Therapy For Patent Ductus Arteriosus Research Articles

Oral Ibuprofen versus Placebo for Management of Patent Ductus Arteriosus in Preterm infants: A Double Blinded, Randomized Controlled Trial

Abstract Background A consensus on the management of patent ductus arteriosus (PDA) in premature neonates remains indefinable. Conservative PDA treatment is based on the premise that in most preterms PDAs spontaneously close before discharge. Ibuprofen has been used for treating PDA, however, no clear guidelines for management have been suggested. Aim of Work The aim of this work is to compare the effect of oral ibuprofen versus placebo on PDA closure in preterm infants less than 34 weeks’ gestation. Methodology This study was conducted on 80 preterm neonates with gestational age ≤ 34 weeks with a hemodynamically significant PDA. They were randomized into a medical treatment group (n = 40) and a placebo group (n = 40). Both groups received conservative PDA therapy in the form of fluid restriction, positive end-expiratory pressure, and/or diuretics. The medical treatment group received oral ibuprofen (at an initial dose of 10 mg/kg/day, followed by 5 mg/kg/day for the next 2 days) and the placebo group received an oral placebo. The open-label option and an extended oral ibuprofen therapy (an offered or a repeated course with the same dose) were only offered if there are concerns over a poor patient condition that was attributed to persistent PDA and only after meeting certain criteria like signs of pulmonary hyperperfusion and/or systemic hypoperfusion. Echocardiography was done on day 1 of recruitment (48-72 hours of age) and was followed up till discharge. The patients were followed up for adverse effects of ibuprofen by serum creatinine and total serum bilirubin after the first course of treatment. Results There was no significant difference in PDA closure rate following the first ibuprofen course (62.5% in the ibuprofen treated group vs 65% in the placebo group, p > 0.05). At discharge time (mean 13.5 days in the ibuprofen group, 14 days in the placebo group), a closure rate of 75% was achieved in both groups, respectively. There was no significant difference in initial serum creatinine levels between the two groups either on day 1 of recruitment or after the first course of the intervention, p > 0.05, respectively. Meanwhile, serum creatinine significantly decreased in both groups after treatment (p-value <0.001, respectively). Also, there was no difference between the two groups in serum bilirubin either on day 1 of recruitment or after the first course of treatment, p > 0.05, respectively. Conclusion Conservative treatment is not inferior to oral ibuprofen therapy in the management of PDA. Oral ibuprofen does not elevate serum creatinine levels or cause hyperbilirubinemia.

The impact of the route of administration on the efficacy and safety of the drug therapy for patent ductus arteriosus in premature infants: a systematic review and meta-analysis.

This systematic review and meta-analysis aims to explore the potential impact of the route of administration on the efficacy of therapies and occurrence of adverse events when administering medications to premature infants with patent ductus arteriosus (PDA). The protocol for this review has been registered with PROSPERO (CRD 42022324598). We searched relevant studies in PubMed, Embase, Cochrane, and the Web of Science databases from March 26, 1996, to January 31, 2022. A total of six randomized controlled trials (RCTs) and five observational studies were included for analysis, involving 630 premature neonates in total. Among these infants, 480 were in the ibuprofen group (oral vs. intravenous routes), 78 in the paracetamol group (oral vs. intravenous routes), and 72 in the ibuprofen group (rectal vs. oral routes). Our meta-analysis revealed a significant difference in the rate of PDA closure between the the initial course of oral ibuprofen and intravenous ibuprofen groups (relative risk (RR) = 1.27, 95% confidence interval (CI) [1.13-1.44]; P<0.0001, I2=0%). In contrast, the meta-analysis of paracetamol administration via oral versus intravenous routes showed no significant difference in PDA closure rates (RR = 0.86, 95% CI [0.38-1.91]; P=0.71, I2=76%). However, there was no statistically significant difference in the risk of adverse events or the need for surgical intervention among various drug administration methods after the complete course of drug therapy. This meta-analysis evaluated the safety and effectiveness of different medication routes for treating PDA in premature infants. Our analysis results revealed that compared with intravenous administration, oral ibuprofen may offer certain advantages in closing PDA without increasing the risk of adverse events. Conversely, the use of paracetamol demonstrated no significant difference in PDA closure and the risk of adverse events between oral and intravenous administration.

Comparative Effectiveness of Surgical Ligation and Catheter Closure of Patent Ductus Arteriosus in Preterm Infants.

