The Effect of Dual (Combined) Treatment in Late Preterm Infants with Patent Ductus Arteriosus

We read the article written by Shah et al with interest and would like to share our opinion on it.[1] In the study in which the synchronous use of ibuprofen and paracetamol treatment was recommended in the article, successful closure rate was observed with dual therapy in 20 infants. In the discussion part of the article, its use was recommended due to the success of a highly effective treatment with combined therapy. At the same time, the authors stated that studies with a large number of cases are needed on the combined approach for patent ductus arteriosus (PDA) treatment in preterm infants.

In this regard, I would like to mention the study we conducted in 2018.[2] In this study, the effectiveness of combined therapy in treatment-resistant cases was evaluated. The cases included in the study were monotherapy resistant cases who had previously received multiple single pharmacological therapy (ibuprofen or paracetamol) but did not respond to treatment. Combined therapy (paracetamol and ibuprofen together) were given to these cases. Two of the three babies who did not respond to medical treatment despite combined treatment were late preterm infants (>34 weeks of gestational age).

After this publication, we experienced monotherapy therapy resistant five late preterm infants in our clinic. Despite combined treatment, three infants required surgical intervention for treatment of PDA. It is already known that the response rate of late preterm infants to medical treatment of patent ductus arteriosus is extremely low. Combined treatment failure in these patients has been associated with the high gestational ages of the babies. At the same time, in late preterm infants, ibuprofen clearance increases due to improving renal maturity, leading to lower drug levels and less response in more. It has also been speculated that the role of adrenergic nerve fibers in the ductal wall is associated with vasoconstriction, thereby mediating the response to nonsteroidal anti-inflammatory drugs.

Combine treatment is very successful in very low birth weight infants with PDA, but unfortunately, its success decreases in more mature preterm infants. I hope that sharing these experiences about combine treatment in more mature preterm (late preterm) with PDA with this article will increase the dominance of the readers on the subject.

Publication History

Article published online:
11 May 2021

• References

• 1 Shah SD, Makker K, Nandula P, Smotherman C, Kropf A, Hudak ML. Effectiveness of dual medication therapy (oral acetaminophen and oral ibuprofen) for the management of patent ductus arteriosus in extremely premature infants: a feasibility trial. Am J Perinatol 2022; 39 (12) 1326-1333
• 2 Yurttutan S, Bozkaya A, Hüdayioglu F, Oncel MY. The effect of combined therapy for treatment of monotherapy-resistant PDA in preterm infants. J Matern Fetal Neonatal Med 2019; 32 (21) 3662-3665