Adriëtte Oostvogels

7 INTRODUCTION In the USA, over 50% of women of reproductive age are overweight or obese. This has consequences not only for the health of these women and their pregnancies, but also for the health of their offspring later in life. Animal and epidemiological studies have shown that environmental factors acting both in utero as well as in early postnatal life can program the child for adverse metabolic outcomes. 1-3 For example, in a large population it was shown that maternal obesity is associated with all-cause mortality and increased risk of cardiovascular events in offspring aged 34-61 years. 4 These effects could be due to prenatal programming of metabolism and the cardiovascular system resulting in higher levels of obesity, 2,5,6 insulin resistance, 5,6 blood pressure 6,7 and an adverse lipid profile. 6,8 Besides the prenatal period, the early postnatal period also has the potential to program increased adverse metabolic outcomes. Increased postnatal growth is associated with BMI, 9 hypertension 10 and insulin resistance 11 in later life. One of the periods in which postnatal growth has detrimental impact on adverse metabolic outcomes in children is the first 3 months of life. 12 In most studies, postnatal growth is mainly based on weight gain alone. However, weight-for-length gain could be more interesting, since this measure reflects adiposity better than weight gain alone, 13 and could be more informative regarding future metabolic outcomes. 14 Because the effects of the combination of maternal prepregnancy body mass index (pBMI) and postnatal growth on metabolic outcomes have not yet been combined into one study, previous studies were unable to separate prenatal from postnatal influences of maternal obesity. This is important as maternal pBMI can influence postnatal growth by changing the endocrine function of adipocytes during the prenatal period with subsequent effects on postnatal growth due to disturbed glucose metabolism. 15 Moreover, obese mothers are less likely to start breastfeeding and introduce solid foods earlier, both known to influence postnatal growth. 16 Therefore, it is important to study maternal pBMI and postnatal growth combined, to determine whether both periods are independently associated with offspring’s metabolic profile or if postnatal growth mediates or moderates the association of maternal pBMI and offspring’s metabolic profile. The present study used data from a large Dutch prospective birth cohort to examine the association of maternal pBMI and early postnatal growth with different metabolic components in children at age 5-6 years. We hypothesized that higher maternal pBMI is associated with adverse metabolic components in early childhood. Moreover, we hypothesized that postnatal growth, specifically accelerated growth in weight-for- length, aggravates this effect. 177 pBMI, postnatal growth and offspring’s CMP