In step 2, a genetic variant is used as a proxy for methylation and related to an outcome of interest (here long- term offspring adiposity, cardiometabolic outcomes or cognitive ability).
Objective: Maternal infection/inflammation may induce fetal inflammatory responses, which have been associated with long-term offspring cerebral injury.
However, whether they also have a beneficial effect on long-term offspring health outcomes remains unclear.
As metformin crosses the placenta and could plausibly alter long-term offspring metabolic phenotype, this study is of particular interest to those physicians and obstetricians who are reluctant to use metformin because of the lack of long-term offspring data.
However, data linking maternal diet and nutrient status to long-term offspring outcomes in humans are limited.
Excessive maternal weight gain in pregnancy is also associated with childhood obesity [ 18] which is subsequently associated with long-term offspring consequences including cardiometabolic and neuro-developmental disorders.
Such findings highlight the potential pivotal importance of maternal endothelial dysfunction during pregnancy, even in the absence of other pre-eclamptic features, on long-term offspring outcome.
A few years ago, epigenetic processes have been suggested as a link between maternal pregnancy diabetes and long-term offspring outcomes.
These will anchor our review of the literature as we critically assess whether it supports a direct causal relationship between maternal pregnancy diabetes and these long-term offspring health outcomes, or not.
The reported relationship was independent of other parental characteristics, potentially mediating peripartum factors, and abnormal dietary behaviors in the child, suggesting a role for the intrauterine environment in long-term offspring weight regulation.
Epigenetic modification has been suggested as a mediator on the pathways from maternal pregnancy diabetes to long-term offspring outcomes and several recent studies that are reviewed here lend some support to this notion, but research in this area is still too novel to be conclusive.
