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)