1. Healthy Pregnancies Healthy Children Healthy Future Generations
The Environment and Healthy Aging: The Role of Preconception and Prenatal Exposures
Patrice Sutton, MPH
Research Scientist
Program on Reproductive Health and the Environment
Healthy Aging Starts at Conception:
Promoting Health Across the Lifespan
March 11, 2011
Healthy Pregnancies Healthy Children Healthy Future Generations

2. Program on Reproductive Health and the Environment
Mission
To create a healthier environment for human reproduction and development
Advance scientific inquiry, clinical care, and health policies that prevent exposures to harmful chemicals in our environment

3. Environmental Influences on Reproductive Health
Chemicals
Built & Social Environment
Genetics
Nutrition 3

4. Critical and Sensitive Windows of Development
Periconception
Prenatal
Postnatal
Blastocyst
Embryo
Fetus
Infant
Child
Adolescent
Environmental Exposure
Immediate & Long Term
Consequences
Childhood 

5. Developmental Origins of Adult Disease
“ It is suggested that poor nutrition in early life increases susceptibility to the effects of an affluent diet”
Barker DJ, Osmond C. Infant mortality, childhood nutrition, and ischaemicheart disease in England and Wales. Lancet May 10;1(8489):

6. Developmental Origins of Adult Disease: Nutrition
Human evidence from study of Dutch famine during WW II
Maternal under-nutrition during gestation had important effects on health in later life
The timing of the nutritional insult determined which organ system is affected
Painter RC, Roseboom TJ, Bleker OP.Prenatal exposure to the Dutch famine and disease in later life: an overview. Reprod Toxicol Sep-Oct;20(3):

7. Prenatal Nutrition and Adult Health Outcomes
Exposure in early gestation: three-fold increase in coronary heart disease, more obesity
Exposure in mid-gestation: increase in obstructive airways disease
Exposure in late gestation: impaired glucose tolerance
A large body of experimental and epidemiologic data have substantiated and further refined scientific understanding of these linkages
Painter RC, Roseboom TJ, Bleker OP.Prenatal exposure to the Dutch famine and disease in later life: an overview. Reprod Toxicol Sep-Oct;20(3):345-52; Warner MJ, Ozanne SE. Mechanisms involved in the developmental programming of adulthood disease. The Biochemical journal May 1;427(3):333-47; Newbold R, Heindel J. Developmental exposures and implications for disease. In: Woodruff TJ JS GJL, Giudice LC, editor. Environmental Impacts on Reproductive Health and Fertility. Cambridge, UK: Cambridge University Press; p

8. Developmental Origins of Adult Disease: Chemicals
DES (Diethylstilboestrol) In utero chemical exposures caused delayed reproductive health impacts
“Proof of principle” of adult disease from prenatal exposure to endocrine disrupting chemicals (EDCs)
Newbold, R.R., Lessons learned from perinatal exposure to diethylstilbestrol. Toxicol Appl Pharmacol, (2): p ; Ibarreta D, Swan SH. The DES story: long-termconsequences of prenatalexposure. In: European Environment Agency Late lessons from early warnings: The precautionary principle 1896—2000. Environmental Issue Report No. 22. Luxembourg: Office for Official Publications of the European Communities. 8 8

9. Contemporary Prenatal Exposure to Endocrine Disrupting Chemicals
Based on analysis of representative sample of U.S. population by NHANES Note, not all women were tested for all chemicals
Source: Woodruff TJ, Zota AR, Schwartz JM Environmental Chemicals in Pregnant Women in the US: NHANES Environ Health Perspect :-. doi: /ehp
Percentage of U.S. Pregnant Women with Detectable Level of Analyte
Persistent environmental contaminants that enter the food system

