Growth and neurodevelopmental outcomes after early low-dose hydrocortisone treatment in extremely low birth weight infants.
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.


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.
Watterberg
Kristi L
KL
Department of Pediatrics/Neonatology, MSC10 5590, 1 University of New Mexico School of Medicine, Albuquerque, NM 87131-0001, USA. kwatterberg@salud.unm.edu
Shaffer
Michele L
ML
Mishefske
Mary J
MJ
Leach
Corinne L
CL
Mammel
Mark C
MC
Couser
Robert J
RJ
Abbasi
Soraya
S
Cole
Cynthia H
CH
Aucott
Susan W
SW
Thilo
Elizabeth H
EH
Rozycki
Henry J
HJ
Lacy
Conra Backstrom
CB
D000309:Adrenal Insufficiency / Q000517:prevention & control; D001997:Bronchopulmonary Dysplasia / Q000401:mortality / Q000628:therapy; D002547:Cerebral Palsy / Q000517:prevention & control; D002657:Child Development; D002821:Chorioamnionitis / Q000097:blood; D002658:Developmental Disabilities / Q000517:prevention & control*; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood; D007223:Infant; D052577:Infant, Extremely Low Birth Weight / Q000254:growth & development*; D007231:Infant, Newborn; D007416:Intestinal Perforation / Q000139:chemically induced; D008297:Male; D009460:Neurologic Examination; D011247:Pregnancy; D011596:Psychomotor Disorders / Q000517:prevention & control; D012121:Respiration, Artificial; D015996:Survival Rate
D003907:Dexamethasone; C007133:hydrocortisone hemisuccinate; D006854:Hydrocortisone