Abstract 1366 Poster Session I, Saturday, 5/1 (poster 60)

Background: PDA has been associated with the development of chronic lung disease (CLD) in premature infants; however, in one randomized trial early ligation of PDA did not decrease the incidence of CLD (Cassady et al, NEJM 320:1511). We have linked low cortisol values during the first week of life with subsequent development of CLD. We therefore undertook to evaluate the relationship of cortisol concentrations in very low birth weight infants during the first week of life to the presence of a clinically significant PDA and to correlate its presence with respiratory outcome. Methods: This was a prospective, observational cohort study of very low birth weight infants at two study sites. Cortisol values were obtained three times during the first week: (1) day 2; (2) day 3 or 4; and (3) day 5, 6 or 7. Patients were considered to have a significant PDA if they were treated with indomethacin or ligation during the first month of life. Cortisol values were analyzed after log transformation, by multiple regression with gestational age as a cofactor. Results: We obtained 311 cortisol values from 125 babies. Infants with PDA (n=57) were smaller and more immature than those without (n=68): mean±SD=975±242 grams birth weight vs 1082±255 grams, p=0.01; 27.4±2.0 weeks gestation vs 28.4±2.2 weeks, p=0.02. On day 2, babies with and without PDA had similar cortisol values; however, after that, babies treated for PDA had significantly lower cortisol values during the first week of life (*p≤0.001). (Table) Cortisol values were similar between infants who had been previously treated with indomethacin vs those who had not (geometric mean day 3-4, 118(n=9) vs 97nmol/l (n=39); day 5-7, 88(n=9) vs 112nmol/l (n=51). PDA correlated with subsequent development of bronchopulmonary dysplasia (BPD, ↑FiO2 at 28 days) (p<0.001) and chronic lung disease (CLD, ↑FiO2 at 36 weeks post conception) (p<0.001). Conclusion: Infants treated for PDA had lower cortisol values early in life, and an increased incidence of BPD and CLD. Cortisol decreases the sensitivity of ductal tissue to prostaglandin E and may decrease prostaglandin production. We speculate that the observed link between PDA and CLD in preterm infants may in part be a reflection of adrenal insufficiency, which may allow persistence of ductal patency and predispose to chronic lung injury.

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