Faculty Disclosure
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Transcript of Faculty Disclosure
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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.
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Does Obesity Begin Before Birth? Influence of the Intrauterine and Infant
Environment on Obesity and Metabolic Disease
Emily Oken, MD, MPHObesity Prevention Program
Department of Population MedicineHarvard Medical School and
Harvard Pilgrim Health Care Institute
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Does the health of mothers influence the health of babies in the short and long term?
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Prevalence of overweight, obesity andextreme obesity among women 20-39* y old:
US, 1963-2004
Year of survey1965 1975 1985 1995 2005
Pro
porti
on o
f wom
en (%
)
0
10
20
30
40
50
60Overweight (BMI > 25 kg/m2)Obese (BMI > 30 kg/m2)Extreme obesity (BMI > 40 kg/m2)
NHANES1963-65,1966-70
NHANES1971-74
NHANES1976-80
NHANES1988-94
NHANES1999-2000,2001-022003-04
From: Health, United States, 2005 and Ogden CL, et al. JAMA 2006;295:1549.*Ages 20-35 through NHANES 1988-94
Overweight and obesity rising in U.S. women age 20-39
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0
5
10
15
Prev
alen
ce o
f Ove
rwei
ght
Year
24-71 months
0-11 months
12-23 months
1980 1985 1990 1995 2000
Obesity is also rising in infants
Kim et al., Obesity 2006; 14(7):1107-12. ~500,000 well child visits in Mass.
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Adapted from Heslehurst, et al. Obesity Reviews 2008. Meta-analysis of published cohort studies.
2.36
1.311.00
0.52
3225
3281
3429
3334
0
0.5
1
1.5
2
2.5
3
Underweight Normal Overweight ObeseMaternal BMI
Odd
s R
atio
3100
3200
3300
3400
3500
Mea
n bi
rth
wei
ght (
g)
Odds of high birth weightMean birth weight
Fetal growth parallels maternal BMI
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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
22.2
22.6
23
23.4
23.8
24.2
24.6
25
<2.5 2.5-3.0 3.0-3.5 3.5-4.0 4.0-4.5 >4.5
Birthweight (kg)
Adu
lt B
MI (
kg/s
q m
)
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Oken, Ob Gyn Clinics of N. America, 2009 Jun;36(2):361-77.
Odds of child obesity for obese vs. normal weight mothers
3.1
4.1 4.35.1
4.3
1
10
Whitaker 2004(age 4)
Li 2005 (ages2-14)
Reilly 2005(age 7)
Li 2007 (Ages2-12, early
onset)
Salsberry 2007(ages 12-13)
Author, year, child age
Odd
s ra
tio fo
r chi
ld o
besi
ty
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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.
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Gestational weight gain
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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
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The prevalence of excessive weight gain is also on the rise
25
30
35
40
45
50
1983 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003
Year
% g
aini
ng e
xces
sive
wei
ght
http://www.cdc.gov/pednss/pnss_tables/html/pnss_national_table16.htm
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Distribution of GWG relative to 1990 guidelinesby prepregnancy BMI category (PRAMS, 2002-03)
Body mass index category (IOM criteria)
Under- Normal- Over- Obese
Pro
porti
on (%
) of w
omen
0
20
40
60
80
100
120
weight weight weight
< IOM Within IOM > IOM
19.5
49.9
30.6
38.4
41.1
20.5
63
26.8
10.3
36.3
30.2
23.5
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Oken et al., Am J Ob Gyn 2007;196(4):322 e1-8.
0.17
0.470.52
0
0.2
0.4
0.6
0.8
Maternal weight gain per 1990 IOM Guidelines
Chi
ld B
MI z
sco
re .
Inadequate Adequate Excessive
Adjusted for maternal race/ethnicity, smoking, BMI, socio-demographics, gestationaldiabetes; paternal BMI; child sex, gestation length, breastfeeding duration
Gestational weight gain and child weight
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0.29
-0.25
-0.6
-0.4
-0.2
0.0
0.2
0.4
0.6
<10 10-14 15-19 20-24 25-29 30-34 35-39 40-44 >=45
Gestational weight gain (pounds)
Cha
nge
in c
hild
BM
I z-s
core
Without adjustment for maternal BMI
With adjustment for maternal BMI
Oken et al. 2008
Gestational weight gain and adolescent weight
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Genes
What accounts for associations of maternal weight with child weight?