To evaluate the association, if any, between closure modality (surgical ligation SL vs. catheter CC) of a hemodynamically significant patent ductus arteriosus (PDA), after failure of or contraindication to medical therapy, and immediate procedural complications, and post-procedure physiologic status in preterm (gestational age < 32weeks) infants. In this single-center retrospective cohort study, data were accessed on infants < 32weeks gestation, who underwent SL or CC of PDA, born from 2019-2021. The choice of modality was determined by parents, after they were provided information on both procedures. Our cohort (n = 112) included 36 (32.1%) infants who underwent SL while 76 (67.9%) underwent CC. The SL group of infants were significantly more immature at birth, younger on admission to the level IV NICU and received more mean (SD) surfactant doses than the CC group. Higher proportions of infants in the SL group had 5-min Apgar scores ≤ 5, seizures, severe intracranial hemorrhage and had received medical therapy for PDA. Both procedures were highly efficacious, with 1 unsuccessful device placement attempt and had low associated adverse events. Two (2.6%) infants had device migration 24h after CC. SL was associated with a higher rate of immediate postoperative hypothermia whereas, in the CC group, mean airway pressure was significantly lower 48h after, compared to before the procedure. SL and CC are comparable in short-term efficacy and safety for PDA closure. Long-term outcomes data are needed following both procedures.

Patent Ductus Arteriosus Device Closure with AMPLATZER Duct Occluder-II in a Low Birth Weight Preterm Neonate- First Experience in Pakistan

We report a successful closure of large patent ductus arteriosus (PDA) in a low-birth weight preterm neonate using an ADO IIdevice for the first time in AFIC/NIHD Rawalpindi. A hemodynamically significant PDA in a preterm neonate carries anincreased risk of morbidity, including chronic lung disease, necrotizing enterocolitis and renal impairment. After the failure ofmedical therapy, successful, timely and safe transcatheter closure of PDA using appropriate equipment is a milestone inmanaging PDA in preterm neonates.

Fluctuations in unbound bilirubin levels during acetaminophen therapy for patent ductus arteriosus.

Fluctuations in unbound bilirubin levels during acetaminophen therapy for patent ductus arteriosus.

Catheter Closure of Clinically Silent Patent Ductus Arteriosus Using the Amplatzer Duct Occluder II-Additional Size: A Single-Center Experience.

ObjectivesTranscatheter closure is the treatment of choice for most patent ductus arteriosus (PDA) in infants, children, and adults. However, there is a controversy regarding transcatheter closure of clinically silent PDAs. Some authors favor device closure to eliminate the lifelong risk of infective endarteritis while others recommend avoiding PDA closure in such patients. The study describes our experience of closing the silent PDAs using the Amplatzer duct occluder II-additional size (ADO II-AS) (St. Jude Medical Corp, St. Paul, MN).Materials and methodsFrom April 2018 through March 2021, 52 consecutive pediatric patients aged 18 years and less with clinically silent PDA who had transcatheter closure at our center were enrolled. Patients were excluded if they had clinically detected PDAs; had surgical ligation of PDA with no residual shunt; had left heart dilatation on echocardiography; or moderate-sized PDAs closed with ADO II-AS. In addition, patients with an innocent murmur or murmur due to an associated lesion were included. This study was retrospective, and all of the 52 patients underwent PDA device closure using ADO II-AS.ResultsFifty-two consecutive patients were enrolled with a median age of 17 months, range (97-2.5) 94.5 months. Mean weight was 11.29 kilogram, range (24.8-3.5) 21.3 kilogram, and mean follow-up was 13.5 months, range (29-0) 29 months. Thirty-one (59.6%) were females, and 21 (40.4%) were males. The mean procedure time was 30.6 min, range (60-10) 50 min, and mean fluoroscopic time was 5.5 min, range (28-1.7) 26.3 min. The mean volume of contrast given was 9.1 milliliter, range (30-4) 26 milliliter. Forty-five (45; 88.2%) patients had immediate closure of PDA. No patients had anesthetic or vascular complications; however, two patients had procedural complications. Device placement was unsuccessful in one patient with Downs syndrome. The mean follow-up for our patients was 13.5 months, range (29-0) 29 months; the patients were asymptomatic at the follow-up, and none of the patients had any residual leak. None of the patients showed coarctation or left pulmonary artery stenosis at the latest follow-up.ConclusionThe usefulness of catheter-based therapy for silent PDA is less well-established by current evidence. Further studies are needed to justify the intervention solely based on the premise that the silent duct is a substrate for infective endarteritis; however, our reason to close silent PDA was to do so primarily because of social reasons. This study found that device closure of silent PDA is safe and effective using an ADO II-AS device with minimal risk of embolization and a low residual shunt rate. Coils have been used to close small PDAs, however, with higher rates of embolization and device malpositioning. We believe ADO-II AS offers an advantage of safety and efficacy over coils. In addition, the study highlights the advantage of using an ADO II-AS device, which can be delivered via a four French delivery system with no arterial complications.

