Parental BMI, gestational weight gain and childhood cardio-metabolic - - PowerPoint PPT Presentation

Parental BMI, gestational weight gain and childhood cardio-metabolic outcomes

Romy Gaillard Power of Programming Conference Munich, 13 March 2014 Note: for non-commercial purpose only

The prevalence of obesity among women of reproductive age is strongly increasing

Haslam et al, 2005

Maternal obesity Prevalence

Maternal obesity Childhood obesity

PLoS One. 2013

Fetal overnutrition hypothesis

Poston L, 2012

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

Intra-uterine mechanisms or confounding factors?

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

Parental BMI and childhood BMI

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%

12 weeks First trimester 20 weeks Second trimester 30 weeks Third trimester

Maximum weight gain during pregnancy Maternal BMI Paternal BMI

Birth

Maternal weight

1-4 years 6 years

Infant growth Childhood cardio-metabolic

• utcomes

Maternal and paternal overweight and obesity Prevalences

Maternal BMI Paternal BMI

10 20 30 40 50 60

underweight normal weight

• verweight
• bese

10 20 30 40 50 60

Underweight Normal weight Overweight Obese Underweight Normal weight Overweight Obese

Maternal and paternal BMI Childhood BMI

Maternal model Body mass index (SDS) Paternal model Body mass index (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

during pregnancy 0.28 (0.25, 0.31)

• 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 0.19 (0.16, 0.22) Fully adjusted model 0.14 (0.11, 0.16)

Gaillard R et al, 2014

Maternal and paternal BMI Childhood BMI

Maternal model Body mass index (SDS) Paternal model Body mass index (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

during pregnancy 0.28 (0.25, 0.31)

• 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 0.19 (0.16, 0.22) Fully adjusted model 0.14 (0.11, 0.16)

Gaillard R et al, 2014

Maternal and paternal BMI Childhood BMI

Maternal model Body mass index (SDS) Paternal model Body mass index (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

during pregnancy 0.28 (0.25, 0.31)

• 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 0.19 (0.16, 0.22) Fully adjusted model 0.14 (0.11, 0.16)

Gaillard R et al, 2014

Combined maternal and paternal model Body mass index (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 and paternal BMI Childhood BMI

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 obesity Childhood clustering of 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

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

Acknowledgements