Cohort profile: the Genetics of Glucose regulation in Gestation and Growth (Gen3G) – a prospective prebirth cohort of mother–child pairs in Sherbrooke, Canada, 3-year and 5-year follow-up visits

Abstract

Purpose

Initiated in 2010, the Genetics of Glucose regulation in Gestation and Growth (Gen3G) prospective cohort investigates the pathophysiology of impaired glycaemic regulation in pregnancy and evaluates its impact on both the mothers and her offspring health trajectory. Follow-up visits 3 and 5 years after delivery aimed to investigate pregnancy-related risk factors such as maternal obesity and gestational hyperglycaemia in relation to the mother’s metabolic health after pregnancy, and with offspring health outcomes such as risk of obesity and neurodevelopmental problems in early childhood. We also investigated molecular mechanisms involved in the fetal programming of these later health outcomes.

Participants

Of the 1024 women originally recruited in the first trimester of pregnancy, we have targeted the 854 who had complete glucose tolerance test data and the 724 newborns who provided placenta and/or cord blood samples for follow-up recruitment. Of these, 695 mother–child dyads agreed to be contacted for the prospective follow-up visits. 448 and 521 mother–child dyads completed the research visits at 3 and 5 years after delivery respectively.

Findings to date

At both visits, we collected the mother’s and child’s medical history, lifestyle (using validated questionnaires), sociodemographic status, anthropometric measurements, mother’s blood samples, child’s saliva samples and growth charts. At the 5-year-old visit, we additionally collected the mother’s and child’s urine and stool samples and the child’s blood samples; we performed a 75 g oral glucose tolerance test in the mothers and assessed the body composition in children using dual-energy X-ray absorptiometry. Using the Gen3G rich longitudinal data set, we have enhanced the understanding of the pathophysiology and characterisation of the heterogeneity of gestational diabetes mellitus, and we have shown that gestational hyperglycaemia and insulin resistance are associated with offspring epigenetics (DNA methylation) variations in the placenta, cord blood and blood at 5 years of age, as well as with offspring anthropometric, metabolic and neurodevelopmental outcomes in early childhood.

Future plans

We are currently conducting a prospective follow-up of mothers and their children 12 years after delivery to study how prenatal and early-life metabolic factors may programme childhood adiposity and obesogenic dietary behaviours. This follow-up should be completed by the end of 2026.