Gillman/Intergenerational Cycles ofObesity2010: 1/3 obese, ½ overweight/obeseIncreased risk of adverse pregnancy outcomes ...
Avoid excessive GWGRCT of limiting GWGsLIMIT trialHealthy MOMSTreatment of GDMACHOIS and MFMUPima Indians sib pair studies...
Butte/Guidelines for IOM GWGExcessive GWG in overweight and obeseAssociations:C/S, postpartum weight retentionpreterm birt...
GWG-SPECIFIC RISKS FOR PREGNANCY OUTCOMESBY PREPREGNANCY BMI CATEGORY AMONGPRIMIPAROUS WOMEN
IOM 2009 GWGRecommendationsPrepregnancy BMIcategoryTotal weight gain(lb, kg)Rate of weight gain2ndand 3rdtrimester(lb/wk, ...
Freeman/Obesity: Metabolic Adaptationsto PregnancyMetabolic adaptations: normal pregnancyearly pregnancy increased adipoge...
Perlow/Strategies to Improve PerinatalOutcomesPerinatal complicationspreeclampsia, IUFD, C/S, operative delivery, GDM,shou...
Friedman/Transgenerational Effects ofMaternal NutritionConcepts or fetal programmingepigenome: lipid excess, oxidative str...
Friedman/Transgenerational Effects ofMaternal NutritionLong-term follow-up:persistent liver TG/macrophage with maternal HF...
Ozanne/Mechanisms UnderlyingMetabolic Programming by MaternalObesityHumanSib-pair studies (GDM/bariatric surgery) GDM RXAn...
Ozanne/Mechanisms UnderlyingMetabolic Programming by MaternalObesityPost receptor insulin signaling defectsIRS-1 p110 beta...
Hauguel DeMouzon/Molecular Signals atthe Maternal-Featal InterfaceExposomeLeptin stimulates inflammatory pathways in thepl...
Hauguel DeMouzon/Molecular Signals atthe Maternal-Fetal InterfaceCell Free DNAmaternal/placenta sourcesincreases from mate...
Van Den Bergh/Maternal Obesity andChild Brain DevelopmentNeurocognitive Overviewreview: increased risk of cognitive delay,...
Van Den Bergh/Maternal Obesity andChild Brain DevelopmentMechanismsHigh fat and high CHO diets, infectionsEvaluation of th...
Oken/Fetal Growth and Metabolic Healthof the OffspringAdverse Perinatal Effects of Maternal Obesityshort-term; congenital ...
Powell/Placental Function in ObeseMexican American MothersMetabolic Phenotypenormal glucose, hyperinsulinemia, hyperleptin...
Powell/Placental Function in ObeseMexican American MothersTLR-4activated with oleic acid in System A activityTNF alphaincr...
Vinter/Lifestyle Interventions DuringPregnancyTypes of lifestyle interventionsdiet, physical activity, behavioralEvaluatio...
Webber/Preconception Care in ObeseWomenEducational objectives (primary care for women)undiagnosed poorly controlled medica...
Webber/Preconception Care in ObeseWomenWhypoor quality embryo and implantationWeight reduction5% GWL associated with impro...
Webber/Preconception Care in ObeseWomenEducational objectives (primary care for women)undiagnosed poorly controlled medica...
Devlieger/Bariatric SurgeryBariatric surgery has an important and complexinfluence on fertility in womenPregnancy after ba...
Clinical Recommendationsfor Obese Pregnant WomenQuestions which were not addressed in depthspecific physical activity reco...
Clinical Recommendationsfor Obese Pregnant WomenGestational Weight GainIOM guidelinesother?Gestational Weight < IOM0-5 Kgw...
Clinical Recommendationsfor Obese Pregnant WomenPhysical Activity (lifestyle interventions)ACOG guidelinesInitiate physica...
Clinical Recommendationsfor Obese Pregnant WomenBreastfeedinghow long is optimal?what benefits?Does breast milk vary depen...
