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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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slide1

Faculty Disclosure

Emily Oken, MD, MPH

Dr. Oken has listed no financial interest/arrangement that would be considered a conflict of interest.

slide2

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

slide4

Overweight and obesity rising

in U.S. women age 20-39

slide5

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.

slide6

Fetal growth parallels maternal BMI

Adapted from Heslehurst, et al. Obesity Reviews 2008.

Meta-analysis of published cohort studies.

slide7

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

slide9

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.

gestational weight gain1
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

slide12

The prevalence of excessive weight gain is also on the rise

http://www.cdc.gov/pednss/pnss_tables/html/pnss_national_table16.htm

gestational weight gain and child weight
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.

slide17

What accounts for associations of maternal weight with child weight?

  • Genes
    • Dad weight is also associated with child weight
slide18

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
slide19

Even in Pima Indians, it’s not just the genes

Schultz et al. Diabetes Care 2006;29(8):1866-71

slide20

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)
slide21

What accounts for associations of maternal weight with child weight?

  • Genes
  • Shared behaviors
  • Mediators
    • Fetal growth & body composition at birth
slide22

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

slide23

What accounts for associations of maternal weight with child weight?

  • Genes
  • Shared behaviors
  • Mediators
    • Fetal growth & body composition
    • GDM
slide24

Offspring of mothers with DM in pregnancy are heavier at 14-17 years

Silverman et al., Diabetes Care, 1998

slide25

What accounts for associations of maternal weight with child weight?

  • Genes
  • Shared behaviors
  • Mediators
    • Fetal growth & body composition
    • GDM
    • Breastfeeding
breastfeeding
Breastfeeding
  • Observational studies suggest small benefit for child obesity (but confounded)
breastfeeding and child overweight

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

large rct no differences at 6 5 years but all infants breastfed
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

slide29

What accounts for associations of maternal weight with child weight?

  • Genes
  • Shared behaviors
  • Mediators
  • Confounders
    • SES
    • Smoking
slide30

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

slide31

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.

slide32

What accounts for associations of maternal weight with child weight?

  • Genes
  • Shared behaviors
  • Mediators
  • Confounders
  • Direct effect of the intra-uterine environment
slide33

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.

slide34

How to study whether maternal weight status programs offspring weight?

  • Randomized trials
slide35

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!!
slide36

How to study whether maternal weight status programs offspring weight?

  • Randomized trials
  • Observational human studies
    • Statistical adjustment for measured factors
slide37

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

odds of child overweight according to maternal gestational weight gain
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.

gwg and child weight gain associations persist after adjustment
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

gwg and child weight gain associations persist after adjustment1
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

gwg and child weight gain associations persist after adjustment2
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

gwg and child weight gain associations persist after adjustment3
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

slide43

How to study whether maternal weight status programs offspring weight?

  • Randomized trials
  • Observational human studies
  • Sibling studies
weights of children born before bms n 45 and after ams n 172 maternal weight loss surgery
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

slide46

How to study whether maternal weight status programs offspring weight?

  • Randomized trials
  • Observational human studies
  • Sibling studies
  • Animal studies
slide47

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

slide48

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

slide49

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

offspring of overfed mother rats have higher body weight

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

higher fat mass
…higher fat mass…

OC – Offspring of control dams

OO – Offspring of obese dams

Samuelsson, A.-M. et al. Hypertension 2008;51:383-392

higher energy intake

Offspring of obese dams

Offspring of control dams

Offspring of obese dams

Offspring of control dams

…higher energy intake…

Samuelsson, A.-M. et al. Hypertension 2008;51:383-392

and adverse cardio metabolic profiles
…and adverse cardio-metabolic profiles

OC – Offspring of control dams

OO – Offspring of obese dams

Samuelsson, A.-M. et al. Hypertension 2008;51:383-392

slide55

Altered Appetite

Regulation

High Neonatal

Adiposity

Altered Adipocyte

Metabolism

peri conceptional exposure only
Peri-conceptional exposure only

Experiment 3: Maternal high fat diet before gestation with embryo transfer after conception

Wu Q. and M. Suzuki. Obes Rev. 2006 May;7(2):201-8

peri conceptional exposure only1
Peri-conceptional exposure only

Wu Q. and M. Suzuki. Obes Rev. 2006 May;7(2):201-8

peri conceptional exposure only2
Peri-conceptional exposure only

Wu Q. and M. Suzuki. Obes Rev. 2006 May;7(2):201-8

epigenetic imprinting
Epigenetic imprinting

Wu Q and M Suzuki. Obes Rev. 2006 May;7(2):201-8.

a vicious cycle
A vicious cycle?

