Note: for non-commercial purpose only Parental BMI, gestational weight gain and childhood cardio-metabolic outcomes Romy Gaillard Power of Programming Conference Munich, 13 March 2014
Maternal obesity Prevalence The prevalence of obesity among women of reproductive age is strongly increasing Haslam et al, 2005
Maternal obesity Childhood obesity PLoS One. 2013
Fetal overnutrition hypothesis Poston L, 2012
Intra-uterine mechanisms or confounding factors? Approaches for assessing causality in observational data: Within siblings comparison study Mendelian randomization study Parental-offspring associations comparison study
Intra-uterine mechanisms or confounding factors? Approaches for assessing causality in observational data: Within siblings comparison study Mendelian randomization study Parental-offspring associations comparison study Comparing associations of maternal and paternal prepregnancy BMI with childhood BMI: Maternal-offspring association > paternal-offspring association: potential intra-uterine mechanism Maternal-offspring association =< paternal-offspring association: environmental or genetic factors
Parental BMI and childhood BMI Studies comparing effect of maternal and paternal BMI with offspring BMI have shown conflicting results: Largest studies suggested no differences in magnitude of maternal and paternal-offspring associations Not much is known about parental BMI and other childhood cardio- metabolic outcomes
The Generation R Study Prospective cohort study Fetal life until young adulthood Urban, multi-ethnic population, Rotterdam In-depth phenotyping Follow-up to 6 jaar >85% Childhood Maternal BMI Infant growth cardio-metabolic Maximum weight gain during pregnancy Paternal BMI outcomes 20 weeks 30 weeks 12 weeks Birth 1-4 years 6 years Second trimester Third trimester First trimester Maternal weight
Maternal and paternal overweight and obesity Prevalences Paternal BMI Maternal BMI 60 60 50 50 40 40 30 30 20 20 10 10 0 0 underweight normal weight overweight obese Underweight Normal weight Overweight Obese Underweight Normal weight Overweight Obese
Maternal and paternal BMI Childhood BMI Maternal model Body mass index Paternal model Body mass index (SDS) (SDS) Basic model 0.27 (0.24, 0.29) Basis model 0.22 (0.19, 0.24) Confounder model 0.25 (0.23, 0.28) Confounder model 0.22 (0.19, 0.24) Mediator models Mediator models Pregnancy complications 0.25 (0.23, 0.28) - Maternal weight gain 0.28 (0.25, 0.31) - during pregnancy Birth characteristics 0.23 (0.20, 0.25) Birth characteristics 0.20 (0.18, 0.23) Infant growth 0.25 (0.22, 0.27) Infant growth 0.19 (0.16, 0.22) Fully adjusted model Fully adjusted model 0.19 (0.16, 0.22) 0.14 (0.11, 0.16) Gaillard R et al, 2014
Maternal and paternal BMI Childhood BMI Maternal model Body mass index Paternal model Body mass index (SDS) (SDS) Basic model 0.27 (0.24, 0.29) Basic model 0.22 (0.19, 0.24) Confounder model 0.25 (0.23, 0.28) Confounder model 0.22 (0.19, 0.24) Mediator models Mediator models Pregnancy complications 0.25 (0.23, 0.28) - Maternal weight gain 0.28 (0.25, 0.31) - during pregnancy Birth characteristics 0.23 (0.20, 0.25) Birth characteristics 0.20 (0.18, 0.23) Infant growth 0.25 (0.22, 0.27) Infant growth 0.19 (0.16, 0.22) Fully adjusted model Fully adjusted model 0.19 (0.16, 0.22) 0.14 (0.11, 0.16) Gaillard R et al, 2014
Maternal and paternal BMI Childhood BMI Maternal model Body mass index Paternal model Body mass index (SDS) (SDS) Basic model 0.27 (0.24, 0.29) Basis model 0.22 (0.19, 0.24) Confounder model 0.25 (0.23, 0.28) Confounder model 0.22 (0.19, 0.24) Mediator models Mediator models Pregnancy complications 0.25 (0.23, 0.28) - Maternal weight gain 0.28 (0.25, 0.31) - during pregnancy Birth characteristics 0.23 (0.20, 0.25) Birth characteristics 0.20 (0.18, 0.23) Infant growth 0.25 (0.22, 0.27) Infant growth 0.19 (0.16, 0.22) Fully adjusted model Fully adjusted model 0.19 (0.16, 0.22) 0.14 (0.11, 0.16) Gaillard R et al, 2014
Maternal and paternal BMI Childhood BMI Combined maternal Body mass index and paternal model (SDS) Basis model Maternal BMI 0.21 (0.18, 0.24) Paternal BMI 0.17 (0.15, 0.20) Confounder model Maternal BMI 0.21 (0.18, 0.24) Paternal BMI 0.18 (0.15, 0.21) Fully adjusted model Maternal BMI 0.16 (0.13, 0.19) Paternal BMI 0.11 (0.09, 0.14) Maternal-offspring association with childhood BMI is stronger
Maternal and paternal BMI Childhood fat mass Gaillard R et al, 2014
Childhood clustering of cardio-metabolic risk factors Defined as any of the 3 or more following components: android fat mass % =>75th percentile systolic or diastolic blood pressure =>75th percentile HDL-cholesterol <=25th percentile or triglycerides => 75th percentile insulin level =>75th percentile Proxy for metabolic syndrome like phenotype Circulation, 2009
Maternal and paternal BMI Childhood obesity and clustering of cardio-metabolic risk factors Childhood clustering of Childhood obesity cardio-metabolic risk factors Gaillard R et al, 2014
Conclusions Maternal and paternal prepregnancy BMI are associated with adverse cardio-metabolic profile in the offspring: Stronger associations for maternal BMI are present Increased early pregnancy weight gain is associated with an adverse cardio-metabolic profile in childhood Biological mechanisms unknown Future preventive strategies focused on reduction of maternal prepregnancy weight and early weight gain to improve health of offspring
Acknowledgements The Generation R Study Group Vincent VW Jaddoe, MD PhD Department of Epidemiology Albert Hofman, MD PhD Oscar H Franco, MD Phd Department of Obstetrics and Gynaecology Eric AP Steegers, MD PhD
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