                                        Cause of Under 5 death

                       Diarrhea       Pneumonia   Measles   Malaria..
Treatment

• Oral Dehydration

• Antibiotic-Pneumonia
• Antimalarials
 ………
• Zinc
• Vitamin A
  Source : Jones et al. Lancet 2003
Maternal IDD
  • stillbirth
  • mild to severe brain damage
  • fetal damage: subcretins,
    neurological cretinism

Childhood and adult hypothyroidism
 • Neonatal Hypothyroidism:
    • high TSH in neonates
  • Cerebral hypothyroidism
  • Mental torpor and apathy
                            Iron and its effects

             Infants      Cognition, growth&
                             development

           Children       Cognition/physical

newborns
           Adolescent     Cognition/Fe store/
                             physical

           Non-pregnant   Productivity
                          Iron store

            Pregnant      Pregnancy outcome

             Lactate      Lactation
SUPPLEMENTATION                 WHEN ?
1. Treat Severe or Clinical Deficiencies
2. Prevention in
  • endemic areas
  • high risk groups
3. NOT possible to meet requirements
   from diet, e.g., pregnancy, lactation
          KEY TO CHANGES
                     Form, Dose, Safety
SUPPLEMENTATION      Bioavailability, Interaction,
                     Delivering System &
                          Compliance
                       Impact on Status
                  Choice of food vehicles &
FORTIFICATION     fortification
                  Processing, sensory, shelf-life
                  QA system
    UPSCALE       Bioavailability
 INTERVENTION
                  Impact on Status
Baby - LBW/Undernutrition


                      Child growth failure


   Early pregnancy
                          Low Wt & Ht
                          teenagers


            Small adult
            women             Small adult
                              men
              Urine I
               TSH                      Urine I
              Hb/Hct
                                       BLOOD         Hct               Monitoring &
               TfR
             Bmilk-VA                   SPOT                           surveillance:
                                                     TGR                 groups &
            Dark Adapt.                (Hb/Hct                           indicators
              Retinol                    TfR,       Urine I
                                       Retinol)


Repro-    Mothers         Neonate      Pre-       School      Adults
ductive    (P+L)              &       school       age
age women     &            infants      age
            fetus         (0-2 yr.)


                          “Iodized salt”                               Quality
                                                                       of I- salt

                                                                       Preventive
  weekly      daily        weekly          weekly                      supplem.
                                                                       & Fd based

                                          Fortified food                  Food
    Periodic vitamin A capsule
                                         Indigenous foods                 based

				
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