Management Of Patent Ductus Arteriosus Research Articles

Comparison of Blalock-Taussig-Thomas Shunts With Patent Ductus Arteriosus Ligated Versus Left Open.

The optimal approach to patent ductus arteriosus management during systemic-to-pulmonary artery shunt placement is currently unknown. The purpose of this study is to examine the outcomes of variable strategies for patent ductus arteriosus management during Blalock-Taussig-Thomas shunt surgery. A retrospective cohort study of infants who underwent shunt placement was performed, comparing those who had the ductus ligated with those who had the ductus left open. Indicators of low cardiac output syndrome, development of necrotizing enterocolitis, and secondary outcomes such as resuscitation events were examined. Thirty-six infants were included all of whom had their shunt placed via median sternotomy. Twenty infants had their ductus ligated at the time of the shunt, and they were compared with 16 infants whose ductus was left open. There was no statistical difference in preoperative baseline characteristics, including corrected gestational age, age in days, weight, mechanical ventilation, vasoactive use, heterotaxy, and gastrointestinal anomalies. There was also no statistical difference in postoperative indicators of low cardiac output, including urine production, total fluids given, renal injury, maximum lactate, and vasoactive-inotropic score. Three patients had postoperative renal injury, and all were in the ligated duct group. There was also no statistical difference in any secondary outcomes, including the development of necrotizing eneterocolitis, resuscitation events, reinterventions, length of intubation, total length of stay, and mortality. This study provides evidence that variable management of the ductus during shunt placement does not significantly impact outcomes. Leaving the ductus open allows for a potential rescue source of pulmonary blood flow and does not appear to increase the risk of postoperative low cardiac output.

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.

Patent ductus arteriosus management in very-low-birth-weight prematurity: a place for an early operation?

The goal was to evaluate neonatal outcomes based on treatment strategies and time points for haemodynamically significant patent ductus arteriosus (hsPDA) in very-low-birth-weight preterm infants, with a particular focus on surgical closure. This retrospective study included very-low-birth-weight infants born between 2014 and 2021 who received active treatment for hsPDA. Neonatal outcomes were compared between (i) primary surgical closure versus primary ibuprofen; (ii) early (<14th post-natal day) versus late primary surgical closure (≥14th post-natal day); and (iii) primary versus secondary surgical closure after ibuprofen failure. Further analysis using 1:1 propensity score matching was performed. Logistic regression was conducted to analyse the risk factors for post-ligation cardiac syndrome (PLCS) and/or acute kidney injury (AKI). A total of 145 infants with hsPDA underwent active treatment for closure. The in-hospital death rate and the incidence of severe bronchopulmonary dysplasia (BPD) were similar between the primary surgical closure group and the primary ibuprofen group in a 1:1 matched analysis. Severe BPD was significantly higher in the late surgical closure group than in the early primary surgical closure group with 1:1 propensity score matching (72.7% vs 40.9%, P=0.033). The secondary surgical closure group showed the mildest clinical condition; however, the probability of PLCS/AKI was highest (38.6%) compared to the early (15.2%) or the late primary surgical group (28.1%, P<0.001), especially in extremely premature infants (gestational age < 28 weeks). Surgical patent ductus arteriosus closure is not inferior to pharmacologic treatment. Considering the harmful effect of a prolonged patent ductus arteriosus shunt exposure, a timely decision and timely efforts should be made to minimize the risk of severe BPD and PLCS/AKI after surgical closure.

Proactive Diagnosis and Tailor-Made Treatment of Patent Ductus Arteriosus in Very Preterm Infants with Routine Echocardiography in Japan: A post hoc Analysis of the PLASE Study