10. Prenatal Exposure to Environmental Chemicals: Health Outcomes Over Lifespan
Exposure to chemicals during fetal development can increase the risk of adverse health consequences across lifespan
Adverse birth outcomes (e.g. preterm birth and birth defects)
Childhood morbidity (e.g. neuro-developmental effects and childhood cancer)
Adult disease and mortality (e.g. cancer and cardiovascular effects)
Gluckman PD, Hanson MA Living with the past: evolution, development, and patterns of disease. Science 305(5691): ; Stillerman KP, Mattison DR, Giudice LC, Woodruff TJ Environmental exposures and adverse pregnancy outcomes: a review of the science. Reprod Sci 15(7):

11. Pesticide Exposure During Pregnancy and Childhood Leukemia
Pesticides at Home
Systematic review and meta-analysis 15 human studies
Exposure during pregnancy positively associated with childhood leukemia
Pesticides at work
Systematic review and meta-analysis 31 human studies
Exposure during pregnancy was positively associated with childhood leukemia
Talking Points
Systematic review and meta-analysis of previous observational epidemiologic studies examining the relationship between residential pesticide exposures during critical exposure time windows (preconception, pregnancy, and childhood) and childhood leukemia. Included 15 studies.
Overall, exposure to residential pesticides during pregnancy was positively associated with childhood leukemia.
References
MC, Wigle DT, Krewski D. Residential pesticides and childhood leukemia: a systematic review and meta-analysis. Environ Health Perspect Jan;118(1):33-41.
Childhood leukemia associated with prenatal maternal occupational pesticide exposure in analyses of all studies combined and in several subgroups.
Associations with paternal occupational pesticide exposure were weaker and less consistent.
Wigle DT, Turner MC, Krewski D. A systematic review and meta-analysis of childhood leukemia and parental occupational pesticide exposure. Environ Health Perspect Oct;117(10): Epub 2009 May 19.
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Original content for this slide submitted by the Expert Clinical Advisory Committee on Environmental Impacts on Reproductive Health in March Content updated March 2010 by Tracey Woodruff, PhD, MPH and Patrice Sutton, MPH. Original funding received by the Passport Foundation and the Richard and Rhoda Goldman Fund through an independent educational grant. This slide is available at
Turner MC et al. Environ Health Perspect. 2010; Wigle DT et al. Environ Health Perspect

12. From Endocrine to Metabolic Disruption
Hypothesized that environmental chemicals can act as “metabolic” disruptors
In vitro, in vivo and human studies link exposure to EDCs with obesity, metabolic syndrome
Prenatal exposure to hexachlorobenzene and obesity in children
Prenatal exposure to DDE and increased body mass in adult women
Casals-Casas C, Desvergne B. Endocrine disruptors: from endocrine to metabolic disruption. Annu Rev Physiol Mar 17;73:

13. Strength of the Evidence
Leading scientists, reproductive health providers & other health care practitioners have called for timely action to prevent harm
2008 Faroes Statement
2008 Proceedings of University of California, San Francisco and Collaborative on Health and the Environment Summit on Reproductive Health and the Environment
2009 Endocrine Society Statement
2010 President’s Cancer Report
Woodruff TJ, Carlson A, Schwartz JM, et al. Proceedings of the Summit on Environmental Challenges to Reproductive Health and Fertility: Executive summary. Fertil Steril 2008;89:e1-e20.; Grandjean P, Bellinger D, Bergman A, Cordier S, Davey-Smith G, Eskenazi B, et al. The faroes statement: human health effects of developmental exposure to chemicals in our environment. Basic & clinical pharmacology & toxicology Feb;102(2):73-5.

14. Taking Action To Prevent Harm
Clinical Arenas
Professional societies
Professional journals/publications/ education
Outreach and education
Policy Arenas
Chemicals Policy
Food system policy

15. Summary
Environmental chemicals and other environmental exposures can harm or nurture human reproduction
Preconception and prenatal environmental exposures can influence the risks of disease and disability across the lifespan
Timely action in clinical and policy arenas is needed to prevent harm 15