Adriëtte Oostvogels

Pathways in the postnatal period As neither early pregnancy lipid profile nor family history of diabetes could explain the associations between maternal pBMI and offspring’s cardiometabolic profile in childhood, a different mechanism probably underlies the association. This could be postnatal growth: maternal anthropometrics are positively associated with postnatal growth, 41,44,45 and increased postnatal growth is associated with higher rates of childhood obesity, insulin resistance and the metabolic risk score. 46-55 Also, in the studies reported in this thesis, children of mothers with overweight and obesity grew more rapidly in weight, height and BMI. No other study has demonstrated that children of women with overweight or obesity have an increased growth in height. These differences in postnatal growth can have consequences for the cardiometabolic profile later in childhood. Both increased early postnatal weight gain and weight- for-length gain were independent of maternal pBMI positively associated with higher waist-to-height ratio and metabolic sum scores. Moreover, increased postnatal weight gain was also associated with higher fasting glucose values. However, neither postnatal weight nor weight-for-length gain mediated the association between maternal pBMI and offspring’s cardiometabolic profile in childhood. Finally, children of mothers with overweight can also differ in growth from children of mothers with normal prepregnancy weight due to differences in postnatal health- related behaviours. Mothers with overweight are less likely to initiate 56,57 and continue 56,58 breastfeeding and introduce solids earlier, 58,59 all these factors can accelerate postnatal growth. 60-63 Also, mothers with overweight tend to have more unhealthy eating habits and are less physically active, which could influence the nutrient intake and physical activity of their children and induce overweight. 59,64-67 Other possible pathways As maternal pBMI is associated with offspring’s cardiometabolic profile independent of offspring’s postnatal growth, other possible mechanisms cannot be ruled out. First, the associations could also have resulted from shared genes: twin studies have shown that about 70% of the individual variation in body composition and 60% of lipid levels can be attributed to genetic factors. 68,69 Second, epigenetic modifications, caused by intra-uterine overnutrition, 29 can serve as mediators between maternal overweight and offspring’s cardiometabolic profile. 24 For instance, intra-uterine overnutrition might modify both the number and content of adipocytes: it can change the endocrine function of adipocytes during adipose tissue development, which leads to impaired glucose metabolism. 6-9 Intra-uterine overnutrition can also 228 Chapter 9