A Pilot Randomized Controlled Trial of Early Targeted Patent Ductus Arteriosus Treatment Using a Risk Based Severity Score (The PDA RCT)

To evaluate the feasibility of recruiting preterm infants to a randomized controlled trial of patent ductus arteriosus (PDA) treatment based on a PDA severity score (PDAsc) and to characterize challenges in obtaining consent, compliance with the protocol, and PDA closure rates. This single-center, randomized control pilot study of 60 infants <29weeks of gestation with a high PDAsc (≥5.0) at 36-48hours of age receiving either ibuprofen or placebo intravenously. The study protocol did not allow for additional PDA therapy within the first 2weeks. We reported the rate of consent, open label treatment, and PDA closure rates. The primary outcome was chronic lung disease or death. We approached 83 families for enrollment with 73 (88%) providing consent; 13 infants had a PDAsc of <5; of the remaining infants, 30 were assigned ibuprofen and 30 received placebo. Eight infants received open label treatment in the first 2weeks (12%). The overall PDA closure rate after treatment was 57% in the intervention group and 17% in the control group (P<.01). There was no difference in the primary clinical outcome (OR, 0.8; 95% CI, 0.3-2.1). Using a PDAsc for infant recruitment to a PDA treatment randomized controlled trial is feasible. There is a high rate of consent and relatively low rate of open-label PDA treatment. The overall PDA closure rate in the intervention arm was low placing the emphasis on devising more effective PDA closure strategies in future randomized controlled trials. ISRCTN (13281214) and European Union Drug Regulating Authorities Clinical Trials Database (2015-004526-33).

Patent ductus arteriosus treatment in preterm neonates, which is the drug of choice paracetamol vs ibuprofen?

Background Patent ductus arteriosus (PDA) is one of the most prevalent problems in preterm infants. Although ibuprofen represents one of the choices for the closure of PDA, this treatment can cause severe gastrointestinal and adverse renal effects and worsen platelet function. Effective therapy for PDA had been suggested as paracetamol. Aim Our study is aiming to compare the efficacy and safety of paracetamol and ibuprofen. Patients and methods A prospective observational, single-center study was performed from December 2016 until August 2017, at ElGalaa Teaching Hospital in Cairo. In this study we included neonates with a gestational age of 28–36 weeks, diagnosed with a significant hemodynamically PDA using clinical and ultrasonographic cardiac evaluation. The pediatric cardiologist performed an echocardiographic examination before the start of the treatment and after seven days. Results We found that paracetamol had good efficacy on PDA in preterm infants, and the closure rate of paracetamol was comparable to that of ibuprofen. Conclusion Paracetamol may confer comparable treatment efficacy for the closure of PDA to ibuprofen, although paracetamol is associated with lower risk of adverse events.

Double Case Control Study on Effect of Ibuprofen and Acetaminophen in Premature Neonate with Patent Ductus Arteriosus in Neonatal Intensive Care Unit in Sulaimania Maternity Hospital

