Patent Ductus Arteriosus In Neonates Research Articles

Effectiveness of Alprostadil for Ductal Patency

OBJECTIVES This study aims to describe the effectiveness of low initial alprostadil dosages to maintain a patent ductus arteriosus (PDA) in infants with ductal-dependent congenital heart disease (DDCHD). Secondary objectives were to describe any adverse drug events, describe prescribing trends, describe ductus arteriosus diameter changes, and compare the safety and efficacy of very low and low initial alprostadil dosage regimens. METHODS This retrospective observational cohort study at the British Columbia’s Women’s and Children’s Hospital neonatal intensive care unit and pediatric intensive care unit examined neonates admitted with DDCHD who received alprostadil to maintain ductal patency. Very low–dose alprostadil (less than 0.01 mcg/kg/min) versus low-dose alprostadil (equal to or greater than 0.01 mcg/kg/min) was examined. Effectiveness was defined as survival and infants not requiring a resuscitation event (cardiac arrest, cardiogenic shock, code blue, extracorporeal life support, requirement for emergent cardiac surgery, and respiratory acidosis). Adverse drug events with a Naranjo score of 3 or more were included. RESULTS Alprostadil was effective for 88% of patients, with no difference between the very low–dose and low-dose groups. Of the 75 patients included, 25 received very low–dose alprostadil. Adverse drug events were common (51%) with neonates in the low-dose group experiencing more apnea and pyrexia than neonates in the very low–dose group. CONCLUSIONS Alprostadil therapy was effective in maintaining the PDA in neonates with DDCHD with low-dosage regimens. Adverse drug events were common with both dosage regimens; however, the very low dosage appeared to have less apnea and pyrexia.

Comparison of acetaminophen with ibuprofen in the treatment of patent ductus arteriosus in neonates admitted to training hospitals in Khorramabad from 2018 to 2022: A retrospective study

Background: Due to the possible complications of a persistent ductus arteriosus (PDA), the treatment of the PDA will be necessary, depending on the opinion of the treating physician. Medical or surgical treatment can be used in this regard. In recent years, acetaminophen has been considered a medication with fewer potential side effects. The present study aimed to compare acetaminophen with ibuprofen in the patent ductus arteriosus in neonates admitted to training hospitals in Khorramabad. Materials and Methods: A total of 28 neonates were included in this retrospective cohort study. The required data were collected by studying the patients' files. The PDA in newborns was diagnosed by primary echocardiography by the attending physician. Thereafter, 12 and 16 cases were treated with ibuprofen and acetaminophen, respectively. After completing the treatment period on days 3 and 5, the attending physician performed echocardiography to check PDA closure. Data were analyzed in SPSS software (version 24) using descriptive indices of mean, standard deviation, frequency, percentage, Fisher's exact test, and Mann-Whitney U test. Results: In this study, the frequency of affected male neonates was the same as that of affected female newborns (n=14; 50%). The mean weight scores of neonates in acetaminophen and ibuprofen groups were obtained at 2831/25±918/49 and 2241/5 ±868/9 gr, respectively. All newborns in both groups were treated; thereafter, 23 cases recovered with 3-day treatment and 5 neonates with 5-day treatment. No significant complications were observed in patients. Conclusion: The effect of acetaminophen on PDA closure was similar to that of ibuprofen. The need for 5-day treatment was higher in the acetaminophen group; nonetheless, no significant side effects were reported in any newborn. According to this study, acetaminophen can be a good alternative to ibuprofen in the treatment of PDA.

Evaluation of the Closure of Patent Ductus Arteriosus With Ibuprofen Compared to Indomethacin.

