IV Paracetamol for closure of patent ductus arteriosus in preterm neonates admitted to a tertiary care centre

Sunil B., Shruthi Patel, Girish N.


Background: Ductus arteriosus is a vascular connection between the pulmonary artery and descending aorta. The incidence is inversely related to birth weight and gestational age (GA). In preterm infants it varies between 40% and 60% on the third day of life. At present, the choice of treatment of clinically significant PDA is with either ibuprofen or indomethacin, but they carry many contraindications and potential side effects. Hence it is important to consider that paracetamol may be used as an alternative to other non steroidal anti-inflammatory drugs and is effective in ductal closure with minimal side effects.

Methods:Thirty six preterm infants with hemodynamically significant PDA(hs-PDA) were treated with intravenous paracetamol and subsequent closure was evaluated clinically and by follow-up 2D-Echo.

Results: PDA closure following intravenous paracetamol was evident in 27 babies (75%). There were no significant side effects noted with paracetamol therapy.

Conclusions: This study shows that paracetamol could offer favourable safety profile in comparison to current treatment options. Therefore, paracetamol may be accepted as a first-line drug treatment for PDA in preterm infants. 


Paracetamol, Preterm infants, Patent ductus arteriosus

Full Text:



Clatworthy HW, Gross RE. In: Rickham P.P. (eds) Historical Aspects of Pediatric Surgery. Progress in Pediatric Surgery. Springer, Berlin, Heidelberg;1986:20.

Noori S, Seri I. The VLBW neonate with a hemodynamically significant patent ductus arteriosus during the first postnatal week. In: Kleinman CS, Seri I (eds). Hemodynamics and Cardiology. Neonatal Questions and Controversies. Saunders Elsevier: Philadelphia, PA; 2008:179.

Koch J, Hensley G, Roy L, Brown S, Ramaciotti C, Rosenfeld CR. Prevalence of spontaneous closure of the ductus arteriosus in neonates at a birth weight of 1000 gram or less. Pediatrics. 2006 Apr 1;117(4):1113-21.

Evans N. Preterm patent ductus arteriosus: should we treat it?. J Paediatr Child Health. 2012 Sep 1;48(9):753-8.

Clyman RI, Couto J, Murphy GM. Patent ductus arteriosus: are current neonatal treatment options better or worse than no treatment at all?. InSeminars Perinatol. 2012 Apr;36(2):123-9.

Meyer S. PDA in neonates: please doctor act individually! Acta Paediatrica. 2012;101(4):145-6.

F. Schena, E. Ciarmoli, and F.Mosca, “Patent ductus arteriosus: wait and see. J Maternal-Fetal Neonat Medicine. 2011 Nov;24(sup3):2-4.

Heymann MA, Rudolf AM. Control of the ductus arteriosus. Physiol Rev. 1975;55:62-78.

Coceani F, Olley PM. The response of the ductus arteriosus to prostaglandins. Can J Physiol Pharmacol. 1973;51:220-5.

Michelakis E, Rebeyka I, Bateson J, Olley P, Puttagunta L, Archer S.Voltage-gated potassium channels in human ductus arteriosus. Lancet. 2000;356:134 -7.

Leonhardt A, Glaser A, Wegmann M, Schranz D, Seyberth H, Nusing R. Expression of prostanoid receptors in human ductus arteriosus. Br J Pharmacol. 2003;138:655-9.

Fay FS, Kooke PH. Guinea pig ductus arteriosus, II: irreversible closure after birth. Am J Physiol. 1972;222:841-9.

Pegoli W. Pericardium and great vessels. In: Oldham KT, Colombiani PM editors. Principles and Practice of Pediatric Surgery. 4th ed. Philadelphia, PA: Lippincot Williams & Wilkins; 2005:1019.

Itabashi K, Ohno T, Nishida H. Indomethacin responsiveness of patent ductus arteriosus and renal abnormalities in preterm infants treated with indomethacin. J Pediatr. 2003;143:203–7

Ohlsson A, Walia R, Shah SS. Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight (or both) infants. Cochrane Database Syst Rev. 2015;2, CD003481.

