Prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia: a multicenter trial.
BACKGROUND
Infants developing bronchopulmonary dysplasia (BPD) show decreased cortisol response to adrenocorticotropic hormone. A pilot study of low-dose hydrocortisone therapy for prophylaxis of early adrenal insufficiency showed improved survival without BPD at 36 weeks' postmenstrual age, particularly in infants exposed to histologic chorioamnionitis.


METHODS
Mechanically ventilated infants with birth weights of 500 to 999 g were enrolled into this multicenter, randomized, masked trial between 12 and 48 hours of life. Patients received placebo or hydrocortisone, 1 mg/kg per day for 12 days, then 0.5 mg/kg per day for 3 days. BPD at 36 weeks' postmenstrual age was defined clinically (receiving supplemental oxygen) and physiologically (supplemental oxygen required for O2 saturation > or =90%).


RESULTS
Patient enrollment was stopped at 360 patients because of an increase in spontaneous gastrointestinal perforation in the hydrocortisone-treated group. Survival without BPD was similar, defined clinically or physiologically, as were mortality, head circumference, and weight at 36 weeks. For patients exposed to histologic chorioamnionitis (n = 149), hydrocortisone treatment significantly decreased mortality and increased survival without BPD, defined clinically or physiologically. After treatment, cortisol values and response to adrenocorticotropic hormone were similar between groups. Hydrocortisone-treated infants receiving indomethacin had more gastrointestinal perforations than placebo-treated infants receiving indomethacin, suggesting an interactive effect.


CONCLUSIONS
Prophylaxis of early adrenal insufficiency did not improve survival without BPD in the overall study population; however, treatment of chorioamnionitis-exposed infants significantly decreased mortality and improved survival without BPD. Low-dose hydrocortisone therapy did not suppress adrenal function or compromise short-term growth. The combination of indomethacin and hydrocortisone should be avoided.
Watterberg
Kristi L
KL
Division of Neonatology, Department of Pediatrics/Neonatology, University of New Mexico School of Medicine, MSC10 5590, Albuquerque, NM 87131-0001, USA. kwatterberg@salud.unm.edu
Gerdes
Jeffrey S
JS
Cole
Cynthia H
CH
Aucott
Susan W
SW
Thilo
Elizabeth H
EH
Mammel
Mark C
MC
Couser
Robert J
RJ
Garland
Jeffery S
JS
Rozycki
Henry J
HJ
Leach
Corinne L
CL
Backstrom
Conra
C
Shaffer
Michele L
ML
D000309:Adrenal Insufficiency / Q000517:prevention & control*; D001997:Bronchopulmonary Dysplasia / Q000517:prevention & control*; D002821:Chorioamnionitis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000009:adverse effects / Q000627:therapeutic use*; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000139:chemically induced / Q000517:prevention & control*; D019102:Infant, Very Low Birth Weight; D007416:Intestinal Perforation / Q000139:chemically induced; D008297:Male; D011247:Pregnancy; D013270:Stomach / Q000187:drug effects; D017211:Treatment Failure
D006854:Hydrocortisone