Clinical Recommendationsfor Obese Pregnant WomenContraception50% of pregnancies in the US unplannedWhat is optimal contrac...
Research Questions/Priorities
Gillman/Intergenerational Cycles ofObesityWhere and when to intervene to prevent childhood obesityOnce pregnancy begins, e...
Freeman/Obesity: Metabolic Adaptationsto PregnancyPregnancy complicationsectopic fat distribution, increased lipolysis/NEF...
Perlow/Strategies to Improve PerinatalOutcomesPrenatal managementscreen for diabetes, HTN, EKG/ECHO, ultrasound,MSAFP, ant...
Ozanne/Mechanisms UnderlyingMetabolic Programming by MaternalObesityEarly tissue markersplacenta/cord bloodTime windows?in...
Friedman/Transgenerational Effects ofMaternal NutritionBased on the non-human primate work where do we goin the human?Resv...
Hauguel DeMouzon/Molecular Signals atthe Maternal-Featal InterfaceImmune pathwaysincrease LPS concentrations in obese wome...
Van Den Bergh/Maternal Obesity andChild Brain DevelopmentDOBHaD paradigmBidirectional interactional process: genes andenvi...
Oken/Fetal Growth and Metabolic Healthof the OffspringIntrauterine environmentenvironmental exposomeair pollution, PCBs, P...
Powell/Placental Function in ObeseMexican American MothersMetabolic Phenotypenormal glucose, hyperinsulinemia, hyperleptin...
Vinter/Lifestyle Interventions DuringPregnancyLifestyle interventions + nutrient supplementsdiet, physical activity, behav...
Webber/Preconception Care in ObeseWomenHow much gestational weight reduction5% , 10%, 15% more?
Devlieger/Bariatric SurgeryBariatric surgery has an important and complexinfluence on fertility in womenWhen to recommnend...
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Wrap up o&p2013

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Wrap up o&p2013

  1. 1. Gillman/Intergenerational Cycles ofObesity2010: 1/3 obese, ½ overweight/obeseIncreased risk of adverse pregnancy outcomes for e.g.GDM,HTN,C/SPostpartum weight retention and lower rates of breastfeedingOffspring are heavier at birth and at increased risk forchildhood obesityWhere and when to interveneOnce pregnancy begins, decrease GWGMetabolic intervention, treat GDMPreconception intervention
  2. 2. Avoid excessive GWGRCT of limiting GWGsLIMIT trialHealthy MOMSTreatment of GDMACHOIS and MFMUPima Indians sib pair studiesEarly follow-up of the Achois; no effect on childhood obesityPre-pregnancy obesityMore challenging issue? Adverse outcomesGillman/Intergenerational Cycles ofObesity
  3. 3. Butte/Guidelines for IOM GWGExcessive GWG in overweight and obeseAssociations:C/S, postpartum weight retentionpreterm birth, LGA, SGA, childhood obesityDanish birth cohort dataGWG guidelines outside the US(13 countries) 7 similar to IOMIs there a role for gestational weight loss (GWL) todecrease adverse pregnancy outcomes?higher in obese women vs. normal weight womenDecreased C/S, LGA, HTN, and ? increased SGA, varies byobesity class I, II, IIICochrane reviewNo (RCTs) effectiveness of GWL need further study toevaluate benefits/risks
  4. 4. GWG-SPECIFIC RISKS FOR PREGNANCY OUTCOMESBY PREPREGNANCY BMI CATEGORY AMONGPRIMIPAROUS WOMEN
  5. 5. IOM 2009 GWGRecommendationsPrepregnancy BMIcategoryTotal weight gain(lb, kg)Rate of weight gain2ndand 3rdtrimester(lb/wk, kg/wk)Underweight(< 18.5 kg/m2)28-40, 12.5-18 1.0 (1.0-1.3),0.51 (0.44-0.58)Normal-weight(18.5-24.9 kg/m2)25-35, 11.5-16 1.0 (0.8-1.0),0.42 (0.35-0.50)Overweight(25.0-29.9 kg/m2)15-25, 7-11.5 0.6 (0.5-0.7),0.28 (0.23-0.33)Obese**(≥ 30.0 kg/m2)11-20, 5-9 0.5 (0.4-0.6),0.22 (0.17-0.27)*Calculations assume a first-trimester weight gain of 1.1-4.4 lb (0.5-2.0 kg)** 1990 IOM Recommendation: for obese women (BMI>29), weight gain at least 6.8 kg (15 lb)
