Ductus Arteriosus In Preterm Infants Research Articles

Transcatheter occlusion of the patent ductus arteriosus in premature infants weighing less than 1200 g

ObjectivesOver the last few decades different strategies have been proposed to treat persistent ductal patency in premature infants. The advent of the Amplatzer Duct Occluder II Additional Size (ADOIIAS) provided...

Abdominal Near-Infrared Spectroscopy Detects Low Mesenteric Perfusion Early in Preterm Infants with Hemodynamic Significant Ductus Arteriosus

Background: The therapeutic decision to close patent ductus arteriosus in preterm infants entails great uncertainty. Near-infrared spectroscopy is a noninvasive bedside technique used to monitor mixed regional oxygen saturation. We hypothesized that near-infrared spectroscopy could identify preterm infants at risk of mesenteric hypoperfusion associated with hemodynamically significant ductus arteriosus. Methods: This is a prospective observational study including consecutively admitted preterm infants with a gestational age <32 weeks. Mesenteric regional oxygenation was blindly monitored using an INVOS 5100 device. The presence of a hemodynamically significant patent ductus arteriosus was routinely confirmed by echocardiography/Doppler. Statistical analysis including Bland-Altman plots was performed to assess near-infrared spectroscopy intraobserver repeatability. Results: A total of 72 preterm infants were enrolled. The daily mean regional oxygen saturation for preterm infants was determined both in mesenteric and cerebral regions and plotted against time. We identified a differential temporary baseline. Hemodynamic significant ductus arteriosus was associated with lower blood pressures and lower regional splanchnic oxygenation. There was a significant relationship between reversal diastolic flow in the descending aorta and the regional oxygen saturation, which remained significant after controlling for ductal size and nil per os. Conclusions: The simultaneous monitoring of splanchnic near-infrared spectroscopy and echocardiography could identify low mesenteric perfusion in the presence of hemodynamic ductus arteriosus.

Morbidities associated with patent ductus arteriosus in preterm infants. Nationwide cohort study

Purpose: To evaluate the predictive factors for the development of haemodynamically significant patent ductus arteriosus (PDA) in preterm infants and to study the morbidities associated with the treatment of PDA during the first hospitalization.Materials and methods: Data were collected from the Finnish national register of preterm infants (<32 gestational weeks) born in 2005–2013. In total, 3668 infants were included. Morbidities during the first hospitalization were analysed and compared between infants who received treatments for the closure of PDA (n = 1132) and infants who received no treatment for PDA (n = 2536). The results were adjusted for the duration of pregnancy, intrauterine growth pattern, antenatal steroids, delivery hospital and respiratory distress syndrome (RDS).Results: RDS and mechanical ventilation were independently associated with an increased risk of PDA requiring treatment. Medical and surgical treatments were associated with the risk of severe bronchopulmonary dysplasia (BPD). Primary surgical ligation was associated with an increased risk of severe intraventricular haemorrhage (IVH) and necrotizing enterocolitis (NEC). Medical treatment itself and also followed by surgical ligation was associated with lower mortality.Conclusion: The severity of lung disease rather than prematurity per se was associated with the development of PDA requiring therapy. Both medical and surgical therapies for PDA were associated with severe BPD, and primary surgical ligation was associated with NEC and severe IVH.

Which Criteria are More Valuable in Defining Hemodynamic Significance of Patent Ductus Arteriosus in Premature Infants? Respiratory or Echocardiographic?

Which Criteria are More Valuable in Defining Hemodynamic Significance of Patent Ductus Arteriosus in Premature Infants? Respiratory or Echocardiographic?

Influence of restrictive fluid therapy on the timing of closing of the ductus arteriosus in preterm infants

Abstract: article reflects features of pharmacological closure for patent ductus arteriosus by restrictive fluid therapy, analyzed the impact of different volume fluid therapy for a period of closure PDA. Based on research in the article proved that the early closure of the arterial duct principle is not only the choice of drug cyclooxygenase inhibitor, and a strict adherence to limit the volume of infusion therapy in the first 5 days of life. The paper analyzed different levels of physiological loss of body weight preterm infants in the first week of life and its impact in the treatment successful closing ductus arteriosus.

Patent ductus arteriosus in premature infants: to treat or not to treat?

