Growth in early life and its impact on adult health:Bone mineral density and effects of a lipid-adjusted infant formula on body composition in early life, and longterm cerebrovascular safety and quality of life in adults born SGA after childhood growth hormone treatment.

This thesis provides the results of 6 studies. Three of them were performed in a large cohort of healthy term-born children aged 0-5 years and aimed to investigate bone mineral density (BMD) and its determinants at ages 6 months and 3 years, compare BMD of 5-year old very preterm-born (VPB) children with 5-year old term-born children and investigate body composition trajectories during the first 2 years of life of infants receiving a Concept infant formula (IF), mimicking the characteristics of human milk by adjusting the size, coating and origin of the lipid droplets, compared to those receiving Control IF or exclusive breastfeeding (EBF). We developed Dual energy X-ray Absorptiometry (DXA) references for infants aged 6 months, which now allows to early identify infants with a low BMD and those who are at risk for a low BMD. Lifestyle interventions that increase lean body mass (LBM) and personalized diets in infants and preschool children could potentially improve BMD in those with a low BMD and those who are at risk for a low BMD. Moreover, VPB children at around 5 years have an increased risk of low BMD compared to term-born children. The difference in BMD was explained by altered growth and body composition of VPB children. Furthermore, no differences in body composition trajectories between the Concept and Control group were found during the first 2 years of life. However, this period might be too short to see the hypothesized potentially beneficial programming effects of exposure to the Concept IF during first 6 months of life, which are considered a critical window for adiposity and metabolic programming. The other three studies were performed in a cohort of adults born small for gestational age (SGA) at 12 years after cessation of childhood growth hormone (GH) treatment, in comparison with three control groups: untreated short adults born SGA, untreated adults born SGA with spontaneous catch-up growth to a normal height and normal statured adults born appropriate for gestational age (AGA), all around age 30 years. The main aims were to investigate the effects of GH-induced catch-up growth, spontaneous catch-up growth and being born SGA on long-term cerebrovascular safety, health-related quality of life and problem behaviour. Long-term GH-treatment does not lead to an increased risk for hemorrhagic and ischemic cerebrovascular disease, while spontaneous catch-up growth and lower birth weight after SGA birth does increase the risk to develop ischemic cerebrovascular disease. Furthermore, during 12 years after GH cessation, HRQoL remained mostly similar in SGA-GH adults, while externalizing problem behavior decreased and internalizing problems tended to decrease. At around age 30 years, SGA-GH and SGA-S adults had similar HRQoL and problem behavior and all adults born SGA had lower HRQoL and more internalizing problem behaviour compared to AGA adults.