Effects of maternal obesity on fetal growthand metabolic health of the offspringEmily Oken, MD, MPHObesity Prevention Prog...
051015PrevalenceofOverweightYear24-71 months0-11 months12-23 months1980 1985 1990 1995 2000Obesity increasing not only in ...
Lancet. 2010 May 15; 375(9727): 1737–1748.
‘Fetal Origins’ hypothesisDavid Barker.Mothers, Babies, andhealth in later life.
‘Developmental Origins’ and obesityHediger et al., Pediatrics, 1998; Sorensen et al., BMJ 1997; Innes et al. JAMA 20022122...
Oken, Ob Gyn Clinics of N. America, 2009; NHANES dataMaternal obesity01020304050601960-1962 1971-1974 1976-1980 1988-1994 ...
Heslehurst, et al. Obesity Reviews 2008. Meta-analysis of published cohort studies.2.361.311.000.52322532813429333400.511....
Birth defects – meta-analysis• Infants of obese mothers at increased risk for:– neural tube defects (OR 1.87; 95% CI, 1.62...
Stillbirth2.07 (1.59, 2.74)
NICU treatmentHeslehurst, et al. Obesity Reviews 2008. Meta-analysis of published cohort studies.1.35 (1.22, 1.49)
Neonatal outcomesHeslehurst, et al. Obesity Reviews 2008. Meta-analysis of published cohort studies.1.52.1 2.11.61.0 1.00....
Other neonatal outcomesHeslehurst, et al. Obesity Reviews 2008. Non meta-analysis results.No association: asphyxia, hyperb...
Infant deathChen A, et al. Epidemiology 2009;20:74-81.
Outcomes in childhood and beyond
Oken, Ob Gyn Clinics of N. America, 2009 Jun;36(2):361-77.Odds of child obesity for obese vs.normal weight mothers3.14.1 4...
Offspring of obese mothers havepoorer cardio-metabolic status At birth, higher body fat, reducedenergy expenditure, and m...
 GenesWhat accounts for associations ofmaternal weight with child weight?
Schultz et al. Diabetes Care 2006;29(8):1866-71Environment matters, too7%38%13%70%0%10%20%30%40%50%60%70%80%Type 2 Diabete...
The uterusis the environment of the fetus
 Genes Shared behaviors Parents and children tend to sharediet, physical activity habits (Oliveria etal, AJCN, 1992)Wha...
 Genes Shared behaviors Mediators Fetal growth GDM Breastfeeding Infant diet quality and feedinginteractionsWhat ac...
0.29-0.25-0.6-0.4-0.20.00.20.40.6<10 10-14 15-19 20-24 25-29 30-34 35-39 40-44 >=45Gestational weight gain (pounds)Changei...
 Genes Shared behaviors Mediators Confounders SES SmokingWhat accounts for associations ofmaternal weight with child...
Maternal prenatal smoking andchild overweight – meta-analysisOdds Ratio.5 1 5Combinedvon Kries, 2002Wideroe, 2003Whitaker,...
 Genes Shared behaviors Mediators Confounders Direct effect of “obese” intrauterineenvironmentWhat accounts for assoc...
Maternal diet0.1110Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4OddsRatioMaternal prenatal diet and child ow/obesity at age 5% Saturated Fat % S...
Obesity disproportionately affectsracial/ethnic minority children• In 2010: 14% of white, 24.3% of Black, and21.2% of Hisp...
Weights of children born before (BMS, n=45)and after (AMS, n=172) maternal weight-loss surgery0%10%20%30%40%50%60%Underwei...
Dabelea et al., Diabetes 2000. 19 Pima families/58 sibs
Animal studies suggested earlyenergy intake can permanentlyprogram body size75 days: Weights 86g, 230g21 days: Weights 14g...
Weight(g)Age (weeks)Food restriction during weeks 0-3results in sustained lower body weight(and food excess in higher weig...
Timing is importantweaningWeight(g)Later food restriction(weeks 9-12) - ratsquickly regain andperhaps overshootbody weight...
Offspring of overfed mother rats havehigher body weight …Samuelsson, A.-M. et al. Hypertension 2008;51:383-392Male offspri...
…higher fat mass…Samuelsson, A.-M. et al. Hypertension 2008;51:383-392OC – Offspring of control damsOO – Offspring of obes...
…higher energy intake…Samuelsson, A.-M. et al. Hypertension 2008;51:383-392Offspring of obese damsOffspring of control dam...
…and adverse cardio-metabolic profilesSamuelsson, A.-M. et al. Hypertension 2008;51:383-392OC – Offspring of control damsO...
Pathways linking maternal weightwith child outcomesMaternalpre-pregnancysizeGestationalweightgainChildadiposityBirthweight...