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What accounts for associations of maternal weight with child weight?
Genes Dad weight is also associated with child weight
Exposure Mom DadReilly, 2005
BMI >=30 4.25 (2.86, 6.32) 2.54 (1.72, 3.75)
Li, 2009
Per 1 kg/m2 1.57 (1.26, 1.95) 1.45 (1.03, 2.05)
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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
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Schultz et al. Diabetes Care 2006;29(8):1866-71
Even in Pima Indians, it’s not just the genes
7%
38%
13%
70%
0%10%20%30%40%50%60%70%80%
Type 2 Diabetes Obesity
MexicoUnited States
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Genes Shared behaviors
Parents and children tend to share diet, physical activity habits (Oliveria et al, AJCN, 1992)
What accounts for associations of maternal weight with child weight?
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Genes Shared behaviors Mediators
Fetal growth & body composition at birth
What accounts for associations of maternal weight with child weight?
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Size at birth and body composition larger babies: more muscle and more fatsmaller babies: less muscle, but not less fat
MU
A m
uscl
e ar
ea z
sco
re
Age (months)
Small for gestational age
Large for gestational age
Hediger et al, Pediatrics, 1998
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Genes Shared behaviors Mediators
Fetal growth & body composition GDM
What accounts for associations of maternal weight with child weight?
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Silverman et al., Diabetes Care, 1998
Offspring of mothers with DM in pregnancy are heavier at 14-17 years
26
23.6
24.6
20.7
20
21
22
23
24
25
26
27
GestationalDiabetes
Pre-gestationaldiabetes
All maternal DMcombined
NCHS reference
Mea
n B
MI (
kg/m
2)
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Genes Shared behaviors Mediators
Fetal growth & body composition GDM Breastfeeding
What accounts for associations of maternal weight with child weight?
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Breastfeeding
• Observational studies suggest small benefit for child obesity (but confounded)
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Breastfeeding and child overweight
Odds of obesity.5 1 1.5
Combined
Taitz (0) Yeung et al (0.5) Dewey et al (1)
Thorogood et al (1) Armstrong & Reilly (3)
Grummer-Strawn and Mei (4) Hediger et al (4)
Neyzi et al (5) O'Callaghan et al (5)
Scaglioni et al (5) Bergmann et al (6) von Kries et al (6)
Wadsworth et al (6) Richter (7)
Strbak et al (1-7) Eid (8)
Li et al (8) Maffeis et al (10)
Frye and Heinrich (10) Liese et al (10)
Toschke et al (6-14) Sung et al (11)
Gillman et al (12) Elliot et al (15)
Kramer (15) Kramer (15)
Tulldahl et al (16) Poulton and Williams (26)
Parsons et al (33)
Breast feeding better Formula feeding better
0.87 (95% CI 0.85, 0.89)
Owen et al, Pediatrics, 2005
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Large RCT: no differences at 6.5 years(but all infants breastfed )
0.70.1 0.3
-0.40 0.2 0.2
-4
-3
-2
-1
0
1
2
3
4
Height, cm BMI, kg/m2 Waistcircumference,
cm
Triceps SF,mm
SubscapularSF, mm
Systolic BP,mm
Diastolic BP,mm
Outcome at age 6.5 years
Clu
ster
-adj
uste
d di
ffere
nce*
*Difference > 0 indicates higher value in experimental group
Kramer et al. Am J Clin Nutr. 2007 Dec;86(6):1717-21
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Genes Shared behaviors Mediators Confounders
SES Smoking
What accounts for associations of maternal weight with child weight?
