Patent Ductus Arteriosus In Preterm Infants Research Articles

Abstract 4135928: Externally Validated Deep Learning Model for Patent Ductus Arteriosus Detection by Echocardiography in Preterm Infants

Introduction: Patent ductus arteriosus (PDA) is a common form of congenital heart disease in premature infants and a source of significant morbidity. Echocardiography is the mainstay modality for diagnosis and monitoring but is resource-intensive and requires expertise for interpretation. Aims: To develop and externally validate a deep learning model to identify PDA in preterm infants by echocardiography. Methods: We trained, validated, and tested a convolutional neural network to detect PDA in raw echocardiogram clips from infants (gestational age <37 weeks) with and without PDAs and no significant additional congenital heart disease at the Medical University of South Carolina (MUSC). For training and validation, we employed a 12-fold cross-validation procedure. Experienced cardiologists defined the ground truth labels. We assessed classification performance on an internal model naïve dataset using the area under the receiver operator curve (AUROC), sensitivity, specificity, positive predictive value, and negative predictive value. For external multicenter testing, we used studies from Children’s Hospital of Orange County (CHOC) and Boston Children’s Hospital (BCH), both of which utilize a different ultrasound system vendor. Results: Training and validation were completed using 1,145 color/color-compare clips (661 clips with PDA and 484 no PDA) from 66 patients. The internal test dataset consisted of 142 clips from 16 patients. The external CHOC and BCH cohorts consisted of 146 clips from 50 patients and 294 clips from 68 patients, respectively. Model performance was similar for internal and external testing (Table 1). Conclusions: Our deep learning model detected the presence of PDA with acceptable performance. This performance generalized well across multiple institutions and ultrasound vendors. This work shows promise for the future development of an automated tool for PDA diagnosis enabling the democratization of pediatric cardiology resources.

Effects of Total Parenteral Nutrition on Serum Osmolality and Patent Ductus Arteriosus.

The persistence of high serum osmolality in the early postnatal period is a risk for developing patent ductus arteriosus (PDA). Early aggressive nutrition (EAN), involving total parenteral nutrition (TPN), by which enough concentrations of glucose and amino acids are administered intravenously, is recommended postnatally to improve the neurological prognosis in preterm infants. However, the effects of EAN involving TPN on serum osmolality and the development of a PDA have not been adequately studied. Thus, in this study, we aimed to investigate the impact of TPN on serum osmolality and determine whether increased serum osmolality could be associated with a higher incidence of PDA in preterm infants. In this single-center retrospective observational study, preterm infants born at <28 weeks of gestation who had been admitted to our neonatal intensive care unit (NICU) before (pre-TPN period) and after the introduction of TPN (post-TPN) were included. We reviewed the medical records of these patients, compared the changes in serum osmolality from birth to five days after birth, the clinical background, and the incidence of PDA between these two periods, and analyzed the risk factors. Additionally, the factors affecting the serum osmolality in very preterm infants were examined. The patients who met the intervention criteria of our NICU and received a cyclooxygenase (COX) inhibitor, Indacin® (Nobelpharma, Tokyo, Japan), within seven days after birth were classified as PDA+; those who could not be identified to have PDA flow by echo and did not receive a COX inhibitor were classified as PDA-. The postnatal day and serum sodium (Na+) were statistically significantly correlated with a higher serum osmolality. Serum osmolality remained statistically significantly higher in the PDA+ cohort compared with the PDA- cohort after the first day of life. However, no statistically significant differences were observed in serum osmolality after 24 hours of age, weeks of gestational age, birth weight, or incidence of PDA between the pre- and post-TPN periods. The results of the multiple logistic regression analyses revealed that the increased serum osmolality correlated with PDA development. In this study, the serum Na+ statistically significantly correlated with a higher serum osmolality. Moreover, the increased serum osmolality correlated with PDA development. Thus, the prevention of hypernatremia might reduce the incidence of PDA. Nonetheless, the findings in this study revealed that no statistically significant differences in serum osmolality were observed between the pre-and post-TPN periods, indicating that TPN had little effect on serum osmolality.

A predictive model for patent ductus arteriosus seven days postpartum in preterm infants: an ultrasound-based assessment of ductus arteriosus intimal thickness within 24 h after birth.

To develop a predictive model for patent ductus arteriosus (PDA) in preterm infants at seven days postpartum. The model employs ultrasound measurements of the ductus arteriosus (DA) intimal thickness (IT) obtained within 24 h after birth. One hundred and five preterm infants with gestational ages ranging from 27.0 to 36.7 weeks admitted within 24 h following birth were prospectively enrolled. Echocardiographic assessments were performed to measure DA IT within 24 h after birth, and DA status was evaluated through echocardiography on the seventh day postpartum. Potential predictors were considered, including traditional clinical risk factors, M-mode ultrasound parameters, lumen diameter of the DA (LD), and DA flow metrics. A final prediction model was formulated through bidirectional stepwise regression analysis and subsequently subjected to internal validation. The model's discriminative ability, calibration, and clinical applicability were also assessed. The final predictive model included birth weight, application of mechanical ventilation, left ventricular end-diastolic diameter (LVEDd), LD, and the logarithm of IT (logIT). The receiver operating characteristic (ROC) curve for the model, predicated on logIT, exhibited excellent discriminative power with an area under the curve (AUC) of 0.985 (95% CI: 0.966-1.000), sensitivity of 1.000, and specificity of 0.909. Moreover, the model demonstrated robust calibration and goodness-of-fit (χ2 value = 0.560, p > 0.05), as well as strong reproducibility (accuracy: 0.935, Kappa: 0.773), as evidenced by 10-fold cross-validation. A decision curve analysis confirmed the model's broad clinical utility. Our study successfully establishes a predictive model for PDA in preterm infants at seven days postpartum, leveraging the measurement of DA IT. This model enables identifying, within the first 24 h of life, infants who are likely to benefit from timely DA closure, thereby informing treatment decisions.

