Docstoc

Update on Preventing Micronutrient Deficiencies

Document Sample
Update on Preventing Micronutrient Deficiencies Powered By Docstoc
					Micronutrient Deficiencies: A Concern throughout Life
Keith West JHU: kwest@jhsph.edu Child and Maternal Health Problems Nutritional Deficiencies •PEM •Micronutrient Deficiencies/Interax: Vitamin A, zinc, iron, iodine, folate, others •Behavioral Causes: Related to poor breast feeding, complementary feeding, HH diet, low SES, poor educatoin

•Infant or Child •Infection (diarrhea, ARI) •Poor growth •Impaired mental, motor and behavioral development •Death •Mother •Obstetric morbidity •Infection/sepsis •Anemia •Death

•Emerging/re-emerging Diseases •HIV/AIDS, Malaria, TB

Photo: K West

Photo: K West, Jr.

Micronutrient Deficiencies: Major Public Health Concern in Low Income Populations
Deficiency Vitamin A Zinc Prev ~25% ~60% Consequences Blindness, mortality, morbidity Infection, mortality

Iron
Iodine Folate

~50%
~50% “high”

Anemia, impaired cognition, obstetric hemorrhage Stunted development, impaired cognition, mortality Neural tube defects (NTDs), anemia, infant mortality

Modern Micronutrient Interventions “Pillars in Public Health”
• Iodizing salt to prevent goiter, cretinism and mental retardation • Vitamin A supplementation to reduce mortality and blindness • Folic acid (periconceptionally) to reduce neural tube defects • Zinc to treat diarrhea (with ORS) • Iron (& folic acid) to control iron-deficiency anemia during pregnancy • Fluoride in water to reduce dental carries • Historically others: Vitamin C (scurvy), Niacin (pellagra), Thiamin (beriberi)

Micronutrient Deficiencies: Important and Preventable

Cause-Specific Deaths (000) and DALYs Lost (000) Due to MN Deficiencies
Children <5 yrs Deaths
Vitamin A * Zinc** Iron***

Pregnant/Lactating Women DALYs DALYs Deaths

647 789 591

22,560 137 28,034 -19,736 240

3,106 -15,321

* Measles, diarrhea, malaria, other infectious causes **Diarrhea, pneumonia, malaria ***Perinatal deaths only; iron deficiency anemia included in maternal figures
Comparative Quantification of Health Risks, Vol 1, WHO: Geneva, 2004

First Innocenti Conference on Micronutrients and Health Florence, Italy April 17-20th, 2005 Emerging Issues in Research on Micronutrient Supplementation (and Reaffirmation of Pillars)
Supported by USAID/W/HIDN Bill & Melinda Gates Foundation

Innocenti Micronutrient Research Conferees
• • • • • • • • • • • • • • • • • Lindsay Allen Zulfiqar A. Bhutta Robert E. Black Erick Boy Parul Christian Anna Coutsoudis Nita Dalmiya Ian Darnton-Hill Frances Davidson Bruno de Benoist Caroline Fall Suzanne Harris Jean Humphrey Betty Kirkwood Katherine Kreis Chewe Luo Sean Lynch • • • • • • • • • • • • • • • • • Barbara MacDonald Samuel Newton Stephen Oppenheimer David Parker Rudiger Pittrof Usha Ramakrishnan Amy L. Rice Nigel Rollins David A. Ross Richard D. Semba Roger Shrimpton Alfred Sommer Sally Stansfield James M. Tielsch Andrew Tomkins Veronica Triana Keith P. West, Jr.

Rapidly Changing World of Micronutrient Deficiency Control
• Micronutrient deficiencies: widespread & affect health and survival • Research is expanding to assess & prevent an increasing number of deficiencies • For a wider range of health outcomes • With progress, existing “Pillars” on which public health programs stand need reaffirmation • Complex findings require careful interpretation & guidance about further research relevant to policy

Innocenti Process
• • • • • • Hot topics pre-selected Experts provided context Conferees read key papers on each topic Speakers presented major findings Commentaries added insight Lively debates to
– – – – Raise questions Rank strength of evidence (for/against benefit, safety) Identify gaps Recommend research

Evidence was evaluated on a three-point scale A: Definitive for an effect, or lack of
effect, for outcomes urgent to policy

B: Strongly suggestive, critical for
health policy formulation

C: Interesting but tentative, or not of
immediate policy relevance

Vitamin A Deficiency Disorders Gradient of Health Consequences
Corneal Blindness Xerophthalmia
Systemic Effects Metaplasia, Impaired immunity, Morbidity, Anemia, Poor growth Preschool children Xerophthalmia: 4.4 m VA deficient: 127 m Pregnant women Night blind: 6 m VA deficient: 7 m Low VA status: 19 m
West KP, J Nutr 2002