Limited data exist comparing indomethacin and ibuprofen for the treatment of patent ductus arteriosus (PDA). The objective was to compare the safety and efficacy of indomethacin and ibuprofen for treatment of PDA closure. This single-center, pre-test/post-test quasi-experiment included preterm infants admitted to the neonatal intensive care unit who received indomethacin (July 1, 2013-September 30, 2015) or ibuprofen (December 1, 2015-July 31, 2019) for PDA. Patients were excluded if they were thrombocytopenic, had existing kidney injury, unresolved intraventricular hemorrhage (IVH) or necrotizing enterocolitis (NEC) at treatment initiation. Data were obtained from the electronic health record. Study outcomes were complete PDA closure, degree of PDA closure, resolution of symptoms, and new-onset acute kidney injury (AKI), IVH, or NEC. A total of 114 patients were included: 44 (39%) received indomethacin and 70 (61%) received -ibuprofen. Twenty-one (21%) patients experienced successful PDA closure within 1 week: 13 (32%) indomethacin patients and 8 (13%) ibuprofen patients (p = 0.023). PDA size reduction occurred in 43 (46%) patients with 29 (25%) experiencing complete symptom resolution. Significantly more indomethacin patients compared with ibuprofen patients experienced new-onset AKI (48% vs 17%; p < 0.001) and received concomitant nephrotoxins (68% vs 39%; p = 0.002). There were no significant differences in new-onset IVH or NEC. Indomethacin administration successfully closed the PDA in more neonates than ibuprofen but resulted in higher rates of AKI. However, this was confounded by more frequent administration of concomitant nephrotoxins. Larger trials are needed to help elucidate the optimal drug for closure of the PDA in neonates.

Targeted neonatal echocardiography for patent ductus arteriosus in neonates reduces the surgical ligation rate without affecting healthcare outcomes.

Surgical ligation of patent ductus arteriosus (PDA) can be associated with long-term morbidity and adverse outcomes in neonates. Targeted neonatal echocardiography (TNE) has been increasingly used to improve the hemodynamic management. We aimed to evaluate the preoperative assessment impacts of the hemodynamic significance of PDA using TNE on PDA ligation rates and neonatal outcomes. This observational study included preterm infants who underwent PDA ligation during two epochs (Epoch I: January 2013 to December 2014; Epoch II: January 2015 to June 2016). During Epoch II, a comprehensive TNE assessment was performed preoperatively to evaluate the hemodynamic significance of PDA. Primary outcome was the incidence of PDA ligation. Secondary outcomes included the incidence of postoperative cardiorespiratory instabilities, individual morbidities, and the composite outcome of death. A total of 69 neonates underwent PDA ligation. No difference in baseline demographics was found between the epochs. The incidence of PDA ligation in very low birth weight (VLBW) infants was lower during Epoch II than Epoch I [7.5% vs. 14.6%, rate ratio =0.51 (95% confidence interval =0.30-0.88)]. No differences were observed between epochs in the proportion of VLBW infants who developed post-operative hypotension or oxygenation failure. The composite outcome of death or major morbidity did not significantly differ between Epoch I and Epoch II (91.1% vs. 94.1%, P=1.000). Incorporating TNE into a standardized hemodynamic assessment program, we demonstrated a 49% reduction in PDA ligation rate without any increase in postoperative cardiopulmonary instability or short-term neonatal morbidities in a cohort of VLBW infants.

Echocardiographic assessment of intimal thickness growth of patent ductus arteriosus in neonates and analysis of influencing factors