  6. 6. Freeman/Obesity: Metabolic Adaptationsto PregnancyMetabolic adaptations: normal pregnancyearly pregnancy increased adipogenesislate pregnancy increased adipose turnoverTurnover higher in subcutaneous vs. visceral fathigh TG; decreased vascular functionhigh HDL prevents activation of ROSMetabolic adaptations: obese pregnancypre-pregnancy lipid metabolismdecreased metabolic flexibilityPregnancy complications (HTN)ectopic fat distribution, increased lipolysis/NEFAoxidative stress and endothelial dysfunction
  7. 7. Perlow/Strategies to Improve PerinatalOutcomesPerinatal complicationspreeclampsia, IUFD, C/S, operative delivery, GDM,shoulder dystocia, macrosomia (>4500g)Increased risk of congenital anomalies (earlyfirst trimester)SAB, NTD, cardiac malformationsDifficulty with detection of anomalieslimitations of ultrasounddecreased concentrations of cell free DNAPrenatal managementscreen for diabetes, HTN, EKG/ECHO, ultrasound,MSAFP, antenatal testing, team approach for C/Se.g. early epidural, evaluate for OSA
  8. 8. Friedman/Transgenerational Effects ofMaternal NutritionConcepts or fetal programmingepigenome: lipid excess, oxidative stressstem cells: increased propensity for adipogenesisMaternal/Fetal: Metabalome/epigenomeMicrobiomechanges over the course of pregnancydifferent microbiome based on route of deliveryNon-Human Primates (HFD)fetal fatty liver/inflammationrole of saturated fat (n-6/n-3)placental cytokineslong-term follow-up: persistent liver TG/macrophagewith maternal HFD
  9. 9. Friedman/Transgenerational Effects ofMaternal NutritionLong-term follow-up:persistent liver TG/macrophage with maternal HFDHUMANIncreased skinfolds, no increase in visceral fat butincreased liver fat.Correlate of maternal pregravid BMIModifications?omega-3Resveratrol
  10. 10. Ozanne/Mechanisms UnderlyingMetabolic Programming by MaternalObesityHumanSib-pair studies (GDM/bariatric surgery) GDM RXAnimal (rodent) modelshighly palatable dietsgestation/lactation; Mat IGT, hyper-leptin/insulinOffspring follow up: wean to control diet(8 weeks): obeseHTN, IGT, IR, fatty liverOffspring follow up: (4 weeks): Nl weightcardiac hypertrophy/ IR (hyperinsulinemia)muscle, liver, adipose; insulin signaling defects
  11. 11. Ozanne/Mechanisms UnderlyingMetabolic Programming by MaternalObesityPost receptor insulin signaling defectsIRS-1 p110 betaMechanismno difference in m RNA/transcription? micro RNA increased (IRS-1)/translationHuman data/ what to target?glucose/insulin/lipids/GWG/inflammation/placentaBest metabolic markers:offspring insulinMaternal Insulin, but not obesity or leptinCardiac hypertrophycholesterol
  12. 12. Hauguel DeMouzon/Molecular Signals atthe Maternal-Featal InterfaceExposomeLeptin stimulates inflammatory pathways in theplacenta, and mitogenesisAdiponectinnot expressed in the placenta+ placental adiponectin receptorsdecrease placental amino acid transportImmune pathwaysincrease LPS concentrations in obese womenincreased placental inflammation TLR4saturated FFA stimulate:placental TLR4 expression/IL-6 and TNF
  13. 13. Hauguel DeMouzon/Molecular Signals atthe Maternal-Fetal InterfaceCell Free DNAmaternal/placenta sourcesincreases from maternal but not placental sources? related to adipose cell apoptosis
  14. 14. Van Den Bergh/Maternal Obesity andChild Brain DevelopmentNeurocognitive Overviewreview: increased risk of cognitive delay, lowverbal/reading skills as well ADHD and ADSMechanismsstress, nutritional (Vit. D), GDM etc.Confoundersdevelop interventional studies, timing ofinterventionsDOBHaD paradigmBidirectional interactional process: genes andenvironmentbrain development, neurotransmitters, immuneactivity HPA axis/ANS
