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Faculty Disclosure. Emily Oken , MD, MPH Dr. Oken has listed no financial interest/arrangement that would be considered a conflict of interest. Does Obesity Begin Before Birth? Influence of the Intrauterine and Infant Environment on Obesity and Metabolic Disease. Emily Oken, MD, MPH

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    1. Faculty Disclosure Emily Oken, MD, MPH Dr. Oken has listed no financial interest/arrangement that would be considered a conflict of interest.

    2. Does Obesity Begin Before Birth? Influence of the Intrauterine and InfantEnvironment on Obesity and Metabolic Disease Emily Oken, MD, MPH Obesity Prevention Program Department of Population Medicine Harvard Medical School and Harvard Pilgrim Health Care Institute

    3. Does the health of mothers influence the health of babies in the short and long term?

    4. Overweight and obesity rising in U.S. women age 20-39

    5. Obesity is also rising in infants 12-23 months 24-71 months Prevalence of Overweight 0-11 months 1980 1985 1990 1995 2000 Year Kim et al., Obesity 2006; 14(7):1107-12. ~500,000 well child visits in Mass.

    6. Fetal growth parallels maternal BMI Adapted from Heslehurst, et al. Obesity Reviews 2008. Meta-analysis of published cohort studies.

    7. Heavier babies remain heavier Danish conscripts 18-26 y.o.Sorensen, Gillman, et al., BMJ 1997;315(7116):1137. Adjusted for gestational age, birth length, maternal factors

    8. Oken, Ob Gyn Clinics of N. America, 2009 Jun;36(2):361-77.

    9. Offspring of obese mothers have poorer cardio-metabolic status • At birth, higher body fat, reduced energy expenditure, and more atherogenic lipid profiles • In childhood, higher blood pressure, risk for metabolic syndrome - even after adjustment for attained BMI • In adulthood, increased risk of death from coronary heart disease Oken, Ob Gyn Clinics of N. America, 2009 Jun;36(2):361-77.

    10. Gestational weight gain

    11. Gestational weight gain • Infant birth weight increases 16-23g per 1kg increase in maternal weight gain • Greater risk for macrosomia, LGA • Lower risk for low birth weight, SGA Viswanathan M, et al. Outcomes of maternal weight gain. 2008. AHRQ Evidence Report. http://www.ahrq.gov/downloads/pub/evidence/pdf/admaternal/admaternal.pdf

    12. The prevalence of excessive weight gain is also on the rise http://www.cdc.gov/pednss/pnss_tables/html/pnss_national_table16.htm

    13. Gestational weight gain and child weight Adjusted for maternal race/ethnicity, smoking, BMI, socio-demographics, gestational diabetes; paternal BMI; child sex, gestation length, breastfeeding duration Oken et al., Am J Ob Gyn 2007;196(4):322 e1-8.

    14. Gestational weight gain and adolescent weight Oken et al. 2008

    15. What accounts for associations of maternal weight with child weight? • Genes

    16. What accounts for associations of maternal weight with child weight? • Genes • Dad weight is also associated with child weight

    17. What accounts for associations of maternal weight with child weight? • Genes • Dad weight is also associated with child weight • but associations not as strong • Identified obesity genes only account for a small proportion of risk • Other factors matter, even when genetic risk is high

    18. Even in Pima Indians, it’s not just the genes Schultz et al. Diabetes Care 2006;29(8):1866-71

    19. What accounts for associations of maternal weight with child weight? • Genes • Shared behaviors • Parents and children tend to share diet, physical activity habits (Oliveria et al, AJCN, 1992)

    20. What accounts for associations of maternal weight with child weight? • Genes • Shared behaviors • Mediators • Fetal growth & body composition at birth

    21. Large for gestational age MUA muscle area z score Small for gestational age Age (months) Size at birth and body composition larger babies: more muscle and more fatsmaller babies: less muscle, but not less fat Hediger et al, Pediatrics, 1998

    22. What accounts for associations of maternal weight with child weight? • Genes • Shared behaviors • Mediators • Fetal growth & body composition • GDM

    23. Offspring of mothers with DM in pregnancy are heavier at 14-17 years Silverman et al., Diabetes Care, 1998

    24. What accounts for associations of maternal weight with child weight? • Genes • Shared behaviors • Mediators • Fetal growth & body composition • GDM • Breastfeeding

    25. Breastfeeding • Observational studies suggest small benefit for child obesity (but confounded)

    26. Parsons et al (33) Poulton and Williams (26) Tulldahl et al (16) Kramer (15) Kramer (15) Elliot et al (15) Gillman et al (12) Sung et al (11) Toschke et al (6-14) Liese et al (10) Frye and Heinrich (10) Maffeis et al (10) Li et al (8) Eid (8) Strbak et al (1-7) Richter (7) Wadsworth et al (6) von Kries et al (6) Bergmann et al (6) Scaglioni et al (5) O'Callaghan et al (5) Neyzi et al (5) Hediger et al (4) Grummer-Strawn and Mei (4) Armstrong & Reilly (3) Thorogood et al (1) Dewey et al (1) Yeung et al (0.5) Taitz (0) Combined .5 1 1.5 Odds of obesity Breastfeeding and child overweight 0.87 (95% CI 0.85, 0.89) Breast feeding better Formula feeding better Owen et al, Pediatrics, 2005