The microbiome and obesityHuh et al. Arch Dis Child 2012.Dominguez-Bello et al. Proc Natl AcadSci USA. 2010;107[26]:11973.)
„Agouti‟ mice - Genetic cause for obesityfirst identified >100 years agoThesemice areidenticaltwins!How do youget from her...
EpigeneticsGenes = hardwareEpigenetic markers = software
The PlacentaAl Wasel et al., Placenta 2010
DietExtrauterineenvironmentMom’s ownintrauterineand childhoodexperiencesMom’sprenatalhealthFetaland placentalmetabolismChi...
Inter- and trans-generational influencesKaati et al. European Journal of Human Genetics(2007) 15, 784–790Excess earlynutri...
Air pollution and obesityFleisch et al. Submitted.FleischEtal0.11101 2 3 4 5Black CarbonTraffic DensityQuintileOverweighta...
Built environmentAir PollutionSocial stressorsOvernutritionWhich comes first?
Taveras et al. Arch Ped Adol Med 2012.What can you do after birth?• Watch out foracceleratedpostnatal growth
What can you do after birth?• Watch out foracceleratedpostnatal growth• Promotepostpartumweight lossLarge for Gestational ...
Dabelea D, et al. Diabetes Care 2008;31(7):1422-6. 79 youth aged 10-22y with Type2 DM and 190 nondiabetic controls% expose...
Oken o&p2013
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  • Thanks so much to the organizers for inviting me to speak here today. It is a great pleasure to be here among such an impressive group of co-speakers, and all of you.Evidence has been accumulating for several decades that risk for chronic health conditions, including obesity has its origins in very early life. As this field if inquiry has begun to pervade the popular press, including books, magazines, and the internet, it is increasingly common for our patients to come to us with questions about the strength of this evidence, and what individuals can do to optimize the health of their children.
  • In research, we generally measure not only height, weight, and BMI, which are indirect measures of adiposity, but also more direct measures of fat and lean mass such as a DEXA scan. This one was taken of a young girl with a BMI of 38 kg/m2. We care about excess adiposity in childhood not only because of its association with chronic disease risk in adulthood, but also because of accumulating evidence that obese kids are at higher risk of a panoply of adverse outcomes on organ systems ranging from the brain to the bones, even when they are still children.
  • Oken o&p2013

    1. 1. Effects of maternal obesity on fetal growthand metabolic health of the offspringEmily Oken, MD, MPHObesity Prevention ProgramDepartment of Population MedicineHarvard Medical School and Harvard Pilgrim Health Care Institute
    2. 2. 051015PrevalenceofOverweightYear24-71 months0-11 months12-23 months1980 1985 1990 1995 2000Obesity increasing not only in adults andchildren, also in infantsKim et al., Obesity 2006; ~500,000 well child visits in Mass.
    3. 3. Lancet. 2010 May 15; 375(9727): 1737–1748.
    4. 4. ‘Fetal Origins’ hypothesisDavid Barker.Mothers, Babies, andhealth in later life.
    5. 5. ‘Developmental Origins’ and obesityHediger et al., Pediatrics, 1998; Sorensen et al., BMJ 1997; Innes et al. JAMA 20022122232425<2.5 2.5-3.0 3.0-3.5 3.5-4.0 4.0-4.5 >4.5AdultBMI(kg/sqm)Birthweight(kg)
    6. 6. Oken, Ob Gyn Clinics of N. America, 2009; NHANES dataMaternal obesity01020304050601960-1962 1971-1974 1976-1980 1988-1994 1999-2002 2005-2008PercentageOverweight (BMI >= 25.0)Obese (BMI >= 30.0)
    7. 7. Heslehurst, et al. Obesity Reviews 2008. Meta-analysis of published cohort studies.2.361.311.000.52322532813429333400.511.522.53Underweight Normal Overweight ObeseMaternal BMIOddsRatio31003200330034003500Meanbirthweight(g)Odds of high birth weightMean birth weightMaternal weight predicts fetal growth
    8. 8. Birth defects – meta-analysis• Infants of obese mothers at increased risk for:– neural tube defects (OR 1.87; 95% CI, 1.62-2.15)– spina bifida (OR 2.24; 95% CI, 1.86-2.69)– cardiovascular anomalies (OR 1.30; 95% CI, 1.12-1.51)– septal anomalies (OR 1.20; 95% CI, 1.09-1.31)– cleft palate (OR 1.23; 95% CI, 1.03-1.47)– cleft lip and palate (OR 1.20; 95% CI, 1.03-1.40)– anorectal atresia (OR, 1.48; 95% CI, 1.12-1.97)– hydrocephaly (OR 1.68; 95% CI, 1.19-2.36)– limb reduction anomalies (OR 1.34; 95% CI, 1.03-1.73)• Lower risk for:– gastroschisis (OR 0.17; 95% CI, 0.10-0.30).Stothard KJ, et al. JAMA 2009;301(6):636-650
    9. 9. Stillbirth2.07 (1.59, 2.74)
    10. 10. NICU treatmentHeslehurst, et al. Obesity Reviews 2008. Meta-analysis of published cohort studies.1.35 (1.22, 1.49)
    11. 11. Neonatal outcomesHeslehurst, et al. Obesity Reviews 2008. Meta-analysis of published cohort studies.1.52.1 2.11.61.0 1.00.1110Low 1mApgarLow 5mApgarFetalcompromiseMeconium ShoulderdystociaJaundiceOddsRatio(95%CI)n=3 n=4 n=4 n=5 n=9 n=4
    12. 12. Other neonatal outcomesHeslehurst, et al. Obesity Reviews 2008. Non meta-analysis results.No association: asphyxia, hyperbilirubinemia, hypoglycemia, cord pH<7.21.6 1.7 1.81.31.5 1.5110IncubatorrequirementRespiratorydistressResuscitation Fetal heartrateabnormalitiesTube feedingrequiredBirth traumaOddsRatio(95%CI)
    13. 13. Infant deathChen A, et al. Epidemiology 2009;20:74-81.