The spontaneous closure rate of patent ductus arteriosus (PDA) is high, and the necessity of early intervention is debated. Quantitative echocardiographic assessment of the intima in PDA has not been reported. This study evaluated intimal thickness growth in neonatal cases of PDA via echocardiography and investigated its correlation with clinical factors. Seventy-three neonates were enrolled, and echocardiography was performed three times: within 24 h post-birth (first echo), 48 h after the first echo (second echo), and before discharge (third echo). According to PDA outcome, the neonates were divided into the PDA-open group (n = 18 cases), PDA-closure at second echo group (n = 32 cases), and non-PDA at first echo group (n = 23 cases). We measured the intimal thickness (IT1 and IT2 at first and second echo, respectively), lumen diameter of ductus arteriosus (D1 and D2 at first and second echo, respectively), IT1/D1 ratio, and intimal thickness growth rate (V). Correlations between echocardiographic indicators, perinatal factors, and clinical treatment were analyzed. On first echo, the PDA-open group showed a significantly lower IT1/D1 than the combined PDA-closure group (P < 0.05). On second echo, the PDA-open group showed a significantly lower IT2 and V than the PDA-closure group as well as a significantly higher D2 (P < 0.05). Smaller gestational age correlated with a larger D2 but smaller IT2 and V (P < 0.05) and a higher level of respiratory support within 72 h post-birth correlated with a larger D2 and smaller IT 2 (P < 0.05). Increasing oxygen demand within 72 h of birth correlated with a larger D1 and D2 (P < 0.05). Echocardiographic assessment of intimal thickness growth in PDA may provide an approach for predicting spontaneous PDA closure, thereby guiding decision-making regarding early intervention.

Incidence, risk and risk factors for acute kidney injury associated with the use of intravenous indomethacin in neonatal patent ductus arteriosus: A 16-year retrospective cohort study.

Background:Intravenous indomethacin has been used in infants for many years as the pharmacological closure of ductus arteriosus, but the incidence, risk, and risk factors of acute kidney injury (AKI) among infants treated with indomethacin, were still scarce.Objectives:To determine the incidence, risk, and risk factors of AKI among infants treated with indomethacin (exposed group) for patent ductus arteriosus (PDA) closure compared with the matched non-exposed infants.Methods:A matched retrospective cohort study of infants admitted to the neonatal intensive care unit of Songklanagarind Hospital from January 2003 to December 2018 was performed. All data were collected from computerized medical records. A non-exposed infant was matched (1:1) by gestational age and birth weight to each exposed infant. AKI, the outcome of interest, was diagnosed according to neonatal AKI definitions. The incidence (95% CI) of AKI was estimated for each group. Conditional logistic regression was used to estimate the odds ratio (OR) of developing AKI among those who received indomethacin compared with those who did not, adjusted for potential confounders (concomitantly used nephrotoxic potential medications including aminoglycosides, amphotericin B, vancomycin, furosemide, systemic corticosteroids, and systemic vasopressors and inotropes). Kaplan-Meier estimate was performed to examine probability of recovery from AKI after AKI events.Results:The matching resulted in 193 pairs of exposed and non-exposed infants. The incidences [95% CI] of AKI in the exposed and the non-exposed group, were 33.7% [27.0%:40.4%] and 15.5% [10.4%:20.7%], respectively. Indomethacin statistically increased the risk for developing AKI, crude OR 2.94[95%CI 1.77:4.90], McNemar’s chi square p<0.001, and adjusted OR 2.73 [95%CI 1.55:4.80], p=0.001. The risk of AKI associated with potentially nephrotoxic medications were inconclusive. Time to recovery from AKI was relatively rapid, median recovery time was 3 days in both groups and all infants who developed AKI recovered within 6 days.Conclusions:The incidence of AKI among infants treated with indomethacin for PDA closure were doubled that in the indomethacin-nonexposed infants. Indomethacin significantly increased the risk of AKI, while the risk associated with other concomitant nephrotoxic medications were inconclusive. Transient nephrotoxicity associated with indomethacin should be balanced with the risk associated with delayed PDA closure. All infants receiving indomethacin should be routinely monitored for serum creatinine and/or urine output, throughout the treatment and one to two weeks after treatment cessation. Alternatives with better renal safety profiles should be considered in the population with higher risk of AKI.

