Bibian van der Voorn

28 CHAPTER 2 AIM In the Netherlands in 2015, 168,773 infants were born at a gestational age (GA) of ≥ 24 wks, of whom 1,882 neonates (1.1%) were born very preterm (GA ≤ 32 wks) 1 . Worldwide, mortality rates due to prematurity and/or low birth weight are declining: in the United States these rates decreased from 4.9% to 4.2% between 2003 and 2013 2 . Despite this improvement in survival, later in life very preterm survivors are facing problems of which some are suggestive of increased glucocorticoid bioactivity, such as an unfavorable fat distribution, raised blood pressure, insulin resistance, growth retardation, and neurodevelopmental impairments, as described in Chapter 1 . Although many studies described these associations, the underlying mechanisms remain to be elucidated. The aim of this thesis was therefore to explore factors, including genetic predisposition, gender, perinatal treatment and early-life feeding, that might affect HPA axis activity in very preterm newborns on the short-term and could predispose to adverse outcomes on the long-term. DESIGN AND OUTLINE PART I Stress in Early Life Assessment of HPA axis activity in very preterm newborns is challenging due to a variety of factors, including the limited availability of blood, the absence of a diurnal rhythm in the secretion of glucocorticoids, as well as immaturity of the adrenals resulting in the production of a variety of glucocorticoid metabolites that necessitates specialized assays. A matrix with the potential to minimize these difficulties is hair, although up till now unable to use for the quantification of glucocorticoid metabolites. Hair cortisol and cortisone levels reflect a longer period of time, i.e., 1 cm hair segment corresponds with 1 month of glucocorticoid exposure 3 . At this moment, studies relating infant hair glucocorticoid levels to clinical parameters are scarce 4,5 Nonetheless, measurement of hair cortisol and cortisone levels has the potential to give a retrospective view on HPA axis development in early life. In addition, neonatal hair glucocorticoid levels assessed directly postpartum might provide insights into fetal HPA axis activity and the placental transfer of maternal glucocorticoids.