Closing patent ductus arteriosus (PDA) is a widely accepted approach in the management of very low birth weight (VLBW) infants. Our objective is to test the hypothesis that conservative management (no treatment) of PDA will not affect survival without chronic lung diseases (CLD). This retrospective study utilizes a prospectively collected database to compare two cohorts of VLBW infants. Infants in the first group (2001 to 2009) had their PDA treated with pharmacological and if necessary with surgical ligation. PDA in the second group (2010 to 2014) was not treated with medical or surgical intervention. The primary outcome was survival without oxygen requirement at 36 weeks. Pulmonary and non-pulmonary morbidities were also compared. Logistic regression analyses were performed to control for confounders. This study included 643 VLBW infants, of them 415 infants in the Treat group and 228 in the No-Treat group. The rate of survival without CLD did not differ between Treat and No-Treat groups (78.4% vs 83.9%, respectively; adjusted odds ratio (aOR)=1.72, confidence interval (CI): 0.92 to 3.23, P=0.09). Mortality declined in No-Treat group (15.2% vs 10.5%, aOR=0.51, CI: 0.25 to 0.99, P=0.049), but the two groups did not differ in the incidence of CLD among survivors (5.8% vs 5.0%,=P0.47). Pulmonary complications and non-pulmonary morbidities did not differ between groups. Conservative management (no treatment) of PDA may not compromise survival without CLD and is not associated with increased morbidities in VLBW infants. Prospective physiological studies are needed to determine the sector of VLBW infants, if any, who could benefit from PDA treatment.

Relationship between perfusion index and patent ductus arteriosus in preterm infants.

Perfusion index (PI) is a noninvasive measure of perfusion. ΔPI (difference between pre- and postductal PI) may identify hemodynamically significant PDA. However, studies are limited to brief and intermittent ΔPI sampling. Our objective is to assess the value of continuous high resolution ΔPI monitoring in the diagnosis of PDA. Continuous ΔPI monitoring in preterm infants was prospectively performed using two high-resolution pulse oximeters. Perfusion Index measures (ΔPI mean and variability, pre- and postductal PI) were analyzed over a 4-h period prior to echocardiography. A cardiologist blinded to the results evaluated for PDA on echocardiography. Linear mixed regression models were utilized for analyses. We obtained 31 echocardiography observations. Mean ΔPI (-0.23 vs. 0.16; P < 0.05), mean pre-PI (0.86 vs. 1.26; P < 0.05), and ΔPI variability (0.39 vs. 0.61; P = 0.05) were lower in infants with PDA compared to infants without PDA at the time of echocardiography. Mean ΔPI, ΔPI variability, and mean pre-PI measured 4 h prior to echocardiography detect PDA in preterm infants. PI is dynamic and should be assessed continuously. Perfusion index is a promising bedside measurement to identify PDA in preterm infants.

Comparative Effectiveness of Nonsteroidal Anti-inflammatory Drug Treatment vs No Treatment for Patent Ductus Arteriosus in Preterm Infants

Patent ductus arteriosus (PDA) is associated with increased mortality and worsened respiratory outcomes, including bronchopulmonary dysplasia (BPD), in preterm infants. Nonsteroidal anti-inflammatory drugs (NSAIDs) are efficacious in closing PDA, but the effectiveness of NSAID-mediated PDA closure in improving mortality and preventing BPD is unclear. To determine the effectiveness of NSAID treatment for PDA in reducing mortality and moderate/severe BPD at 36 weeks postmenstrual age. This cohort study included 12 018 infants born at 28 gestational weeks or younger discharged between January 2006 and December 2013 from neonatal intensive care units in 25 US children's hospitals included in the Pediatric Health Information System. We performed an instrumental variable analysis that incorporated clinician preference-based, institutional variation in NSAID treatment frequency to determine the effect of NSAID treatment for PDA on mortality and BPD. Proportion of NSAID-treated infants born at each infant's institution within ±6 months of that infant's birth. The primary composite outcome was death, moderate, or severe BPD at 36 weeks postmenstrual age. Of the 6370 male and 5648 female infants in this study, 4995 (42%) were white, 3176 (26%) were African American, 1823 (15%) were Hispanic, and 1555 (13%) were other races/ethnicities. The proportion of NSAID-treated infants at each infant's hospital within ±6 months of that infant's birth was associated with NSAID treatment and not associated with gestation, race/ethnicity, or sex. An infant's chances of receiving NSAID treatment increased by 0.84% (95% CI, 0.8-0.9; P < .001) for every 1% increase in the annual NSAID treatment percentage at a given hospital. An instrumental variable analysis demonstrated no association between NSAID treatment and the odds of mortality or BPD (odds ratio, 0.94; 95% CI, 0.70-1.25; P = .69), mortality (odds ratio, 0.73; 95% CI, 0.43-1.13; P = .18), or BPD (odds ratio, 1.01; 95% CI, 0.73-1.45; P = .94) in survivors. When we incorporated clinician preference-based practice variation as an instrument to minimize the effect of unmeasured confounding, we detected no changes in the odds of mortality or moderate/severe BPD among similar preterm infants born at 28 weeks or younger following NSAID treatment for PDA initiated 2 to 28 days postnatally. Our findings agree with available randomized clinical trial evidence and support a conservative approach to PDA management.

