Closure of patent ductus arteriosus with oral ibuprofen suspension in premature newborns: a pilot study.
OBJECTIVE
Patent ductus arteriosus (PDA), a common finding among premature infants, is conventionally treated by intravenous indomethacin. Intravenous ibuprofen was recently shown to be as effective and to have fewer adverse reactions in preterm infants. If equally effective, then oral ibuprofen for PDA closure would have several important advantages over the intravenous route. This study was designed to determine whether oral ibuprofen treatment is efficacious and safe in closure of a PDA in premature infants with respiratory distress syndrome.


METHODS
Twenty-two preterm newborns (gestational age: 27.5 +/- 1.75 [range: 23.9-31 weeks]; weight: 979 +/- 266 [range: 380-1500 g]) with PDA and respiratory distress syndrome were studied prospectively. They received oral ibuprofen suspension 10 mg/kg/body weight for the first dose, followed at 24-hour intervals by 2 additional doses of 5 mg/kg each, if needed, starting on the second day of life. Echocardiography was performed before treatment and 24 hours after each dose. Every child underwent cranial ultrasonography before and after each ibuprofen dose. The rate of ductal closure, the need for additional treatment, side effects, complications, and the infants' clinical courses were recorded.


RESULTS
Ductal closure was achieved in all newborns except for 1 (95.5%), in whom clinically nonsignificant ductal shunting persisted. No infant required surgical ligation of the ductus. There was no reopening of the ductus after closure had been achieved. Fourteen newborns were treated with 1 dose of ibuprofen, 6 were treated with 2 doses, and the remaining 2 were treated with 3 doses. The survival rate at 1 month was 86.4% (19 of 22). Three (13.6%) infants died from the following causes: 1 who was born at 24 weeks' gestation with a birth weight of 380 g died as a result of extreme prematurity complications, necrotizing enterocolitis, and low birth weight; 1 died as a result of Candida sepsis; and the third died as a result of Klebsiella sepsis. Intraventricular hemorrhage was observed in 7 infants. The classification was changed from grade 2 to grade 3 in 1 and from grade 0 to grade 1 or higher in 3 others. The rate of survival to discharge was 86.4% (19 of 22). No bronchopulmonary dysplasia was observed in the study group, and there was no case of tendency to bleed. There were no significant differences in the levels of serum creatinine before and after treatment with oral ibuprofen.


CONCLUSIONS
Oral ibuprofen suspension may be an effective and safe alternative for PDA closure in premature infants with PDA. However, larger comparative studies are warranted.
Neonatal Intensive Care Unit, Assaf Harofeh Medical Center, Zerifin, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Eli
E
Heyman
Iris
I
Morag
David
D
Batash
Rimona
R
Keidar
Shaul
S
Baram
Matitiahu
M
Berkovitch
D000284:Administration, Oral; D002543:Cerebral Hemorrhage / Q000000981:diagnostic imaging; D004341:Drug Evaluation; D004374:Ductus Arteriosus, Patent / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D005865:Gestational Age; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007234:Infant, Premature; D007969:Leukomalacia, Periventricular / Q000000981:diagnostic imaging; D010865:Pilot Projects; D011446:Prospective Studies; D012127:Respiratory Distress Syndrome, Newborn / Q000150:complications; D012449:Safety; D013535:Suspensions; D016896:Treatment Outcome; D014463:Ultrasonography
D013535:Suspensions; D007052:Ibuprofen