Left Vocal Cord Paralysis, Lung Function and Exercise Capacity in Young Adults Born Extremely Preterm With a History of Neonatal Patent Ductus Arteriosus Surgery—A National Cohort Study

Background: Left vocal cord paralysis (LVCP) is a known complication of patent ductus arteriosus (PDA) surgery in extremely preterm (EP) born neonates; however, consequences of LVCP beyond the first year of life are insufficiently described. Both voice problems and breathing difficulties during physical activity could be expected with an impaired laryngeal inlet. More knowledge may improve the follow-up of EP-born subjects who underwent PDA surgery and prevent confusion between LVCP and other diagnoses.Objectives: Examine the prevalence of LVCP in a nationwide cohort of adults born EP with a history of PDA surgery, and compare symptoms, lung function, and exercise capacity between groups with and without LVCP, and vs. controls born EP and at term.Methods: Adults born EP (<28 weeks' gestation or birth weight <1,000 g) in Norway during 1999–2000 who underwent neonatal PDA surgery and controls born EP and at term were invited to complete questionnaires mapping voice-and respiratory symptoms, and to perform spirometry and maximal treadmill exercise testing. In the PDA-surgery group, exercise tests were performed with a laryngoscope positioned to evaluate laryngeal function.Results: Thirty out of 48 (63%) eligible PDA-surgery subjects were examined at mean (standard deviation) age 19.4 (0.8) years, sixteen (53%) had LVCP. LVCP was associated with self-reported voice symptoms and laryngeal obstruction during exercise, not with lung function or peak oxygen consumption (VO2peak). In the PDA-surgery group, forced expiratory volume in 1 second z-score (z-FEV1) was reduced compared to EP-born controls (n = 30) and term-born controls (n = 36); mean (95% confidence interval) z-FEV1 was −1.8 (−2.3, −1.2), −0.7 (−1.1, −0.3) and −0.3 (−0.5, −0.0), respectively. For VO2peak, corresponding figures were 37.5 (34.9, 40.2), 38.1 (35.1, 41.1), and 43.6 (41.0, 46.5) ml/kg/min, respectively.Conclusions: LVCP was common in EP-born young adults who had undergone neonatal PDA surgery. Within the PDA-surgery group, LVCP was associated with self-reported voice symptoms and laryngeal obstruction during exercise, however we did not find an association with lung function or exercise capacity. Overall, the PDA-surgery group had reduced lung function compared to EP-born and term-born controls, whereas exercise capacity was similarly reduced for both the PDA-surgery and EP-born control groups when compared to term-born controls.

Pre-procedural CT imaging aids neonatal PDA stenting for ductal-dependent pulmonary blood flow with reduction in overall procedural morbidity.

Patent ductus arteriosus stenting for ductal-dependent pulmonary blood flow is a technically challenging neonatal procedure to maintain a stable pulmonary circulation. Pre-procedural computed tomography imaging aids in outlining ductal origin, insertion, size, course and curvature. Computed tomography imaging may add value to procedural outcomes and reduce overall procedural morbidity in neonatal patent ductus arteriosus stenting. We conducted a single centre retrospective chart review of neonates with ductal-dependent pulmonary blood flow who underwent patent ductus arteriosus stenting between January 1, 2014 and June 31, 2020. We compared patients variables between patients who underwent pre-procedural computed tomography imaging to those who did not. A total of 64 patients were referred for patent ductus arteriosus stenting with 33 (52%) obtaining pre-procedural computed tomography imaging. Average age [19 days; range 1-242 days (p = 0.85)] and weight [3.3 kg (range 2.2-6.0 kg; p = 0.19)] was not significantly different between the groups. A diagnosis of pulmonary atresia was made in 42 out of 64 (66%) patients prior to patent ductus arteriosus stenting. The cohort with pre-intervention computed tomography imaging had a significant reduction in the total number of access sites (1.2 versus 1.5; p = 0.03), contrast needed (5.9 versus 8.2 ml/kg; p = 0.008), fluoroscopy (20.7 versus 38.8 minutes; p = 0.02) and procedural time (83.4-128.4 minutes; p = 0.002) for the intervention. There was no significant difference in radiation burden between the groups (p = 0.35). Pre-procedural computed tomography imaging adds value by aiding interventional planning for neonatal patent ductus arteriosus stenting. A statistically significant reduction in the number of access sites, contrast exposure, as well as fluoroscopic and procedural time was noted without significantly increasing the cumulative radiation burden.