Introduction: A feature of the management of extremely preterm infants in Japan is proactive circulatory management using early routine echocardiography performed by neonatologists. Methods: This study was a post hoc analysis of the Patent ductus arteriosus and Left Atrial Size Evaluation in preterm infants (PLASE) study, which is a prospective cohort study including preterm infants admitted to 34 tertiary neonatal intensive care units in Japan between October 2015 and December 2016. We described the details of the treatment strategy of patent ductus arteriosus (PDA) based on early routine echocardiography. Results: In total, 613 preterm infants were included into the analysis. Twenty percent of infants with prophylactic indomethacin were switched to therapeutic cyclooxygenase inhibitor (COX-I) before the completion of the full prophylactic indomethacin course. Therapeutic COX-I was mostly administered based on echocardiographic findings before PDA became symptomatic or hemodynamically significant. Therapeutic COX-I was frequently discontinued after one or two doses before the full course (three doses) was completed. The proportion of infants requiring additional treatment (additional therapeutic COX-I course or surgical PDA closure) after discontinued COX-I courses (<3 doses) compared to infants after completed 3 doses course was significantly lower (after the first therapeutic COX-I course 46% vs. 68%, p < 0.001) or without a significant difference (after the second or third course). Conclusions: The clinical management of PDA in Japan featured (1) COX-I administration based on echocardiographic findings before symptomatic or hemodynamically significant PDA appeared and (2) frequent discontinuation of therapeutic COX-I before completing the standard three doses course.

Contemporary fluid management, humidity, and patent ductus arteriosus management strategy for premature infants among 336 hospitals in Asia.

The management of patent ductus arteriosus (PDA) is a critical concern in premature infants, and different hospitals may have varying treatment policies, fluid management strategies, and incubator humidity. The Asian Neonatal Network Collaboration (AsianNeo) collected data on prematurity care details from hospitals across Asian countries. The aim of this study was to provide a survey of the current practices in the management of PDA in premature infants in Asian countries. AsianNeo performed a cross-sectional international questionnaire survey in 2022 to assess the human and physical resources of hospitals and clinical management of very preterm infants. The survey covered various aspects of hospitals resources and clinical management, and data were collected from 337 hospitals across Asia. The data collected were used to compare hospitals resources and clinical management of preterm infants between areas and economic status. The policy of PDA management for preterm infants varied across Asian countries in AsianNeo. Hospitals in Northeast Asia were more likely to perform PDA ligation (p < 0.001) than hospitals in Southeast Asia. Hospitals in Northeast Asia had stricter fluid restrictions in the first 24 h after birth for infants born at <29 weeks gestation (p < 0.001) and on day 14 after birth for infants born at <29 weeks gestation (p < 0.001) compared to hospitals in Southeast Asia. Hospitals in Northeast Asia also had a more humidified environment for infants born between 24 weeks gestation and 25 weeks gestation in the first 72 h after birth (p < 0.001). A logistic regression model predicted that hospitals were more likely to perform PDA ligation for PDA when the hospitals had a stricter fluid planning on day 14 after birth [Odds ratio (OR) of 1.70, p = 0.048], more incubator humidity settings (<80% vs. 80%-89%, OR of 3.35, p = 0.012 and <80% vs. 90%-100%, OR of 5.31, p < 0.001). In advanced economies and Northeast Asia, neonatologists tend to adopt a more conservative approach towards fluid management, maintain higher incubator humidity settings and inclined to perform surgical ligation for PDA.

International Online Survey on the Management of Patent Ductus Arteriosus

Introduction: There is uncertainty and lack of consensus regarding optimal management of patent ductus arteriosus (PDA). We aimed to determine current clinical practice in PDA management across a range of different regions internationally. Materials and Methods: We surveyed PDA management practices in neonatal intensive care units using a pre-piloted web-based survey, which was distributed to perinatal societies in 31 countries. The survey was available online from March 2018 to March 2019. Results: There were 812 responses. The majority of clinicians (54%) did not have institutional protocols for PDA treatment, and 42% reported variable management within their own unit. Among infants <28 weeks (or <1,000 g), most clinicians (60%) treat symptomatically. Respondents in Australasia were more likely to treat PDA pre-symptomatically (44% vs. 18% all countries [OR 4.1; 95% CI 2.6–6.5; p < 0.001]), and respondents from North America were more likely to treat symptomatic PDA (67% vs. 60% all countries [OR 2.0; 95% CI 1.5–2.6; p < 0.001]). In infants ≥28 weeks (or ≥1,000 g), most clinicians (54%) treat symptomatically. Respondents in North America were more likely to treat PDAs in this group of infants conservatively (47% vs. 38% all countries [OR 2.3; 95% CI 1.7–3.2; p < 0.001]), and respondents from Asia were more likely to treat the PDA pre-symptomatically (21% vs. 7% all countries [OR 5.5; 95% CI 3.2–9.8; p < 0.001]). Discussion/Conclusion: There were marked international differences in clinical practice, highlighting ongoing uncertainty and a lack of consensus regarding PDA management. An international conglomeration to coordinate research that prioritises and addresses these areas of contention is indicated.

