Preventing Chronic Disease

1. Preventing Chronic Disease David Barker Professor of Clinical Epidemiology, University of Southampton Professor of Cardiovascular Medicine, Oregon Health and Science University

2. The poor diets of girls and young women are causing disease in the next generation

3. The highest levels of coronary heart disease are in West Virginia, followed by Kentucky. Within any state poorer people are more at risk than wealthier people. Poorly educated people are more at risk than the well educated: one in ten people who did not finish high school have the disease.

4. “The explanation would come from differences in cultural norms, poverty rates and other social factors, and not environmental causes” New York Times, February 16.

5. Death rates from Coronary Heart Disease in men 1968-78 Gardner MJ et al. 1984 Atlas of mortality from selected diseases in England and Wales, 1968-78. John Wiley, Chichester.

7. Coronary heart disease and neonatal mortality: England and Wales Standardised mortality ratio for coronary heart disease 1968-78 Neonatal Mortality 1911-15 Barker and Osmond 1986 Lancet;1:1077-81

9. Programming Malnutrition and other adverse environmental exposures during development alter gene expression and programme the body’s structures and functions for life. Adverse exposures also result in slow growth and small body size.

10. Lacerta vivipara

11. Undernutrition, stress, hypoxia Gene defect Critical window of development Fewer cells, altered structure Altered gene expression Adaptation DISEASE

12. Mortality from coronary heart disease in 15726 men and womenin Hertfordshire

13. The fetal origins theory Coronary heart disease, stroke, type 2 diabetes, hypertension and osteoporosis, originate through developmental plasticity, in response to malnutrition during fetal life and infancy. Certain cancers,including breast cancer,also originate in fetal life.

15. Small body size at birth People who were small at birth are biologically different: • Reduced functional capacity e.g. fewer nephrons, less muscle • Altered metabolic settings e.g. insulin resistance • Altered hormonal production e.g. stress responses, sex hormones

17. Normotensive Severe hypertension or CHD z score Mild hypertension or stroke Weight gain in childhood and later disease

18. Compensatory growth Growth at above normal rates after a period of retarded growth. Rapid growth has long-term physiological and metabolic costs

19. 80 60 % 40 -3.0 -3.5 Birth -weight (kg) 20 -4.0 >4.0 0 M F -74.8 -62.6 -81.5 -68.7 -88.0 -75.2 -96.5 -83.9 >96.5 >83.9 M F Fifths of currentweight(kg) Prevalence of hypertension

20. Hazard ratio BMI at 11 years (kg/m2) BMI at 2 years (kg/m2) Hazard ratios for coronary heart disease among 8760 men and women Barker DJ, Osmond C, Forsen TJ, Kajantie E, Eriksson JG. N Engl.J Med. 2005;353:1802-9

21. Age at adiposity rebound in 8760 children Eriksson JG, Forsen T, Tuomilehto J, Osmond C, Barker DJP. Diabetologia. 2003; 46:190-194

22. Cumulative incidence (%) of Type 2 diabetes in a cohort of 8760 men and women Eriksson JG, Forsen T, Tuomilehto J, Osmond C, Barker DJP. Diabetologia. 2003; 46:190-194

23. Fetal Nutrition • The fetus is nourished by • the mother’s diet • the nutrients stored in her body • the placenta’s ability to transport nutrients from mother to baby

24. Associations between early growth and later disease extend across the range of fetal and infant growth. This implies that what are regarded as normal variations in the supply of nutrients to the baby have important long–term effects.

26. Preventing chronic disease • Chronic disease may be prevented in the next generation by improving :- • • Children’s growth • • The diets of mothers before and during pregnancy • • Transport of nutrients across the placenta • The diets of girls

27. Odds ratios for hypertension p for trend = 0.009 Odds ratio Placental area (cm2)

28. Mean systolic blood pressure of men and women, aged 50, born at term.

29. Conclusions • A small placental surface area is associated with later cardiovascular disease • (2) In well nourished mothers the placental surface can expand to compensate for fetal malnutrition. This has long-term costs that include cardiovascular disease and cancer

30. Breast Cancer Hypothesis Breast cancer is initiated in utero when developing breast tissue is exposed to the mother’s circulating hormones

31. The intercristal diameter is the maximal distance between the iliac crests, while the interspinous diameter is the distance between the anterior superior iliac spines. The intercristal is usually 2.5 cm (one inch) longer than the interspinous. The more the intercristal diameter exceeds the interspinous, the rounder the iliac crest.

32. Puberty Atpuberty the bony pelvis becomes broader. This is controlled by growth hormone and androgens. The intercristal diameter increases more rapidly in girls, and the iliac crests become rounder. This is controlled by oestrogens.

33. <40 <40 40 40 Mothers’ intercristal diameter (cm) -28 -30 >30 Hazard ratios for breast cancer All mothers Multiparous mothers Hazard ratio Length of gestation (weeks)

34. Conclusions • Cancers of the breast, ovary and prostate are initiated by nutritional/hormonal events during the mother’s puberty that lead to broad hips • (2) The children of mothers with wide hips are at increased risk of cancer because their mothers’ sex hormones cause genetic instability in the stem cells of the breast, ovary or prostate • (3) The cancers are not related to the mother’s height. We postulate that they are the result of poor nutrition in the mother’s early childhood followed by pre-pubertal catch-up growth

35. The poor diets of girls and young women are causing disease in the next generation

36. www. Barker.org