Prophylactic ibuprofen for the prevention of intraventricular hemorrhage among preterm infants: a multicenter, randomized study.
OBJECTIVE
Ibuprofen enhances cerebral blood flow autoregulation and was shown to protect neurologic functions after oxidative stresses in an animal model. For these reasons, we hypothesized that the prophylactic use of ibuprofen would reduce the occurrence of intraventricular hemorrhage (IVH) and its worsening toward grades 2 to 4 among preterm infants. To confirm this hypothesis, we planned the present prospective study.


METHODS
This was a double-blind, randomized, controlled trial in which preterm infants with gestational ages of <28 weeks received ibuprofen or placebo within the first 6 hours of life. The infants were assigned randomly, at 7 neonatal care units, to receive ibuprofen (10 mg/kg, followed by 5 mg/kg after 24 and 48 hours) or placebo. Serial echoencephalography was performed 24 and 48 hours after the initial cerebral ultrasound study, on postnatal days 7, 15, and 30, and at 40 weeks' postconceptional age. Grade 1 IVH or no IVH was considered a successful outcome, whereas grade 2 to 4 IVH represented failure. The rates of ductal closure, side effects, and complications were recorded.


RESULTS
We studied 155 infants. Grade 2 to 4 IVH developed for 16% of the ibuprofen-treated infants and 13% of the infants in the placebo group. The occurrence of patent ductus arteriosus was less frequent only on day 3 of life in the ibuprofen group. There were no significant differences with respect to other complications or adverse effects.


CONCLUSIONS
Our study demonstrated that prophylactic ibuprofen is ineffective in preventing grade 2 to 4 IVH and that its use for this indication cannot be recommended.
Dani
Carlo
C
Department of Surgical and Medical Critical Care, Section of Neonatology, Careggi University Hospital of Florence, Florence, Italy. cdani@unifi.it
Bertini
Giovanna
G
Pezzati
Marco
M
Poggi
Chiara
C
Guerrini
Pietro
P
Martano
Claudio
C
Rubaltelli
Firmino F
FF
D002543:Cerebral Hemorrhage / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000517:prevention & control*; D002552:Cerebral Ventricles; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004311:Double-Blind Method; D004374:Ductus Arteriosus, Patent / Q000000981:diagnostic imaging / Q000188:drug therapy; D004453:Echoencephalography; D005260:Female; D005865:Gestational Age; D006474:Hemorrhagic Disorders / Q000139:chemically induced; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control*; D007363:Intensive Care Units, Neonatal / Q000706:statistics & numerical data; D015931:Intensive Care, Neonatal / Q000379:methods*; D007558:Italy / Q000453:epidemiology; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D012720:Severity of Illness Index; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D007052:Ibuprofen