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Published on: November 20, 2015
Growth and neurodevelopmental outcomes after early low-dose hydrocortisone treatment in extremely low birth weight
Kristi L Watterberg1, Michele L Shaffer, Mary J Mishefske
1Department of Pediatrics/Neonatology, MSC10 5590, 1 University of New Mexico School of Medicine, Albuquerque, NM 87131-0001, USA. kwatterberg@salud.unm.edu
Insights
Early hydrocortisone treatment in premature infants did not increase cerebral palsy and showed improved developmental outcomes. These findings support further research into treating adrenal insufficiency in extremely premature babies.
Area of Science:
- Neonatal care
- Pediatric neurology
- Endocrinology
Background:
- Low cortisol levels in premature infants are linked to severe illness, hypotension, mortality, and bronchopulmonary dysplasia.
- A trial investigated hydrocortisone prophylaxis for early adrenal insufficiency in mechanically ventilated infants (birth weight 500-999g).
- Previous findings showed reduced mortality and bronchopulmonary dysplasia with hydrocortisone in infants exposed to chorioamnionitis.
Purpose of the Study:
- To evaluate the long-term neurodevelopmental outcomes at 18-22 months corrected age in extremely premature infants receiving early hydrocortisone prophylaxis.
- To assess the safety and efficacy of hydrocortisone in preventing bronchopulmonary dysplasia and improving survival.
- To determine the impact of hydrocortisone on neurodevelopmental impairment, including cerebral palsy, cognitive, and psychomotor development.
Main Methods:
- A randomized, multicenter trial involving 360 mechanically ventilated premature infants.
- Surviving infants underwent standardized neurologic examinations and Bayley Scales of Infant Development-II assessments.
- Neurodevelopmental impairment was defined by specific developmental index scores, cerebral palsy, blindness, or deafness.
Main Results:
- No significant difference in cerebral palsy rates between hydrocortisone (13%) and placebo (14%) groups.
- Hydrocortisone-treated infants showed fewer instances of Mental Development Index <70 and improved object permanence awareness.
- Overall incidence of neurodevelopmental impairment was similar (39% vs. 44%), with no differences in physical growth.
- Chorioamnionitis-exposed infants on hydrocortisone were shorter but showed no neurodevelopmental impairment.
- Among infants not exposed to chorioamnionitis, hydrocortisone use correlated with lower rates of Mental Development Index <70 and reduced need for follow-up glucocorticoids.
Conclusions:
- Early, low-dose hydrocortisone treatment is not associated with an increased risk of cerebral palsy in extremely premature infants.
- Hydrocortisone treatment demonstrated indicators of improved developmental outcomes in treated infants.
- These findings, combined with short-term benefits, warrant further investigation into hydrocortisone for adrenal insufficiency in this vulnerable population.
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.
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