Echocardiographic comparison between oral acetaminophen versus ibuprofen in management of patent ductus arteriosus in neonates

BackgroundPatent ductus arteriosus (PDA) is a common complication in preterm neonates with the incidence of 30–67% in extremely preterm neonates, which results in increased pulmonary blood flow and increased incidence of further comorbidities such as chronic lung disease.ObjectiveTo evaluate the effect of oral acetaminophen versus ibuprofen in the management of PDA in premature infants by echocardiography.Patients and methodThe study was carried out on 50 preterm neonates diagnosed by echocardiography to have PDA in the neonatal intensive care unit in Menoufia University Hospital from March 2019 to September 2019. Patients were classified into two groups: group 1 included neonates who received oral acetaminophen at a dose of 15 mg/kg every 6 h for 3 days and group 2 included neonates who received oral ibuprofen at the initial dose of 20 mg/kg followed by 10 mg/kg for 3 days. Both acetaminophen and ibuprofen were administrated via an orogastric tube, which was flushed with 1–2 ml of sterile water to ensure delivery of the drug. Both groups were evaluated by echocardiography. All patients were subjected to complete history taking, thorough clinical examination, complete blood count, and kidney and liver function tests.ResultsAfter the first course of treatment, PDA closed in 21 (84%) patients who received oral acetaminophen versus 21 (84%) of those given oral ibuprofen (P = 0.766). After the second course of treatment, PDA closed in 12% of oral acetaminophen group and 8% of oral ibuprofen group.ConclusionThere was no significant difference between the treatment of PDA with either oral acetaminophen or oral ibuprofen in preterm neonates, but acetaminophen has minimal adverse effects.

Assessing the clinical significance of echocardiograms in determining treatment of patent ductus arteriosus in neonates.

To evaluate the utility of echocardiogram (ECHO) in detection and treatment of patent ductus arteriosus (PDA) and hemodynamically significant PDA (hsPDA) in preterm neonates. This was a retrospective case-control study of all preterm infants born or admitted to the level III Neonatal Intensive Care Unit in McMaster Children's Hospital from January 2009 to January 2013. These cases were further classified into the following sub-groups: group A) hsPDA confirmed on ECHO; and the control, group B) PDA (but not hemodynamically significant) confirmed on ECHO. Patients without an ECHO were excluded from all analyses. The primary outcome was incidence of treatment for PDA. PDA treatment was administered in 83.3% and 11.2% of patients in groups A and B respectively (P < 0.05). Among patients with a hsPDA within group A, 17% did not receive treatment, while 11% of patients with non-hemodynamically significant PDA received treatment for the PDA. Within the cohort of patients who received treatment for a hsPDA, gestational age below 35 weeks as well as murmurs heard on auscultation were both found to be predictors of treatment. While the ECHO remains the gold standard for detecting pathological PDA, there is evidence that other traditional clinical measures continue to guide clinical practice and treatment decisions. Further research is required to gain an understanding of how clinical measures and ECHO may be used in conjunction to optimize resource utilization.

The type and timing of patent ductus arteriosus treatment was associated with neurodevelopment when extremely preterm infants reached 6.5years.

This study investigated patent ductus arteriosus (PDA) treatment and neurodevelopmental outcomes when extremely preterm born children reached 6.5years. Our cohort was 435 children with neonatal PDA treatment data and neurodevelopmental follow-up data, born in 2004-2007, who participated in the Extremely Preterm Infants in Sweden Study. Pharmacological or surgical PDA treatment and the age at PDA treatment, were investigated in relation to the risks of moderate to severe neurodevelopmental impairment (NDI) and full-scale intelligence quotient (FSIQ) at 6.5years. The children who received PDA drug treatment, including those who also had surgery, had the same risk of moderate to severe NDI or lower FSIQ as untreated children. However, children who had primary PDA surgery faced increased risks of NDI, with an adjusted incidence rate ratio of 1.62 (95% confidence interval [CI] 1.28-2.06) and a lower adjusted mean difference FSIQ of -7.1 (95% CI -11 to -3.2). Surgery at less than 10days of life was associated with a significantly increased risk of moderate to severe NDI and lower FSIQ than surgery after 20days. Drug treatment followed by deferred surgery appeared to be a safer option for extremely preterm infants severely affected by PDA.

