PEDIATRICS Vol. 104 No. 6 December 1999, pp. 1258-1263

Prophylaxis Against Early Adrenal Insufficiency to Prevent Chronic Lung Disease in Premature Infants

Received Feb 15, 1999; accepted May 26, 1999.

Kristi L. Watterberg^*, Jeffrey S. Gerdes^§, Kathleen L. Gifford^*, and Hung-Mo Lin

From the ^* Departments of Pediatrics and  Health Evaluation Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; and the ^§ Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.

Background.  Many extremely low birth weight infants (<1000 g) show biochemical evidence of adrenal insufficiency in the first week of life, correlating with subsequent development of chronic lung disease (CLD).

Methods.  We conducted a randomized, double-masked, placebo-controlled pilot study to test whether early treatment with low-dose hydrocortisone for 12 days (1 mg/kg/day for 9 days followed by .5 mg/kg/day for 3 days), begun before 48 hours of life, would increase the likelihood of survival without CLD.

Results.  Forty patients were enrolled at two centers. Birth weight and gestation were similar for treatment and placebo groups: 732 ± 135 g versus 770 ± 135 g and 25.2 ± 1.3 weeks versus 25.4 ± 1.5 weeks. More infants treated with hydrocortisone achieved study success, defined as survival without supplemental oxygen at 36 weeks' postconception (12/20 [60%] vs 7/20 [35%]). Lower birth weight, histologic chorioamnionitis, and preeclampsia were significant risk factors, whereas study center, prenatal steroids, sex, and ethnicity were not significant. Hydrocortisone treatment decreased days on >40% oxygen, days on >25% oxygen, days on ventilator, and oxygen at discharge. Among infants exposed to chorioamnionitis, hydrocortisone treatment also was associated with increased enteral intake during the first month of life and with increased weight at 36 weeks' postconception. Five treated infants and 6 placebo infants developed sepsis; 3 in each group died.

Conclusions.  First, early treatment with low-dose hydrocortisone in this population of extremely low birth weight infants increased the likelihood of survival without CLD. Second, the benefit was particularly apparent in infants with chorioamnionitis. Third, a larger multicenter trial is needed to verify the primary outcome and to better evaluate risks and benefits.  Key words:  chronic lung disease, bronchopulmonary dysplasia, premature infant, adrenal function, hydrocortisone, chorioamnionitis.

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