Finding the optimal pharmacological treatment of a patent ductus arteriosus (PDA) in preterm neonates remains challenging. There is a growing interest in paracetamol as a new drug for PDA closure. In this prospective observational cohort study, we evaluated the effectiveness of intravenous paracetamol in closing a PDA in very low birth weight infants with a hemodynamically significant PDA who either did not respond to ibuprofen or had a contraindication for ibuprofen. They received high-dose paracetamol therapy (15 mg/kg/6 h intravenous) for 3–7 days. Cardiac ultrasounds were performed before and 3 and 7 days after treatment. Thirty-three patients were included with a median gestational age of 251/7 weeks (IQR 1.66), a median birth weight of 750 g (IQR 327), and a median postnatal age of 14 days (IQR 12). Paracetamol was ineffective in 27/33 patients (82 %). Even more, after previous exposure to ibuprofen, this was even 100 %. Conclusion: In this study, paracetamol after ibuprofen treatment failure was not effective for PDA closure in VLBW infants. From the findings of this study, paracetamol treatment for PDA closure cannot be recommended for infants with a postnatal age >2 weeks. Earlier treatment with paracetamol for PDA might be more effective.What is known:• The ductus arteriosus fails to close after birth in 30 to 60 % of prematurely born neonates and is a significant cause of morbidity and mortality in these infants.• Paracetamol gained importance as an alternative drug in PDA closure.What is new:• Paracetamol for PDA closure after ibuprofen treatment failure was not effective in VLBW infants.• Effect of paracetamol on PDA closure was observed when given as primary treatment.

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Keywords Ibuprofen contraindication, Ibuprofen treatment failure, Paracetamol, Patent ductus arteriosus, VLBW infants
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Journal European Journal of Pediatrics
Roofthooft, D.W.E, van Beynum, I.M, de Klerk, J.C.A, van Dijk, M, van den Anker, J.N, Reiss, I.K.M, … Simons, S.H. (2015). Limited effects of intravenous paracetamol on patent ductus arteriosus in very low birth weight infants with contraindications for ibuprofen or after ibuprofen failure. European Journal of Pediatrics, 174(11), 1433–1440. doi:10.1007/s00431-015-2541-5