Prophylaxis against early adrenal insufficiency to prevent chronic lung disease in premature infants

Background. Many extremely low birth weight infants (< 1000 g) show biochem ical evidence of adrenal insufficiency in the first week of life, correlati ng 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 be fore 48 hours of life, would increase the likelihood of survival without CL D. Results. Forty patients were enrolled at two centers. Birth weight and gest ation were similar for treatment and placebo groups: 732 +/- 135 g versus 7 70 +/- 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 wi thout supplemental oxygen at 36 weeks' postconception (12/20 [60%] vs 7/20 [35%]). Lower birth weight, histologic chorioamnionitis, and preeclampsia w ere significant risk factors, whereas study center, prenatal steroids, sex, and ethnicity were not significant. Hydrocortisone treatment decreased day s on >40% oxygen, days on >25% oxygen, days on ventilator, and oxygen at di scharge. Among infants exposed to chorioamnionitis, hydrocortisone treatmen t 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 po pulation of extremely low birth weight infants increased the likelihood of survival without CLD. Second, the benefit was particularly apparent in infa nts with chorioamnionitis. Third, a larger multicenter trial is needed to v erify the primary outcome and to better evaluate risks and benefits.