Persistent ductus arteriosus in extremely preterm infants

Patent ductus arteriosus (PDA) is common in infants born <28 weeks gestational age (GA) and associated with significant morbidity. Despite extensive research efforts, the indications for PDA treatment remain controversial. The aims of these studies were to gain knowledge of factors affecting ductal closure during the early postnatal period and provide better means for identification of preterm infants that may benefit from PDA treatment. In Paper I, infants born <28 weeks GA and pharmacologically treated for PDA were retrospectively identified and their echocardiographic examinations were reviewed. Twenty-nine (52%) infants successfully closed and 27 (48%) infants failed to close PDA during treatment. High maximal ductal flow velocity (Vmax) was independently associated with closure (OR 3.04, p=0.049). Paper II prospectively included infants born <28 weeks GA and assessed early respiratory, circulatory and echocardiographic parameters. PDA was persistent in 18 (30%) and ultimately closed or insignificant in 42 (70%) infants. Echocardiographic criteria for hemodynamically significant PDA on days 2-7 did not predict persistent PDA (p=1.000). Mechanical ventilation (p=0.025), high mean airway pressure (p=0.020) and low Vmax (p=0.024) during day two were associated with future persistent PDA. Blood samples were obtained during the second day of life from 47 of the infants in Paper II and serum markers previously associated with PDA or factors affecting PDA were analyzed for Paper III. Inflammatory markers and erythropoietin (EPO) were elevated in infants with future persistent PDA. EPO levels were also higher in infants that did not close PDA during pharmacological treatment. In Paper IV, 44 infants born <28 weeks GA with surgically ligated PDA were retrospectively compared to non-surgically treated controls. Ligated infants had larger ductal diameter prior to, and lack of diameter decrease after pharmacological treatment for PDA (p=0.048 and p=0.022 respectively), and higher incidence of severe bronchopulmonary dysplasia (p=0.025). Longer periods with invasive ventilation was independently associated with ligation (OR 1.04, p=0.018). In conclusion, early hsPDA do not predict persistence of ductus arteriosus in extremely preterm infants, but Vmax and EPO are promising early markers for prediction of persistence and should be subjects of future studies