Personalized Evidence-Based Management of Patent Ductus Arteriosus in Preterm Infants.

There is no universal consensus on management of patent ductus arteriosus (PDA) in preterm infants and it varies significantly worldwide, even among the clinicians within units. The decision to treat requires a thorough understanding of the clinical status of the patient, clinical evaluation of PDA, echocardiographic diagnosis, and hemodynamic impact of ductal shunt on the pulmonary and systemic circulation. In this article, updated evidence on the efficacy and adverse effects of pharmacological treatment options and expectant management are presented, while highlighting the long-term benefits of PDA treatment remains equivocal and controversial. The authors propose a schematic targeted PDA treatment approach based on gestational and chronological age for practical clinical use, and they emphasize important future directions including advancement in PDA device closure techniques, diagnostic echo-parameters, hemodynamic evaluation to assess the impact on other organs, and understanding the long-term outcomes.

Secular Trends in Patent Ductus Arteriosus Management in Infants Born Preterm in the National Institute of Child Health and Human Development Neonatal Research Network

We evaluated changes in patent ductus arteriosus (PDA) diagnosis and treatment from 2012 through 2021 in a network of US academic hospitals. PDA treatment decreased among infants born at 26-28weeks but not among infants born at 22-25weeks. Rates of indomethacin use and PDA ligation decreased while acetaminophen use and transcatheter PDA closure increased.

Patent Ductus Arteriosus and Bronchopulmonary Dysplasia–Associated Pulmonary Hypertension

Bronchopulmonary dysplasia (BPD) is often associated with pulmonary vascular disease and secondary pulmonary hypertension (PH). The pathogenesis of BPD-associated PH (BPD-PH) is complex and involves prenatal and postnatal factors that disrupt pulmonary vascular development, and patent ductus arteriosus (PDA) is a factor potentially associated with risk of BPD-PH that has been identified in very recent studies. To explore the association of PDA with BPD-PH using a bayesian model-averaged (BMA) meta-analysis of studies. PubMed and Embase were searched up to April 2023. Key search terms included BPD and PH. Studies examining infants with gestational age 32 weeks or less and reporting data on PDA and risk of BPD-PH. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Meta-Analysis of Observational Studies in Epidemiology reporting guidelines. Two independent reviewers extracted data, with a third reviewer checking for accuracy and completeness. Data pooling and effect size calculations were performed by BMA. The primary outcome was BPD-PH. BMA was used to calculate Bayes factors (BFs). The BF10 is the ratio of the probability of the data under the alternative hypothesis (H1, association of PDA with BPD-HP) over the probability of the data under the null hypothesis (H0). A total of 32 studies (8513 infants) were included. BMA showed that the evidence in favor of H1 was weak for any PDA (BF10 = 2.90; 10 studies), moderate for hemodynamically significant PDA (BF10 = 3.77; 3 studies), and extreme for surgically ligated or catheter-occluded PDA (BF10 = 294.9; 16 studies). In contrast, the evidence in favor of H0 was weak for medically treated PDA (BF10 = 0.55; 6 studies). In addition, BMA found strong evidence in favor of H1 when prolonged exposure to PDA was analyzed as a dichotomous variable (BF10 = 11.80; 6 studies) and extreme evidence (BF10 = 113.60; 3 studies) when PDA exposure time was analyzed as a continuous variable. In this bayesian meta-analysis, the data suggest that prolonged exposure to PDA might be associated with increased risk of pulmonary vascular disease in extremely preterm infants. This highlights the need to monitor for PH in high-risk preterm infants with prolonged exposure to PDA and to incorporate PH risk into clinical decisions regarding PDA management.

