12 Reduction of Urinary PGE2 Induced by Ibuprofen Treatment in Preterm Infants with Patent Ductus Arteriosus.

Abstract

Background: Patent ductus arteriosus (PDA) is a common finding among preterm infants. Hemodynamically significant PDA requires medical treatment with cyclooxygenase inhibitors such as indomethacin or ibuprofen (IBU). IBU has been shown to be as effective as indomethacin in ductal closure, with fewer adverse effects.Aim: To investigate urinary excretion changes of PGE2 induced by IBU treatment in preterm infants with PDA.Methods: Twenty preterm infants (gestational age, 24 to 32 weeks; birth weight, 640 to 1820 g) with a significant PDA at 48–72 hours of age were enrolled. Two serial urine samples were noninvasively collected in each patient, by a cotton wool ball method, just before and 12–24 hours after a conventional course of IBU treatment, respectively. Urinary PGE2 concentrations were measured by a sensitive and accurate enzyme immunoassay (EIA) method (Cayman Chem, Ann Arbor, MI, USA). Furthermore, serum creatinine and other renal function parameters were assessed before and after IBU treatment.Results: Mean urinary PGE2 concentrations decreased significantly after IBU treatment (from baseline values of 66.95+/-16.78 to 27.15+/-17.92 pg/mL, P<0.001). Post-treatment urinary levels of PGE2 particularly low (<5 pg/mL) were found in two patients, who developed clinically relevant manifestations (intraventricular hemorrhage, acute renal failure, and intestinal perforation). Serum creatinine concentration increased from baseline value in 7 of 20 patients, 4 of them having an increase of >20%, after IBU treatment.Conclusions: The adverse effects of cyclooxygenase inhibitors may involve different organs of newborn, but particularly the kidney, which is considered prostaglandin-dependent. Although IBU represents the most safe drug in ductal closure, it induced a significant reduction of urinary PGE2 concentrations in our study population. In newborns with relevant side effects this reduction was dramatic. Further studies are needed to confirm these data and to determine whether urinary PGE2 may represent an index of toxicity in clinical settings.