Background: Low cortisol concentrations in premature infants have been correlated with increased severity of illness, hypotension, mortality, and development of bronchopulmonary dysplasia. A total of 360 mechanically ventilated infants with a birth weight of 500 to 999 g were enrolled in a randomized, multicenter trial of prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia. Mortality and bronchopulmonary dysplasia were decreased in the hydrocortisone-treated patients exposed to chorioamnionitis. We now report outcomes at 18 to 22 months' corrected age.
Patients and methods: Surviving infants were evaluated with standardized neurologic examination and Bayley Scales of Infant Development-II. Neurodevelopmental impairment was defined as a Mental Developmental Index or Psychomotor Developmental Index of <70, cerebral palsy, blindness or deafness.
Results: A total of 252 (87%) of 291 survivors were evaluated. Cerebral palsy was diagnosed in 13% of hydrocortisone-treated versus 14% of placebo-treated infants. Fewer hydrocortisone-treated infants had a Mental Development Index <70, and more of the hydrocortisone-treated infants showed evidence of awareness of object permanence. Incidence of neurodevelopmental impairment was not different (39% [hydrocortisone] vs 44% [placebo]). There were no differences in physical growth measures. Chorioamnionitis-exposed infants treated with hydrocortisone were shorter and weighed less than controls but had no evidence of neurodevelopmental impairment. Among infants not exposed to chorioamnionitis, hydrocortisone-treated patients were less likely to have a Mental Development Index of <70 or to be receiving glucocorticoids at follow-up.
Conclusions: Early, low-dose hydrocortisone treatment was not associated with increased cerebral palsy. Treated infants had indicators of improved developmental outcome. Together with the short-term benefit previously reported, these data support additional studies of hydrocortisone treatment of adrenal insufficiency in extremely premature infants.