Impact of Targeted Neonatal Echocardiography on Patent Ductus Arteriosus Management in a Canadian Tertiary Care Neonatal Unit: A Retrospective Cohort Study.

Comprehensive assessment of hemodynamic significance of a patent ductus arteriosus (PDA) is a common indication to perform targeted neonatal echocardiography (TNE). Impact of implementation of such an assessment on PDA management decisions remains to be reported. The objective of this study is to compare PDA-related hemodynamic information and PDA treatment decisions before and after introduction of TNE service. This was a retrospective cohort study at a tertiary level neonatal intensive care unit in Southwestern Ontario. We investigated two time periods: Epoch-1 (non-TNE 2013-2016) versus Epoch-2 (TNE 2018-2021). We included neonates < 32 weeks with PDA. Data on baseline clinical characteristics, PDA-related echocardiographic parameters, PDA treatment details, and relevant long-term outcomes were collected. Primary outcome was defined as PDA treatment rates and need for multiple courses. Secondary outcomes included availability of PDA hemodynamic data and neonatal mortality/morbidity (PDA-related) RESULTS: A total of 275 neonates were included. A total of 162 were assessed by conventional echocardiography in Epoch-1, whereas 113 were assessed by TNE in Epoch-2. Baseline clinical characteristics were similar. Epoch-2 had more echocardiographic assessments per patient of 2.7 (±1.8) versus 1.9 (± 1.3), p < 0.001 in Epoch1. The mean postnatal age at first echocardiographic assessment was higher in Epoch-2 (12.7 days [ ± 14.6]) than in Epoch-1 (7.9 days [ ± 10.4]), p < 0.001. Comprehensive hemodynamic assessment of PDA-related echocardiographic parameters such as PDA size, shunt pattern, effect on systemic circulation, and pulmonary circulation were higher in Epoch-2. Overall, PDA treatment rates were comparable in the two time periods. The use of multiple courses of treatment was higher in Epoch-1 than in Epoch-2 (47.8 vs. 31.7%, p = 0.047). In Epoch-1, neonates received PDA treatment earlier than in Epoch-2. With the implementation of the TNE service, increased echocardiographic evaluations per patient were completed with availability of more comprehensive hemodynamic information about PDA. PDA treatment rates were similar in the two epochs, but need for multiple courses were less in TNE era. · TNE allows comprehensive hemodynamic assessment of PDA.. · Implementation of dedicated TNE service led to increased use of echocardiography to assess PDA.. · Standardized hemodynamic assessment of PDA may allow improved individualization of treatment need..

Closing the Gap: Investigation of Various Approaches in the Management of Patent Ductus Arteriosus.

In preterm newborns with extremely low birth weights, patent ductus arteriosus (PDA), which is defined as a remnant connection between the aorta and pulmonary artery after 72 hours of birth, is frequently linked to substantial morbidity and mortality. If left untreated, a hemodynamically significant PDA (hsPDA) increases the risk for bronchopulmonary dysplasia, necrotizing enterocolitis, and intraventricular hemorrhage among other morbidities, and can even lead to death. While instances of patent ductus arteriosus (PDA) resolving on their own are frequent, the primary approach for managing PDA closure in premature infants involves pharmacological interventions, commonly utilizing indomethacin, ibuprofen, or paracetamol. However, with these pharmacological treatment options, there is an increased risk of renal toxicity, gastrointestinal bleeding, and reopening of PDA among other complications. If pharmacological interventions are not successful or contraindicated, PDA can be closed via transcatheter closure or surgical ligation. As with any medically invasive procedure, it is not without risks and can lead to long-term complications. This review explores the different management options and the benefits and outcomes of conservative management vs. active management in order to get one step closer to standardizing the treatment for PDA. With so much controversy surrounding the best management option, there is a lack of evidence to support one treatment method superior to the other in reducing overall mortality, and this needs to be explored further.