High-resolution iris and retinal imaging in multisystemic smooth muscle dysfunction syndrome due to a novel Asn117Lys substitution in ACTA2: a case report

BackgroundCongenital mydriasis and retinal arteriolar tortuosity are associated with the life-threatening multisystemic smooth muscle dysfunction syndrome (MSMDS) due to mutations in the gene, ACTA2, which encodes alpha-smooth muscle actin (α-SMA). Previous reports attributed MSMDS-related congenital mydriasis to the absence of iris sphincter muscle. Similarly, it has been hypothesized that abnormal proliferation of the vascular smooth muscle cells causes the marked tortuosity of retinal arterioles in MSMDS. In this report, high-resolution ocular imaging reveals unexpected findings that reject previous hypotheses.Case presentationThe proband is a 37-year-old female with a history of neonatal patent ductus arteriosus (PDA) ligation, left-sided choreiform movements at the age of 11 and a transient aphasia with right-sided weakness at the age of 30. Her older sister also had PDA ligation and congenital mydriasis but no neurological deficit up to age 41. Magnetic resonance angiogram demonstrated cerebrovascular lesions resembling but distinct from Moyamoya disease, characterised by internal carotid artery dilatation, terminal segment stenosis and absent basal collaterals. Their mother had poorly reactive pupils with asymptomatic cerebral arteriopathy resembling her daughters. All three had prominent retinal arteriolar tortuosity. The daughters were heterozygous and the mother was a somatic mosaic for a novel c.351C > G (p.Asn117Lys) transversion in ACTA2. Iris optical coherence tomography (OCT) showed a hyporeflective band anterior to the pigment epithelium indicating the presence of dysfunctional sphincter muscle. Adaptive optics retinal imaging showed no thickening of the arteriolar vessel wall whilst OCT angiography showed extreme corkscrew course of arterioles suggesting vessel elongation.ConclusionsIn addition to the known association between Met46, Arg179 and Arg258 substitutions and ACTA2-related arteriopathy, this case illustrates the possibility that Asn117 also plays an important role in α-SMA function within the cerebrovascular smooth muscle cell. MSMDS-related congenital mydriasis is due to reduced iris sphincter contractility rather than its absence. Retinal arteriolar tortuosity might be due to longitudinal proliferation of arteriolar smooth muscle cells. The described cerebrovascular and ocular signs are consistent with predicted effects of the novel Asn117Lys substitution in ACTA2.

Compression of the left mainstem bronchus by patent ductus arteriosus in neonates under consideration for ductal stenting

Stent angioplasty of patent ductus arteriosus has been shown to be a viable alternative to operative shunt placement in cyanotic neonates. With broader implementation of this strategy, novel complications are bound to arise. We present a series of cases evaluated for ductal stent angioplasty in which a dilated and torturous ductus arteriosus compressed the left mainstem bronchus. After reviewing our recent experience with ductal stenting and isolated Blalock-Taussig shunts, our best estimate of the incidence of bronchial compression by the dilated ductus is 4.6% (3/64, 95% confidence interval 1.0-12.9%). Awareness of the airway and other nonvascular contents of the thorax is an important consideration prior to ductal stenting.