Is there a relationship between platelet parameters and patency of ductus arteriosus in preterm infants?

Postnatal closure of the ductus arteriosus is a complicated two-phase process involving functional and structural changes. So far, the precise mechanisms regulating this process are not fully understood. A growing body of evidence from recent studies suggests that platelets play a key role in inflammatory processes including ductal closure via interaction with endothelial cells. The aim of this study is to assess whether a relationship exists between the occurrence and/or closure of hemodynamically significant ductus arteriosus (HSDA) and platelet parameters (platelet count, circulating platelet mass, mean platelet volume, platelet distribution width) in preterm newborns. This single-center, retrospective study included 824 premature infants between 24 and 34 gestational weeks, evaluated by echocardiography at postnatal 72-96 h. Infants with and without HSDA (n = 208 vs. n = 616) were compared in terms of platelet parameters recorded within the first 3 days of life. Oral or intravenous ibuprofen was commenced for medical treatment, and echocardiography was repeated 24 h thereafter to determine ductal closure. No statistically significant difference could be demonstrated between the groups in terms of baseline platelet parameters. HSDA was independently associated with early-onset neonatal sepsis. Thrombocytopenia, low circulating platelet mass, high platelet distribution width, or high mean platelet volume could not be demonstrated as a risk factor for HSDA. None of the platelet parameters had an influence on ductal closure after medical treatment. Unlike most reports in the literature, presence of HSDA was not associated with any platelet parameter in our study. We could not demonstrate an association between any platelet parameter and either persistence or closure after medical treatment.

Outcomes of Left Ventricular Function According to Treatment Response for a Patent Ductus Arteriosus in Preterm Infants.

BackgroundTo evaluate the outcomes of left ventricular (LV) function according to treatment response for a hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants.MethodsEchocardiograms of 21 preterm infants born at gestational age < 31 weeks obtained at term-equivalent age were retrospectively studied. Among preterm infants with a hsPDA, 9 underwent ligation after failure of pharmacological closure (ligation group) and 6 experienced successful pharmacological closure (medication group). Six preterm infants without hsPDA (no-hsPDA group) were studied as controls. LV peak longitudinal systolic strain (ε) of each infant was retrospectively obtained from echocardiograms using velocity vector imaging, along with neonatal outcomes.ResultsPharmacological closures were attempted at postnatal day 2–3. In the ligation group, the median postnatal age at ligation was 20 days. In the ligation group, LV peak longitudinal systolic ε was significantly decreased at term-equivalent age compared to the other groups. Between the medication and no-hsPDA groups, LV peak longitudinal systolic ε did not differ significantly. Among the neonatal outcomes, infants who experienced necrotizing enterocolitis (NEC) showed significantly decreased LV peak longitudinal systolic ε compared to the infants who did not experience NEC .ConclusionWe speculate that in preterm infants with an hsPDA, in cases of medical treatment failure, early PDA ligation at less than 20 days of postnatal age would be beneficial for preserving LV systolic function.

Chorioamnionitis appears not to be a Risk Factor for Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-Analysis.