Artificial Intelligence-Based Diagnostic Support System for Patent Ductus Arteriosus in Premature Infants.

Background: Patent ductus arteriosus (PDA) is a prevalent congenital heart defect in premature infants, associated with significant morbidity and mortality. Accurate and timely diagnosis of PDA is crucial, given the vulnerability of this population. Methods: We introduce an artificial intelligence (AI)-based PDA diagnostic support system designed to assist medical professionals in diagnosing PDA in premature infants. This study utilized electronic health record (EHR) data from 409 premature infants spanning a decade at Severance Children's Hospital. Our system integrates a data viewer, data analyzer, and AI-based diagnosis supporter, facilitating comprehensive data presentation, analysis, and early symptom detection. Results: The system's performance was evaluated through diagnostic tests involving medical professionals. This early detection model achieved an accuracy rate of up to 84%, enabling detection up to 3.3 days in advance. In diagnostic tests, medical professionals using the system with the AI-based diagnosis supporter outperformed those using the system without the supporter. Conclusions: Our AI-based PDA diagnostic support system offers a comprehensive solution for medical professionals to accurately diagnose PDA in a timely manner in premature infants. The collaborative integration of medical expertise and technological innovation demonstrated in this study underscores the potential of AI-driven tools in advancing neonatal diagnosis and care.

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.

Correlation between the Closure Time of Patent Ductus Arteriosus in Preterm Infants and Long-Term Neurodevelopmental Outcome.

In patent ductus arteriosus (PDA) in preterm infants, the relationship between treatment timing and long-term developmental prognosis remains unclear. The purpose of this study was to clarify the relationship between the age in days when ductus arteriosus closure occurred and long-term development. Preterm infants with a birth weight of less than 1500 g who were admitted to our NICU over a period of 9 years (2011-2019) and were diagnosed with PDA were included. A new version of the K-type developmental test for corrected ages of 1.5 and 3 years was used as an index of development. The relationship between the duration of PDA and the developmental index was evaluated using Pearson's correlation coefficient, and multiple regression analysis was performed. Development quotient (DQ) at the ages of 1.5 and 3 years showed a correlation with the PDA closure date and the standard deviation (SD) value of the term birth weight. Multiple regression analysis showed a positive correlation of the DQ at 1.5 and 3 years with the SD value of the term birth weight and a negative correlation with the PDA closure date. In addition, a stronger correlation was found in the "posture/motor" sub-item at 3 years. On the other hand, the analysis including preterm infants without PDA showed that preterm infants with PDA closure on the 6th day or later after birth had a significantly lower 3-year-old DQ than preterm infants with a PDA exposure within 5 days. In conclusion, it is suggested that the decrease in cerebral blood flow due to PDA in preterm infants has an adverse effect on long-term neurodevelopment. Appropriate interventions, including surgical treatment for PDA in preterm infants without delay, ideally within 5 days of birth, may be effective in improving the developmental prognosis.

Left Pulmonary Artery Occlusion Following Device Closure of Patent Ductus Arteriosus in Premature Infants

BackgroundDevice closure of a patent ductus arteriosus (PDA) is rapidly evolving, with the Amplatzer Piccolo Occluder (Abbott) receiving US Food and Drug Administration approval and becoming the first device approved for PDA closure in patients ≥700 g. We report on the first known cases of complete left pulmonary artery (LPA) occlusion following Piccolo closure of a PDA in premature infants. MethodsRetrospective chart analysis of PDA closures. ResultsWe have performed over 50 cases of Piccolo device closure of the PDA in preterm neonates in the past 2 years, with these 2 cases representing our only complications (4%). This represents a total complication rate similar to or lower than most centers that have published data for this procedure. ConclusionsAlthough rare, severe LPA obstruction can be seen in premature infants following device closure of the PDA. The Piccolo device is designed to ideally remain entirely intraductal. Although our device selection appeared to provide a device short enough for the given ductal length, we recommend, whenever possible, giving consideration to using the shortest possible device. We also recommend increasing the frequency of echocardiographic surveillance to weekly studies if at any time the imaging demonstrates an increase in the degree of obstruction/turbulence.

Time to Stop Early Treatment of Patent Ductus Arteriosus?

