Adriëtte Oostvogels

9 “ Mendelian randomization studies are therefore defined as any study that uses genetic variation that serves as a robust proxy for an environmentally modifiable exposure in order to make causal inferences about the outcomes of the modifiable exposure ”. 121 For instance, based on this method, Lawlor et al. showed that, by using the Fat Mass and Obesity-Related gene as genetic variation, maternal pBMI did not have an effect on offspring’s fat mass. 122 However, in a more recent paper, it is shown that also Mendelian randomisation studies are prone to bias, especially when maternal exposure and offspring outcome are the same characteristic. 123 Lastly, randomised clinical trials can be used to compare the effect of a weight loss intervention on pBMI and metabolic parameters in pregnancy and offspring’s outcomes in the short- and long-term. Implications for public profile practice Based on the work in this thesis, it appears that several periods might be eligible for the prevention of adverse cardiometabolic profile in childhood. The first period is before pregnancy, as an increased maternal pBMI was associated with an adverse cardiometabolic profile in childhood, also weight- and weight-for-length gain in the first 3 months were associated with an adverse cardiometabolic profile. Moreover, around age 2-3 years, differences in growth patterns became apparent between children of mothers with normal weight, overweight and obesity, and between children of mothers with low or high socioeconomic background. In 2015 the United Nations set Sustainable Development Goals in which prevention of non-communicable diseases is one of the core priorities. As obesity is an important risk factor for non-communicable diseases, the World Profile Organisation established a committee to end childhood obesity, as a risk factor for adult obesity and non-communicable diseases. 124 Moreover, promoting a healthy weight status in childhood might influence the profile of upcoming generations, due to the potential vicious cycle of obesity. A healthy weight in girls, in childhood or adolescence, which is maintained up to her child-bearing age, will also improve the profile of her offspring. This thesis has shown that both the pre- and postnatal period are associated with cardiometabolic profile in childhood, which provides additional time points to start interventions to prevent non-communicable diseases. Preventing childhood obesity might start during preconception by promoting a healthy lifestyle directed at healthy nutrition and sufficient physical activity. 125 Women might be more prone to lifestyle interventions when these affect not only their own health, but also their chances to conceive, and the health of their unborn child. 126 The results emerging from this thesis on the effects of early pregnancy lipid 233 General discussion