  15. 15. Van Den Bergh/Maternal Obesity andChild Brain DevelopmentMechanismsHigh fat and high CHO diets, infectionsEvaluation of the Child in models of Mat anxietyEEG responsepossibly related to later life appetite and otherbehaviors
  16. 16. Oken/Fetal Growth and Metabolic Healthof the OffspringAdverse Perinatal Effects of Maternal Obesityshort-term; congenital anomalies, stillbirthlong-term; metabolic dysfunctionGenes vs. EnvironmentPima Indianspostnatal shared risks/common environmentair pollutionConfoundersSES, SmokingObese intrauterine environmentdiet quality, omega-3, health care disparities,bariatric surgery
  17. 17. Powell/Placental Function in ObeseMexican American MothersMetabolic Phenotypenormal glucose, hyperinsulinemia, hyperleptinemia,hyperlipidemia lower Adpn, high TNF but not IL-6Placental physiologysyncytiotrophoblast: BM/MVMMVM [Glut 1] correlated with birth weightMVM AA transporters System A and Lincrease SNAT 1correlates with birth weightBM fatty acids FATP2 increased in obese mothersRegulation of Nutrient transportinsulin/leptin stimulate system A activitymTOR responds to leptin, insulin, cytokines etc
  18. 18. Powell/Placental Function in ObeseMexican American MothersTLR-4activated with oleic acid in System A activityTNF alphaincrease AA transportOmega DHA supplementationplacental DHA correlates with maternal DHAdecreasing System A and L activityincreased GLUT 1 and FATB4Adiponectindecreased System A and L and pup sizemodulates nutrient transport
  19. 19. Vinter/Lifestyle Interventions DuringPregnancyTypes of lifestyle interventionsdiet, physical activity, behavioralEvaluationGWG, GDM, HTN, birth weight, long-term outcomesIntervention studiesdecreased GWG, decreased anxiety, GDM,LIP/LIPO studiesMeta-Analyses (quality of data?)1.4 kg decrease in GWG, HTN, shoulder dystociaInter-pregnancy weight loss/gain
  20. 20. Webber/Preconception Care in ObeseWomenEducational objectives (primary care for women)undiagnosed poorly controlled medical conditions,immunizations, nutrition, genetics, substance abuse,environmental, social, mental health, isolationPreconceptionweight reduction, bariatric surgery, risks duringpregnancy, nutritional supplementsWeight reductiongoals?Impact on fertilitydecreased conception rate, ovulation/PCOS,ovulation induction
  21. 21. Webber/Preconception Care in ObeseWomenWhypoor quality embryo and implantationWeight reduction5% GWL associated with improved ovulation andpregnancy rateSupplementsconsider folic acid, vitamin D
  22. 22. Webber/Preconception Care in ObeseWomenEducational objectives (primary care for women)undiagnosed poorly controlled medical conditions,immunizations, nutrition, genetics, substance abuse,environmental, social, mental health, isolationPreconceptionweight reduction, bariatric surgery, risks duringpregnancy, nutritional supplementsWeight reductiongoals?Impact on fertilitydecreased conception rate, ovulation/PCOS,ovulation induction
  23. 23. Devlieger/Bariatric SurgeryBariatric surgery has an important and complexinfluence on fertility in womenPregnancy after bariatric surgery is best delayeduntil after the period of rapid weight loss.Obesity surgery reduces the obesity-related risksduring pregnancy like GDM, macrosomia, &hypertension...but increases the risk for growthretardation, and prematurity.Nutritional deficiencies are frequent after all types ofbariatric surgery and need to be actively detectedand corrected.Surgical complications of bariatric patients duringpregnancy need to be taken seriously.