Expectant management of patent ductus arteriosus for preterm infants: A meta-analysis of randomized controlled trials

We conducted this meta-analysis to compare expectant management of patent ductus arteriosus (PDA) with active treatment for PDA closure in preterm infants. Data from 7 randomized controlled trials (RCTs) showed that all-cause mortality and other clinical adverse outcomes did not differ between expectant management of PDA and active treatment. Future large-scale and double-blinded RCTs with a consistent definition for hemodynamically significant PDA, and focusing on clearly delineated high-risk subgroups or later selective treatment are needed to further evaluate the role of expectant management.

A Global Perspective on PDA Management in the Extremely Premature: Shifting Trend Toward Transcatheter Closure.

Patent ductus arteriosus (PDA) is a frequently encountered defect in infants born extremely premature (≤26 weeks' gestation). Historically, closure of the PDA was performed using cyclooxygenase inhibitor medications or by surgical ligations. However, the benefits of PDA closure using these therapies have never been demonstrated, albeit studies have previously not focused on the extremely premature infants. Therefore, there was a worldwide trend toward conservative management of the PDA. With improved survival of extremely premature infants, comorbidities associated with the PDA has increased, resulting in finding alternate treatments such as transcatheter patent ductus arteriosus closure (TCPC) for this population. Currently, there is a renewed interest toward selective treatment of the PDA in this high-risk cohort of small infants. This Comprehensive Review article inspects the globally changing trends in the management of the PDA in premature infants, with a special focus on the rising adoption of TCPC. Moreover, this article compiles data from several neonatal networks worldwide to help understand the problem at hand. Understanding the current management of premature infants and their outcomes is fundamentally essential if pediatric cardiologists are to offer TCPC as a viable therapeutic option for this population. This article aims to serve as a guide for pediatric cardiologists on this topic by compiling the results on landmark clinical trials on PDA management and the controversies that arise from these trials. Comparative outcomes from several countries are presented, including interpretations and opinions of the data from experts globally. This is a step toward coming to a global consensus in PDA management in premature infants.

Increasing the dose of ibuprofen with postnatal age to close a hemodynamically significant patent ductus arteriosus in very preterm infants.

Patent ductus arteriosus (PDA) is associated with neonatal morbidities in high-risk preterm infants. Early neonatal treatment by ibuprofen induces the ductus arteriosus (DA) closure in approximatively 60% of infants. Dose escalation of ibuprofen according to postnatal age has been suggested for improving the DA closure rate. The aim of this study was to assess the efficacy and tolerance of an increasing dose regimen of ibuprofen. This single-center retrospective cohort study involved infants hospitalized from 2014 to 2019 in our neonatal unit. Selection criteria were gestational age < 30weeks, birth weight < 1000g, and treatment by ibuprofen. Three dose levels were used and consisted of a daily intravenous injection of ibuprofen-tris-hydroxymethyl-aminomethane (ibuprofen-THAM) for three consecutive days: (i) 10 -5 -5mg/kg before the 70th h of life (H70) (dose level 1), (ii) 14 -7 -7mg/kg between H70 and H108 (dose level 2), (iii) 18 -9 -9mg/kg after H108 (dose level 3). The ibuprofen-induced DA closure was compared between ibuprofen schedules, and the Cox proportional-hazard regression was performed to identify factors associated with the ibuprofen efficacy. Tolerance was assessed through renal function, acidosis, and platelet count. One hundred forty-three infants met the inclusion criteria. The ibuprofen-induced DA closure was observed in 67 infants (46.8%). One course of ibuprofen at dose level 1 was more efficient in closing the DA than other schedules (dose level 1, one course (n = 70): 71%, dose level 2 or 3, one course (n = 20): 45%, two-course schedules (n = 53): 15%, p < 0.0001). Independent factors associated with ibuprofen-induced DA closure were a complete antenatal schedule of steroids (p = 0.001), a lower CRIB II score (p = 0.009), and a lower and earlier exposure to ibuprofen (p < 0.0001 and p = 0.002). No severe side effects were observed. Neonatal mortality and morbidities were similar regardless of the infant's response to ibuprofen. Conclusion: Increasing ibuprofen doses with postnatal age failed to reach an efficacy similar to earlier treatment. Although the infant response to ibuprofen was likely to depend on multiple factors, the optimal use of ibuprofen included its early initiation. What is Known: • Ibuprofen is the current first-line treatment for patent ductus arteriosus during the early neonatal period in very preterm infants. • However, the ibuprofen efficacy rapidly declined with postnatal age during the first week of life. A dose escalation of ibuprofen according to postnatal age has been suggested to improve the ibuprofen-induced ductus arteriosus closure. What is New: • The rapid drop of ibuprofen's ability to close hemodynamically significant patent ductus arteriosus persisted beyond the postnatal day 2 despite the dose adjustment arguing for an early initiation to optimize its efficacy. • The early selection of patients who will suffer from patent ductus arteriosus-related morbidities and who will positively respond to ibuprofen is an issue that could determine the future place of ibuprofen in the patent ductus arteriosus management.