    14. 14. Outcomes in childhood and beyond
    15. 15. Oken, Ob Gyn Clinics of N. America, 2009 Jun;36(2):361-77.Odds of child obesity for obese vs.normal weight mothers3.14.1 4.35.14.3110Whitaker 2004(age 4)Li 2005 (ages2-14)Reilly 2005(age 7)Li 2007 (Ages2-12, earlyonset)Salsberry 2007(ages 12-13)Author, year, child ageOddsratioforchildobesity
    16. 16. Offspring of obese mothers havepoorer cardio-metabolic status At birth, higher body fat, reducedenergy expenditure, and moreatherogenic lipid profiles In childhood, higher bloodpressure, risk for metabolicsyndrome - even afteradjustment for attained BMI In adulthood, increased risk ofdeath from coronary heart diseaseOken, Ob Gyn Clinics of N. America, 2009 Jun;36(2):361-77.
    17. 17.  GenesWhat accounts for associations ofmaternal weight with child weight?
    18. 18. Schultz et al. Diabetes Care 2006;29(8):1866-71Environment matters, too7%38%13%70%0%10%20%30%40%50%60%70%80%Type 2 Diabetes ObesityMexicoUnited States
    19. 19. The uterusis the environment of the fetus
    20. 20.  Genes Shared behaviors Parents and children tend to sharediet, physical activity habits (Oliveria etal, AJCN, 1992)What accounts for associations ofmaternal weight with child weight?
    21. 21.  Genes Shared behaviors Mediators Fetal growth GDM Breastfeeding Infant diet quality and feedinginteractionsWhat accounts for associations ofmaternal weight with child weight?
    22. 22. 0.29-0.25-0.6-0.4-0.20.00.20.40.6<10 10-14 15-19 20-24 25-29 30-34 35-39 40-44 >=45Gestational weight gain (pounds)ChangeinchildBMIz-scoreWithout adjustment for maternal BMIWith adjustment for maternal BMIIOM 2009;Oken et al., AJOG 2008Gestational weight gainDistribution of GWG relative to 1990 guidby prepregnancy BMI category (PRAMS, 2Body mass index category (IOM criteriUnder- Normal- Over- ObeseProportion(%)ofwomen020406080100120weight weight weight< IOM Within IOM > IOM19.549.930.638.441.120.56326.810.336.330.223.5(25-35 lb)(15-25 lb)(12-20 lb)(28-40 lb)
    23. 23.  Genes Shared behaviors Mediators Confounders SES SmokingWhat accounts for associations ofmaternal weight with child weight?
    24. 24. Maternal prenatal smoking andchild overweight – meta-analysisOdds Ratio.5 1 5Combinedvon Kries, 2002Wideroe, 2003Whitaker, 2004Toschke, 2003Toschke, 2002Salsberry, 2005Reilly, 2005Power, 2002 MPower, 2002 FOken, 2005Dubois, 2006Chen, 2006 MChen, 2006 FBergmann, 2003Al Mamun, 2006Adams, 2005OR 1.50, 95% CI: 1.36, 1.65Oken, et al. Int J Obes (Lond) 2008; 32(2):201-10
    25. 25.  Genes Shared behaviors Mediators Confounders Direct effect of “obese” intrauterineenvironmentWhat accounts for associations ofmaternal weight with child weight?
