Bibian van der Voorn

18 CHAPTER 1 EXPLORING THE RELATION BETWEEN PREMATURITY AND INCREASED HPA AXIS ACTIVITY IN LATER LIFE ANTENATAL GLUCOCORTICOID THERAPY There is no doubt that administrating glucocorticoids to mothers with impending preterm delivery is highly efficacious for the prevention of the respiratory distress syndrome and associated complications 75 . Although numerous animal studies in various species showed that administrationof synthetic glucocorticoids throughout, or during part of, gestation causes permanent metabolic perturbations, neurobehavioral alterations and dysregulation of the HPA axis in offspring 2 , it remains unclear whether a single treatment course of antenatal glucocorticoids could explain at least a part of the association between preterm birth and long-term outcome. First, associations between preterm birth and DM2 were also reported in middle-aged populations born before the introduction of antenatal glucocorticoid therapy 13,15 . Second, findings from studies investigating long-term outcome after antenatal glucocorticoid therapy were highly contradictory 76-81 . However, some of these studies were restricted to infants born very preterm or with VLBW 79-81 , whereas others had followed all infants, regardless of whether they were born preterm or not 76-78 . POSTNATAL GLUCOCORTICOID THERAPY Dexamethasonehas beengiven toprevent or treat BPD. Compared toantenatal therapy, postnatal glucocorticoids are administered for a longer time (e.g., 1–3wks), resulting in substantially higher cumulative doses. Although dexamethasone during the first week of life was effective in the prevention of BPD, the risk of adverse outcomes, including poor growth and neurodevelopmental impairment, was increased, and therefore this therapy is not recommended 82 . However, dexamethasone could be considered after the 1 st week of life to infants who cannot be weaned from the ventilator, provided that the dose and duration are kept to a minimum 83,84 . Hydrocortisone may be as effective as dexamethasone in the prevention and treatment of BPD, and it has fewer side effects, though long-term follow-up data from randomized trials are lacking 83,85 . Observational data, however, suggest that dexamethasone, when compared to hydrocortisone, for the facilitation of extubation was associated with an increased risk of adverse neurodevelopmental outcome and with reductions in cardiovascular and adrenal responses during a psychosocial stress test 86-88 .