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Maternal prenatal smoking and child overweight – meta-analysis
Odds Ratio.5 1 5
Combined
von Kries, 2002
Wideroe, 2003
Whitaker, 2004
Toschke, 2003
Toschke, 2002
Salsberry, 2005
Reilly, 2005
Power, 2002 M
Power, 2002 F
Oken, 2005
Dubois, 2006
Chen, 2006 M
Chen, 2006 F
Bergmann, 2003
Al Mamun, 2006
Adams, 2005
OR 1.50, 95% CI: 1.36, 1.65
Oken, et al. Int J Obes (Lond) 2008; 32(2):201-10
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Pathways linking maternal weight with child outcomes
Maternal pre-pregnancysize
Gestationalweightgain
Child adiposity
Birth weight
Diseaseoutcomes
Fetalgrowth
Gestationlength
Shared genes and behaviors
GestationalDiabetes
Infant feeding &growth
Oken, E. In “Influence of Pregnancy weight on maternal and child health.” IOM 2007.
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Genes Shared behaviors Mediators Confounders Direct effect of the intra-uterine environment
What accounts for associations of maternal weight with child weight?
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Pathways linking maternal weight with child outcomes
Maternal pre-pregnancysize
Gestationalweightgain
Child adiposity
Birth weight
Diseaseoutcomes
Fetalgrowth
Gestationlength
Shared genes and behaviors
GestationalDiabetes
Infant feeding &growth
Oken, E. In “Influence of Pregnancy weight on maternal and child health.” IOM 2007.
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• Randomized trials
How to study whether maternal weight status programs offspring weight?
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• 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!!
How to study whether maternal weight status programs offspring weight?
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• Randomized trials• Observational human studies
– Statistical adjustment for measured factors
How to study whether maternal weight status programs offspring weight?
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Maternal BMI associated with child weight even after adjustment
0.1
1
10
< 18.5 18.5-24.9 25-29.9 30-39.9 >= 40
Maternal 1st trimester BMI (kg/m2)Adj
uste
d od
ds o
f chi
ld
over
wei
ght
2 year olds3 year olds4 year olds
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
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3.77 4.35
Inadequate Adequate ExcessiveMaternal weight gain per IOM recommendations
Odd
s Ra
tio .
10
Odds of child overweight according to maternal gestational weight gain
Adjusted for maternal race/ethnicity, smoking, BMI, sociodemographics, gestationaldiabetes; paternal BMI; child sex, gestation length, breastfeeding duration
Oken et al., Am J Ob Gyn 2007;196(4):322 e1-8.
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GWG and child weight gain associations persist after adjustment
4.33.4
4.2 4.2
1
10
100O
dds
ratio
Excessive gain vs inadequate gain
GDM, BF
+ fetal growth
+ child diet & activity
+ mom diet & activity
Also djusted for maternal race/ethnicity, smoking, BMI, sociodemographics, gestationaldiabetes; paternal BMI; child sex, gestation length, breastfeeding duration
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GWG and child weight gain associations persist after adjustment
4.33.4
4.2 4.2
1
10
100O
dds
ratio
Excessive gain vs inadequate gain
GDM, BF
+ fetal growth
+ child diet & activity
+ mom diet & activity
Also djusted for maternal race/ethnicity, smoking, BMI, sociodemographics, gestationaldiabetes; paternal BMI; child sex, gestation length, breastfeeding duration
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GWG and child weight gain associations persist after adjustment
4.33.4
4.2 4.2
1
10
100O
dds
ratio
Excessive gain vs inadequate gain
GDM, BF
+ fetal growth
+ child diet & activity
+ mom diet & activity
Also djusted for maternal race/ethnicity, smoking, BMI, sociodemographics, gestationaldiabetes; paternal BMI; child sex, gestation length, breastfeeding duration
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GWG and child weight gain associations persist after adjustment
4.33.4
4.2 4.2
1
10
100O
dds
ratio
Excessive gain vs inadequate gain
GDM, BF
+ fetal growth
+ child diet & activity
+ mom diet & activity
Also djusted for maternal race/ethnicity, smoking, BMI, sociodemographics, gestationaldiabetes; paternal BMI; child sex, gestation length, breastfeeding duration
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• Randomized trials• Observational human studies• Sibling studies
How to study whether maternal weight status programs offspring weight?