The contribution of chorioamnionitis (CA) to mortality and morbidity in preterm infants is difficult to assess because observational studies frequently present significant differences in baseline characteristics of the infants exposed or non-exposed to CA. In an attempt to perform a thorough assessment of the possible association between CA and patent ductus arteriosus (PDA) in preterm infants, we conducted a meta-analysis in which adjusted odds ratios (ORs) were pooled and we analyzed the effects of potential confounders, such as gestational age (GA) or birth weight (BW). We identified 45 relevant studies (27186 patients, 7742 CA cases). Random effects meta-analysis of crude ORs showed a significant positive association between CA and PDA (OR 1.352, 95% CI 1.172 to 1.560). Adjusted ORs were reported in 11 studies (19577 infants). Meta-analysis of these studies showed a significant negative association between CA and PDA (OR 0.802, 95% CI 0.751 to 0.959). Meta-regression showed that the differences in GA or BW between the CA-exposed and non-exposed groups were significantly correlated with the effect size of the association between PDA and CA. In conclusion, our study confirms that confounders need to be taken into account when assessing the association between CA and clinical outcomes in preterm infants.

THE MODERN VIEW ON THE PROBLEM OF BRONCHOPULMONARY DYSPLASIA AND PATENT DUCTUS ARTERIOSUS IN PRETERM INFANTS

The article reflects the modern aspects of the pathogenesis and clinic of bronchopulmonary dysplasia in premature infants. An analysis of the impact of various antenatal and intranatal factors on the development and course of bronchopulmonary dysplasia. Separately the problem of patent ductus arteriosus. Pathogenesis, mechanisms of influence on the development of bronchopulmonary dysplasia and encumbrance of her condition. Discussed the clinical and pathogenetic apects functioning of patent ductus arteriosus in preterm infants.

Oral paracetamol vs. oral ibuprofen in the treatment of symptomatic patent ductus arteriosus in premature infants: A randomized controlled trial.

The aim of the present study was to analyze the changes of plasma and urinary prostaglandin E2 (PGE2) levels in preterm infants with symptomatic patent ductus arteriosus (sPDA) treated with oral ibuprofen and acetaminophen. A total of 87 preterm infants with sPDA admitted to the Neonatal Ward of the Affiliated Xuzhou Hospital of Medical College of Southeast University from October, 2012 to June, 2015 were selected and randomly divided into the ibuprofen group (n=43, 10 mg/kg ibuprofen administered orally as initial dose, followed by 5 mg/kg during the first 24 and 48 h later) and acetaminophen group (n=44, 15 mg/kg acetaminophen administered orally once every 6 h for three days). The levels of plasma and urinary PGE2 in the two groups were estimated before and after treatment. The treatment of sPDA infants with ibuprofen (ibuprofen group) or acetaminophen (acetaminophen group) caused a significant decrease in the plasma and urinary PGE2 levels in comparison with plasma and urinary PGE2 levels before treatment (P<0.05). Furthermore, plasma and urinary PGE2 levels in the acetaminophen group (45.0±36.9 ng/l) were significantly lower than those in the ibuprofen group (73.5±44.8 ng/l, P=0.002). The arterial duct closure rate was similar between the acetaminophen [31 (70.5%)] and ibuprofen groups [33 (76.7%), P=0.506]. The incidence of oliguria was less among sPDA infants of the acetaminophen group [1 (2.3%)] than observed among the sPDA infants of the ibuprofen group [6 (14.0%)]; however, this difference was not statistically significant (P=0.108). Additionally, the incidences of fecal occult blood positive rate, intraventricular hemorrhage, neonatal necrotizing enterocolitis and bronchopulmonary dysplasia were distributed similarly in the ibuprofen and acetaminophen groups (P>0.05). The levels of platelet, serum creatinine and alanine transaminase showed no significant changes between the ibuprofen and acetaminophen groups (P>0.05). Following treatment with ibuprofen or acetaminophen, the extent of decrease of plasma and urinary PGE2 was significantly higher among sPDA infants with oliguria (135.0±38.0 ng/l) than that observed in sPDA infants without oliguria (52.5±37.0 ng/l) (P=0.01). The study also found a significant correlation between plasma and urinary PGE2 levels (r=0.648, P=0.01) and the coefficient of variation of urinary PGE2 (0.427) was less than that of plasma PGE2 (0.539). The clinical efficacy of oral ibuprofen and acetaminophen in the treatment of preterm infants with sPDA was similar with low adverse events, whereas acetaminophen-induced PGE2 levels were less than the levels observed in the ibuprofen-treated group. The incidence of oliguria was also lower in the acetaminophen group compared to the ibuprofen group. In addition, monitoring urinary PGE2 levels was more suitable because of its non-invasiveness in the clinical setting than monitoring of plasma PGE2 in preterm infants with sPDA.

