Nutrition and the Lifelong Continuum

Nutrition and the Lifelong Continuum

Michael C. Lu, MD, MPHAssociate Professor

Department of Obstetrics & GynecologyDavid Geffen School of Medicine at UCLA

Department of Community Health SciencesUCLA School of Public Health

ASTPHND 2010 Annual MeetingBaltimore, MD

June 14, 2010

“If you want 1 year of prosperity, grow grain. If you want 10 years of prosperity, grow trees. If you want 100 years of prosperity, grow people.”

Chinese Proverb

Life-Course Perspective

A way of looking at life not as disconnected stages, but as an integrated continuum

Life Course Perspective

Lu MC, Halfon N. Racial and ethnic disparities in birth outcomes: a life-course perspective.Matern Child Health J. 2003;7:13-30.

Life Course Perspective

Early programming Cumulative pathways Prevention of childhood obesity

Early Programming

Barker HypothesisBirth Weight and Coronary Heart Disease

0

0.25

0.5

0.75

1

1.25

1.5

<5.0 5.0-5.5 5.6-7.0 7.1-8.5 8.6-10.0 >10.0

Birthweight (lbs)

Age Adjusted Relative Risk

Rich-Edwards JW, Stampfer MJ, Manson JE, Rosner B, Hankinson SE, Colditz GA et al. Birth weight and risk of cardiovascular disease in a cohort of women followed up since 1976. Br Med Jr 1997;315:396-400.

Barker HypothesisBirth Weight and Hypertension

155

160

165

170

Syst

olic

Pre

ssur

e (m

mH

g)

<=5.5 5.6-6.5 6.6-7.5 7.6-8.5 >8.5

Birthweight (lbs)

Law CM, de Swiet M, Osmond C, Fayers PM, Barker DJP, Cruddas AM, et al. Initiation of hypertension in utero and its amplification throughout life. Br Med J 1993;306:24-27.

Barker HypothesisBirth Weight and Insulin Resistance Syndrome

0

2

4

6

8

10

12

14

16

18

<5.5 5.6-6.5 6.6-7.5 7.6-8.5 8.6-9.5 >9.5

Birthweight (lbs)

Odds ratio adjusted for BMI

Barker DJP, Hales CN, Fall CHD, Osmond C, Phipps K, Clark PMS. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (Syndrome X): Relation to reduced fetal growth. Diabetologia 1993;36:62-67.

Maternal Stress & Fetal Programming

Prenatal Stress & Programming of the Brain

Prenatal stress (animal model) Hippocampus

Site of learning & memory formation Stress down-regulates glucocorticoid receptors Loss of negative feedback; overactive HPA axis

Amygdala

Site of anxiety and fear Stress up-regulates glucocorticoid receptors Accentuated positive feedback; overactive HPA

axis

Welberg LAM, Seckl JR. Prenatal stress, glucocorticoids and the programming of the brain.J Neuroendocrinol 2001;13:113-28.

Prenatal Programming of the Hypothalamic-Pituitary-Adrenal Axis

Welberg LAM, Seckl JR. Prenatal stress, glucocorticoids and the programming of the brain.J Neuroendocrinol 2001;13:113-28.

Epigenetics

Gibbs WW. The Unseen Genome: Beyond DNA. Scientific American 2003

EpigeneticsSame Genome, Different Epigenome

R.A. Waterland, R.A. Jirtle, "Transposable elements: targets for early nutritional effects on epigenetic gene regulation," Mol Cell Biol, 23:5293-300, 2003. Reprinted in the New Scientist 2004

Prenatal Programming of Childhood Obesity

Epidemic of Childhood Overweight & Obesity

0

5

10

15

20

25

1976-1980 1988-1994 1999-2002

Perc

en

t

Black Hispanic White

Source: National Center for Health Statistics, National Health and Nutrition Examination Survey

Note: Estimate not available for 1976-1980 for Hispanic; overweight defined as BMI at or above the 95th percentile ofr the CDC BMI-for-age growth charts

Children 6-18 Overweight

Prenatal Programming ofChildhood Overweight & Obesity

Maternal Diabetes & Intrauterine Hyperglycemia

Intrauterine Hyperinsulinemia (Fetal Pancreatic β Cells)

