Preventing Maternal Micronutrient Deficiency

(including Vitamin A Deficiency Prevention in Indonesia)

Keith P. West, Jr., DrPH, MPH, RD

George G. Graham Professor of Infant and Child Nutrition
Department of International Health
Johns Hopkins Bloomberg School of Public Health
Baltimore, Maryland, USA
kwest1@jhu.edu
 An undernourished population may
suffer from several micronutrient
deficiencies, not just one.

Preventing only clinical deficiency does not

insure good nutrition, as a subclinically
deficient mother and infant may still suffer
poor health, and be at risk of high mortality.

Marginal, subclinical deficiency, resulting

from a poor diet, may be of far greater
public health importance than (more rare)
1918 clinical disease.
 Malnutrition and Disease throughout Life
Nutritional Exposures Coexist
• Protein-energy deficits
• Energy Excess
• Micronutrient deficiencies
Vitamins A, E, D,
B-complex, folate,
zinc, iron, iodine, others
• Behavioral Causes
Breast /complementary feeding
SES, hygiene, education, etc
• Food Systems Causes
Agricultural/animal husbandry,
seasonality, infrastructure,
Markets
•Societal and Political Causes
Child and Maternal
Health Problems
• Infant or Child
• Infection
•Inflammation
• Poor growth
• Impaired cognition,
motor development
• Mortality
•Adolescent or Maternal
•Short stature
•Thinness…. overweight
•Infection/sepsis
•Obstetric problems
Chronic disease, disabilty, mortality •Anemia
•Mortality
Photos: Paul Joseph Brown
Micronutrients are Essential Throughout Pregnancy & Gestation
Based on reviews of in vitro studies,
animal experiments, observational
studies, and intervention trials that
have explored mechanisms
Adverse Health Consequences of
Gestational Micronutrient Deficiency

Gernand A et al Nature Rev Epidemiol 2016

Dr. Lucy Widasari, 2018
Micronutrient Deficiencies among Women of
Reproductive Age – A Global View

Bourassa M et al Ann NY Acad Sci 2019;1444(1):6-21

UNICEF/WHO Multiple
Micronutrient Supplement:

Recommended for use under

emergency conditions…
but used everywhere
 Established 2000
18 Unions
4 x area of Wash DC
Population: 600,000
Density: 1130 /km2
RANGPUR 60 Field Offices
750 Project Staff

GAIBANDHA
(Field Station)

The 450 km2 JiVitA Project Area Labrique AB et al

BMC Trials 2011
 • RDA amounts of vit A, D, E, B1, B2, B3,
B6, folic acid, B12, C, Fe, Zn, Cu, Se, I vs
Fe and folic acid alone (MM vs IFA)
• 44,567 pregnancies; 28,516 live births
• Increased GA by 0.3 weeks and thus:
birth weight by 54 g, therefore -
• Reduced preterm by 15%
• Reduced LBW by 12%
JAMA 2014;312(24):2649-2658.
• Reduced still birth by 11%
• Reduced infant mortality –
Funded by the Bill and Melinda Gates Foundation
in girls but not boys
Beximco & DSM through Sight & Life produced
16 m supplements & provided technical assistance • Led to a healthier pregnancy &
infant
• May not have resolved most
MNDs
 Effects of MMS vs IFA: Birth and Infant Outcomes
Outcomes Cochrane Review (15 RCTs) IPD Meta-Analysis (17 RCTs)
Relative Risks (RR (95% CI)) Relative Risks (RR (95% CI))

Small for Gestational Age 0.92 (0.88-0.97)a 0.97 (0.96-0.99)b

(<10th percentile)

Low Birth Weight (<2500g) 0.88 (0.85-0.91) 0.88 (0.85-0.90)

Very Low Birth Weight (<2000g) Not Reported 0.78 (0.72-0.85)
Preterm Birth (<37 weeks) 0.95 (0.90-1.01) 0.92 (0.88-0.95)
Very Preterm Birth (<34 weeks) Not Tested 0.87 (0.79-0.95)
Large for Gestational Age Not Tested 1.05 (0.95-1.15)
(>90th percentile Oken)

