Hidden hunger: micronutrient deficiencies in resource-poor populations

Lora Iannotti, PhD Translating Global Health; Lucille P. Markey Special Emphasis

Pathway in Human Pathobiology September 16, 2014

Pathways to Global Public Health and Wash U

• Degrees of freedom – political science & French, foreign affairs

• 1990 – First trip to Haiti

• Professional experiences beyond academia

– US Congressional Select Committee on Hunger – NGOs, UN/FAO, World Bank, IDB

• Nonparametric paths back to Haiti – Haiti, Ghana, Benin, Haiti, Kenya, Tanzania, Zambia, Zimbabwe,

Sudan, Egypt, Kenya, Tanzania, Haiti, Peru, Haiti

• PhD International Nutrition

– Bloomberg/JHSPH, infectious disease, epi, and public health

Why undernutrition?

45% child deaths due to undernutrition

• Undernutrition (IUGR, sub-optimal BF, stunting, wasting, vit A and zinc deficiencies) cause 3.1 million or 45% of all childhood deaths (Black et al. Lancet 2013)

• More than 10% of total global burden of disease is attributable to maternal and child undernutrition (Black et al. Lancet 2008)

• OR 3.0 (1.0-8.9) dying from malaria if a child is wasted (WHZ<-2) (Black et al. 2008)

WHO 2011

Essential Nutrients • Constituents in the diet required for growth,

health, and survival - not endogenously produced in sufficient levels

– Macronutrients – protein/amino acids, carbohydrates,

lipids/fatty acids, fiber

– Micronutrients • Vitamins (organic) – A (β-carotene, retinol), B (thiamin), riboflavin, niacin,

pyridoxine, cobalamin, pantothenic acid, folate), C (ascorbic acid), D (calciferol), E (α-tocopherol), K, choline

• Minerals/elements/trace minerals (inorganic) – calcium, iron, zinc, iodine,

selenium, copper, fluoride, phosphorus, magnesium, manganese

– Water & electrolytes – sodium, chloride, potassium, inorganic sulfate

It’s all in the packaging

Deconstruct & reconstruct

http://www.countingblocks.com/building-blocks/

Vitamin A

• Physiology – Vision: retinal opsin → rhodopsin – Immunity: epithelial tissue, adaptive immunity – Gene expression: reproductive health, cellular

differentiation, embryogenesis, etc.

• Deficiency – Leading cause of preventable blindness globally – 250 million preschool age children have VAD

• Dietary sources – Preformed retinol – liver, meats, fish, eggs, and milk – Proformed retinoids - dark green, yellow, and orange

fruits and vegetables – 1 RE = 1μg retinol = 12 μg β-carotene =24 μg carotenoid

Vitamin B12 (cobalamin)

• Physiology – Synthesized by anaerobic bacteria in ileal, after deuodenum – Cobalamin needed to synthesize succinyl CoA and methionine

• Deficiency – megalobastic anemia – neurological disease (demyelination and peripheral

neuropathy); impaired brain development

• Dietary sources – No plants except algae – Meat, poultry, fish, eggs, milk, and fortified foods

Choline

• Physiology – Cell membrane structure and signaling – Source of methyl groups – Neurotransmission, precursor for acetylcholine

• Deficiency – De novo synthesis, but dietary intakes required (1998)

– Brain development (cognition & memory), fetal development, fatty liver, and hepatocarcinomas

• Dietary sources – Eggs, human and animal milk, wheat germ (betaine),

beef liver, spinach (betaine)

– Most abundant in animal source foods

Iron

• Physiology – Oxidation-reduction reactions – Oxygen transport, enzyme activity in cellular respiration, division, neurotransmission, immunity, and growth

• Deficiency

– 115,000 maternal deaths; 18% of children < 5 yrs – 3.4 million DALYs attributable to IDA

• Dietary sources – Heme iron (20-50% absorbed): meat, poultry; Non-heme

(0.1-35% absorbed): fruits, vegetables, grain – Enhancers: meat, vitamin C; Inhibitors: phytates and

polyphenols

Zinc

• Physiology – Zn > 300 enzymes structural & regulatory roles

– Protein and nucleic acid synthesis

– Growth & immune functioning

• Deficiency – 30% of children < 5yrs stunted

– 17.3% of world’s population inadequate zinc intake

• Dietary sources – Fish, shellfish meats, whole grains, nuts, and legumes

– Enhancers: protein-rich foods/meat; Inhibitors: phytates in maize, legumes, oxylates

Key concepts: Brown School MPH Program

• CELLS TO SOCIETY

• TRANSDISCIPLINARITY

Agriculture and Food Systems

• Food production and processing

•Availability of micronutrient-rich foods

• Food safety and quality

Inadequate practices • Infrequent feeding • Inadequate feeding

during and after illness • Thin food consistency • Non-responsive feeding

Health and Healthcare • Access to healthcare • Qualified healthcare

providers • Availability of supplies

•Infrastructure •Health care systems and

policies

Education • Access to quality

education • Qualified teachers

• Qualified health educators • Infrastructure (schools and

training institutions)

