The way an infant's blood is circulated changes soon after birth. Initially, premature infants have an opening (a patent ductus arteriosus, PDA) between the large blood vessel to the lungs and the large blood vessel that carries oxygenated blood to the rest of the body. Early symptomatic treatment of PDA, when clinical signs first appear, helps reduce the amount of time an infant needs assisted breathing (mechanical ventilation) and the likelihood of chronic lung disease and damaging inflammation of the gut (necrotizing enterocolitis). Standard therapy includes restricting fluids, diuretics, and cyclooxygenase inhibitors like indomethacin or ibuprofen. The PDA is closed surgically if these medical treatments do not work. Only one randomised controlled study could be included in this review (including 154 preterm infants that needed breathing support). Indomethacin and surgery gave similar benefits. There were no differences in deaths during the hospital stay, chronic lung disease, necrotizing enterocolitis, cerebral or other bleeding. Surgery was more effective in closing the PDA (three needed to treat for one to benefit) but it was associated with complications (pneumothorax and retinopathy of prematurity). The one study found was carried out over 20 years ago. Clinical practice has changed a great deal and surgical closure of a PDA is safer. Therefore, whether the results of the study are applicable today is debatable. An update of this review in July 2007 did not identify any additional randomised controlled studies for inclusion, but three observational studies indicated an increased risk for one or more of the following outcomes associated with PDA ligation; chronic lung disease, retinopathy of prematurity and neurosensory impairment .

This is a Cochrane review abstract and plain language summary, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2010 Issue 7, Copyright © 2010 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).
This record should be cited as: Malviya MN, Ohlsson A, Shah SS. Surgical versus medical treatment with cyclooxygenase inhibitors for symptomatic patent ductus arteriosus in preterm infants. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD003951. DOI: 10.1002/14651858.CD003951.pub2

Editorial Group: Neonatal Group

This version first published online: July 21. 2003
Last assessed as up-to-date: October 27. 2007

Abstract

Background

Patent ductus arteriosus (PDA) with significant left to right shunt in preterm infants increases morbidity and mortality. Early closure of the ductus arteriosus may be achieved pharmacologically using cyclooxygenase inhibitors or by surgery. The efficacy of both treatment modalities is well established. However, the preferred initial treatment of a symptomatic PDA in a preterm infant, surgical ligation or treatment with indomethacin, has not been well established.

Objectives

To compare the effect of surgical ligation of PDA vs. medical treatment with cyclooxygenase inhibitors (using indomethacin, ibuprofen, or mefenamic acid), each used as the initial treatment, on neonatal mortality in preterm infants with a symptomatic PDA.

Search strategy

The standard search strategy of the Cochrane Neonatal Review Group was used. This included search of electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2007), MEDLINE (1966 - July 2007), CINAHL (1982 - July 2007), EMBASE (1980 - July 2007); and hand search of abstracts of Pediatric Academic Societies annual meetings published in Pediatric Research (1990 - April 2002) or on line from May 2002 -July 2007. No language restrictions were applied.

Selection criteria

All trials 1) using randomized or quasi-randomized patient allocation, 2) in preterm infants < 37 weeks gestational age or low-birth-weight infants (< 2500 grams) with symptomatic PDA in the neonatal period (< 28 days) and 3) comparing surgical ligation with medical treatment with cyclooxygenase inhibitors, each used as the initial treatment for closure of PDA.

Data collection and analysis

Assessment of methodological quality and extraction of data for included trials was undertaken independently by the authors. RevMan 4.1 was used for analysis of the data.

Main results

Only one study, trial B in the report of Gersony 1983, was found eligible. No additional studies were identified in the literature searches performed in July 2007. The trial compared the effect of surgical ligation of PDA vs. medical treatment with indomethacin, each used as the primary treatment. No trials comparing surgery to other cyclooxygenase inhibitors (ibuprofen, mefenamic acid) were found. Trial B of Gersony 1983 enrolled 154 infants. The study found no statistically significant difference between surgical closure and indomethacin treatment in mortality during hospital stay, chronic lung disease, other bleeding, necrotizing enterocolitis, sepsis, creatinine level, or intraventricular hemorrhage. There was a statistically significant increase in the surgical group in incidence of pneumothorax [RR 2.68 (95% CI 1.45, 4.93); RD 0.25 (95% CI 0.11, 0.38); NNH 4 (95% CI 3, 9)] and retinopathy of prematurity stage III and IV [RR 3.80 (95% CI 1.12, 12.93); RD 0.11 (95% CI 0.02, 0.20), NNH 9 (95% CI 5, 50] compared to the indomethacin group. There was as expected a statistically significant decrease in failure of ductal closure rate in the surgical group as compared to the indomethacin group: [RR 0.04 (95% CI 0.01, 0.27); RD -0.32 (95% CI -0.43, -0.21), NNT 3 (95% CI 2, 4)].

Authors' conclusions

The data regarding net benefit/harm are insufficient to make a conclusion as to whether surgical ligation or medical treatment with indomethacin is preferred as initial treatment for symptomatic PDA in preterm infants. It should be noted that three recent observational studies indicated an increased risk for one or more of the following outcomes associated with PDA ligation; chronic lung disease, retinopathy of prematurity and neurosensory impairment . It is possible that the duration of the "waiting-time" and transport to another facility with surgical capacity to have the PDA ligated could adversely affect outcomes, as could the perioperative care.

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