Adriëtte Oostvogels

1 11 General introduction offspring’s TG levels in cord blood were reported, 46 while maternal HDL levels were negatively associated with offspring’s birth weight and offspring’s TG levels in cord blood. 44,46 Moreover, the Rhea Cohort found associations between maternal TC and LDL, and offspring’s TC. 47 Associations between maternal lipids and offspring’s lipids do not only seem to be the result of shared genetics, but also of the intra-uterine environment, as it was shown that offspring with familial hypercholesterolemia from the maternal side had significantly higher TC, LDL, and ApoB levels than offspring with familial hypercholesterolemia from the paternal side. 48 In addition, animal studies showed that a maternal high fat diet in pregnancy resulted in hyperphagia and altered adipocyte function, accelerated weight gain after weaning, adiposity, and higher cholesterol levels in the offspring. 21,49,50 However, conflicting results on offspring’s glycaemic control were found. 51 Although animal models suggest long-term effects of early pregnancy lipid profile on the offspring, most human studies only focussed on perinatal outcomes. 32-39, 41-43 Moreover, little is known about the role of the early pregnancy lipid profile in the association between maternal overweight and offspring’s cardiometabolic profile. Assessing the contribution of the early pregnancy lipid profile to these outcomes broadens the understanding of the short- and long-term health consequences of the maternal early pregnancy lipid profile. Family history of diabetes As mentioned before, women with overweight are at increased risk of gestational diabetes mellitus. 26-28 Children born to mothers with GDM have higher birth weight, are at increased risk of developing childhood overweight and a more adverse cardiometabolic profile. 10,52-55 Furthermore, first-degree relatives of patients with diabetes are at increased risk of developing the disease themselves, without being exposed in utero to GDM. 56-60 Even when they have not developed diabetes (yet), their body composition and metabolic parameters are less favourable compared with people with no family history of diabetes (FHD). 57,61-68 Not only first-degree relatives are at increased risk, also second-degree relatives are at a twofold increased risk of developing diabetes and tend to have more adverse metabolic outcomes. 67,69-74 FHD might therefore influence both maternal overweight and her metabolic profile and therefore indirectly the cardiometabolic profile of her child. FHD may, however, also be directly linked to the cardiometabolic profile of the child. If exposure to maternal FHD has more impact on childhood metabolic health than exposure to paternal FHD, the effect of FHD on childhood metabolic health may, in part, be mediated by intra- uterine pathways.