Evidence-Based Neonatal Pharmacotherapy: Postnatal Corticosteroids

Normal hypothalamic-pituitary-adrenal (HPA) axis production of cortisol and a normal renin-angiotensin-aldosterone axis are needed for the normal regulation of volume status; blood pressure; and serum sodium, potassium, and glucose levels in the neonate. Disorders of these axes can be life-threatening. Cortisol deficiency can be due to a disorder of the adrenal gland itself or to impaired adrenocorticotropic hormone (ACTH) secretion from the pituitary gland. Mineralocorticoid deficiency can result from deficient production of aldosterone from the adrenal gland or from impaired mineralocorticoid signaling. A disorder of sex development, resulting in virilization of a 46,XX fetus or undervirilization of a 46,XY fetus, may indicate an underlying disorder of adrenal steroid synthesis. Transient, relative glucocorticoid deficiency can occur in all newborns in the transition to extrauterine life. This may be exacerbated in the premature infant due to immaturity of the HPA axis and as a consequence of critical illness.

Individuals born extremely preterm (before 28 weeks of gestation) comprise only about 0.7% of births in the United States and an even lower proportion in other high resource countries. However, these individuals account for a disproportionate number of children with cerebral palsy, intellectual deficit, autism spectrum disorder, attention deficit hyperactivity disorder, and epilepsy. This review describes two large multiple center cohorts comprised of individuals born extremely preterm: the EPICURE cohort, recruited 1995 in the United Kingdom and the Republic of Ireland, and the Extremely Low Gestational Age Newborn (ELGAN), recruited 2002–2004 in five states in the United States. The primary focus of these studies has been neurodevelopmental disorders, but also of interest are growth, respiratory illness, and parent- and self-reported global health and well-being. Both of these studies indicate that among individuals born extremely preterm the risks of most neurodevelopmental disorders are increased. Early life factors that contribute to this risk include perinatal brain damage, some of which can be identified using neonatal head ultrasound, bronchopulmonary dysplasia, and neonatal systemic inflammation. Prenatal factors, particularly the family's socioeconomic position, also appear to contribute to risk. For most adverse outcomes, the risk is higher in males. Young adults born extremely preterm who have neurodevelopmental impairment, as compared to those without such impairment, rate their quality of life lower. However, young adults born extremely preterm who do not have neurodevelopmental impairments rate their quality of life as being similar to that of young adults born at term. Finally, we summarize the current state of interventions designed to improve the life course of extremely premature infants, with particular focus on efforts to prevent premature birth and on postnatal efforts to prevent adverse neurodevelopmental outcomes

Postnatal corticosteroids are effective in preventing or treating bronchopulmonary dysplasia (BPD) in preterm newborns, but their benefits need to exceed their risks. Several types of corticosteroids, and different timing and administration modes have been trialed. Systemic corticosteroids, given either early or late, have proven efficacy for reducing BPD and the combined outcome of death or BPD. Inhaled corticosteroids are less effective. However, systemic dexamethasone given early is associated with more neurosensory disability and cerebral palsy in survivors. The risk of adverse neurodevelopment is highest if dexamethasone is given to preterm infants at low risk of BPD. Current trials focus on corticosteroids, mixed with surfactant, delivered intratracheally directly to the lung, which may avoid some systemic adverse effects of corticosteroids. Early trials of intratracheal corticosteroids are encouraging, but more data are needed to determine whether this method of administration is preferable to systemic corticosteroids for preventing or treating BPD.

The majority of surviving infants with surgical necrotizing enterocolitis (NEC) will have some degree of neurodevelopmental impairment. The impact of specific medial and surgical treatments for infants with severe NEC remains largely unknown but is being actively investigated. It is incumbent upon all providers caring for these infants to continue to focus on long term neurodevelopmental outcomes and to develop more widespread methods of neurodevelopmental assessment.