Food and water safety • Contaminated food

and water • Poor hygiene

practices • Unsafe storage and preparation of foods

Concurrent problems & short-term consequences Long-term consequences

Poor quality foods • Poor micronutrient

quality • Low dietary diversity and intake of animal-

source foods • Anti-nutrient content • Low energy content of

complementary foods

Water, Sanitation and Environment

• Water and sanitation infrastructure and

services • Population density •Climate change •Urbanization

Political economy • Food prices and trade

policy •Poverty, income and wealth

• Financial services

• Employment and livelihoods

Community and societal factors

Inadequate Complementary Feeding

Stunted Growth and Development

Health ↑Mortality

↑Morbidities

Developmental ↓Cognitive, motor,

and language development

Economic ↑Health

expenditures ↑Opportunity costs for care of sick child

Economic ↓ Work capacity

↓ Work productivity

Developmental ↓School

performance ↓ Learning capacity

Unachieved potential

Health ↓Adult stature ↑Obesity and associated co-

morbidities ↓ Reproductive

health

Infection

Clinical and subclinical infection

Enteric infection: Diarrheal disease,

environmental enteropathy, helminths • Respiratory infections

• Malaria • Reduced appetite due

to infection • Inflammation

Household and family factors

Maternal factors • Poor nutrition during

pre-conception, pregnancy and lactation • Short maternal stature

• Infection • Adolescent pregnancy

• Mental health •IUGR and preterm birth • Short birth spacing • Hypertension

Inadequate practices • Delayed initiation • Non-exclusive breastfeeding

• Early cessation of breastfeeding

Context

Causes

Consequences

Society and Culture • Beliefs and norms

• Social support networks • Child caregivers (parental

and non-parental) • Women’s status

Home environment • Inadequate child

stimulation and activity • Poor care practices •Inadequate sanitation

and water supply • Food insecurity

• Inappropriate intra-household food

allocation • Low caregiver education

Breastfeeding

Application:

HAITI, KENYA,

ECUADOR

Rotovirus,

ETEC,

campylobacter,

v. cholera

WASH

Nutributter

Mamba

Eggs

Urban poverty

livelihoods

Research focus

• What are the most effective interventions to promote healthy growth and development among young children living in resource-poor countries?

– Address micronutrient deficiencies related to poverty and infectious diseases in vitamins A, B12, choline, iron, & zinc

Global public health research Brown School

(St. Louis) *PI *Office of Research, Business, IT, Service, Communications, etc. *RAs

Nutributter RCT (Cap Haitien)

* Study Coordinator * 3 enumerators * 2 data managers * Wash U students

Eggs for young child nutrition (Ecuador)

* 2 Study Coordinators *5 enumerators *Wash U student

Mamba School Study (Cap Haitien)

* Study Coordinators * 6 enumerators * 2 data managers * Wash U students

Partners: MSPP, PNCS/MENFP, Meds & Food for Kids, Konbit Sante, NSRL, Edesia

Funders: World Bank, USDA, Alive & Thrive, Inter-American Development Bank, World Food Program

Partners: University of San Francisco in Quito, PAHO, UC-Davis Funders: Mathile Institute

• Infrastructure & logistics: research site, banking, vehicles, accommodations

• Human resources: university partnerships, training, communication

• IRB: 2 committees, 3 languages, culture • Environment: drought, political volatility

RESTORING THE PEARL OF THE CARIBBEAN

Haiti

Haiti: context • History

– Occupation, dependencies→ weakened

healthcare system

– Major earthquake Jan 2010

– Cholera & widespread diarrhea

• Rapid urbanization and poverty

– >50% population live urban areas; 3.9 % per year

– 80% in poverty (less than $2); 54% in abject poverty (<$1)

• Nutrition (DHS/EMMUS 2012)

– 20.9% stunted, 11.4% underweight, 5.1% wasted

– Hidden hunger: 65% of infants 6-59 mo were anemic; and 16.9% of children 6-59 mo live in HH with iodized salt

Study Site – Cap Haitien Cap Haitien

Partners & Funders

Funders:

Bill & Melinda Gates Foundation to FHI 360, through the Alive & Thrive Small Grants Program managed

by UC Davis; World Bank; World Food Program; Inter-American Development Bank

Objectives

To test the efficacy of a small-quantity lipid-based supplement (LNS), Nutributter® (NB), delivered within an integrated package of services (IP) on promoting linear growth, over time

