The action has led to more than 100 scientific peer reviewed publications, including papers in Nature, JAMA, PLOS Medicine, Nature Genetics, and Nature Communications.
The new preconception cohort study, now referred to as the Generation R Next Study, has been approved by the Institutional Ethical Review Board. We have also set up the complex logistics in the city of Rotterdam, and developed the full study protocol. The start date of the study is now May/ June 2017. We have anticipated on a delay in starting by (1) enlarging the study area, which increases the number of eligible pregnant women by 50% and (2) including not only women before their conception but also in early pregnancy (< 8 weeks of gestation). These changes in recruitment (later start, larger area, wider gestational age period range) will NOT affect the total project, main expected results or needed overall budget.
We have completed the MRI scanning in children participating in the Generation R Study. In total, we were able to scan 3,000 children, more than expected. This larger group enables detection of smaller differences and more variation in relation to adverse exposures. Of these children, 1,100 children were born to mothers enrolled in first trimester of pregnancy. These measurements include right and left ventricular end-diastolic volume (RVEDV and LVEDV), right and left ventricular ejection fraction (RVEF and LVEF), left ventricular mass (LVM) and left ventricular mass-to-volume ratio (LMVR), pericardial fat, liver steatosis, and visceral abdominal fat. We have now related fetal and childhood socio-demographic, growth, nutritional factors (e.g. maternal obesity, breastfeeding) and genetic factors with these MRI outcomes (manuscripts submitted). We have also related these various exposures with growth and cardio-metabolic outcomes throughout childhood. Blood samples have been collected and are currently analyzed for metabolomics measurements, and insulin, glucose and lipid concentrations.
We have established successful collaborations with several cohorts to increase power for the main analyses. This collaboration, now established in the Pregnancy and Childhood Epigenetics (PACE) Consortium brings together 29 pregnancy and childhood cohorts, with in total more than 25,000 mothers and their children and measured DNA methylation at over 450,000 methylation sites (CpGs). We have started to analyze the associations of several adverse maternal and fetal exposures, including maternal smoking during pregnancy, folic acid supplement use and stress in relation to DNA-methylation changes. Current analyses are focused on the identification of DNA-methylation variants in relation to cardiovascular outcomes in children.
