European Journal of Pediatrics

, Volume 176, Issue 2, pp 233–240 | Cite as

Comparative study of the efficacy and safety of paracetamol, ibuprofen, and indomethacin in closure of patent ductus arteriosus in preterm neonates

  • Abd El-Rahman El-Mashad
  • Heba El-Mahdy
  • Doaa El AmrousyEmail author
  • Marwa Elgendy
Original Article


In this prospective study, we compared the efficacy and side effects of indomethacin, ibuprofen, and paracetamol in patent ductus arteriosus (PDA) closure in preterm neonates. Three hundred preterm neonates with hemodynamically significant PDA (hs-PDA) admitted at our neonatal intensive care unit were enrolled in the study. They were randomized into three groups. Group I (paracetamol group) received 15 mg/kg/6 h IV paracetamol infusion for 3 days. Group II (ibuprofen group) received 10 mg/kg IV ibuprofen infusion followed by 5 mg/kg/day for 2 days. Group III (indomethacin group) received 0.2 mg/kg/12 h indomethacin IV infusion for three doses. Laboratory investigations such as renal function test, liver function test, complete blood count, and blood gases were conducted in addition to echocardiographic examinations. All investigations were done before and 3 days after treatment. There was no significant difference between all groups regarding efficacy of PDA closure (P = 0.868). There was a significant increase in serum creatinine levels and serum blood urea nitrogen (BUN) in the ibuprofen and indomethacin groups (P < 0.001). There was a significant reduction in platelet count and urine output (UOP) in both ibuprofen and indomethacin groups (P < 0.001). There was a significant increase in bilirubin levels in only the ibuprofen group (P = 0.003). No significant difference of hemoglobin (HB) level or liver enzymes in all groups (P > 0.05). Ventilatory settings improved significantly in patients with successful closure of PDA than those with failed PDA closure (P < 0.001).

Conclusion: Paracetamol is as effective as indomethacin and ibuprofen in closure of PDA in preterm neonates and has less side effects mainly on renal function, platelet count, and GIT bleeding.

What is Known:

Hemodynamically significant patent ductus arteriosus has many complications for preterm and low birth weight neonates and better to be closed. Many drugs were used for medical closure of PDA e.g. indomethacin, ibuprofen and recently paracetamol. Many studies compare safety and efficacy of paracetamol with either indomethacin or ibuprofen.

What is New:

It is the first large study that compares the efficacy and side effects of the three drugs in one study.


PDA closure Preterm neonate Paracetamol Ibuprofen Indomethacin 



Blood urea nitrogen




Gastrointestinal tract




Hemodynamically significant patent ductus arteriosus




Intraventricular hemorrhage


Mechanical ventilation


Necrotizing enterocolitis


Neonatal intensive care unit


Nonsteroidal anti-inflammatory drugs


Patent ductus arteriosus




Positive intermittent pressure


Retinopathy of prematurity


Serum glutamate-oxaloacetic transaminase


Serum glutamate-pyruvate transaminase


Urinary output


Authors’ contributions

Abd El-Rahman El-Mashad: the idea of the research, supervising the work of research, and revising and approving the manuscript.

Heba El-Mahdy: selecting patients and dividing them into groups, supervising and following up patients, and revising the manuscript.

Doaa El-Amrousy: performing the echocardiography, writing the manuscript, doing the statistical analysis, and following up the patients.

Marwa Elgendy: following up the patients, gathering the data, and helping in writing the manuscript.

Compliance with ethical standards


None to declare.

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants

The study was approved by the local Ethics Committee of Faculty of Medicine of our University and has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all parents of the participants included in the study.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Abd El-Rahman El-Mashad
    • 1
  • Heba El-Mahdy
    • 1
  • Doaa El Amrousy
    • 1
    Email author
  • Marwa Elgendy
    • 1
  1. 1.Pediatric DepartmentTanta University HospitalTantaEgypt

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