Backgrounds and objectives: Persistent patency of the ductus arteriosus is a major cause of morbidity and mortality in premature infants. Cyclooxygenase inhibitors remain the mainstay of medical therapy for patent ductus arteriosus. The aim of this study is to evaluate the pharmacological closures of Patent Ductus Artriosus in premature babies. Patients and Methods: Double case-control study done on sixty premature neonates with a gestational age (25-37) weeks, who were admitted to the Sulaimania maternity hospital from February to September 2017. Patent ductus artriosus diagnosis was confirmed by echocardiography. Twenty neonates received oral ibuprofen, an initial dose of 20mg/kg, followed by 10mg/kg at 24 or 48 hours later, twenty cases received oral acetaminophen in dose of 20mg/kg as initial dose, followed by 15mg/kg every eight hours for 3 days. Twenty cases not received treatment after taking consent from their family. The second echo was done after completed treatment. Results: In sixty premature neonates with patent ductus arteriosus; twenty cases received ibuprofen 14 cases responded to the treatment (70%), and 7 cases (35%) developed side effects, twenty cases received acetaminophen 11 cases responded to the treatment (55%), and side effects developed in just 3 cases (15%). lastly twenty cases received no treatment patent ducts arteriosus closed in just 8 cases (40%). Conclusions: Ibuprofen is slightly more effective on the closing of the PDA in preterm infants than acetaminophen, but the latter has fewer side effects and using medication is preferred on using no medication

Association between Furosemide Exposure and Patent Ductus Arteriosus in Hospitalized Infants of Very Low Birth Weight

To evaluate the association between furosemide exposure and patent ductus arteriosus (PDA) in a large, contemporary cohort of hospitalized infants with very low birth weight (VLBW). Using the Pediatrix Medical Group Clinical Data Warehouse, we identified all inborn infants of VLBW <37 weeks of gestation discharged from the neonatal intensive care unit after the first postnatal week from 2011 to 2015. We defined PDA as any medical (ibuprofen or indomethacin) or surgical PDA therapy. We collected data up to the day of PDA treatment or postnatal day 18 for infants not diagnosed with PDA. We performed multivariable logistic regression to evaluate the association between PDA and exposure to furosemide. We included 43 576 infants from 337 neonatal intensive care units, of whom 6675 (15%) underwent PDA treatment. Infants with PDA were more premature and more often exposed to mechanical ventilation and inotropes. Furosemide was prescribed to 4055 (9%) infants. On multivariable regression, exposure to furosemide was associated with decreased odds of PDA treatment (OR 0.72; 95% CI 0.65-0.79). Increasing percentage of days with furosemide exposure was not associated with PDA treatment (OR 1.01; 95% CI 0.97-1.06). Furosemide exposure was not associated with increased odds of PDA treatment in hospitalized infants of VLBW. Further studies are needed to characterize the efficacy and safety of furosemide in premature infants.

Association between Platelet Counts before and during Pharmacological Therapy for Patent Ductus Arteriosus and Treatment Failure in Preterm Infants.

The role of platelets for mediating closure of the ductus arteriosus in human preterm infants is controversial. Especially, the effect of low platelet counts on pharmacological treatment failure is still unclear. In this retrospective study of 471 preterm infants [<1,500 g birth weight (BW)], who were treated for a patent ductus arteriosus (PDA) with indomethacin or ibuprofen, we investigated whether platelet counts before or during pharmacological treatment had an impact on the successful closure of a hemodynamically significant PDA. The effects of other factors, such as sepsis, preeclampsia, gestational age, BW, and gender, were also evaluated. Platelet counts before initiation of pharmacological PDA treatment did not differ between infants with later treatment success or failure. However, we found significant associations between low platelet counts during pharmacological PDA therapy and treatment failure (p < 0.05). Receiver operating characteristic (ROC) curve analysis showed that platelet counts after the first, and before and after the second cyclooxygenase inhibitor (COXI) cycle were significantly associated with treatment failure (area under the curve of >0.6). However, ROC curve analysis did not reveal a specific platelet cutoff-value that could predict PDA treatment failure. Multivariate logistic regression analysis showed that lower platelet counts, a lower BW, and preeclampsia were independently associated with COXI treatment failure. We provide further evidence for an association between low platelet counts during pharmacological therapy for symptomatic PDA and treatment failure, while platelet counts before initiation of therapy did not affect treatment outcome.

Prediction of Therapeutic Response to Cyclooxygenase Inhibitors in Preterm Infants with Patent Ductus Arteriosus.

Patent ductus arteriosus (PDA) is a morbid condition commonly seen in premature infants. Cyclooxygenase (COX) inhibitors, such as indomethacin and ibuprofen, are often used for the treatment of PDA in preterm infants, and they work by reducing the production of prostaglandin. However, as observed in clinical practice, not all PDAs in preterm infants can be closed using COX inhibitors. Some studies have demonstrated that gestational age, birth weight, B-type natriuretic peptide (BNP), and ductal diameter can predict the therapeutic responsiveness to COX inhibitors. This paper reviews the factors that can predict successful closure of the PDA in preterm infants using indomethacin or ibuprofen and presents new opinions and recent findings on this topic, including the predictive roles of intrauterine growth restriction, timing of the treatment, and the importance of platelet count and arterial pH. We also discuss the prospects for future studies to improve the individualized therapy of PDA in premature neonates.

