Lifecourse Approach to Women’s Reproductive Health: Focus on Psychosocial Stress

1. Lifecourse Approach to Women’s Reproductive Health: Focus on Psychosocial Stress Janet Rich-Edwards, ScD Assistant Professor Connors Center for Women’s Health and Gender Biology Brigham and Women’s Hospital

4. “With the exception of the stomach, there is no organ that holds such numerous ramifications of sympathy with other organs as the womb.” J.M. Good, The Study of Medicine, 1826

5. Lifecourse approach: Reproductive success or failure reflects both cumulative and current exposures Reproductive events are sentinels of chronic disease in the mother Maternal exposures and maternal health predict chronic disease in the child

6. Past Birthweight Growth Social position

7. PastPresent Birthweight Growth Social position Previous pregnancy outcomes Social position Pregnancy complications Stress

8. PastPresentFuture Birthweight Growth Social position Previous pregnancy outcomes Social position Pregnancy complications Stress Cardiovascular dz Diabetes Cancer

9. PastPresentFuture Birthweight Growth Social position Previous pregnancy outcomes Social position Pregnancy complications Stress Cardiovascular dz Diabetes Cancer Next generation

10. Lifecourse approach: Reproductive success or failure reflects both cumulative and current exposures Reproductive events are sentinels of chronic disease in the mother Maternal exposures and maternal health predict chronic disease in the child

11. Lifecourse approach: Reproductive success or failure reflects both cumulative and current exposures Theory: reproductive responsiveness Example: psychosocial stress and pregnancy outcome Reproductive events are sentinels of chronic disease in the mother

12. Reproduction is expensive: + Physiologic cost to mother Lactation Labor and delivery Fetal growth Pregnancy maintenance Placentation Conception Fully competent cycles Ovulatory failure Amenorrhea - Adapted from Ellison, 1993

13. Reproduction Survival Adversity Advantage Environment

14. The optimal reproductive system: Adapts with agility while expending minimal resources Can shut down quickly in response to immediate threat

15. Childhood Setpoint

16. Possible in utero or childhood set points: Number or quality of ova Hormone synthesis Hormone receptors Uterine vascularization Pelvic cavity size

17. Adult variation S R Childhood Setpoint

18. R S Advantageous Adult Environment

19. S R Adverse Adult Environment

20. The optimal reproductive system: Adapts with agility while expending minimal resources Can shut down quickly in response to immediate threat Customized to early environment Retains some plasticity in response to enduring environment

21. ExamplePregnancy outcome: preterm birth and low birthweight

22. Preterm (<37 weeks) and Very Preterm (<32 weeks) BirthsUnited States, 1985-2005 Percent Objective Source: National Center for Health Statistics, final natality data Prepared by March of Dimes Perinatal Data Center

23. Preliminary preterm birth rates, 2005: 11.7% non-Hispanic whites 12.4% Hispanics 18.4% non-Hispanic Blacks www.cdc.gov/nchs

24. Preterm Birth among Singletons by Maternal Education and Race/Ethnicity, U.S. 1999 Percent Hispanic Non-Hispanic White Non-Hispanic Black Source: National Center for Health Statistics Prepared by March of Dimes Perinatal Data Center, 2002

25. Maternal age

26. Preterm birth by maternal age US, 2002-2004 Average

27. Preterm Birthsby Maternal Age, United States, 2000 Percent Preterm is less than 37 competed weeks gestation Source: National Center for Health Statistics, 2000 final natality data Prepared by March of Dimes Perinatal Data Center, 2002

28. The next slides show associations of maternal age with poor pregnancy outcomes, stratified by maternal race/ethnicity. Pay attention to: Absolute black:white differences in risk of poor pregnancy outcomes at any age Different slopes for blacks and whites with age

29. Percent low birthweight (<2500 gm) by maternal age, births to Black and White mothers, Chicago 1994-1996 Percent White mothers Black mothers Rich-Edwards, IJE

30. Preterm Birth among Singletons by Maternal Age and Race/Ethnicity, United States, 1999 Percent Hispanic Non-Hispanic White Non-Hispanic Black Source: National Center for Health Statistics Prepared by March of Dimes Perinatal Data Center, 2002

31. Absolute black:white differences in risk of poor pregnancy outcomes at any age effect of factors before reproductive maturity genes? early environment of girls: birthweight, nutrition, stress, etc. Different slopes for blacks and whites with age exposures more prevalent with age cumulative exposures

32. Weathering Hypothesis, Geronimus 1992 Health of African Americans “may begin to deteriorate in early adulthood as a physical consequence of cumulative socioeconomic disadvantage”

33. Measurable elements of weathering Financial stress Chronic strain Family function Neighborhood function Violence Racism

34. Weathering Poverty, racism, family fx Preconceptional Vulnerability Stress-related behaviors Altered endocrine reactivity to stress Immune defense degradation Underlying chronic disease Preterm/FGR Risk Factors CRH, BV, inflammation, HTN, preeclampsia Preterm/LBW

35. ? PSYCHOSOCIAL STRESS NEUROENDOCRINE FACTORS IMMUNE FACTORS VASCULAR FACTORS PRETERM/LBW

36. Three PropositionsWeathering manifests during pregnancy as: 1) neuroendocrine maladaptations 2) immune dysfunction3) vasculopathy

37. Proposition 1:Weathering manifests as neuroendocrine maladaptations in pregnancy

38. MOTHER CRH ACTH CORTISOL

39. Mean peak ACTH responses to laboratory stressor by childhood abuse history and adult depression status Heim et al., JAMA, 2000

40. Changes in maternal CRH in human pregnancy

41. MOTHERPLACENTAFETUS CRH ACTH CORTISOL CRH CORTISOL

42. Physiologic stressors raise CRH levels: Infection Inflammation Preeclampsia Pregnancy-induced hypertension Fetal growth restriction Hemorrhage Uteroplacental vascular insufficiency

43. MOTHERPLACENTAFETUS CRH ACTH CORTISOL CRH CORTISOL NE

44. Does psychologic stress raise CRH? 2 out of 3 studies report ‘yes’ (Hobel 1999, Hermann 2001, Petraglia 2001) 1 study: higher CRH with lower income (Hermann 2001)

45. Odds ratios for prenatal depression for a one standard deviation increase in mid-pregnancy ln CRH, Project Viva Prenatal depressive symptoms Odds ratio Rich-Edwards et al., submitted

46. Is race/ethnicity associated with CRH levels? 1 study: African Americans have higher CRH (Hermann, 2001) 1 study: African Americans have same CRH (Holzman, 2001) 1 study: Latinas have lower CRH (Ruiz, 2001)

47. Proposition 2:Weathering manifests as immune dysfunction in pregnancy

48. Infection and preterm delivery • Vaginal and uterine infections associated with preterm delivery (especially BV) • However, antibiotic treatment trials have equivocal results • Suggests that infection/inflammation starts before pregnancy

49. Stress and Infection • Non-pregnant state: psychosocial stress raises risk of viral illness, slows healing time (Kiecolt-Glaser, Cohen) • High stress and low social support associated with depressed lymphocyte activity in pregnancy (Herrera 1998) • High chronic stress associated with bacterial vaginosis during pregnancy (Culhane 2001)

50. Maternal stress and bacterial vaginosis status Culhane, MCH Journal 2001