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Weights of children born before (BMS, n=45) and after (AMS, n=172) maternal weight-loss surgery
0%
10%
20%
30%
40%
50%
60%
Underweight Normal weight Overweight Obese
BMSAMS
Kral JG, et al. Pediatrics. 2006 Dec;118(6):e1644-9
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Dabelea et al., Diabetes 2000. 19 Pima families/58 sibs
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• Randomized trials• Observational human studies• Sibling studies• Animal studies
How to study whether maternal weight status programs offspring weight?
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Animal studies suggested early energy intake can permanently program body size
75 days: Weights 86g, 230g21 days: Weights 14g, 60g
Widdowson and McCance, 1960
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Wei
ght (
g)
Age (weeks)
Food restriction during weeks 0-3results in sustained lower body weight (and food excess in higher weight)
21 day period of food restriction
weaning
Timing is important
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Timing is important
weaning
Wei
ght (
g)
Later food restriction (weeks 9-12) –rats quickly regain and (perhapsovershoot) body weight
Age (weeks)
Widdowson and McCance, 1963 21 day period of food restriction
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Offspring of overfed mother rats have higher body weight …
Samuelsson, A.-M. et al. Hypertension 2008;51:383-392
Male offspring Female offspring
Offspring of obese damsOffspring of control dams
Offspring of obese damsOffspring of control dams
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…higher fat mass…
Samuelsson, A.-M. et al. Hypertension 2008;51:383-392
OC – Offspring of control damsOO – Offspring of obese dams
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…higher energy intake…
Samuelsson, A.-M. et al. Hypertension 2008;51:383-392
Offspring of obese damsOffspring of control dams
Offspring of obese damsOffspring of control dams
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…and adverse cardio-metabolic profiles
Samuelsson, A.-M. et al. Hypertension 2008;51:383-392
OC – Offspring of control damsOO – Offspring of obese dams
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What are the mechanisms?
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Altered AppetiteRegulation
High NeonatalAdiposity
Altered AdipocyteMetabolism
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Wu Q. and M. Suzuki. Obes Rev. 2006 May;7(2):201-8
Experiment 3: Maternal high fat diet before gestation with embryo transfer after conception
Peri-conceptional exposure only
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Peri-conceptional exposure only
050
100150200250300350
Body Weight Gain (g)
HF LF
Wu Q. and M. Suzuki. Obes Rev. 2006 May;7(2):201-8
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Peri-conceptional exposure only
0
5
10
15
20
Food Consumption(MJ rat-1)
Food Effiency (gMJ-1)
Abdominal AdiposeTissue
Plasma InsulinConc (ng Ml)
Plasma LeptinConc (ng Ml)
HF LF
Wu Q. and M. Suzuki. Obes Rev. 2006 May;7(2):201-8
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Epigenetic imprinting
Wu Q and M Suzuki. Obes Rev. 2006 May;7(2):201-8.
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A vicious cycle?
Catalano PM. JCE&M 2003, 88(8):3505-3506.)
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What is the overall impact?
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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?
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Clinician advice matters
How frequently do you…when you see an obese woman at her initial prenatal visit?
% almost always
Tell woman she is overweight or obese 40%Discuss risks associated with obesity 41%Recommend a specific range of weight gain 74%Recommend regular physical activity 74%Discuss her diet 64%Order GTT testing in 1st trimester 26%Obtain anesthesia referral 3%Obtain nutrition referral 14%
Herring SJ. Journal of Women’s Health, 2010.
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Clinician Knowledge of BMI categories
Maternal BMI Correct response % CorrectUnderweight < 18.5 kg/m2 48%
Normal >= 18.5 kg/m2
< 25 kg/m241%57%
Overweight >= 25 kg/m2
< 30 kg/m276%57%
Obese >= 30 kg/m2 60%
Please indicate the body mass index (BMI) that reflects each weight status listed below:
Herring SJ. Journal of Women’s Health, 2010
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Postpartum weight loss is key
Gestational Diabetes
0.1
1
10
<-1 -1 to <1 1 to <2 2 to <3 >= 3
Change in BMI
Odd
s R
atio
BMI < 25BMI >= 25
Large for Gestational Age
0.1
1
10
<-1 -1 to <1 1 to <2 2 to <3 >= 3
Change in BMI
Odd
s R
atio
BMI < 25BMI >= 25
Villamor, Lancet 2006;368:1164-70
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Modifiable postpartum behaviors and PPWR
Oken et al., AJPM 2007; 32(4):305-311.