Tissue and plasma depletion

Chronic dietary deficit

Vitamin A in Preschool Years
Level A for Benefit (reaffirmed)
% reductions in mortality

Effective in reducing risk of preschool child mortality based on 8 previous RCTs
Sommer A, West KP Jr 1996

Avg: ~30%

May reduce mortality among preschool HIVpositive children in Africa
Fawzi et al Ped Inf Dis J 1999

National Vitamin A Supplementation Programs
• > 400 million high potency VA supplements (200,000 IU) distributed each yr by UNICEF • Usually 2x/yr; 6-72 mo of age • Campaigns are way to go! – National Child Health Days/Weeks • Aim for > 80% coverage • Reduces blindness • Reduces child mortality

National VA campaign in Bangladesh

Vitamin A Given from ~2 Wks to 4 Mo of Age

Level A for No Benefit
1.000

Nepal: 50,000 (<1 mo) or 100,000 IU (1-5 mo) of vitamin A given < 6 mo of age failed to reduce mortality (NNIPS-1)
Based on K West et al AJCN 1995;62:143

Placebo Vitamin A 0.995

0.990

0.985

Probability of Survival

0.980 0 10 20 30 40 50 60 70 80 90 100 110 120

Days

Ghana, Peru and India: Vitamin A (25,000) given at each EPI visit at 6, 10 & 14 weeks of age had no effect
WHO/CHD Lancet 1998;352:1257

Vitamin A at Birth?
Level A-B for Benefit
In W Java, Indonesia: Vitamin A (50,000 IU) at birth reduced mortality 64% Humphrey et al J Pediatr 1996;128:489
Relative Risk = 0.36 (95% CI: 0.16 to 0.87)

Kaplan-Meier Survival Curves for all Children given at least one dose
1.00

Prob of Survival

South India: VA (~50,000 IU) at birth reduced infant mortality by 23% Rahmathullah, Tielsch, Katz et al BMJ 2003

0.99

0.98

Vitamin A

0.97
Placebo

0.96

Relative Hazard = 0.77 (0.62, 0.96)
0.95 0 30 60 90 Days since Birth 120 150

p = 0.02
180

Zimbabwe (Zvitambo Project): 2x2 factorial trial of newborn getting and/or mother getting VA in population with high prevalence and incidence of HIV. Humphrey et al, in press
Probability of death

0.00

0.10

0.20

0.30

Mortality Rates for all babies

0

42

90

180

270

360 450 analysis time

540

630

720

Time (Days)

Vitamin A deficiency in mothers?

Rataundi (Nepal) Ratkana (Bangla) Buta Ayam (Indo) Matang Manok (Phil)

Twilight Blindness Twilight Blindness Chicken Eyes Chicken Eyes

Maternal night blindness: 10-20% of poor rural women in many countries Photo: P Christian

Mortality of Women by Night Blindness Status during Pregnancy, Sarlahi, Nepal
Maternal Period
900 800 700 600 500 400 300 200 100 0 Pregnant 0-6 wk Postpartum
Night blindness disappears shortly after birth

Late Pregnancy-related Period
Night blind Not night blind

Post-Late Pregnancy

Mortality rate per 100,000

7-12 wk 13-24 wk 25-36 wk 37-52 wk >52 wk
Extended risk of infection/death

Christian et al, Am J Epidemiol 2000;152:542-7

Weekly Maternal Vitamin A Supplementation @ RDA: In undernourished Nepalese population showed a ~40% reduction in maternal mortality with either vitamin A or beta-carotene Level B for Benefit
Deaths per 100,000 pregnancies
1000 800 600 400 200 0 Pregnancy To 6 Wk To 12 Wk

PL VA BC

West et al BMJ 1999

ObaapaVitA trial, Ghana
Navrongo Health Research Centre

• Started with Ghana VAST trial vitamin A and child health and mortality trials, Navrongo 1988-93 • Kintampo Health Research Centre (KHRC) established 1994 • Currently 120,000 pregnancy vitamin A trial underway to examine effects on maternal and infant mortality

Kintampo Health Research Centre

JiVitA Bangladesh
(Supported by USAID, Gates and GOB)

JiVitA-1: Maternal VA or beta-carotene supplementation trial JiVitA-2: Newborn vitamin A supplementation trial

Zinc Deficiency
• Vast problem! • Results from low meat (low zinc), high grain (high phytate) diets • Lowers immune competence • Increases risk of Diarrhea Respiratory infection

Zinc for Treating Diarrhea
Level A for Benefit (Reaffirmed)
• Zinc reduces both incidence & severity of diarrhea
Incidence Prevalence

~25%
Reduction

Protective Not Protective Odds Ratio and 95% CI
Zinc Investigators’ Collaborative Group J Pediatrics 1999;135:689

