Pulmonary hypertension after ibuprofen treatment for patent ductus arteriosus in very low birth weight infants

Abstract

Background: Patent ductus arteriosus (PDA), affecting approximately 70% of preterm infants, associated with substantial infant mortality and morbidity. Ibuprofen has been recommended as well as indomethacin to close PDAs but cardiopulmonary effects such as pulmonary hypertension could happen which is rare but potentially fatal complication. This study aimed to describe the clinical courses of and risk factors for pulmonary hypertension after ibuprofen treatment to close PDA. Method: All neonates weighing <1,500 g at birth who received ibuprofen to close PDA and were admitted to Seoul National University Childrens Hospitals neonatal intensive care unit in 2010-2014 were eligible for this study. The study population was divided into the PH and non-PH groups, and medical records were retrospectively reviewed. PH was diagnosed by echocardiogram, more than one of followings were documented

1) Interventricular septum flattening, 2) tricuspid regurgitation jet velocity was more than 3 meter per second. 3) right to left or bidirectional shunt through PDA. Logistic regression analysis was done for the univariate assessment of the risk factors for PH after ibuprofen treatment. Results: Of the 144 eligible infants, 10 developed PH (6.9%). Relative to the non-PH group, the PH group exhibited greater respiratory severity aggravation (P=0.07), with severe bronchopulmonary dysplasia (BPD) or death prior to 36 weeks postmenstrual age occurring more frequently (P=0.023). Gestational age is younger in infants of PH group than infants of non-PH group (P=0.006). Birth weight < 3rd percentile for gestational age (P<0.001), maternal hypertensive disorders (P<0.001) and oligohydramnios (P=0.003) were independent risk factors for PH. Multivariable OR for PH were 0.644 [95%CI 0.41-0.98, P=0.043] for younger gestational age(day) infant, 1.71 x105 [95%CI 1.65-1.76 x1010, P=0.041], for infants with birth weight < 3rd percentile for gestational age, 1.32 x103 [95%CI 3.86-4.51 x105, P=0.016], for infants with maternal hypertension during pregnancy, 47.98 [95%CI 1.10-2.10 x103, P=0.045] for infants with oligohydramnios in utero. Multivariable analysis demonstrated that lower gestational age (GA), birth weight <3rd percentile for gestational age, maternal hypertension of pregnancy and oligohydramnios were risk factors for developing PH after ibuprofen treatment. Conclusion: A high incidence of PH after ibuprofen treatment was observed in the study population. Furthermore, lower GA and several prenatal conditions were identified as risk factors for developing PH after ibuprofen treatment. Because of the fatal complications of ibuprofen such as PH, neonatologist should be very careful in choosing a treatment method for PDA. Additional large cohort studies are necessary to confirm our results.