Dear Editor,

Persistent patent ductus arteriosus (PDA) is a common pathology in the preterm whose traditional treatment has been indomethacin. Recently, ibuprofen has shown its effectiveness in closing the PDA with less hemodynamic effects.

I read different various studies on Ibuprofen versus indomethacin in the treatment of PDA with great interest. Despite this common occurrence, opinion about the use of interventions to promote closure of a PDA is controversial (1). There are no universal guidelines. There is no clear benefit of one therapy or intervention over other. However, now with more and more studies evidence is accumulating.

Su et al (2) clearly demonstrated from their study that Ibuprofen is as effective as indomethacin for the early-targeted PDA treatment in extremely premature infants, without increasing the incidence of complications. These results are similar to the metaanalysis from 11 studies by Gimeno Navarro et al (3) where they found that ibuprofen was as effective as indomethacin in closing PDA. There was no significant differences were found in the incidence of complications except for less renal impairment with ibuprofen.

Some studies have raised concerns regarding the incidence of raised bronchopulmonary dysplasia (BPD) in patients treated with ibuprofen as compared to indomethacin. However, most of the studies have shown lower incidence of oliguria (renal complications) in patients treated with ibuprofen as compared to indomethacin.

In my experience from working in the different neonatal units I have found ibuprofen equally effective to indomethacin. We have tried to treat patients with indomethacin if they are few days old and in that case indomethacin also prevents the intraventricular haemorrhage. If a patient with haemodynamically significant PDA has been about 2 weeks old or had other recent medications with renal side effects then ibuprofen may prove safer.

Now evidence is accumulating that if PDA is not haemodynamically significant then it may be best to leave untreated. Because of the lack of evidence of benefit from treatments for closure, and recent data that suggest that both medical (4) and surgical (5) treatments for the PDA are associated with poor outcomes, an increasing number of clinicians rarely treat PDAs, unless haemodynamically significant.

References:

1. Laughon MM, Simmons MA, Bose CL. Patency of the ductus arteriosus in the premature infant: is it pathologic? Should it be treated? Curr Opin Pediatr 2004; 16:146–51.

2. Su BH, Lin HC, Chiu HY, Hsieh HY, Chen HH, Tsai YC. Comparison of ibuprofen and indomethacin for early-targeted treatment of patent ductus arteriosus in extremely premature infants: a randomised controlled trial. Archives of Disease in Childhood - Fetal and Neonatal Edition 2008;93:F94- F99.

3. Gimeno Navarro A, Modesto Alapont V, Morcillo Sopena F, Fernández Gilino C, Izquierdo Macián I, Gutiérrez Laso A. Ibuprofen versus indomethacin in the preterm persistent patent ductus arteriosus therapy: review and meta-analysis. An Pediatr (Barc) 2007; 67(4):309-18.

4. Schmidt B, Roberts RS, Fanaroff A, et al. Indomethacin prophylaxis, patent ductus arteriosus, and the risk of bronchopulmonary dysplasia: further analyses from the Trial of Indomethacin Prophylaxis in Preterms (TIPP). J Pediatr 2006; 148: 730–4.

5. Kabra NS, Schmidt B, Roberts RS, et al. 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: 129–34.

Dear Editor,

Persistent patent ductus arteriosus (PDA) is a common pathology in the preterm whose traditional treatment has been indomethacin. Recently, ibuprofen has shown its effectiveness in closing the PDA with less hemodynamic effects.

I read different various studies on Ibuprofen versus indomethacin in the treatment of PDA with great interest. Despite this common occurrence, opinion about the use of interventions to promote closure of a PDA is controversial (1). There are no universal guidelines. There is no clear benefit of one therapy or intervention over other. However, now with more and more studies evidence is accumulating.

Su et al (2) clearly demonstrated from their study that Ibuprofen is as effective as indomethacin for the early-targeted PDA treatment in extremely premature infants, without increasing the incidence of complications. These results are similar to the metaanalysis from 11 studies by Gimeno Navarro et al (3) where they found that ibuprofen was as effective as indomethacin in closing PDA. There was no significant differences were found in the incidence of complications except for less renal impairment with ibuprofen.

Some studies have raised concerns regarding the incidence of raised bronchopulmonary dysplasia (BPD) in patients treated with ibuprofen as compared to indomethacin. However, most of the studies have shown lower incidence of oliguria (renal complications) in patients treated with ibuprofen as compared to indomethacin.

In my experience from working in the different neonatal units I have found ibuprofen equally effective to indomethacin. We have tried to treat patients with indomethacin if they are few days old and in that case indomethacin also prevents the intraventricular haemorrhage. If a patient with haemodynamically significant PDA has been about 2 weeks old or had other recent medications with renal side effects then ibuprofen may prove safer.

Now evidence is accumulating that if PDA is not haemodynamically significant then it may be best to leave untreated. Because of the lack of evidence of benefit from treatments for closure, and recent data that suggest that both medical (4) and surgical (5) treatments for the PDA are associated with poor outcomes, an increasing number of clinicians rarely treat PDAs, unless haemodynamically significant.

References:

1. Laughon MM, Simmons MA, Bose CL. Patency of the ductus arteriosus in the premature infant: is it pathologic? Should it be treated? Curr Opin Pediatr 2004; 16:146–51.

2. Su BH, Lin HC, Chiu HY, Hsieh HY, Chen HH, Tsai YC. Comparison of ibuprofen and indomethacin for early-targeted treatment of patent ductus arteriosus in extremely premature infants: a randomised controlled trial. Archives of Disease in Childhood - Fetal and Neonatal Edition 2008;93:F94- F99.

3. Gimeno Navarro A, Modesto Alapont V, Morcillo Sopena F, Fernández Gilino C, Izquierdo Macián I, Gutiérrez Laso A. Ibuprofen versus indomethacin in the preterm persistent patent ductus arteriosus therapy: review and meta-analysis. An Pediatr (Barc) 2007; 67(4):309-18.

4. Schmidt B, Roberts RS, Fanaroff A, et al. Indomethacin prophylaxis, patent ductus arteriosus, and the risk of bronchopulmonary dysplasia: further analyses from the Trial of Indomethacin Prophylaxis in Preterms (TIPP). J Pediatr 2006; 148: 730–4.

5. Kabra NS, Schmidt B, Roberts RS, et al. 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: 129–34.