Bibian van der Voorn

29 AIM, DESIGN AND OUTLINE OF THIS THESIS In Chapter 2, we explored factors that influence infant hair glucocorticoid levels in early life, as well as their relation with prenatal, maternal HPA axis activity. In Chapter 3, we assessed whether maternal stress experienced during gestation and/or peripartum was associated with neonatal and maternal hair glucocorticoid levels directly postpartum. For both term and preterm neonates, human milk is recommended for its beneficial effect on growth, body composition, metabolism, neurodevelopment and long- term disease risk, all of which has been attributed to the nutritive and nonnutritive, bioactive components in human milk. Glucocorticoids are known to be present in mother’s milk. Knowledge was lacking about the clinical range in which these human milk glucocorticoids were present, as well as inter- and intra-individual differences in concentrations. Therefore, the Cortisol in Mother’s milk Study (COSMOS) was set-up with the aim to explore variations in human milk glucocorticoid concentrations. We started the COSMOS project with the development of a reliable LC–MS/MS assay to determine cortisol and cortisone in human breast milk ( Chapter 4 ), after which COSMOS was set up in two consecutive phases. In COSMOS 1 ( Chapter 5 ), we tested the hypothesis that human milk cortisol and cortisone concentrations during the first month postpartum were higher for mothers who delivered very prematurely (GA ≤ 32wks) as compared tomothers who delivered at term. Subsequently, in COSMOS 2 ( Chapter 5 ) we tested the hypothesis that breast-milk glucocorticoid concentrations follow a diurnal rhythm corresponding to the diurnal rhythm of the maternal HPA axis activity, by assessing multiple paired maternal salivary and breast-milk samples, collected over a 24h period by healthy lactating mothers who gave birth to a term infant. In Chapter 6 , we tested the effect of pasteurization on human milk glucocorticoid levels. PART II Later life consequences of early life stress Adaptation to early life stress, such as very preterm birth, is suggested to result in a permanent increase in HPA axis activity with possible unfavorable disease risks later in life (Chapter 1). Moreover, gender differences in later life morbidity and mortality have been described and have been hypothesized to be partly attributable to a sexual dimorphism in HPA axis activity and reactivity. Although sex-specific differences in HPA axis activity have been postulated to emerge during puberty as a result of rises in sex steroids, already early in life a male disadvantage on the risk of premature birth 6 ,