Center on Early Life Origins

of Disease

Xiaobin Wang, MD, MPH, ScD

Zanvyl Krieger Professor

Director

Center on the Early Life Origins of Disease

Johns Hopkins University

Department of Population, Family, and

Reproductive Health

Center on Early Life Origins of Disease

Mission

Research natural history, etiology, and early life

precursors of common and important health

problems in across the life span

Translate scientific discoveries in clinical and

public health settings: early prediction and

prevention, and personalized medicine

Educate and Train a new generation of child

health interdisciplinary and transdisciplinary

researchers and future leaders

Major Emphasis of the Center

• Diseases of major clinical and public health significance

• A life course approach and longitudinal cohorts

• Integration of multi-level-dimension-factors

• Bridge social behavioral science with biomedicine

• Collaboration within and cross departments and schools

• Ultimate Goal: to translation our research findings to

• clinical and public health practice in order to meet the

needs of 21st century medicine and public health

4

Prospective Study Cohorts

Boston Birth

Cohort

Chinese Twin

Cohort

Chicago Family

Cohort

8,000 mother-infant

pairs

(~2,500 preterm)

2,000 twin pairs

MZ: DZ ratio 1:1

6 years and older

Over 1,000 families

Biological parents and

children 0-21 yr

Enrolled at Birth

F/U at pediatric

primary care visits

Baseline

6 yr follow-up

Baseline study

completed

Inner city, minority

(65% blacks)

in Boston

Homogeneous

Rural Chinese

White, suburb

In Chicago

Research Focus Ongoing:

• Prematurity: 12.5% of babies

• Obesity: 20 to 40% of children & adults

• Asthma: 10 to 20% of children & adults

• Food allergy: 5 to 10% of children

• Early life Origins of adult diseases:

Cardiovascular diseases; Prediabetes,

Diabetes; Metabolic syndrome;

Osteoporosis

Future growth areas:

• Neuro-developmental outcomes

• Behavioral outcomes

Emerging Science: Early Life Origins

of Health and Disease Great challenge and

opportunity for all of us:

Coronary heart disease, type 2

diabetes, breast cancer and

many other chronic diseases

are unnecessary. Their

occurrence is not mandated by

genes passed down to us

through thousands of years of

evolution. Chronic diseases

are not the inevitable lot of

humankind. They are the result

of the changing pattern of

human development. We could

readily prevent them, had we

the will to do so.

Barker DJP, 2011

Previous Research Focused on Adults

Campion J et al. obesity review 2009, 10:383

ALMOST

ALL

RESEARCH

The New Science Emphasizes the First 1000 days

Campion J et al. obesity review 2009, 10:383

VERY

IMPORTANT

UNDER

RESEARCHED

Replicated and widely accepted association with small birth size Hypertension Elevated clotting factors

Non-insulin dependent diabetes Coronary artery disease

Dislipidaemia Stroke

Impaired neurodevelopment

Described but less well replicated and accepted association with

small birth size

Chronic lung disease Schizophrenia

Depression

Behavioral problems Fingerprint patterns

Left handedness Reduced uterine and ovarian size

Precocious pubarche

Described and replicated association with large birth size

Polycystic ovary disease Testicular cancer

Breast cancer Prostate cancer

Testicular cancer

Childhood leukaemia

Diseases linked with Birth Weight

De Boo HA and Harding JE, Australian and New Zealand Journal of Obstetrics and Gynaecology ,2006, 4-14

Landmark Longitudinal Cohort Study

The Framingham Heart Study

• Objective: led by NIH/NHLBI, to identify the

common factors or characteristics that

contribute to CVD

• Longitudinal Cohort Design: by following

CVD development in a large group of adults

(3 generations) over the past 60 years

• Age Groups: 30 to 62 years at enrollment

• Accomplishments: cited by the American

Heart Association among the top 10

cardiovascular research achievements of

2009.

What Framingham Study

Can’t Accomplish?

What are the root causes of chronic diseases

How to prevent chronic diseases and stop the

current epidemics at early critical time windows (preconception, prenatal, early childhood, adolescence)

(Obesity, Diabetes, Hypertension, Dyslipidimia, Heart Disease)

Mechanisms of

Early Life Origins of Disease

Individual

Genetics

Pre- and Post-

Natal

Environmental

Exposures

Epigenetics

(gene expession)

DISEASE OUTCOMES

Environmental and Early Life

Experience

• Nutrition

• Overnutrition (too many prenatal calories)

• Undernutrition (too few prenatal calories)

• Malnutrition (insufficient vitamins or other essential nutrients)

• Environmental Toxicants

• .Chemicals originating outside the body, such as pesticides and

heavy metals

• .Chemicals originating inside the body, such as hormones and

oxygen radicals

• Psychosocial Stress and Behaviors

• Maternal use of substances, medicines, stress

• Pregnancy Complications and Birth Outcomes: preeclampsia

GDM, intrauterine growth restriction, preterm birth

Cystic fibrosis Adult onset diabetes AIDS

Epigenome and Health Outcomes

http://nihroadmap.nih.gov/epigenomics/pdf/epigeneticmechanisms.pdf

How to Advance the Field?

• Life Course Approach: Longitudinal

cohort studies

• Leverage Cutting-edge Science and

Technology: Integration of multi-level-

dimensional data; Biomarkers

• Inter-disciplinary Collaboration: to

bridge age groups and disciplines in

order to improve health for all ages and

transform clinical and public health

practice and policy

Life Course and Gene to Society Framework

AUG - B1…Bn - STOP

SPLICING

TRANSLATION

3’

pre-mRNA

Mature mRNA

Protein Sequence protein 3D structure

Exon 1 Exon 2 Exon 3 Exon 4

Intron 1 Intron 2 Intron 3

DNA

TRANSCRIPTION

5’

cSNP ssSNP iSNP rSNP

Phenotype

ORF

AAAAAAAA

Leverage Cutting-edge Science & Technology Genomics, Epigenomics, Proteomics, Metabolomics

Multidisciplinary Collaboration

Transdisciplinary Research

Patient

Care Epidemiology

Bench

Research Biotechnology

Clinical

Medicine

Behavioral

Neuro-developmental

Env Health

Epidemiology

Biostatistics

Nutrition

Biochemistry MB

International

Collaboration

Early Life Origins

of Health &

Diseases

SOM SPH

SON JHH

Source: Zerhouni, EA. Annual Meeting of NIH Roadmap Multidisciplinary Clinical

Research Career Development Program, 2007

Thank you!