Adriëtte Oostvogels

7 early period. Nonetheless, this is the first study to show that accelerated postnatal weight gain aggravated the association between maternal pBMI and offspring’s SBP and metabolic score, and that postnatal weight-for-length gain aggravated the association between maternal pBMI and offspring’s TG and metabolic score. Underlying mechanisms Different pathways may underlie the associations between maternal pBMI, postnatal growth and the metabolic components. First shared genetic and environmental factors could influence our results. We were unable to control for shared genetic background since we lack information on genetic profile of the children and their parents. However we controlled for environmental factors in utero and offspring’s present environment by taking maternal socioeconomic status, ethnicity, smoking status and offspring’s screen time hours and energy intake per day into account, still we cannot rule out residual confounding. Second epigenetic modifications can be important mediators between maternal overweight/obesity and long-term offspring outcomes 28 and can be caused by exposure to intra-uterine or postnatal overnutrition. 3 Overnutrition might modify the endocrine function through changes in adipose tissue resulting in disturbances in the insulin signalling pathway. 15 Moreover it can cause changes in the arcuate nucleus of the hypothalamus, an important structure related to the regulation of energy homeostasis and appetite control. 29 This can result in overeating and obesity later in life. 30 Adjusting for energy intake in our analyses could therefore have underestimated the true size of our associations, as appetite control regulating the energy intake of the child could be modified pre- or postnatal. Animal studies have also shown that exposure to maternal overnutrition in utero and lactation exacerbates the effect of postnatal overnutrition alone. 31-33 The underlying mechanisms are still under study but the roots may lie in the adipocyte. Both the number and size of adipocytes are affected by overnutrition and adipocyte function is changed by differences in gene expression. 32 Adipocyte dysfunction leads to inflammation and oxidative stress, resulting in the deterioration of the pancreatic β -cell function and insulin resistance. 33 It seems that maternal overnutrition can program gene expression profiles resulting in altered metabolic response to postnatal overnutrition. 33 Finally, breastfeeding could be an important factor contributing to the combined effect of maternal overweight/obesity and accelerated postnatal growth. Women with a higher BMI are less likely to breastfeed their children 16 and breastfed 189 pBMI, postnatal growth and offspring’s CMP