Surgical Closure of Isolated Patent Ductus Arteriosus in Neonates

Surgical Closure of Isolated Patent Ductus Arteriosus in Neonates

043 Feasibility, Efficacy and Safety of PDA Stenting With IBS ® in Duct-Dependent Cyanotic CHD

PDA (Patent ductus arteriosus) stenting is an acceptant way of temporarily palliating congenital heart diseases (CHD) while waiting surgical repair which incorporates stent removal and often reconstruction of branch pulmonary arteries in 6–12 months. IBS (iron based bioresorbable stent) has recently undergone multicenter clinical trial for coronary artery disease and case reported in stenting PDAs in neonates. The aim is to prospectively evaluate the feasibility, safety and early outcome of this stent (non-drug eluting) in a non-complex PDA morphology. Nine neonates included in this study (CHD with weight >3 kg and age less than 3 months with non-complex PDA anatomy) had PDA IBS stented in the period September 2018 – August 2019.Complex PDAs were excluded. Three monthly follow-up with clinical examination, serum iron and echocardiographic assessment were performed to assess patency of PDA till next surgical intervention/PDA not required as a source of pulmonary blood flow or 9 months post PDA stent. Nine patients underwent PDA IBS stent. Median age and weight at time of intervention were 20.44 days (±5.98) and 3.36 kg (±0.36) respectively. All stents were implanted successfully. Median procedure length 89.30 minutes (±38.52). At least 6 months follow-up. Only one patient (11%) needed earlier reintervention with re-stenting 4months post stent. No stent related mortality /morbidity (one non-cardiac death) Serum iron levels remained normal at all times. PDA shunt noted in all but one at time of planned surgical intervention. IBS stent appears to be feasible, safe and comparable to standard approach from early outcome point of view.

Negligible risk of prenatal ductus arteriosus closure or fetal renal impairment after third-trimester paracetamol use: evaluation of the German Embryotox cohort.

Risk of fetotoxicity after paracetamol exposure in the third trimester. Observational cohort study and retrospective case assessment. Germany, 2008-2017. Pregnant women exposed to paracetamol. Prospectively enrolled third-trimester pregnancies that had been exposed to paracetamol (604) were compared with pregnancies exposed to paracetamol in the first and/or second trimester only (1192). Exclusion criteria were exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) in the second or third trimester. Additionally, the Embryotox 'adverse drug reaction in pregnancy' database was screened for cases of fetotoxicity. The prenatal study end points focused on narrowing or closure of ductus arteriosus Botalli, late fetal death, and oligohydramnios. The postnatal end points included patent ductus arteriosus (PDA), primary pulmonary hypertension (PPHT), and impaired renal function. In both cohorts, no fetus with intrauterine narrowing or closure of the ductus arteriosus Botalli was reported (0/604 versus 0/1192). Oligohydramnios was diagnosed at a similar frequency in both cohorts: 1.3% (8/604) versus 1.6% (19/1192). There was one stillbirth in the study cohort (1/604, 0.2%) and four stillbirths in the comparison cohort (4/1192, 0.3%). The rates of PDA in neonates were similar: 0.7% (4/615) versus 0.7% (9/1212). PPHT as well as serious postnatal renal disorders were reported once in each cohort. In 12 out of 96 retrospective cases, there were indicators for study end points; however, co-exposure to NSAIDs or complex situations weaken the assumption of paracetamol toxicity. Fetal cardiovascular or renal toxicity of maternal third-trimester paracetamol use appears to be negligible. Paracetamol use in the third trimester does not seem to be associated with a relevant risk of fetotoxicity.

Risk factors influencing the persistence of patent ductus arteriosus in neonates with CHD in the RS (Ya)

Risk factors influencing the persistence of patent ductus arteriosus in neonates with CHD in the RS (Ya)

Management strategies for the preemie ductus.

Patent ductus arteriosus (PDA) remains the most common cardiovascular condition afflicting neonates. Despite 5 decades of scientific inquiry pediatric cardiologists and neonatologists still cannot answer the simple question of which PDAs should be treated. Although the volume of the shunt is difficult to calculate, echocardiography, biochemical markers, and clinical exam can provide clues to the magnitude and physiologic consequences of the shunt. Epidemiologic data exists showing a positive relationship between a PDA and numerous morbidities. As a result, for most of the 20th and early 21st century, nearly all PDAs where indiscriminately considered to be hemodynamically significant and attempts to close it where initiated shortly after birth. However, no randomized trials of PDA closure have been able to show significant differences between affected and unaffected groups. In fact, surgical ligation has repeatedly been associated with increased morbidities and worse long-term neurodevelopmental outcomes. As a result, most clinicians favor a strategy of watchful waiting. In this review, we aim to summarize the scientific literature, along with some of the contemporary biases, that exist with regards to the pathophysiology, genetics, and treatment strategies for the neonatal PDA.

