Paracetamol for the treatment of patent ductus arteriosus in preterm neonates: a systematic review and meta-analysis.
OBJECTIVE
We performed a systematic review and meta-analysis of all the available evidence to assess the efficacy and safety of paracetamol for the treatment of patent ductus arteriosus (PDA) in neonates, and to explore the effects of clinical variables on the risk of closure.


METHODS
MEDLINE, Scopus and ISI Web of Knowledge databases, using the following medical subject headings and terms: paracetamol, acetaminophen and patent ductus arteriosus. Electronic and manual screening of conference abstracts from international meetings of relevant organisations. Manual search of the reference lists of all eligible articles.


METHODS
Studies comparing paracetamol versus ibuprofen, indomethacin, placebo or no intervention for the treatment of PDA.


METHODS
Data regarding efficacy and safety were collected and analysed.


RESULTS
Sixteen studies were included: 2 randomised controlled trials (RCTs) and 14 uncontrolled studies. Quality of selected studies is poor. A meta-analysis of RCTs does not demonstrate any difference in the risk of ductal closure (Mantel-Haenszel model, RR 1.07, 95% CI 0.87 to 1.33 and RR 1.03, 95% CI 0.92 to 1.16, after 3 and 6 days of treatment, respectively). Proportion meta-analysis of uncontrolled studies demonstrates a pooled ductal closure rate of 49% (95% CI 29% to 69%) and 76% (95% CI 61% to 88%) after 3 and 6 days of treatment with paracetamol, respectively. Safety profiles of paracetamol and ibuprofen are similar.


CONCLUSIONS
Efficacy and safety of paracetamol appear to be comparable with those of ibuprofen. These results should be interpreted with caution, taking into account the non-optimal quality of the studies analysed and the limited number of neonates treated with paracetamol so far.
Department of Gynecology-Obstetrics and Perinatal Medicine, Sapienza University of Rome, Rome, Italy.
Gianluca
G
Terrin
Department of Pediatrics and Pediatric Neuropsychiatry, Sapienza University of Rome, Rome, Italy.
Francesca
F
Conte
Division of Neonatology, Zekai Tahir Burak Maternity Teaching Hospital, Ankara, Turkey.
Mehmet Yekta
http://orcid.org/0000-0003-0760-0773
MY
Oncel
Department of Pediatrics and Pediatric Neuropsychiatry, Sapienza University of Rome, Rome, Italy.
Antonella
A
Scipione
Department of Neonatology, The Hospital for Sick Children, Toronto, Canada.
Patrick J
PJ
McNamara
Division of Neonatology, Department of Pediatrics, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
Sinno
S
Simons
Department of Pediatrics and Neonatology, 167 Military Hospital, Pathankot, Punjab, India.
Rahul
R
Sinha
Division of Neonatology, Department of Pediatrics, Ankara University School of Medicine Children's Hospital, Ankara, Turkey.
Omer
O
Erdeve
Department of Neonatology, Ataturk University Medical Faculty, Erzurum, Turkey.
Kadir S
KS
Tekgunduz
Division of Cardiology, Department of Pediatrics, Pamukkale University, Denizli, Turkey.
Mustafa
M
Dogan
Department of Neonatology, Carmel Medical Center, Haifa, Israel.
Irena
I
Kessel
Department of Neonatology, Shaare Zedek Medical Center, Hebrew University, Jerusalem, Israel.
Cathy
C
Hammerman
Department of Neonatology, Hillel Yaffe Medical Center, Hadera, Israel.
E
E
Nadir
Division of Neonatology, Zekai Tahir Burak Maternity Teaching Hospital, Ankara, Turkey.
Sadik
S
Yurttutan
Department of Neonatology, KEM Hospital, Mumbai, India.
Bonny
B
Jasani
Division of Neonatology, Hitit University, Corum, Turkey.
Serdar
S
Alan
Division of Gastroenterology, Cardarelli Hospital, Naples, Italy.
Francesco
F
Manguso
Department of Pediatrics and Pediatric Neuropsychiatry, Sapienza University of Rome, Rome, Italy.
Mario
M
De Curtis
D000082:Acetaminophen / Q000627:therapeutic use*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy*; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use; D007231:Infant, Newborn; D007234:Infant, Premature
D016861:Cyclooxygenase Inhibitors; D000082:Acetaminophen; D007052:Ibuprofen
Cardiology; Intensive Care; Neonatology; Therapeutics