Prenatal& PostnatalHyperleptinemia

Preadipocyte Differentiation

Adipocyte Hyperplasia

HypothalamicLeptin Resistance

Pancreatic β- Cell Leptin Resistance

HyperphagiaHyperinsulinism

Programmed Insulin

Resistance

Postnatal Hyperinsulinemia

Adipogenesis

Prenatal Programming of Childhood Obesity

Cumulative Pathways

Photo: http://www.lam.mus.ca.us/cats/encyclo/smilodon/

Allostasis: Maintain Stability through Change

McEwen BS. Protective and damaging effects of stress mediators. N Eng J Med. 1998;338:171-9.

Allostastic Load:Wear and Tear from Chronic Stress

McEwen BS. Protective and damaging effects of stress mediators. N Eng J Med. 1998;338:171-9.

HPA Axis & Immune SystemChikanza 2000

Stressed vs. Stressed Out Stressed

Increased cardiac output

Increased available glucose

Enhanced immune functions

Growth of neurons in hippocampus & prefrontal cortex

Stressed Out

Hypertension & cardiovascular diseases

Glucose intolerance & insulin resistance

Infection & inflammation

Atrophy & death of neurons in hippocampus & prefrontal cortex

Allostasis & Allostatic Load

McEwen BS, Lasley EN. The end of stress: As we know it. Washington DC: John Henry Press. 2002

Rethinking Preterm Birth

Sequelae of Preterm BirthSequelae of Preterm Birth

Term Births

Preterm Birth

75%Perinatal Perinatal MortalityMortality

NeurologicNeurologicDisabilitiesDisabilities

50%

12.3%

Racial & Ethnic DisparitiesPreterm Births

18.4

11.7

0

2

4

6

8

10

12

14

16

18

20

African American White

Percent of Live Births

NCHS 2009

Year 2010 Goal

Racial & Ethnic DisparitiesVery Preterm Births

4.17

1.64

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

African American White

Percent of Live Singleton Births

Year 2010 Goal

NCHS 2009

Racial & Ethnic DisparitiesInfant Mortality

13.7

5.7

0

2

4

6

8

10

12

14

African American White

Deaths Per 1,000 Live Births

NCHS 2009

Year 2010 Goal

Rethinking Preterm Birth

Vulnerability to preterm delivery may be traced to not only exposure to stress & infection during pregnancy, but host response to stress & infection (e.g. stress reactivity & inflammatory dysregulation) patterned over the life course (early programming & cumulative allostatic load)

Preterm Birth &Maternal Ischemic Heart Disease

Kaplan-Meier plots of cumulative probability of survival without admission or death from ischemic heart disease after first pregnancy in relation to preterm birth

Smith et al Lancet 2001;357:2002-06

Prevention of Childhood Obesity

Preventing Childhood Obesity

1. Prevention has to begin before birth

White House Task Force on Childhood Obesity

Recommendation 1.1: Pregnant women and women planning a pregnancy should be informed of the importance of conceiving at a healthy weight and having a healthy weight gain during pregnancy, based on the relevant recommendations of the Institute of Medicine

Prenatal Care 1.0

ReceptionistMedical

Assistant

UltrasoundTechNurse Manager

Prenatal Care 2.0

Oral Health

TeratogenInformationServices

Primary &Specialty Care

SocialServices

Mental Health

NutritionalCounseling

ReceptionistMedical

Assistant

Ultrasound TechNurse Manager

High RiskOB

Family Support

Prenatal Care 3.0

Oral Health

TeratogenInformationServices

WIC

Prenatal care

Preconception & interconceptionCare

FamilyPlanning

Primary & Preventive

Services

NutritionCounseling

Health EducationFamily Support

High RiskOB

Mental Health

0 10 20 30 40 Years

Prenatal Care 3.0

NHVFRCPED

Rep

rodu

ctiv

e P

oten

tial

Optimal Health Development

Lower Health Development

Trajectory

Medical Home for Women’s Health

Medical Home for Adolescent Health

Pediatric Medical Home

White House Task Force on Childhood Obesity

Recommendation 1.3: Hospitals and health care providers should use maternity care practices that empower new mothers to breastfeed, such as the Baby-Friendly hospital standards