    26. 26. Maternal diet0.1110Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4OddsRatioMaternal prenatal diet and child ow/obesity at age 5% Saturated Fat % SugarMurrin et al. EJCN 2013Donahue et al. AJCN 2011
    27. 27. Obesity disproportionately affectsracial/ethnic minority children• In 2010: 14% of white, 24.3% of Black, and21.2% of Hispanic children 2-19 yearswere obese• Overall rates are stubbornly high;racial/ethnic disparities are starting earlyand appear to be wideningOgden et al. JAMA 2012.Weden et al. AJPH 2012.0510152025Non-HispanicWhiteNon-HispanicBlackHispanic1.591.461.18Odds of obesity for black vs. white children in the USAdjusted forsociodemographiccharacteristicsAdjusted forprenatal &perinatalfactors• Pre- and peri-natalfactors explainmost of thedisparity in obesity
    28. 28. Weights of children born before (BMS, n=45)and after (AMS, n=172) maternal weight-loss surgery0%10%20%30%40%50%60%Underweight Normal weight Overweight ObeseBMSAMSKral JG, et al. Pediatrics. 2006 Dec;118(6):e1644-9
    29. 29. Dabelea et al., Diabetes 2000. 19 Pima families/58 sibs
    30. 30. Animal studies suggested earlyenergy intake can permanentlyprogram body size75 days: Weights 86g, 230g21 days: Weights 14g, 60gWiddowson and McCance, 1960
    31. 31. Weight(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 restrictionweaning
    32. 32. Timing is importantweaningWeight(g)Later food restriction(weeks 9-12) - ratsquickly regain andperhaps overshootbody weightAge (weeks)Widdowson and McCance, 196321 day period of food restriction
    33. 33. Offspring of overfed mother rats havehigher body weight …Samuelsson, A.-M. et al. Hypertension 2008;51:383-392Male offspring Female offspringOffspring of obese damsOffspring of control damsOffspring of obese damsOffspring of control dams
    34. 34. …higher fat mass…Samuelsson, A.-M. et al. Hypertension 2008;51:383-392OC – Offspring of control damsOO – Offspring of obese dams
    35. 35. …higher energy intake…Samuelsson, A.-M. et al. Hypertension 2008;51:383-392Offspring of obese damsOffspring of control damsOffspring of obese damsOffspring of control dams
    36. 36. …and adverse cardio-metabolic profilesSamuelsson, A.-M. et al. Hypertension 2008;51:383-392OC – Offspring of control damsOO – Offspring of obese dams
    37. 37. Pathways linking maternal weightwith child outcomesMaternalpre-pregnancysizeGestationalweightgainChildadiposityBirthweightDiseaseoutcomesFetalgrowthGestationlengthShared genes and behaviorsGestationalDiabetesInfantfeeding &growthOken, E. In “Influence of Pregnancy weight on maternal and child health.” IOM 2007.
    38. 38. The microbiome and obesityHuh et al. Arch Dis Child 2012.Dominguez-Bello et al. Proc Natl AcadSci USA. 2010;107[26]:11973.)
    39. 39. „Agouti‟ mice - Genetic cause for obesityfirst identified >100 years agoThesemice areidenticaltwins!How do youget from hereback tohere?
    40. 40. EpigeneticsGenes = hardwareEpigenetic markers = software
    41. 41. The PlacentaAl Wasel et al., Placenta 2010
    42. 42. DietExtrauterineenvironmentMom’s ownintrauterineand childhoodexperiencesMom’sprenatalhealthFetaland placentalmetabolismChild growthand behaviors
    43. 43. Inter- and trans-generational influencesKaati et al. European Journal of Human Genetics(2007) 15, 784–790Excess earlynutritionin grandmother(pink line)results in shorterlifespan ingrandchildInnes et al,. JAMA 2002Longevity of grandchild
    44. 44. Air pollution and obesityFleisch et al. Submitted.FleischEtal0.11101 2 3 4 5Black CarbonTraffic DensityQuintileOverweightat6m
    45. 45. Built environmentAir PollutionSocial stressorsOvernutritionWhich comes first?
    46. 46. Taveras et al. Arch Ped Adol Med 2012.What can you do after birth?• Watch out foracceleratedpostnatal growth
    47. 47. What can you do after birth?• Watch out foracceleratedpostnatal growth• Promotepostpartumweight lossLarge for Gestational Age0.1110<-1 -1 to <1 1 to <2 2 to <3 >= 3Change in BMIOddsRatioBMI < 25BMI >= 25Gestational Diabetes0.1110<-1 -1 to <1 1 to <2 2 to <3 >= 3Change in BMIOddsRatioBMI < 25BMI >= 25
    48. 48. Dabelea D, et al. Diabetes Care 2008;31(7):1422-6. 79 youth aged 10-22y with Type2 DM and 190 nondiabetic controls% exposed to maternal diabetes % exposed to maternal obesityCasesControlsWhat is the impact?Overall, 47.2% (95% CI 30.9–63.5) of type 2 diabetes inyouth could be attributed to intrauterine exposure tomaternal diabetes and obesity.
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