Meta-Analysis of the Effect of Chest Shielding on Preventing Patent Ductus Arteriosus in Premature Infants.

Objective This study aims to perform a meta-analysis of randomized studies to evaluate if chest shielding during phototherapy is associated with decreased incidence of patent ductus arteriosus (PDA) in premature infants. Design/Methods We used published guidelines for the meta-analysis of clinical trials. The search strategy included electronic searches of CINAHL, CENTRAL Cochrane Library, MEDLINE, PubMed, and abstracts presented at the Pediatric Academic Societies. Inclusion criteria were randomized controlled trials (RCTs), quasi-RCTs or cluster RCTs published in English and involving chest shielding during phototherapy in premature infants with PDA as an outcome. Exclusion criteria involved case reports, case series, and multiple publications from the same author. Heterogeneity testing using Q statistics was performed to evaluate the variance between studies. Results Two RCTs met study criteria. There was heterogeneity (I2: 55.4%) between the two trials. Meta-analysis of RCTs using the random effect model demonstrated that chest shielding during phototherapy was associated with decreased incidence of PDA (odds ratio: 0.47, 95% confidence interval: 0.23-0.96). There was no publication bias on Eggers test. Heterogeneity was seen in gestational age, gender, prophylactic use of postnatal indomethacin, duration of phototherapy, and assessment of PDA. Conclusion Chest shielding during phototherapy may be associated with decreased incidence of PDA among premature infants.

Consider pharmacological treatment to close patent ductus arteriosus in preterm infants when the condition is haematologically significant

The management of patent ductus arteriosus (PDA) in preterm infants may take a conservative, pharmacological and/or surgical approach. Pharmacological treatment to close the ductus may be indicated in symptomatic preterm infants with haematologically significant PDA. Indomethacin and ibuprofen (the only approved agents for PDA in the USA) appear to have similar efficacy in this indication; however, ibuprofen generally has a better tolerability profile. Paracetamol (acetaminophen) is becoming increasingly used, despite a lack of clinical data. Surgery is an option in infants with refractory PDA or contraindications to drug therapy.

Meta-Analysis to Assess Efficacy and Safety of High-Dose Ibuprofen Compared with Standard Treatment of Patent Ductus Arteriosus in Premature Infants

Background: Patent ductus arteriosus (PDA) is a common congenital heart defect in premature infants. Intravenous injection of ibuprofen is used for PDA treatment, but its optimum dose, efficacy, and safety are unclear. Objectives: This meta-analysis aimed to access randomized controlled trials that compared high- or low-dose ibuprofen with a standard dose of ibuprofen for closure of PDA in preterm infants. Methods: The standard search methods of the Cochrane neonatal review group were used to screen ibuprofen versus indomethacin trials. All groups that used ibuprofen in those trials were filtered out. The high-dose group was defined as those using an average dose of ibuprofen greater than or equal to 10 mg/kg in the first three days. Results: We identified 14 studies of good methodological quality comparing ibuprofen to indomethacin trials among neonates. Results showed that high-dose ibuprofen could remarkably raise the closure rate (relative risk = 0.90, 95% CI = [0.81, 1.00], P = 0.04). No significant differences were found in adverse effects, bleeding disorders, or oliguria. The closure rate in neonates with PDA increased with the ibuprofen dosage (R2 = 0.9990). The loading dose produced a significant closure rate compared with the low-dose group (relative risk = 1.91, 95% CI = [1.25, 2.92], P = 0.003), with no increase in toxic side effects. Conclusions: Loading dose is a necessary strategy for infants with PDA. A high dose of ibuprofen for PDA closure was more effective than a normal dose of ibuprofen. The side effects in both treatment groups were not significantly different. Given the small sample size and risk of bias in all trials, the tolerability and safety of the dose regimen should be assessed in a large population before considering the use of these doses for PDA.