Effectiveness of Injectable Ibuprofen Salts and Indomethacin to Treat Patent Ductus Arteriosus in Preterm Infants: Observational Cohort Study

There is no injectable ibuprofen product marketed to treat patent ductus arteriosus (PDA) in newborns in Canada. The authors' institution has used ibuprofen arginine in the past. In the absence of published evidence supporting use of this salt form of ibuprofen for neonatal PDA, a retrospective analysis was undertaken. To compare the effectiveness and adverse effects of ibuprofen arginine, ibuprofen tromethamine, and indomethacin in the treatment of PDA. This retrospective observational cohort study, for patients admitted between 2009 and 2015, included preterm infants with symptomatic PDA who received at least one dose of injectable indomethacin, ibuprofen tromethamine, or ibuprofen arginine. Three effectiveness end points were analyzed: closure after one course of treatment, repeat medical treatment, and surgical ligation. The secondary end points included acute kidney injury, necrotizing enterocolitis, chronic lung disease, and time to full enteral feeding. A total of 179 infants were included. There were no differences among groups in terms of closure after one course of treatment (37/54 [69%] with indomethacin, 42/70 [60%] with ibuprofen tromethamine, and 28/55 [51%] with ibuprofen arginine; p = 0.21) or surgical ligation (10/54 [19%] with indomethacin, 13/70 [19%] with ibuprofen tromethamine, and 12/55 [22%] with ibuprofen arginine; p = 0.88). However, there was a difference regarding use of a repeat course of treatment, ibuprofen arginine having the highest rate (8/54 [15%] with indomethacin, 18/70 [26%] with ibuprofen tromethamine, and 20/55 [36%] with ibuprofen arginine; p = 0.04). After adjustment for gestational age, the association between ibuprofen arginine and increased use of a repeat course of treatment remained significant. The groups did not differ with respect to adverse effects. These results highlight the potential for differences in effectiveness among various salt forms of injectable ibuprofen and indomethacin. Because of the small sample size and retrospective methodology, confirmation of the present results through a larger prospective study is needed.

Neonatal Patent Ductus Arteriosus Ligation Operations Performed by Adult Cardiac Surgeons.

BackgroundPatent ductus arteriosus (PDA) ligation is usually performed by congenital cardiac surgeons. However, due to the uneven distribution of congenital cardiac surgeons in South Korea, many institutions depend solely on adult cardiac surgeons for congenital cardiac diseases. We report the outcomes of PDA ligations performed by adult cardiac surgeons at our institution.MethodsThe electronic medical records of 852 neonates at Chung-Ang University Hospital, Seoul, South Korea from November 2010 to May 2014 were reviewed to identify patients with PDA.ResultsOf the 111 neonates with a diagnosis of PDA, 26 (23%) underwent PDA ligation. PDAs were ligated within 28 days of birth (mean, 14.5±7.8 days), and the mean gestational age of these patients was 30.3±4.6 weeks (range, 26 to 40 weeks) with a mean birth weight of 1,292.5±703.5 g (range, 480 to 3,020 g). No residual shunts through the PDA were found on postoperative echocardiography. There was 1 case of 30-day mortality (3.8%) due to pneumonia, and 6 cases of in-hospital mortality (23.1%) after 30 days, which is comparable to results from other centers with congenital cardiac surgery programs.ConclusionAlthough our outcomes may not be generalizable to all hospital settings without a congenital cardiac surgery program, in select centers, PDA ligations can be performed safely by adult cardiac surgeons if no congenital cardiac surgery program is available.