Adriëtte Oostvogels

10 Chapter 1 Adverse childhood cardiometabolic profile in offspring of women with overweight: pathways in the intra-uterine period Part 1 of this thesis focuses on how maternal overweight can affect childhood cardiometabolic profile during pregnancy, in particular through the maternal early pregnancy lipid profile and family history of diabetes. Maternal metabolic markers during pregnancy, such as lipids, are an important indicator of the intra-uterine environment. During the nine months in utero, the most rapid and ingenious development of the child takes place. The intra-uterine environment is therefore of major importance for the development of the child. The developmental origins of health and disease (DOHaD) hypothesis or “foetal programming” states that development of the foetus in utero has long-term consequences for disease risk later in life. 16 Adaptations made in physiology and hormonal axes in early life to improve short-term survival can become maladaptations in later life, which may result in increased risk of cardiometabolic diseases. 16,17 At first, research on foetal programming focussed on an adverse intra-uterine environment as a consequence of maternal undernutrition. However, during the last decades, with the rise in overweight and obesity worldwide, 18,19 the “developmental overnutrition hypothesis” has been postulated. 12,13,20,21 This hypothesis proposes that “the increased fuel supply to the foetus in maternal obesity or overnutrition leads to permanent changes in offspring metabolism, behaviour, and appetite regulation with resultant obesity, metabolic, and behavioural problems in adult life”. 12,13,20-23 Previous studies demonstrated that women with overweight are at increased risk of developing pregnancy complications such as gestational diabetes mellitus (GDM) or gestational hypertensive disorders, such as pregnancy–induced hypertension (PIH) or preeclampsia (PE). 24-28 Women with overweight often also have a more atherogenic lipid profile consisting of higher total cholesterol (TC), triglycerides (TG), and low density lipoprotein (LDL) concentrations, but lower high density lipoproteins (HDL) concentrations. 29-31 An atherogenic lipid profile was found to be associated with hypertensive disorders of pregnancy, including PIH and PE, 32-37 and possibly with GDM. 38,39 Early pregnancy lipid profile Maternal lipid profile can also influence foetal developmental processes. 40 Positive associations between maternal TG and TC and offspring’s birth weight, 32,41-45 and