Role of Zinc and Vitamin A in Child

Role of Zinc and Vitamin A in Child Health Emorn Wasantwisut Institute of Nutrition Mahidol University

Millennium Development Goals 1 Eradicate extreme poverty and hunger 2 Achieve universal primary education 3 Promote gender equality and empower women 4 Reduce child mortality 5 Improve maternal health (75% of MMR by 2015) 6 Combat HIV/AIDS, malaria, and other diseases 7 Ensure environmental sustainability 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 • Under weight (%< 2 SD W/A) • Iron def (Mean Hb in g/dl) • Vitamin A def. (% VAD+NB) • Zinc def. (% inadequate intake) 26 46 11. 0 10. 4 28 18 0 9 34 73 4 9 World Health Rep: 2002 Very Low 4 12. 5 16 11. 0

Leading 10 selected risk factors as percentage causes of disease burden measured in DALYs Developing countries High mortality countries Under weight Unsafe sex Unsafe water, sanitation and hygiene Indoor smoke from solid fuels Zinc deficiency Iron deficiency Vitamin A deficiency Blood pressure Tobacco Cholesterol World Health Rep: 2002 14. 9% 10. 2% 5. 5% 3. 7% 3. 2% 3. 1% 3. 0% 2. 5% 2. 0% 1. 9%

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

Vitamin A Supplementation Age Treatment at Diagnosis Prevention 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 (? 400, 000 IU) < 8 wks after delivery Refs : WHO/UNICEF/IVACG 1997, IVACG 2000

Impact of Vitamin A on child Mortality % Reduction Indonesia • Aceh • Bogor Nepal • Sarlahi • Jumla India • Tamil Nadu (wkly dose) • Hyderabad Sudan Ghana Source : Sommer & West 1996 34 45 30 29 54 6 +6 19

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: 2857 S-2866 S

VA and mortality related to pregnancy Placebo # Pregnancies VA 7, 241 7, 747 # Deaths 51 Mortality 704 (per 100, 000 pregnancies) RR (95%CI) Refs : West et al 1999 1. 0 12 wks Post partum b -carotene VA or b - C 7, 201 14, 948 33 26 59 426 361 395 0. 60 (0. 37 -0. 97) 0. 51 (0. 30 -0. 86) 0. 56 (0. 37 -0. 84)

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

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 non-stunted) children respond to zinc supplementation with increased linear growth

Mean + 95% C. I. for effect size of change in height, by mean initial height-for-age z-score Data from Brown KH et al, AJCN, 2002

Risk of zinc deficiency, based on absorbable zinc in food supply and prevalence of growth-stunting Low Intermediate 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. 75 1 1. 25 1. 75 Odds Ratio and 95% CI 2

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 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 <2 y old with severe pneumonia • 270 randomized to 20 mg 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 Location The Gambia Papua New Guinea Combined Reduction in Clinic Visits for Malaria 32% (p=0. 09) 38% (p<0. 05) 36% (CI 9 -55%, p<0. 05)

Trial of Zinc or Vitamin/Iron Supplementation in SGA Infants on Mortality Group Zinc No Zinc Children Deaths Mortality Hazards 0. 32 (0. 12, 581 5 0. 89) 573 15 p = 0. 028 Vit. /Iron 570 9 No. Vit. /Iron 584 11 0. 83 (0. 34, 2. 0) p = 0. 677

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 Treatment • Oral Dehydration • Antibiotic-Pneumonia • Antimalarials ……… • Zinc • Vitamin A Source : Jones et al. Lancet 2003 Pneumonia Measles Malaria. .

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 newborns Cognition/physical Adolescent Cognition/Fe store/ physical Non-pregnant Productivity Iron store Pregnant Lactate Pregnancy outcome Lactation Immunity Children

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 SUPPLEMENTATION Form, Dose, Safety Bioavailability, Interaction, Delivering System & Compliance Impact on Status FORTIFICATION UPSCALE INTERVENTION Choice of food vehicles & fortification Processing, sensory, shelf-life QA system Bioavailability Impact on Status

Baby - LBW/Undernutrition Child growth failure Early pregnancy Small adult women Low Wt & Ht teenagers Small adult men

Urine I TSH Hb/Hct Tf. R Bmilk-VA Dark Adapt. Retinol Iron Vit A BLOOD SPOT (Hb/Hct Tf. R, Retinol) Neonate & infants (0 -2 yr. ) Preschool age TGR Urine I School age daily weekly Periodic vitamin A capsule Adults Quality of I- salt “ Iodized salt” weekly Monitoring & surveillance: groups & indicators Hct weekly Fortified food Indigenous foods Preventive supplem. & Fd based Food Industry Iodine Repro. Mothers (P+L) ductive & age women fetus Urine I