0.50
0.23
0.95
0.1
1
10
Odd
s R
atio
(95%
CI) ThreeTwoOneNone
Number of beneficial postpartum behaviors
TV viewing < 2 h/day, walking > 30 min/day, trans fat < median
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Physical activity before, during, and after pregnancy
2.2
5.4
2.3
9.8
1.5
5.1
0.7
7.2
1.4
5.8
1.3
8.4
0
2
4
6
8
10
12
Light-moderate
Walking forexercise
Vigorous Total activity
hour
s / w
k
Prepregnancy (n=1895)2nd trimester (n=1623)6 mo postpartum (n=1124)
Pereira et al, AJPM, 2007
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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
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0.1
1
10
<= 5 6 7 8
Hours of sleep
Odd
s ra
tio (9
5% C
I) .
3.1
Gunderson, et al. AJE 2007
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.
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Childhood
• Beware of ‘catch up growth’
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Infant weight gain
02468
101214
Pre
vale
nce
over
wei
ght a
ge 7
ye
ars
WG5 WG3 WG1B
W1
BW
2
BW
3
BW
4
BW
5
Early infancy weight gain categories
Birth weight categories
Stettler N, Pediatrics 2002
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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
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First Steps for Mommy and Me
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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
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Breastfeeding Promotion
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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
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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)
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Preliminary Results – Weight for Length
Anthropometric Outcomes
Overall Intervention
Usual Care
P-value
N (%) or Mean (SD)Change in weight-for-length (WFL-Z), birth to 6-months
0.33 (1.5) 0.24 (1.5) 0.50 (1.4) 0.09
WFL >85th percentile at 6-months, N (%)
13 (15.5) 7 (11.7) 6 (25.0) 0.18
Highest quartile of WFL at 6-months, N (%)
23 (27.4) 13 (21.7) 10 (41.7) 0.04
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Intrauterine nutrition is not only about maternal behavior in pregnancy
Mom’s ownintrauterine
and childhoodexperiences
Mom’s peri-
conceptionalhealth
Utero-placental blood flow,placental function
Diet duringpregnancy
Fetalmetabolism
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IDM = infants of mothers with GDM
Boloker et al., Diabetes 2002;51(5):1499-506.
Intergenerational influences
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Mom’s own birth weight is associated with her risk for GDM
Innes et al., JAMA, 2002
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Intrauterine nutrition is not only about maternal behavior in pregnancy
Mom’s ownintrauterine
and childhoodexperiences
Mom’s peri-
conceptionalhealth
Utero-placental blood flow,placental function
Diet duringpregnancy
Fetalmetabolism
Extrauterine environment
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SGA and LGA trends since 1990
Oken et al. Obstet Gynecol. 2010 Feb;115(2 Pt 1):357-64
0.9
-2.2
-3
-2
-1
0
1
2
3
1990 1995 2000 2005Year
Cha
nge
in %
SG
A o
r LG
A fr
om 1
990 Small for Gestational Age,
Low-Risk Subgroup
Large for Gestational Age,Low-Risk Subgroup
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SGA and LGA trends since 1990
Oken et al. Obstet Gynecol. 2010 Feb;115(2 Pt 1):357-64
0.9
-2.2
-3
-2
-1
0
1
2
3
1990 1995 2000 2005Year
Cha
nge
in %
SG
A o
r LG
A fr
om 1
990 Small for Gestational Age,
Low-Risk Subgroup
Large for Gestational Age,Low-Risk Subgroup
SGA
LGA
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Birth weight trends since 1990
Oken et al. Obstet Gynecol. 2010 Feb;115(2 Pt 1):357-64
-51
-79
-100
-80
-60
-40
-20
0
1990 1995 2000 2005Year
Cha
nge
in B
irth
Wei
ght (
g) fr
om 1
990
All Births
Low Risk Subgroup
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Questions?“Anything on women of pre-childbearing age?”