10 mg oral zinc daily for 10-14 days

Additional Effects of Zinc
• Pneumonia: 5 RCTs, ~35% reduction to date in incidence • Malaria: 2 RCTs, ~36% reduction in incidence of febrile, clinic-based illness • Growth: improved linear & ponderal gains
Walker CF & Black RD Ann Rev Nutr 2004;24:255-75

Iodine is required for normal thyroid function. Iodine deficiency has far-reaching effects on human development, all of which are preventable through policy and action.
Photo: Goiter, John Dunn Photo: Cretin, John Stanbury

Iodine Deficiency Disorders

1.6 B at risk
Intellectual impairment

Iodine Iron

Vitamin A
Iodize salt to achieve intake of ~150 ug/day of iodine

M Zimmermann et al (2000 onward)

Iron Deficiency/Anemia: A Major Global Problem
• Upto 2 billion anemic based on low Hb • Severe anemia  high mortality, obstetric hemorrhage • Mild to moderate anemia Impairs child development Decreases work capacity

Prevalence (%) of Anemia among Pregnant Women (Illustrative): ~30-60%
80 70 60 50 40 30 20 10 0

Mason J et al, The Micronutrient Report, 2001

Alg eri B'd a es Br h az i Ch l ile Cu ba Eg Eth ypt iop Ga ia My mbia an ma Nig r Pa eria Ph kist ilip an pin es PN G

Iron deficiency vs. anemia

Iron deficiency

Anemia

IDA

Anemia as a Public Health Problem
Many Causes
• Iron deficiency • Other nutritional deficiencies • Hookworm • Malaria • Chronic infection (HIV)

Many Solutions
• Iron (+folate) • Supplement with other nutrients • Deworm/hygiene • Malaria prophylaxis • Treat/ Prevent chronic infections

Research Issue: Iron for Preschool Aged Children
• Potential public health benefits:
– Prevent anemia – Stimulate neurobehavioral development – Improve growth

• Potential concerns:
– May increase risk of infection

• Two trials: Nepal (NNIPS-4), Zanzibar
• Reviewed by S Lynch and S Oppenheimer at Innocenti. • Oppenheimer S. J Nutr 2001;131:616S-635S

Iron Supplementation to Preschool Children in Nepal
• 2x2 factorial daily zinc or/and iron+folate trial in 136 mo old children. • Iron = 12.5 mg/d • Iron arm stopped due to no effect on mortality or morbidity
Tielsch J, Khatry S, Stoltzfus R, Katz J Le Clerq S, Adhikari R,Mullany LC, Shrestha SR, Black RE Lancet 2005 (in press)

Zanzibar: Effects of Daily Iron+Folate in Children
• • 42,000 preschool aged children 2x2 factorial RCT
– Zinc, Iron+folate, Zinc plus iron+folate, Placebo

•

Outcomes – Mortality
– Morbidity, including hospitalizations

Sazawal S, Black RE et al, submitted

Zanzibar: Increased Risk of Adverse Events*

Children

Compared to non-receipt of iron+folate: • 12% higher adverse event rate • 15% trend for higher mortality rate • Mostly seen >12 mo of age • Higher morbidity and mortality from malaria-related causes, and other infections • Implication: More work needed to establish cognition benefits of iron; need to control malaria 1st, where it exists
* Adverse Event = death or hospitalization

Level A-B for Harm

Maternal Micronutrient Deficiencies
• Common with plausible benefits of maternal supplements with respect to
– Newborn status (LBW, IUGR, PTB) – Fetal/infant morbidity and mortality – Growth and development – Maternal morbidity and mortality

Christian P; Innocenti Presentation April 2005

Micronutrient deficiencies during 3rd trimester in Haryana, India
80 70 60 50 43.6 26.3 73.5 73.4

%

40 30 20 10 0
Zinc Copper Magnesium Iron Folic acid Iodine

2.7

6.4

Pathak et al; Indian J Pediatr 2004

Prevalence of low serum concentrations of micronutrients among women in the first trimester in rural Nepal
100 80
61

60

%

46.3

40
20.6

Vitam

27.7

31.8

32.8

20
0.7

11.6

13.9

0
.6 <8 um /L ol on <8 5 .9 ol m u /L 8 1. 1 r< um /L ol te <6 .8 nm /L ol 4 <1 7 7. /L ol pm B6 0 <2 Ri ol m n /L 1 <1 .3 ol m n /L E 0 <1 um /L ol tD 5 <2 nm /L ol

Z

c in

Ir

Co

e pp

F

a ol

B

12

in av fl bo

t Vi

Vi

Jiang et al, J Nutr 2005

Tian et al, J Nutr 2005

Nepal Maternal Micronutrient Trial (NNIPS-3) Key Findings (vs Control)
Treatment BW Diff (g) LBW 3-mo Mortality