Interventions for patent ductus arteriosus (PDA) in preterm infants: an overview of Cochrane Systematic Reviews.

Interventions for patent ductus arteriosus (PDA) in preterm infants: an overview of Cochrane Systematic Reviews.

Acetaminophen versus indomethacin for patent ductus arteriosus management in premature infants: systematic review and meta-analysis of randomized controlled trials.

Acetaminophen has gained interest in the neonatal community for its use in the management of hemodynamically significant patent ductus arteriosus (HsPDA) in preterm infants. We conducted a systematic review of randomized controlled trials (RCTs) comparing the efficacy and safety of acetaminophen with indomethacin for the management of HsPDA in preterm infants. We searched PROSPERO, OVID Medline, OVID EMBASE, Wiley Cochrane Library (CDSR and Central), EBSCO CINAHL, and SCOPUS from inception to June 15, 2021. Bibliographies of identified studies were searched for additional references. Data were analyzed with Review Manager (RevMan) Version 5.3. Four RCTs were identified, enrolling a total of 380 subjects. There was no difference between the interventions for the outcome of PDA closure after one course (RR 1.04 [95% CIs: 0.84, 1.29], P-value 0.70) or after two courses of treatment (RR 1.01 [95% CIs: 0.92, 1.12], P-value 0.77); and for the outcome of PDA ligation (RR 1.56 [95% CIs: 0.48, 5.12], P-value 0.46). However, patients who received acetaminophen had lower rates of necrotizing enterocolitis (RR 0.37 [95% CIs: 0.14, 0.95], P-value 0.04). There were no significant differences noted in the other clinical outcomes, that is, intraventricular hemorrhage, bronchopulmonary dysplasia, retinopathy of prematurity requiring treatment, and death. Two studies noted significant post-treatment elevation of serum creatinine and blood urea with indomethacin, as compared to none with acetaminophen use. Acetaminophen has comparable efficacy to indomethacin for the outcome of HsPDA closure, with a better safety profile, that is, lesser rates of necrotizing enterocolitis and post-treatment azotemia noted with its use.

Pathogenesis and Prevention of Intraventricular Hemorrhage in Preterm Infants.

Intraventricular hemorrhage (IVH) is a serious concern for preterm infants and can predispose such infants to brain injury and poor neurodevelopmental outcomes. IVH is particularly common in preterm infants. Although advances in obstetric management and neonatal care have led to a lower mortality rate for preterm infants with IVH, the IVH-related morbidity rate in this population remains high. Therefore, the present review investigated the pathophysiology of IVH and the evidence related to interventions for prevention. The analysis of the pathophysiology of IVH was conducted with a focus on the factors associated with cerebral hemodynamics, vulnerabilities in the structure of cerebral vessels, and host or genetic predisposing factors. The findings presented in the literature indicate that fluctuations in cerebral blood flow, the presence of hemodynamic significant patent ductus arteriosus, arterial carbon dioxide tension, and impaired cerebral venous drainage; a vulnerable or fragile capillary network; and a genetic variant associated with a mechanism underlying IVH development may lead to preterm infants developing IVH. Therefore, strategies focused on antenatal management, such as routine corticosteroid administration and magnesium sulfate use; perinatal management, such as maternal transfer to a specialized center; and postnatal management, including pharmacological agent administration and circulatory management involving prevention of extreme blood pressure, hemodynamic significant patent ductus arteriosus management, and optimization of cardiac function, can lower the likelihood of IVH development in preterm infants. Incorporating neuroprotective care bundles into routine care for such infants may also reduce the likelihood of IVH development. The findings regarding the pathogenesis of IVH further indicate that cerebrovascular status and systemic hemodynamic changes must be analyzed and monitored in preterm infants and that individualized management strategies must be developed with consideration of the risk factors for and physiological status of each preterm infant.