    27. Large RCT: no differences at 6.5 years(but all infants breastfed ) Kramer et al. Am J Clin Nutr. 2007 Dec;86(6):1717-21

    28. What accounts for associations of maternal weight with child weight? • Genes • Shared behaviors • Mediators • Confounders • SES • Smoking

    29. Adams, 2005 Al Mamun, 2006 Bergmann, 2003 Chen, 2006 F Chen, 2006 M Dubois, 2006 Oken, 2005 Power, 2002 F Power, 2002 M Reilly, 2005 Salsberry, 2005 Toschke, 2002 Toschke, 2003 Whitaker, 2004 Wideroe, 2003 von Kries, 2002 Combined .5 1 5 Odds Ratio Maternal prenatal smoking and child overweight – meta-analysis OR 1.50, 95% CI: 1.36, 1.65 Oken, et al. Int J Obes (Lond)  2008; 32(2):201-10

    30. Gestational Diabetes Infant feeding & growth Pathways linking maternal weight with child outcomes Gestational weight gain Child adiposity Gestation length Birth weight Fetal growth Maternal pre-pregnancy size Disease outcomes Shared genes and behaviors Oken, E. In “Influence of Pregnancy weight on maternal and child health.” IOM 2007.

    31. What accounts for associations of maternal weight with child weight? • Genes • Shared behaviors • Mediators • Confounders • Direct effect of the intra-uterine environment

    32. Gestational Diabetes Infant feeding & growth Pathways linking maternal weight with child outcomes Gestational weight gain Child adiposity Gestation length Birth weight Fetal growth Maternal pre-pregnancy size Disease outcomes Shared genes and behaviors Oken, E. In “Influence of Pregnancy weight on maternal and child health.” IOM 2007.

    33. How to study whether maternal weight status programs offspring weight? • Randomized trials

    34. How to study whether maternal weight status programs offspring weight? • Randomized trials • None of pre-pregnancy interventions • Few studies to prevent excess gestational weight gain • Most not powered to study weight at birth • None with f/u after early infancy • Stay tuned!!

    35. How to study whether maternal weight status programs offspring weight? • Randomized trials • Observational human studies • Statistical adjustment for measured factors

    36. Maternal BMI associated with child weight even after adjustment 8494 children in WIC Ohio. Adjusted for maternal, race/ethnicity, parity, smoking, education, marital status, age; gestational weight gain, and child sex, fetal growth and birth year Whitaker, Pediatrics 2004;114(1):e29

    37. Odds of child overweight according to maternal gestational weight gain Adjusted for maternal race/ethnicity, smoking, BMI, sociodemographics, gestational diabetes; paternal BMI; child sex, gestation length, breastfeeding duration Oken et al., Am J Ob Gyn 2007;196(4):322 e1-8.

    38. GWG and child weight gain associations persist after adjustment Also djusted for maternal race/ethnicity, smoking, BMI, sociodemographics, gestational diabetes; paternal BMI; child sex, gestation length, breastfeeding duration

    39. GWG and child weight gain associations persist after adjustment Also djusted for maternal race/ethnicity, smoking, BMI, sociodemographics, gestational diabetes; paternal BMI; child sex, gestation length, breastfeeding duration

    40. GWG and child weight gain associations persist after adjustment Also djusted for maternal race/ethnicity, smoking, BMI, sociodemographics, gestational diabetes; paternal BMI; child sex, gestation length, breastfeeding duration

    41. GWG and child weight gain associations persist after adjustment Also djusted for maternal race/ethnicity, smoking, BMI, sociodemographics, gestational diabetes; paternal BMI; child sex, gestation length, breastfeeding duration

    42. How to study whether maternal weight status programs offspring weight? • Randomized trials • Observational human studies • Sibling studies

    43. Weights of children born before (BMS, n=45) and after (AMS, n=172) maternal weight-loss surgery Kral JG, et al. Pediatrics. 2006 Dec;118(6):e1644-9

    44. Dabelea et al., Diabetes 2000. 19 Pima families/58 sibs

    45. How to study whether maternal weight status programs offspring weight? • Randomized trials • Observational human studies • Sibling studies • Animal studies

    46. 21 days: Weights 14g, 60g 75 days: Weights 86g, 230g Widdowson and McCance, 1960 Animal studies suggested early energy intake can permanently program body size

    47. Timing is important Weight (g) weaning Food restriction during weeks 0-3 results in sustained lower body weight (and food excess in higher weight) Age (weeks) 21 day period of food restriction

    48. Weight (g) weaning Later food restriction (weeks 9-12) – rats quickly regain and (perhaps overshoot) body weight Age (weeks) Timing is important Widdowson and McCance, 1963 21 day period of food restriction

    49. Offspring of obese dams Offspring of control dams Offspring of obese dams Offspring of control dams Offspring of overfed mother rats have higher body weight … Male offspring Female offspring Samuelsson, A.-M. et al. Hypertension 2008;51:383-392