  24. 24. Clinical Recommendationsfor Obese Pregnant WomenQuestions which were not addressed in depthspecific physical activity recommendationsfetal gender differencescontraception
  25. 25. Clinical Recommendationsfor Obese Pregnant WomenGestational Weight GainIOM guidelinesother?Gestational Weight < IOM0-5 Kgweight loss?
  26. 26. Clinical Recommendationsfor Obese Pregnant WomenPhysical Activity (lifestyle interventions)ACOG guidelinesInitiate physical activity during pregnancyif so what activity and how muchInitiate dietary changesLow simple sugar, high complex carbohydratesdecrease saturated fats, increase PUFAs andMUFA’s?Other factors?Affordability, culturally sensitive
  27. 27. Clinical Recommendationsfor Obese Pregnant WomenBreastfeedinghow long is optimal?what benefits?Does breast milk vary depending on the mother’smetabolic status?Is all human breast milk the same?
  28. 28. Clinical Recommendationsfor Obese Pregnant WomenContraception50% of pregnancies in the US unplannedWhat is optimal contraception for obese women
  29. 29. Research Questions/Priorities
  30. 30. Gillman/Intergenerational Cycles ofObesityWhere and when to intervene to prevent childhood obesityOnce pregnancy begins, e.g. decrease GWGMetabolic intervention, treat GDMPreconception intervention
  31. 31. Freeman/Obesity: Metabolic Adaptationsto PregnancyPregnancy complicationsectopic fat distribution, increased lipolysis/NEFAoxidative stress and endothelial dysfunctionIs there a role for antioxidants?
  32. 32. Perlow/Strategies to Improve PerinatalOutcomesPrenatal managementscreen for diabetes, HTN, EKG/ECHO, ultrasound,MSAFP, antenatal testing, team approach for C/Se.g. early epidural, evaluate for OSA.Nutrient supplements?
  33. 33. Ozanne/Mechanisms UnderlyingMetabolic Programming by MaternalObesityEarly tissue markersplacenta/cord bloodTime windows?in utero vs. early neonatal periodTargeted interventionsappropriate individuals/ benefits/risks
  34. 34. Friedman/Transgenerational Effects ofMaternal NutritionBased on the non-human primate work where do we goin the human?ResveratrolOmega-3
  35. 35. Hauguel DeMouzon/Molecular Signals atthe Maternal-Featal InterfaceImmune pathwaysincrease LPS concentrations in obese womenincreased placental inflammation TLR4saturated FFA stimulate:placental TLR4 expression/IL-6 and TNFIs diet/microbiome the key?
  36. 36. Van Den Bergh/Maternal Obesity andChild Brain DevelopmentDOBHaD paradigmBidirectional interactional process: genes andenvironmentbrain development, neurotransmitters, immuneactivity HPA axis/ANSHow much follow-up is necessary/plasticity?
  37. 37. Oken/Fetal Growth and Metabolic Healthof the OffspringIntrauterine environmentenvironmental exposomeair pollution, PCBs, Phthalates
  38. 38. Powell/Placental Function in ObeseMexican American MothersMetabolic Phenotypenormal glucose, hyperinsulinemia, hyperleptinemia,hyperlipidemia lower Adpn, high TNF but not IL-6Improve insulin sensitivityMetformin, TZDs
  39. 39. Vinter/Lifestyle Interventions DuringPregnancyLifestyle interventions + nutrient supplementsdiet, physical activity, behavioralomega-3, vit D, folic acidDo we continue with exercise recommendationsduring pregnancy?
  40. 40. Webber/Preconception Care in ObeseWomenHow much gestational weight reduction5% , 10%, 15% more?
  41. 41. Devlieger/Bariatric SurgeryBariatric surgery has an important and complexinfluence on fertility in womenWhen to recommnend?How young is too young?

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