Bibian van der Voorn

12 CHAPTER 1 GLUCOCORTICOIDS ANDRESILIENCE TONEONATAL THREATS Worldwide, of all live-born children, 11.1% (range: 5–18%) are born prematurely (i.e., <37 wks of gestation) 16 . Approximately 1–2% of all babies are born very preterm (i.e., <32 wks) 17,18 , necessitating admission to a NICU. In this review, we will focus specifically on the latter group. Although pregnancy dating can be reliably assessed with ultrasound these days, birth weight is still being used as a surrogate for gestational age by many studies. Therefore, we also included studies in infants with very low birth weight (VLBW; i.e., <1,500 g) or extremely low birth weight (ELBW; i.e., <1,000 g). Owing to improvements in neonatal care, the chances for survival of infants born between 26 and 32 wks of gestation have improved from 70% in the early 1980s to more than 90% nowadays 19 . The limit of viability has been set at 22–24 wks. Overall, infants born at the threshold of viability experience a more complicated neonatal course and, consequently, carry much higher risks of neonatal mortality and long- term morbidities 20 . Cortisol is necessary for the maintenance of both blood pressure and glucose homeostasis. It influences the sensitivity of the peripheral tissues to the actions of insulin, glucagon and catecholamines. Other mechanisms of action include inhibition of nitric oxide-induced vasodilatation, inhibition of vasodilator prostanoids, upregulation of angiotensin II receptors and, at higher molar concentrations, activation of renal mineralocorticoid receptors 21 . Hypotension is a common threat during the early postnatal course of very preterm infants. Among the causes of hypotension are abnormalities in the regulation of the vascular tone (e.g., by sepsis or adrenocortical insufficiency), left-to-right shunting through a persistent ductus arteriosus, volume depletion and myocardial dysfunction 22,23 . Although systemic hypotension has been associated with adverse neurological outcome, it is unclear whether low blood pressure alone, in the absence of other signs of hemodynamic instability, is harmful for the very preterm infant’s brain 22,23 . Hypoglycemic episodes are frequently observed in the early postnatal course of very preterm infants. Acute illnesses, such as the respiratory distress syndrome, infections and necrotizing enterocolitis, and asphyxia increase the glucose demands in tissues. The endogenous glucose production can only partly compensate for sudden declines in the circulating glucose level 24 , attributable to low hepatic glycogen content 25 , poor availability of the gluconeogenic substrates alanine and glycerol 26 , impaired glucose- 6-phosphatase activity (the final step in both glycogenolysis and gluconeogenesis) 27 and a reduced capacity to secrete counter-regulatory hormones like cortisol 28,29 . Also lipolysis and ketogenesis are severely impaired, even at low blood glucose levels 26,30 .