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Pharmacological closure of the patent ductus arteriosus: when treatment still makes sense

Journal of Perinatology volume 39, pages 1439–1441 (2019)Cite this article

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Management decisions regarding patent ductus arteriosus (PDA) have become a hand-wringing exercise during daily rounds in the neonatal ICU. Rigorous re-evaluation of the evidence beginning 20 years ago called into question the benefit of PDA treatments long considered standard care [1]. As a result, pervasive use of pharmacological agents to treat PDA decreased during the last decade in favor of more selective management, including decreased prophylactic use of cyclooxygenase inhibitor (COX-I) therapy to prevent PDA, longer periods of expectant management, and fewer infants treated [2,3,4,5]. The consequences of this trend are unclear, and an evidence basis for therapeutic decisions is lacking in an era where infants born as early as 22 weeks gestation are surviving. Neonatologists are left wondering which PDAs should we treat? Which medication should we use?

These unadjusted observational studies cannot ascertain the true relationship between changing PDA treatment and changes in outcomes and therefore offer no relief to the daily consternation over PDA decision-making in the NICU. Their conflicting results underscore our uncertainty on this topic and preserve equipoise for future clinical trials comparing alternative PDA management strategies. Moreover, the number of studies reporting increased adverse outcomes temporally associated with decreasing COX-I use suggests that foregoing treatment for PDA closure altogether should be approached cautiously. Current best evidence supports the possibility that PDA closure may benefit some extremely preterm infants. In particular, a recent study from the California Perinatal Quality Care Collaborative (CPQCC) reported that COX-I treatment may benefit infants 400–749 g birth weight [14]. In the context of improving mortality for these infants in California NICUs, this multivariable multilevel analysis found that improvement in NICU-level mortality was significantly slowed in NICUs in direct proportion to their reduction in COX-I use in this weight subgroup (Fig. 1, bottom panel). While we await definitive clinical trials, the observational literature suggests gestational ages, chronological ages, and shunt sizes where treatment may be beneficial.

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Fig. 1

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Acknowledgements

Supported in part by NIH grant HL128386.

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Authors and Affiliations

  1. Mildred T. Stahlman Division of Neonatology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA

    Maria Gillam-Krakauer & Jeff Reese

  2. Division of Neonatology, Connecticut Children’s Medical Center, Hartford, CT, USA

    James I. Hagadorn

  3. Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT, USA

    James I. Hagadorn

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  1. Maria Gillam-Krakauer
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Correspondence to Maria Gillam-Krakauer.

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Gillam-Krakauer, M., Hagadorn, J.I. & Reese, J. Pharmacological closure of the patent ductus arteriosus: when treatment still makes sense. J Perinatol 39, 1439–1441 (2019). https://doi.org/10.1038/s41372-019-0518-3

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