White House Task Force on Childhood Obesity

Recommendation 1.4: Health care providers and insurance companies should provide information to pregnant women and new mothers on breastfeeding, including the availability of educational classes, and connect pregnant women and new mothers to breastfeeding support programs to help them make an informed infant feeding decision

White House Task Force on Childhood Obesity

Recommendation 1.5: Local health departments and communitybased organizations, working with health care providers, insurance companies, and others should develop peer support programs that empower pregnant women and mothers to get the help and support they need from other mothers who have breastfed

Preventing Childhood Obesity

2. Prevention has to begin before conception

Early Prenatal Care Is Too LateTo Prevent Some Birth Defects

The heart begins to beat at 22 days after conception The neural tube closes by 28 days after conception The palate fuses at 56 days after conception

Early Prenatal Care Is Too LateTo Prevent Implantation Errors

Norwitz ER, Schust DJ, Fisher SJ. Implantation and the survival of early pregnancy. N Engl J Med. 2001 Nov 8;345(19):1400-8.

Early Prenatal Care Is Too LateTo Prevent Obesogenic Chemical Exposures

Dioxins Endocrine disruptors

Disrupt neruodevelopment Disrupt immune development May promote development of childhood obesity and diabetes

Lipophilic Half life of up to 7 years Crosses the placenta easily

White House Task Force on Childhood Obesity

Recommendation 1.7: Federal and State agencies conducting health research should prioritize research into the e!ects of possibly obesogenic chemicals.

Early Prenatal Care Is Too LateTo Restore Allostasis &

Optimize Fetal Programming

McEwen BS, Lasley EN. The end of stress: As we know it. Washington DC: John Henry Press. 2002

Interconception Care

Preventing Childhood Obesity

3. Prevention has to change not only individual behaviors, but also

physical & social environments

White House Task Force on Childhood Obesity

Access to healthy, affordable food Convenient physical access to grocery stores

and other retailers that sell a variety of healthy foods;

Prices that make healthy choices affordable and attractive;

A range of healthy products available in the market place

Adequate resources for consumers to make healthful choices, including access to nutrition assistance programs to meet the special needs of low-income Americans

Food Desert in Urban America

Food Desert in Rural America

White House Task Force on Childhood Obesity

Recommendation 4.1: Launch a multi-year, multi-agency Healthy Food Financing Initiative to leverage private funds to increase the availability of a!ordable, healthy foods in underserved urban and rural communities across the country.

White House Task Force on Childhood Obesity

Recommendation 4.2: Local governments should be encouraged to create incentives to attract supermarkets and grocery stores to underserved neighborhoods and improve transportation routes to healthy food retailers.

White House Task Force on Childhood Obesity

Recommendation 4.5: Encourage the establishment of regional, city, or county food policy councils to enhance comprehensive food system policy that improve health

White House Task Force on Childhood Obesity

Recommendation 4.7: Provide economic incentives to increase production of healthy foods such as fruits, vegetables, and whole grains, as well as create greater access to local and healthy food for consumers.

White House Task Force on Childhood Obesity

Increasing physical activity in schools and in activities outside of school in the community with the built environment to improve the accessibility of parks and

playgrounds; in indoor and outdoor recreational settings

White House Task Force on Childhood Obesity

Recommendation 5.3: State and local educational agencies should be encouraged to increase the quality and frequency of sequential, ageand developmentally- appropriate physical education for all students, taught by certi#ed PE teachers

White House Task Force on Childhood Obesity

Recommendation 5.10: Communities should be encouraged to consider the impacts of built environment policies and regulations on human health.

White House Task Force on Childhood Obesity

Recommendation 5.12: “Active transport” should be encouraged between homes, schools, and community destinations for afterschool activities, including to and from parks, libraries, transit, bus stops, and recreation centers.

White House Task Force on Childhood Obesity

Recommendation 5.13: Increase the number of safe and accessible parks and playgrounds, particularly in underserved and low-income communities

All this will not be finished in the first 100 days. Nor will it be finished in the first 1,000 days, nor in the life of this Administration, nor even perhaps in our lifetime on this planet. But let us begin.

John F Kennedy (1961)