Does ibuprofen treatment in patent ductus arteriosus alter oxygen free radicals in premature infants?

This prospective randomised study enrolled 102 preterm infants with patent ductus arteriosus. The patent ductus arteriosus closure rate was significantly higher in the oral ibuprofen group (84.6 versus 62%) after the first course of treatment (p=0.011). No significant difference was found between the pre- and post-treatment total oxidant status and total antioxidant capacity in the groups. Discussion Ibuprofen treatment does not change the total oxidant status or total antioxidant capacity. We believe that the effect of ibuprofen treatment in inducing ischaemia overcomes the scavenging effect of ibuprofen.

Does platelet mass influence the effectiveness of ibuprofen treatment for patent ductus arteriosus in preterm infants?

Objective: The aim of this study is to evaluate whether the platelet mass in the first 24 h of life is effective on closure of patent ductus arteriosus (PDA) or not.Study design: Preterm infants with a gestational age of < 32 weeks, hospitalized at a tertiary neonatal intensive care unit (NICU) and requiring medical treatment (intravenous or oral ibuprofen) for hemodinamically significant PDA (hsPDA) were enrolled in this study. The patients were divided into two groups after first course of pharmacologic treatment according to closure of PDA (Group 1: PDA closure, Group 2: PDA without closure). Groups were compared in terms of demographics findings, morbidities, platelet measurements like counts, mean platelet volume (MPV) and platelet mass (platelet count × mean platelet volume).Results: The study included 77 preterm newborns in Group 1, and 30 preterms in Group 2. There were no differences in birth weight, gestational age, gender and maternal risk factors between the study groups. The mean platelet count in the first postnatal blood count was in Group 1: 211.3 ± 89.2 × 103/mm3 and in Group 2: 216.5 ± 26 × 103/mm3, respectively (p = 0.783). The mean platelet volumes (MPV) were similar in both groups (p = 0.535). No statistically significant difference between platelet mass values was detected (Group 1: 1811 ± 884 fl/nl, Group 2: 1868 ± 717 fl/nl) (p = 0.753).Conclusion: Our data suggest that platelet count, MPV and platelet mass did not affect the closure of hsPDA with ibuprofen.

Repeatability of echocardiographic parameters to evaluate the hemodynamic relevance of patent ductus arteriosus in preterm infants: a prospective observational study.

BackgroundThe hemodynamically relevant patent ductus arteriosus in preterm infants is not well defined. Different clinical and echocardiographic parameters are used and the diagnostic accuracy is unknown because of the lack of a gold standard definition. Our study evaluates the inter-observer repeatability of echocardiographic and Doppler-ultrasound parameters.MethodsThis prospective observational study included 19 very low birth weight preterm infants (median [interquartile range]: gestational age 28.0 (28.0–29.0) weeks, birth weight 1130 (905–1321) g, postnatal age at measurement 8.7 (4.8–23.5) d) with a clinical suspicion of ductal patency in whom 27 repeated echocardiographic and Doppler-ultrasound examinations were performed within 30 min by 2 of 3 independent observers (54 measurements overall). The repeatability index (=2 times the standard deviation of the differences/mean of all measurements) according to Bland and Altman was used to assess repeatability of different parameters.ResultsThe repeatability indices of the echocardiographic parameters (left Atrium-to-Aortic root-ratio, diameter of the patent ductus arteriosus at its narrowest part, the left-ventricular-preejection-period-to-ejection-time-ratio and the ratio of the velocity time integrals in the large vessels were 16, 21, 23 and 26 % respectively. The repeatability indices of Doppler-ultrasound measurements (resistance index in celiac artery and anterior cerebral artery) were 11 and 14 %, respectively.ConclusionsThe inter-observer repeatability of all echocardiographic parameters was poor compared to that of resistance indices in peripheral vessels. Therefore, interventions for ductal patency should be indicated based on averaged repeated rather than single measurements, especially when measured values are close to their cut-off value - both in clinical routine and for study purposes.

Confusion and thinking in the management of patent ductus arteriosus in preterm infants

Confusion and thinking in the management of patent ductus arteriosus in preterm infants