Large for Gestational Age (>90th Not Tested 1.11 (1.04-1.19)

percentile INTERGROWTH)

Stillbirth 0.95 (0.86-1.04) 0.92 (0.86-0.99)

Neonatal Mortality (<28 days) 1.00 (0.89-1.12) 0.98 (0.90-1.05)
Infant Mortality Not Reported 0.97 (0.88-1.06)
aSGA defined by authors of trials; bSGA defined by the INTERGROWTH-21 standard
MMS, multiple micronutrient supplementation; IFA iron with or without folic acid;
Source: Keats EC, et al. Cochrane Rev 2019
IPD, individual participant data; RCTs, randomized controlled trials. Smith ER, et al Lancet Global Health 2017
RR in green show a significant decrease in RR.
Power for Mothers: Bringing a Solution for Better
Nutrition to All
 In JiVitA-3: MMS vs IFA Reduced Micronutrient Deficiencies in 3rd TM …
But Did Not Eliminate Them
IFA
MM

No or little effect on
iron or folate deficiencies

Schulze K et al J Nutr 2019 Prevalence (%)

J Nutr 2019

J Nutr 2019 MMS may improve health of

materno-placental mitochondria
and, thus, bioenergetics of
pregnancy
Universe or Population At-Risk
“Representative” Sample

Once randomized,
R always randomized

Control Intervention
Plausible
Biology
Short Term Health Outcomes

----------Time----------
High
Later Life Outcomes Compliance/
Effects of Time Effects of Time Follow-up
plus Intervention

Causal Inference w/ith respect to differences

 Handgrip strength Portable spirometry
Blood drawing for measuring
to assess lung function
Plasma lipids, insulin, glucose,
Hb1Ac, micronutrients, etc

Anthropometry
SES, dietary and Cognition testing
morbidity interviews

Audiometry,
NNIPS Follow-up Studies typmanometry,
ear health
Sarlahi District, Nepal
AGRICULTURE TO NUTRITION PATHWAYS
Crops, Gardens and Markets lead to

...Inform Policies and Programs …Household Food Security & Wealth

... Dietary Intake, Quality of Life & Services

… Nutritional Status of Women & Children

Potential Nutritional Prophylaxis/Treatment Options
for COVID-19?

Zjhang and Liu. Medical Virology 4 Feb 2020;

Secretary of State
Henry Kissenger
at the World
Food Conference
November, 1974
Within a decade… No child will go to bed hungry
No human being’s future and capacity will be stunted by malnutrition

The United States calls for an immediate campaign against two of the most
prevalent and blighting forms of malnutrition:
vitamin A blindness responsible for more than a half million cases of blindness
24
and iron deficiency anemia, responsible for low productivity in the world
 Mild Xerophthalmia & Mortality
N = ~4000 Indonesian Preschoolers Followed Quarterly
Nml = Normal eyes
XN = Night blindness
X1B = Bitot’s spots

XN+X1B

Sommer A et al Lancet 1983

The “Aceh Study”: 1982-84
• 450 N Sumatran villages
randomized to semi-
annual, 200,000 IU
vitamin A, or not.
• ~26,000 preschool
children enrolled, dosed,
followed
• Vitamin A reduced
1-6 yr mortality by 34%
 World Development Report 1993
Cost-Effectiveness of Health Interventions

Breast feeding
 Prevention

Public Health
Concern

Biology – Nutriture - Disease

Thank You
Acknowledgements
US Agency for Internatinoal Development
Bill and Melinda Gates Foundation
Sight and Life Foundation/DSM

Photo: Paul Joseph Brown

Hypothetical Micronutrient Status Distribution
and Health/Function

Target Range for Women

Supplemented with 1 RDA
by a Multiple Micronutrient
Supplement

Bailey R, West KP Jr, Black RE Ann Rev Metab

31 2015
Strategies for Preventing Micronutrient Deficiencies

Diet
Deficient Population

Fortification Supplements

Biofortification