Bibian van der Voorn

197 GENERAL DISCUSSION AND SUMMARY analyze the data as transparent as possible, enabling readers to interpret the results by themselves. FUTURE PERSPECTIVES The results reported in this thesis are too preliminary to be translated to tailor made approaches, titrated to the needs in early life while minimally harming later life outcomes. With that as our ultimate goal and the hypotheses that were generated with this thesis in mind, we recommend the following items to focus on in future research: * To develop valid, reliable and easy to apply measurements of HPA axis functioning for very preterm newborns, to use as indication of adrenal functioning, prior to clinical symptoms of insufficiency. Nowadays, assessment of HPA axis activity in very preterm newborns is not common practice. Among other challenges, adrenal immaturity results in different steroid patterns that necessitates specialized assays 12,13 . In addition, isolated cortisol levels might not be a valid representative of glucocorticoid bioactivity in the very preterm newborn, while other substances also have the potential to activate the glucocorticoid receptor 14 . * To determine sex-specific differences in HPA axis functioning of very preterm newborns, with the aim to clarify part of the male disadvantage on short- and long-term morbidity and mortality 15-17 . While our data indicated a gender-specific difference in HPA axis functioningof healthy children,we recommend to studygender-specificdifferences in glucocorticoid production and metabolism in very preterm newborns under both basal and stressful conditions. * To assess the effect of early life interventions that support HPA axis functioning. Based on current research, hypotheses can be formulated on how HPA axis functioning can be supported over time, as secondary prevention of adverse later life outcomes. Plausible supportive effects can come from co-administration of a physiologic dose of hydrocortisone which is thought to refill depleted mineralocorticoid receptors. 18,19 . In addition, animal studies have suggested that enhanced maternal care after perinatal exposure to synthetic glucocorticoids, could result in a reduced risk of glucocorticoid-induced impairments in later life