Folate
Folate+Fe

-20
+37

0%
16%↓

22%↓*
21%↓*

Folate+Fe +Zn Multiple MNs

-11
+64

4%↓
14%↓

13%↓
7% ↑

* 50-60% reduction in preterm born infant mortality Christian et al, BMJ 2003; Christian et al, AJCN 2003

Survival of infants through the first year of life
Christian et al, AJCN 2003;78:1194-1202
1.00 0.99 0.98
Survival probability

0.97 0.96
FAFe

0.95
FAFeZn

FA

0.94 0.93 0.92

C MN

0.00 0 30 60 90 120 150 180 210 240 270 300 330 360

Days following birth

Pooled Mortality Effects from Two RCTs in Nepal
(Christian et al 2003; Osrin et al Lancet 2005;365:955-62 Neonatal Mortality Iron+Folate N Rate N 919 36.2 47 571 MM Rate 53.9 1.49 (0.94, 2.35) 1.53 (0.72, 3.23) 1.52 (1.03, 2.25) RR (95% CI)

Sarlahi (NNIPS) 802 28 Janakpur 568 Combined

11 20.0 17 30.6 1370 1490 39 29.5 64 44.8

Christian et al Lancet 2005;366:711

Tanzania: Effects of Multiple Vitamins or Vitamin A on Maternal and Infant Outcomes in HIV+ Women
• 2x2 supplementation trial
– HIV pregnant women given Vitamin A, Multivitamins, Both or Neither
• VA = 5000 IU + 30 mg beta-carotene • MVs = 8 vitamins, ranging from 2 to 23 x RDA • All women received Fe (120 mg) and folic acid (5 mg)

• N=1085 pregnant women, 12-27 wks GA • Supplemented through 2 years post partum

Tanzania: Multivitamin & Vitamin A Trial in HIV+ Women (Fawzi W and colleagues, 1998-2005)
Outcome Multivitamins vs No Multivitamins VA/BC vs Not

LBW (RR)
Preterm Birth (<34 wks) (RR) SGA (RR) 2-yr wt gain (g)

0.56
0.61 0.57 459

0.89
1.09 0.83 9

2-yr IMR (RR)
HIV MTCT (RR)

0.91
1.04

1.08
1.38

Maternal Micronutrient Supplementation
• Level B for reducing LBW with iron+folate • Level B for adverse outcomes when taking multiple micronutrient supplements • Urgent Research:
– Large-scale multiple micronutrient trials to establish benefits and safety with respect to perinatal and infant outcomes in HIV- and HIV+ populations

Fortification

Diet Supplements Deficient Population

2-Dimensional Differential In-Gel Electrophoresis Gel (2-D DIGE) Map pI 3 CyDye 2 = Yellow (Internal Std/ both TMs) CyDye 3= Green (1st TM only) pI 10 CyDye 5 = Red (3rd TM only)

MW

Plasma Proteomics
Nepalese Pregnant Woman, “Subject #1”, NNIPS-3 1st and 3rd TM sera processed with dyes, mixed, run out on gels

ceruloplasmin

a-2-macroglobulin

hemopexin

vitamin D-binding protein

pregnancy-zone protein

pro-apolipoprotein

transthyretin

One Subject, Mid-pH Range Spots Identified

THANK YOU

Multiple Micronutrient Supplements for Infants
• • • • IRIS: International Research on Infant Supplementation RCTs in 4 countries: South Africa, Peru, Viet Nam and Indonesia Infants 6-11 mo of age enrolled Given micronutrient fortified “foodlets” (dissolvable tablets) With vitamins A, D, E, K, C, B1, B2, B6 and B12, niacin, folate, iron, zinc, copper, and iodine
IRIS Study Group J Nutr 2005;135:631S-638S

IRIS Trials: Multiple Micronutrients for Infants
• Four treatment groups for 6 mo duration:
– Daily multiple micronutrients – Weekly multiple micronutrients (2-day’s intake) – Daily iron (10 mg elemental Fe) – Placebo - no micronutrients daily

• Multiple outcomes: Differences in growth, micronutrient status and other outcomes

IRIS Study Group J Nutr 2005;135:631S-638S

IRIS Outcomes: Effects of MNs in Infants

Level B-C for Benefit
• Weight gain (kg/mo)
– Daily micronutrients: 0.21 – Weekly micronutrients: 0.19 – Daily iron: 0.19 – Placebo: 0.19

• Micronutrient concentrations vs placebo:
– Hb: all higher – Plasma ferritin: all higher – Daily MM higher for plasma zinc, tocopherol
IRIS Study Group J Nutr 2005;135:631S-638S


				
DOCUMENT INFO
Shared By:
Categories:
Stats:
views:212
posted:4/26/2008
language:English
pages:51