Steroids and injury to the developing brain: net harm or net benefit?

Abstract

Deleterious effects result from both glucocorticoid insufficiency and excess glucocorticoid tissue exposure in the developing brain. Accumulating evidence suggests a net benefit of postnatal glucocorticoid therapy when administered shortly after the first week of life to premature infants with early and persistent pulmonary dysfunction, particularly in those with evidence of relative adrenal insufficiency. The decision to treat with steroids should ensure maximum respiratory benefit at the lowest possible neurologic risk, while avoiding serious systemic complications. Ongoing clinical trials must validate this approach.

Keywords: Brain injury; Cerebral palsy; Controversy; Development; Glucocorticoids; Infant; Outcomes; Premature infant.

Fig. 1

Inverse-U–shaped hypothesis as a guide for risk/benefit analysis of glucocorticoid administration in experimental and clinical scenarios. Note that during the first few days of life, although a degree of MR occupancy by hydrocortisone may be neurotrophic in premature infants, systemic side effects of very early administration of hydrocortisone outweigh the potential benefits. See text for details.

Fig. 2

Speculative predictive analysis for risk of death or cerebral palsy after postnatal glucocorticoid therapy according to pattern of respiratory disease in premature infants. Patterns of respiratory disease during the first 2 postnatal weeks among newborns with extremely low gestational age show that the incidence of chronic lung disease was 67% in infants with early and persistent pulmonary dysfunction. Doyle et al observed significant steroid-related benefit only when the incidence of chronic lung disease exceeded 65%. These data suggest that the risk of cerebral palsy may be reduced if postnatal glucocorticoids are given to sick premature infants with early and persistent pulmonary dysfunction whose risk for developing BPD may exceed 65%, particularly if they also have low basal levels of cortisol. This predictive analysis must be validated in randomized clinical trials. CLD, chronic lung disease; EPPD, early and persistent pulmonary dysfuntion; FiO₂, fraction of inspired oxygen; PD, pulmonary dysfunction. (Adapted from Laughon M, Allred EN, Bose C, et al. Patterns of respiratory disease during the first 2 postnatal weeks in extremely premature infants. Pediatrics 2009;123(4):1124–31; with permission.)