Association between early echocardiography, therapy for patent ductus arteriosus, and outcomes in very low birth weight infants

In very low birth weight infants, persistence of a patent ductus arteriosus results in morbidity and mortality. Therapies to close the ductus are effective, but clinical outcomes may depend on the accuracy of diagnosis and the timing of administration. The objective of the present study was to characterise the association between early echocardiography, therapy for patent ductus arteriosus, and outcomes in very low birth weight infants. This retrospective cohort study used electronic health record data on inborn infants of gestational age ⩽28 weeks and birth weight <1500 g who were discharged after day of life 7 from 362 neonatal ICU from 1997 to 2013. The primary outcome was death between day of life 7 and discharge. Secondary outcomes included bronchopulmonary dysplasia, necrotising enterocolitis, and grade 3 or 4 intraventricular haemorrhage. This study included a total of 48,551 infants with a median gestational age of 27 weeks (interquartile range 25, 28) and birth weight 870 g (706, 1050). Early echocardiography - that is, performed during days of life 2 to 6 - was performed in 15,971/48,551 (33%) infants, and patent ductus arteriosus was diagnosed in 31,712/48,551 (65%). The diagnosis was more common in infants who had undergone early echocardiography (14,549/15,971 [91%] versus 17,163/32,580 [53%], p<0.001). In multivariable analysis, early echocardiography was not associated with reduced mortality (odds ratio 0.97, 95% CI 0.89-1.05). Results were similar in the subset of infants who received therapy for patent ductus arteriosus (odds ratio 1.01, 95% CI 0.90-1.15). Early echocardiography was associated with an increased diagnosis of patent ductus arteriosus, but not with decreased mortality.

Oral medications regarding their safety and efficacy in the management of patent ductus arteriosus.

Patent ductus arteriosus (PDA) is a common clinical condition in preterm infants which is inversely related to birth weight and gestational age. Cyclooxygenase inhibitors such as indomethacin and ibuprofen which block the prostaglandin conversion from arachidonic acid are the most commonly used drugs for ductal closure. This review focuses on the safety and efficacy oral medications in the management of PDA in preterm infants. Ibuprofen seems to be the first choice due to its higher safety profile, as it is associated with fewer gastrointestinal and renal side effects when compared to indomethacin. PDA closure rates are better with oral than with intravenous ibuprofen probably due to the pharmacokinetic of the drug. However, these medications were reported to be associated with several adverse including transient renal failure, gastrointestinal bleeding and perforation, hyperbilirubinemia and platelet dysfunction. Paracetamol seems be an alternative to PDA therapy with lower adverse events and side effects.

Acetaminophen for patent ductus arteriosus.

To evaluate the literature describing acetaminophen use in treatment of patent ductus arteriosus (PDA). Searches were conducted in MEDLINE with full text (EBSCOhost; 1946 to September 2014) using the search terms acetaminophen, paracetamol, and patent ductus arteriosus. The references of identified articles were reviewed to identify other relevant articles. Human clinical trials and case reports limited to the English language were reviewed. In all, 12 case reports and 2 randomized, controlled clinical trials explored the use of acetaminophen in treating PDA. The case reports described the use of oral or intravenous acetaminophen in patients with contraindications to or who had previously failed nonsteroidal anti-inflammatory drug therapy for PDA. More than 76% of patients achieved successful PDA closure in reported cases. The clinical trials compared the efficacy of oral acetaminophen versus oral ibuprofen in preterm infants. Acetaminophen was noninferior to ibuprofen, with closure rates from 72.5% to 81.2%. The acetaminophen dose used in most case series and trials was 15 mg/kg dose every 6 hours for 3 days. Acetaminophen therapy was well tolerated, with only a few incidents of elevated liver enzymes being reported. Oral acetaminophen is an alternative to PDA therapy in preterm infants when indomethacin/ibuprofen is not effective or is contraindicated, and it may be considered before surgical ligation.