Gournay V, Roze JC, Kuster A, Daoud P, Cambonie G, Hascoet JM, et al. Prophylactic ibuprofen versus placebo in very premature infants: a randomised, double-blind, placebo-controlled trial. Lancet. 2004;364:1939-44.

Aranda JV, FRCPC FAAP, Thomas R. Intravenous ibuprofen for preterm newborns. NeoReviews. 2005;6:e516-e23.

Rao R, Bryowsky K, Mao J, Bunton D, McPherson C, Mathur A. Gastrointestinal complications associated with ibuprofen therapy for patent ductus arteriosus. J Perinatol. 2011 Jul;31(7):465-70.

Kushnir A, Pinheiro JMB. Comparison of renal effects of ibuprofen versus indomethacin during treatment of patent ductus arteriosus in contiguous historical cohorts. BMC Clin Pharmacol. 2011;11:8.

Shah NA, Hills NK, Waleh N, McCurnin D, Seidner S, Chemtob S et al. Relationship between circulating platelet counts and ductus arteriosus patency after indomethacin treatment. J Pediatr. 2011;158:919-23.

Ohlsson A, Walia R, Shah SS. Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database System Rev. 2010;4:CD003481.

Adrouche-Amrani L, Green RS, Gluck KM, Lin J. Failure of a repeat course of cyclooxygenase inhibitor to close a PDA is a risk factor for developing chronic lung disease in ELBW infant. BMC Pediatr. 2012;12:10.

Kabra NS, Schmidt B, Roberts RS, Doyle LW, Papile L, Fanaroff A. (2007) Neurosensory impairment after surgical closure of patent ductus arteriosus in extremely low birth weight infants: results from the Trial of Indomethacin Prophylaxis in Preterms. J Pediatr. 2007;150:229-34.

Malviya M, Ohlsson A, Shah S. Surgical versus medical treatment with cyclooxygenase inhibitors for symptomatic patent ductus arteriosus in preterm infants. Cochrane Database Syst Rev. 2008;1:CD003951.

Hammerman C, Bin-Nun A, Markowitz E, Schimmel MS, Kaplan M. Ductal closure with paracetamol: a surprising new approach to patent ductus arteriosus treatment. Pediatrics. 2011;128:e1618-21.

Jones LJ, Craven PD, Attia J, Thakkinstian A, Wright I. Network meta-analysis of indomethacin versus ibuprofen versus placebo for PDA in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2011;96:F45-52.

Saldeño YP, Favareto V, Mirpuri J. Prolonged persistent patent ductus arteriosus: Potential perdurable anomalies in premature infants. J Perinatol. 2012;32:953-8.

Allegaert K, Anderson B, Simons S, van Overmeire B. Paracetamol to induce ductus arteriosus closure: Is it valid? Arch Dis Child. 2013;98:462-6.

Oncel MY, Yurttutan S, Degirmencioglu H, Uras N, Altug N, Erdeve O et al. Intravenous paracetamol treatment in the management of patent ductus arteriosus in extremely low birth weight infants. Neonatology. 2013;103:165-8.

Terrin G, Conte F, Scipione A, Bacchio E, Conti MG, Ferro R, et al. Efficacy of paracetamol for the treatment of patent ductus arteriosus in preterm neonates. Ital J Pediatr. 2014;40(1):21.

Schildknecht S, Daiber A, Ghisla S, Cohen RA, Bachschmid MM. Acetaminophen inhibits prostanoid synthesis by scavenging the PGHS-activator peroxynitrite. FASEB J. 2008;22(1):215-24.

Sinha R, Negi V, Dalal SS. An interesting observation of PDA closure with oral paracetamol in preterm neonates. J Clin Neonatol. 2013;2(1):30-2.

Singh Y, Gooding N. Paracetamol for the Treatment of Patent Ductus Arteriosus in Very Low Birth Weight Infants. J Neonatal Biol. 2016;5:e116.

Dang D, Wang D, Zhang C, Zhou W, Zhou Q, Wu H. Comparison of oral paracetamol versus ibuprofen in premature infants with patent ductus arteriosus: a randomized controlled trial. PLOS One. 2013;8(11):e77888.