Factors Determining Late Reopening of Ductus Arteriosus in Very Preterm Infants

BACKGROUND: A significant proportion of premature infants undergoes to late reopening of ductus arteriosus after an initial functional closure. Lower gestational age, infections and excessive fluid administration are frequently considered risk factors for ductal reopening(DR)but weight of each factor is still to determine. OBJECTIVE: To evaluate the incidence of DR and to verify which risk factors are associated with late DR and what is the contribution of each of them. DESIGN/METHODS: Clinical data in all infants with a gestational age below 28 wks born between January 2006 and June 2009 were retrospectively analyzed. To document initial ductal closure and ductal reopening echocardiography was used in all cases. GA,BW, gender, twin birth, IUGR, sepsis (both culture proven and suspected), previous treatment with ibuprofen or indomethacin and excessive fluide intake were considered. We used multiple-random effects logistic regression to calculate adjusted odds ratio of ductal reopening. The final model included the variables associated with DR in univariate analysis. RESULTS: 151 infants (84/151 male) with mean GA 26,1±1,6 wks and BW 813±251g were included. 23% were SGA and 71% were singleton. 44/151 (28%) infants experienced one or more episodes of DR after a previous echocardiographically proven closure (71 episodes in all). First episode occurred at a mean postnatal age of 12 days and never occurred beyond 26 days. We defined as sepsis-related a DR occurring within 3 days from the sepsis diagnosis. 52/71 (73%) DR were sepsis-related. DR was more frequent in infants with at least 1 episode of sepsis (OR 7,2 p<0,027). DR was also strongly positively associated with male gender (OR 10.4 p=0.037), previous course of cox-inhibitors (OR 16,6 p=0,024) and inversely related with GA (OR=0,4, p=0,015). Excessive fluid intake or excessive weight gain were related only to 7% of sepsis-related and to 18% of non-sepsis related reopenings. CONCLUSIONS: Late reopening of ductus arteriosus is associated to a systemic infection in most cases. Male gender and lower gestational age are also significative risk factors. An excessive fluid intake does not appear to be relevant.