Year : 2016 | Volume
: 7 | Issue : 2 | Page : 131--132
Paracetamol-responsive patent ductus arteriosus in a late preterm very low birth weight neonate at 4 weeks postnatal age
Amitoj Singh Chhina, Arvind Shenoi
Department of Neonatology, Cloudnine Hospital, Bangalore, Karnataka, India
Amitoj Singh Chhina
Department of Neonatology, Cloudnine Hospital, Old Airport Road, Bangalore - 560 017, Karnataka
Pharmacological closure with cyclooxygenase (COX) inhibitors, such as indomethacin and ibuprofen, forms the first line of treatment for a patent ductus arteriosus (PDA) in preterm neonates. However, their efficacy decreases with increasing postnatal and postconceptual age. Paracetamol is gaining acceptance worldwide as an alternative drug for PDA closure and can be used when COX inhibitors are contraindicated, although its efficacy at advanced postnatal age is not well described. Here, we describe a late preterm neonate (36 weeks, 1150 g birth weight) with a hemodynamically significant PDA, where COX inhibitor therapy could not be initiated due to thrombocytopenia, and where oral paracetamol was started at 4 weeks postnatal age and caused ductal closure after a 6-day course.
|How to cite this article:|
Chhina AS, Shenoi A. Paracetamol-responsive patent ductus arteriosus in a late preterm very low birth weight neonate at 4 weeks postnatal age.Muller J Med Sci Res 2016;7:131-132
|How to cite this URL:|
Chhina AS, Shenoi A. Paracetamol-responsive patent ductus arteriosus in a late preterm very low birth weight neonate at 4 weeks postnatal age. Muller J Med Sci Res [serial online] 2016 [cited 2023 Jun 4 ];7:131-132
Available from: https://www.mjmsr.net/text.asp?2016/7/2/131/185014
Nonselective cyclooxygenase (COX) inhibitors, such as indomethacin and ibuprofen, form the first line of pharmacotherapy for patent ductus arteriosus (PDA) closure.  The closure rates for these drugs range from approximately 70-85%, but their use is associated with various contraindications and potential side effects,  and also, their effectiveness decreases with postnatal , as well as postconceptual age.  If COX inhibitors fail or are contraindicated, the only currently available option is surgical ligation, which is associated with the risks of cardiothoracic surgery and impaired neurological outcome.  However, of late, evidence has started to emerge about paracetamol as an alternative drug for PDA closure.  Its effectiveness with increasing postnatal age is uncertain, but it may not be effective beyond 2 weeks postnatal age. 
Here, we describe a patient where a hemodynamically significant PDA closed after paracetamol therapy at 4 weeks postnatal age (38 weeks postconceptual age).
A 1150 g female baby was born at 36 weeks via emergency cesarean section conducted due to severe growth restriction and abnormal fetal Doppler study. She needed resuscitation at birth and later developed sepsis and was treated with antibiotics for 14 days, and did not develop any symptoms apart from thrombocytopenia, which also required platelet transfusion. An echocardiographic scan on Day 3 of life showed a 1.7 mm PDA with left atrium to aorta ratio (LA/Ao) of 1.3, but no treatment was administered as it was asymptomatic. On Day 24, the baby had multiple apneic episodes, and investigation revealed no abnormality except a 3.8 mm PDA with LA/Ao 1.8. Oral paracetamol was started instead of COX inhibitors due to persistent thrombocytopenia (50 × 10 3 /μL), at a dose of 15 mg/kg/dose, every 6 h and continued for 6 days. The PDA was monitored echocardiographically and found to be reducing in size after initiation of therapy and the apneic episodes also reduced thereafter. After 6 days, the PDA size had reduced to 1.3 mm and was found to have closed at Day 36 and the baby remained stable afterwards.
No adverse effects, such as oliguria, worsening of thrombocytopenia, or intestinal dysfunction, were encountered.
The ductus arteriosus (DA) closes spontaneously by the seventh day of life in only 70% of very low birth weight infants, and if a PDA is hemodynamically significant and symptomatic, therapeutic closure may be needed.  Reported efficacy rate for closure using both indomethacin and ibuprofen is about 70-85%.  However, both of these drugs have been associated with potential side effects including peripheral vasoconstriction, gastrointestinal morbidity, renal impairment, and impaired platelet function and counts. ,,, Although the evidence is limited, paracetamol appears to be as effective as ibuprofen in closing a PDA. 
Prostaglandin (PG) E2 regulates the DA tone in the fetus and PG H synthase (PGHS) plays a major role in its generation.  PGHS possesses two different catalytic activities: a COX and a peroxidase.  The inhibition of PGHS leads to reduced PGE2 levels and ductal constriction and this mechanism is exploited postnatally by the use of nonselective COX inhibitors to close PDA.  Paracetamol is also thought to be a potent PGHS inhibitor and is believed to act via the peroxidase segment. 
The decreased effectiveness of COX inhibitors, , and possibly paracetamol,  with postnatal age may be due to a reduced role of PG in ductal patency and increased nitric oxide production in the ductal wall with increasing postnatal age.  However, peroxidase is activated at peroxide concentrations 10 times lower than that for COX, suggesting that paracetamol may theoretically still work effectively in situations where COX inhibitors are ineffective. 
Our report demonstrates that PDA may remain responsive to doses of paracetamol even at an advanced postnatal age, and without any significant side effects. It may therefore be worth attempting pharmacotherapy with paracetamol in similar cases, before opting for surgical treatment and its associated set of morbidities.
We thank our esteemed colleagues, Dr. Malathi Raja and Dr. Nilesh Rao, for their input that helped in improving the manuscript vastly. We gratefully acknowledge Dr. Namrata Nagendra for her help in editing the final draft of the manuscript.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
|1||Hermes-DeSantis ER, Clyman RI. Patent ductus arteriosus: Pathophysiology and management. J Perinatol 2006; 26(Suppl 1):S22-3.|
|2||Ohlsson A, Walia R, Shah SS. Ibuprofen for the treatment of patent ductus arteriosus in preterm or low birth weight (or both) infants. Cochrane Database Syst Rev 2015;2:CD003481.|
|3||Achanti B, Yeh TF, Pildes RS. Indomethacin therapy in infants with advanced postnatal age and patent ductus arteriosus. Clin Invest Med 1986;9:250-3.|
|4||McCarthy JS, Zies LG, Gelband H. Age-dependent closure of the patent ductus arteriosus by indomethacin. Pediatrics 1978;62: 706-12.|
|5||Ohlsson A, Shah PS. Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low-birth-weight infants. Cochrane Database Syst Rev 2015;3:CD010061.|
|6||Roofthooft DW, van Beynum IM, de Klerk JC, van Dijk M, van den Anker JN, Reiss IK, et al. Limited effects of intravenous paracetamol on patent ductus arteriosus in very low birth weight infants with contraindications for ibuprofen or after ibuprofen failure. Eur J Pediatr 2015;174:1433-40.|
|7||El-Khuffash A, Jain A, Corcoran D, Shah PS, Hooper CW, Brown N, et al. Efficacy of paracetamol on patent ductus arteriosus closure may be dose dependent: Evidence from human and murine studies. Pediatr Res 2014;76:238-44.|
|8||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:e77888. |
|9||Sinha R, Negi V, Dalal SS. An interesting observation of PDA closure with oral paracetamol in preterm neonates. J Clin Neonatol 2013;2:30-2.|