Serial echocardiography in very preterm infants: a pilot randomized trial

To determine whether routine echocardiography increases diagnosis and treatment for patent ductus arteriosus (PDA) and whether randomized nondisclosure is a feasible strategy for studying PDA management. Two-centre, pilot randomized, controlled trial. 88 infants with birth weights ≤1250 grams and gestational ages ≤30weeks were randomized to disclosure or nondisclosure of serial echocardiogram findings. Echocardiograms were performed at 3-5 and 7-10days of life. The primary outcome was time to regain birth weight. 100% of echocardiograms in the disclosure group were disclosed; 16% (echocardiogram #1) and 29% (echocardiogram #2) were disclosed in the nondisclosure group. There was a statistically nonsignificant decrease in drug therapy for PDA in the nondisclosure group (adjusted odds ratio [AOR] 0.56, 95% confidence interval [CI] 0.24-1.34). There was no difference in time to regain birth weight or in other important neonatal outcomes. However, infants in the nondisclosure group were more likely to demonstrate appropriate weight loss and then regain birth weight within 7-14days (AOR 2.64, 95% CI 1.08-6.44). Randomized nondisclosure of echocardiograms is a feasible strategy for evaluation of approaches to PDA management in very preterm infants. Avoidance of routine echocardiography may reduce drug therapy for PDA without adverse clinical effects.

Effects of Indomethacin on Patent Ductus Arteriosus in Neonates with Genetic Disorders and/or Congenital Anomalies

The study aimed to evaluate the effectiveness of intravenous indomethacin (IND) therapy for patent ductus arteriosus (PDA) in neonates with genetic disorders and/or congenital anomalies soon after birth. A total of 301 neonates with a genetic disorder and/or congenital anomalies and with a gestational age of ≥ 35 weeks were admitted during the study period. Eighty-five neonates with 56 genetic disorders (30 cases of trisomy 21, 10 cases of trisomy 18, and 16 others) and 29 congenital anomalies, and with clinical symptoms received intravenous IND therapy. The management methods were similar to those used for PDA in low-birth-weight infants. IND therapy had a clinical benefit at a high rate of 79% in these patients (90% and 70% in neonates with trisomies 21 and 18, respectively), including complete closure of the PDA in 52% of the patients. Although oliguria was observed in 43 infants (51%) and slight gastrointestinal bleeding was observed in 12 (14%), no infants had severe complications such as intracranial bleeding. IND therapy is an effective treatment option before considering surgery for PDA in neonates with genetic disorders and/or congenital anomalies. This therapy may reduce the difficulty of treatment in the acute stage among these neonates.

Response to “High-Dose Ibuprofen Therapy for Patent Ductus Arteriosus in Extremely Preterm Neonates: Do We Have a Final Answer?”

Response to “High-Dose Ibuprofen Therapy for Patent Ductus Arteriosus in Extremely Preterm Neonates: Do We Have a Final Answer?”

Changes in Cerebral Hemodynamics in Response to Medical Therapy for Patent Ductus Arteriosus: Prediction of Treatment Outcome in Preterm Infants

Changes in Cerebral Hemodynamics in Response to Medical Therapy for Patent Ductus Arteriosus: Prediction of Treatment Outcome in Preterm Infants

Patent Ductus Arteriosus in Premature Neonates

Persistent patency of the ductus arteriosus is a major cause of morbidity and mortality in premature infants. In infants born prior to 28 weeks of gestation, a haemodynamically significant patent ductus arteriosus (PDA) can cause cardiovascular instability, exacerbate respiratory distress syndrome, prolong the need for assisted ventilation and increase the risk of bronchopulmonary dysplasia, intraventricular haemorrhage, renal dysfunction, cerebral palsy and mortality. We review the pathophysiology, clinical features and assessment of haemodynamic significance, and provide a rigorous appraisal of the quality of evidence to support current medical and surgical management of PDA of prematurity. Cyclo-oxygenase inhibitors such as indomethacin and ibuprofen remain the mainstay of medical therapy for PDA, and can be used both for prophylaxis as well as for rescue therapy to achieve PDA closure. Surgical ligation is also effective and is used in infants who do not respond to medical management. Although both medical and surgical treatment have proven efficacy in closing the ductus, both modalities are associated with significant adverse effects. Because the ductus does undergo spontaneous closure in some premature infants, improved and early identification of infants most likely to develop a symptomatic PDA could help in directing treatment to the at-risk infants and allow others to receive expectant management.