• improve complementary feeding practices in poor urban context

• examine effects of NB on infant and young child feeding (IYCF) practices

Fortified peanut butter paste

• Prevention, not treatment! – Intervene early to prevent stunting

– Micronutrient nutrition in school age children

• Poverty intervention – high quality food + education

– Local peanut farmers &

economic development

A. Boshara photo 2012

MFK 2013

Intervention: Nutributter ®

Ingredients: peanut

paste, sugar, vegetable

fat, dry skimmed milk

powder, maltodextrines,

whey, vitamin and

mineral pre-mix,

emulsifier

Interventions MOH Integrated Package

• Integrated Management of Childhood Illness (IMCI) – Health education: community

health agents provide information at clinic & rally posts

– Vaccinations

– Vitamin A supplementation

– Growth monitoring & promotion

– Reproductive health

Study Design – mixed methods • RCT & impact evaluation

• Control, 3-mo NB, 6-mo NB

• Followed monthly for anthropometry, morbidity, and development outcomes

• Sustained growth effect→ 6 mo post-intervention

• Qualitative research & process evaluation

– In-depth interviews, matrix scoring, focus groups, observations, etc.

• Geospatial analyses

– Handheld Global Positioning System (GPS) units to map (n=150) of households, water sources, sanitation, markets, health service providers, churches

Trial profile

Group 1

Control

group

(n=191)

Group 2

Nutributter

3 mo

(n=196)

Group 3

Nutributter

6 mo

(n=202)

Monthly follow-up visits: → 6 months

GIS analyses

RCT

*Recruited and screened (n=709)

* Enrolled and randomized (n=589)

Qualitative

research &

process

evaluation

POST-

Intervention (6 mo)

Intervention Period

(6 mo)

Control (n=144)

NB 3 mo (n=126)

NB 6 mo

(n=150)

48 losses to

follow-up

70 losses to

follow-up

52 losses to

follow-up

Nadege: qualitative research

Growth effects – longitudinal regression

3-mo NB

vs. control

6-mo NB

vs. control

Unadj β

(SE) P

Adj β

(SE)2 P

Unadj β

(SE) P

Adj β

(SE)2 P

At 6 mo

LAZ -0.10

(0.05) 0.06

-0.12

(0.05) 0.03 0.08 (0.05) 0.16

0.13

(0.05) 0.02

WAZ 0.02

(0.05) 0.65

0.01

(0.05) 0.86 0.08 (0.05) 0.09

0.12

(0.05) 0.02

At 12 mo

LAZ -0.09

(0.05) 0.06

-0.11

(0.05) 0.03 0.06 (0.05) 0.20

0.10

(0.05) 0.04

WAZ 0.03

(0.05) 0.54

0.02

(0.05) 0.73 0.08 (0.04) 0.09

0.11

(0.04) 0.02

Iannotti et al AJCN 2014

Public health: entire distribution shifted

0

.02

.04

.06

.08

.1

Den

sity

65 70 75 80 85 90 95 100child height (cm)

Group 1: Control

Group 2: NB for 3 mo

Group 3: NB for 6 mo

kernel = epanechnikov, bandwidth = 1.4094

Kernel density estimate

Do no harm: looking for unintended consequences

• Increased dietary diversity 0.23 ±0.07 SE (P<0.001)

• ↓ BF frequency 1.17 ±0.25 SE (P<0.001)

• ↑ water (84%) & sugar drinks (51%)

• Vitamin A supplementation – VAS in last 6 mo (99.3%)

– 3-4 doses

– 80% in NB groups >upper level

Upper level VA

Mamba School Feeding Project

• McGovern-Dole International Food for Education and Child Nutrition – Micronutrient-fortified food aid products pilot

• Partners: Meds & Food for Kids (MFK), Washington University, Edesia, National Soybean Research Laboratory, Ministry of Education/Haiti

• Why does it matter? – School age children in Haiti – BIA, anemia, & anthropometry – First time RUSF tested in this age group – Global, bilateral, and national policies and food aid program

Design & Methods

• Cluster-randomized controlled trial (quasi-experimental design)

– Formative research/school profiles used to collect SES and nutrition to help match schools

• Sample & comparison groups (6 schools):

– 1,200 school aged children 3-13 years

– 1) control; 2) Tablet Sereyal (unfortified biscuit); 3) Mamba Lespri

• Impact & Process Evaluation

– Impact outcomes – anemia, BIA, anthropometry, school attendance

– Process outcomes – food acceptability, functionality, feasibility

Egg nutrition – Pastocalle, Ecuador

Egg study – Pastocalle, Ecuador

• RCT to test effects of daily egg consumption among children 6-12 mo (n=180)

• Eggs purchased from local producers

• Outcomes: anthropometry, biomarkers of choline, vitamin B12, lipids and amino acids

To conclude • Travel abroad & across campus

– Learn language, build relationships, make a commitment

– Understand larger context and population

– Attend public health and global health speaker series

• Think and work holistically – Integrated systems of actors

– Multitude of health determinants, and apply transdisciplinary approaches

Thank you!