Catalano PM. JCE&M 2003, 88(8):3505-3506.)

summary maternal obesity and offspring outcomes
Summary – maternal obesity and offspring outcomes
  • Maternal obesity and GWG
    • Increasing in prevalence
    • Excesses of each are associated with increased risks for the child during pregnancy and at birth
    • Associated with child weight
      • Probably not just genes
      • Can we reverse the cycle?
      • When/how to intervene?
clinician advice matters
Clinician advice matters

Herring SJ. Journal of Women’s Health, 2010.

clinician knowledge of bmi categories
Clinician Knowledge of BMI categories

Please indicate the body mass index (BMI) that reflects each weight status listed below:

Herring SJ. Journal of Women’s Health, 2010

postpartum weight loss is key
Postpartum weight loss is key

Villamor, Lancet 2006;368:1164-70

modifiable postpartum behaviors and ppwr
Modifiable postpartum behaviors and PPWR

TV viewing < 2 h/day, walking > 30 min/day, trans fat < median

Oken et al., AJPM 2007; 32(4):305-311.

sleep and ppwr
Sleep and PPWR
  • Chronic sleep curtailment is associated with
    • Higher prevalence of obesity and weight gain in young adults
    • CAD and type 2 DM in women
    • Higher mortality
  • The postpartum period is characterized by sleep deprivation
substantial ppwr 5 kg at 1 year by sleep at 6 mo postpartum

3.1

Substantial PPWR >= 5 kg at 1 year by sleep at 6 mo postpartum

Adjusted for race/ethnicity, marital status, education, age, parity pre-pregnancy BMI, gestational weight gain (IOM categories), postpartum behaviors (dietary fiber intake, PA, inactivity, dieting and breastfeeding.

Gunderson, et al. AJE 2007

childhood
Childhood
  • Beware of ‘catch up growth’
infant weight gain
Infant weight gain

Stettler N, Pediatrics 2002

childhood1
Childhood
  • Beware of ‘catch up growth’
  • Promote healthy postnatal and child behaviors
    • Breastfeeding
    • Less TV, fast food, sugar sweetened beverages
    • More physical activity
  • Engage mothers & families
first steps for mommy me study aims
First Steps for Mommy & MeStudy Aims
  • Develop and test feasibility of an intervention to promote healthy eating and physical activity behaviors among mother-infant pairs in the first 6 months of life
preliminary results feeding and media exposure
Preliminary Results – Feeding and Media Exposure
  • At 6-months of age, compared to usual care participants:
    • fewer intervention participants had been introduced to solid foods (57% v. 82%; p=0.04)
    • intervention infants viewed less screen media (median 0.5 v. 1.0 h/d; p= .07)
    • no differences in breastfeeding duration
preliminary results sleep
Preliminary Results – Sleep
  • At 6-months of age, compared to usual care participants, intervention participants:
    • Had fewer nighttime awakenings (median 1.0 v. 2.0 times per night; p=.05)
    • Had longer duration of nighttime sleep (median increase 24 minutes v. 10 minutes; p=.03)
    • Intervention mothers reduced time spent putting their infants to sleep at night (median reduction 19.0 v. 0 min; p=.03)
slide82

Intrauterine nutrition is not only about maternal behavior in pregnancy

Mom’s own

intrauterine

and childhood

experiences

Mom’s

peri-

conceptional

health

Utero-placental

blood flow,

placental

function

Diet during

pregnancy

Fetal

metabolism

slide83

IDM = infants of

mothers with

GDM

Intergenerational influences

Boloker et al., Diabetes 2002;51(5):1499-506.

slide85

Intrauterine nutrition is not only about maternal behavior in pregnancy

Extrauterine environment

Mom’s own

intrauterine

and childhood

experiences

Mom’s

peri-

conceptional

health

Utero-placental

blood flow,

placental

function

Diet during

pregnancy

Fetal

metabolism

sga and lga trends since 1990
SGA and LGA trends since 1990

Oken et al. Obstet Gynecol. 2010 Feb;115(2 Pt 1):357-64

sga and lga trends since 19901
SGA and LGA trends since 1990

SGA

LGA

Oken et al. Obstet Gynecol. 2010 Feb;115(2 Pt 1):357-64

birth weight trends since 1990
Birth weight trends since 1990

Oken et al. Obstet Gynecol. 2010 Feb;115(2 Pt 1):357-64

slide89

Questions?

“Anything on women of pre-childbearing age?”