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.
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
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.
‘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 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)
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)
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
Oken, Ob Gyn Clinics of N. America, 2009 Jun;36(2):361-77.Odds of child obesity for obese vs.normal weight mothers3.14.1 184.108.40.20610Whitaker 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
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.
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 Diabetes ObesityMexicoUnited States
Genes Shared behaviors Mediators Confounders Direct effect of “obese” intrauterineenvironmentWhat accounts for associations ofmaternal weight with child weight?
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
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
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
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, 60gWiddowson and McCance, 1960
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
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
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
…higher fat mass…Samuelsson, A.-M. et al. Hypertension 2008;51:383-392OC – Offspring of control damsOO – Offspring of obese dams
…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
…and adverse cardio-metabolic profilesSamuelsson, A.-M. et al. Hypertension 2008;51:383-392OC – Offspring of control damsOO – Offspring of obese dams
Pathways linking maternal weightwith child outcomesMaternalpre-pregnancysizeGestationalweightgainChildadiposityBirthweightDiseaseoutcomesFetalgrowthGestationlengthShared genes and behaviorsGestationalDiabetesInfantfeeding &growthOken, E. In “Influence of Pregnancy weight on maternal and child health.” IOM 2007.
The microbiome and obesityHuh et al. Arch Dis Child 2012.Dominguez-Bello et al. Proc Natl AcadSci USA. 2010;107:11973.)
„Agouti‟ mice - Genetic cause for obesityfirst identified >100 years agoThesemice areidenticaltwins!How do youget from hereback tohere?
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
Air pollution and obesityFleisch et al. Submitted.FleischEtal0.11101 2 3 4 5Black CarbonTraffic DensityQuintileOverweightat6m
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 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
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.