Bronchopulmonary Dysplasia in Extremely Premature Infants: A Scoping Review for Identifying Risk Factors

Over the years, bronchopulmonary dysplasia (BPD) affects the pulmonary function of infants, resulting in chronic health burdens for infants and their families. The aim of this scoping review was to screen available evidence regarding perinatal risk factors associated with the development and severity of BPD. The eligibility criteria of the studies were year of publication between 2016 and 2021; setting of a developed country; English or Japanese as the study language; and randomized controlled, cohort, or case-control design. The titles and abstracts of the studies were screened by independent reviewers. Of 8189 eligible studies, 3 were included for severe BPD and 26 were included for moderate BPD. The risk factors for severe BPD were male sex, iatrogenic preterm birth, maternal hypertensive disorders of pregnancy (HDP), low gestational age, small-for-gestational-age (SGA) birth weight, mechanical ventilation on day 1, and need for patent ductus arteriosus (PDA) management. The risk factors for moderate or severe BPD included male sex, premature rupture of membranes, clinical chorioamnionitis, maternal HDP, SGA birth weight, bubbly/cystic appearance on X-ray, and PDA management. We identified several risk factors for BPD. We plan to confirm the validity of the new classification using the existing dataset.

Reply to the comment on "Fluid restriction in management of patent ductus arteriosus in Italy: a nationwide survey".

The Authors Chang Liu B.S and Yuan Shi commented our paper on Fluid restriction in management of patent ductus arteriosus (PDA) in Italy. With our study, we conducted a prospective cross-sectional survey among all Italian Neonatal Intensive Care Units (NICUs) to address conservative management of patent ductus arteriosus (PDA) in preterm infants below 29 weeks' gestational age (GA), with specific regard to fluid restriction (FR). The Authors wondered if the heterogeneity of use of fluid restriction both as a prophylactic tool and as a conservative tool when a hemodynamically significant PDA is diagnosed, was due to economic disparities among areas of the included centers. Conducting a secondary analysis of our data, we observed that if we separately consider the responses of two areas, northern and central-southern Italy, FR is slightly more frequently applied in Central and Southern regions (82%) as compared to Northern regions (78%), although this finding does not reach statistical significance. No correlation between the likelihood to adopt conservative measures and the amount of allowed fluid intake was found. The hypothesis that "less fluid intake resulted in milder clinical and echocardiographic presentations of PDA, and thus a lower rate of pharmacological treatment" cannot be supported by our current study design and might deserve future investigations.

Different Medicinal Treatment Modalities in the Management of Patent Ductus Arteriosus in Paediatric Population- A Narrative Review of Available Drug Approaches

Regardless of the size of a patient’s Patent Ductus Arteriosus (PDA), it is crucial for paediatric and adult cardiologists to have a thorough understanding of the condition’s origin, clinical ramifications, and treatment options. Possessing a PDA, no matter how little, might cause complications. Ibuprofen and indomethacin, both cyclo-oxygenase (COX) inhibitors, are used as the gold standard pharmacologic therapy for closing a PDA that has been produced surgically. These non selective COX inhibitors bring about ductal constriction, in addition to lowering the synthesis of prostaglandin. However, these drugs may also have a broad array of unintended consequences. Interest in paracetamol for PDA constriction has recently increased due to fewer adverse effects than indomethacin or ibuprofen. Evidence that paracetamol is now a topic of intense study lends credence to this hypothesis. Information on the long term effects of paracetamol is scarce in paediatric population.