(N Engl J Med. 2023;388:1050–1051) The ductus arteriosus briefly closes soon after birth in healthy term infants while staying open in most extremely preterm infants (&lt;28 wk of gestation). While patent ductus arteriosus (PDA) has been shown to increase the risk of adverse outcomes, no causative pathway between PDAs and these complications have been established and optimal treatment for PDA in preterm infants is unclear.

Nutrition of the preterm infant with persistent ductus arteriosus: existing evidence and practical implications.

The persistence of a patent ductus arteriosus (PDA) is a common condition in preterm infants with a prevalence inversely proportional to gestational age. PDA is associated with mild-to-severe gastrointestinal complications such as feeding intolerance, gastrointestinal perforation, and necrotizing enterocolitis, which represent a major challenge for the nutritional management in preterm infants. In this context, the Section on Nutrition, Gastroenterology and Metabolism and the Circulation Section of the European Society for Pediatric Research have joined forces to review the current knowledge on nutritional issues related to PDA in preterm infants. The aim of the narrative review is to discuss the clinical implications for nutritional practice. Because there is little literature on postnatal nutrition and PDA in preterm infants, further research with well-designed studies on this topic is urgently needed. Guidelines should also be developed to clearly define the implementation and course of enteral nutrition and the target nutritional intake before, during, and after pharmacologic or surgical treatment of PDA, when indicated. IMPACT: Persistent ductus arteriosus (PDA) is associated with gastrointestinal complications such as feeding intolerance, gastrointestinal perforation, and necrotizing enterocolitis, which pose a major challenge to the nutritional management of preterm infants. In PDA infants, fluid restriction may lead to inadequate nutrient intake, which may negatively affect postnatal growth and long-term health. The presence of PDA does not appear to significantly affect mesenteric blood flow and splanchnic oxygenation after enteral feedings. Initiation or maintenance of enteral nutrition can be recommended in infants with PDA.

Association of the EPAS1 rs7557402 Polymorphism with Hemodynamically Significant Patent Ductus Arteriosus Closure Failure in Premature Newborns under Pharmacological Treatment with Ibuprofen.

Patent ductus arteriosus (PDA) is frequent in preterm newborns, and its incidence is inversely associated with the degree of prematurity. The first choice of pharmacological treatment is ibuprofen. Several genes, including EPAS1, have been proposed as probable markers associated with a genetic predisposition for the development of PDA in preterm infants. EPAS 1 NG_016000.1:g.84131C>G or rs7557402 has been reported to be probably benign and associated with familial erythrocytosis by the Illumina Clinical Services Laboratory. Other variants of EPAS1 have been previously reported to be benign for familial erythrocytosis because they decrease gene function and are positive for familial erythrocytosis because the overexpression of EPAS1 is a key factor in uncontrolled erythrocyte proliferation. However, this could be inconvenient for ductal closure, since for this process to occur, cell proliferation, migration, and differentiation should take place, and a decrease in EPAS1 gene activity would negatively affect these processes. Single-nucleotide polymorphisms (SNPs) in EPAS1 and TFAP2B genes were searched with high-resolution melting and Sanger sequencing in blood samples of preterm infants with hemodynamically significant PDA treated with ibuprofen at the National Institute of Perinatology. The variant rs7557402, present in the EPAS1 gene eighth intron, was associated with a decreased response to treatment (p = 0.007, OR = 3.53). The SNP rs7557402 was associated with an increased risk of pharmacological treatment failure. A probable mechanism involved could be the decreased activity of the product of the EPAS1 gene.

Automated Identification of Patent Ductus Arteriosus Using a Computer Vision Model.

Patent ductus arteriosus (PDA) is a vascular defect common in preterm infants and often requires treatment to avoid associated long-term morbidities. Echocardiography is the primary tool used to diagnose and monitor PDA. We trained a deep learning model to identify PDA presence in relevant echocardiographic images. Echocardiography video clips (n = 2527) in preterm infants were reviewed by a pediatric cardiologist and those relevant to PDA diagnosis were selected and labeled (PDA present/absent/indeterminate). We trained a convolutional neural network to classify each echocardiography frame of a clip as belonging to clips with or without PDA. A novel attention mechanism that aggregated predictions for all frames in each clip to obtain a clip-level prediction by weighting relevant frames. In early model iterations, we discovered training with color Doppler echocardiography clips produced the best performing classifier. For model training and validation, 1145 such clips from 66 patients (661 PDA+ clips, 484 PDA- clips) were used. Our best classifier for clip level performance obtained sensitivity of 0.80 (0.83-0.90), specificity of 0.77 (0.62-0.92) and AUC of 0.86 (0.83-0.90). Study level performance obtained sensitivity of 0.83 (0.72-0.94), specificity of 0.89 (0.79-1.0) and AUC of 0.93 (0.89-0.98). Our novel deep learning model demonstrated strong performance in classifying echocardiography clips with and without PDA. Further model development and external validation are warranted. Ultimately, integration of such a classifier into auto detection software could streamline PDA imaging workflow. This work is the first step toward semi-automated, bedside detection of PDA in preterm infants.

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.

Predictors of a non-response to prophylactic indomethacin for patent ductus arteriosus in preterm infants.

Preterm infants are recommended for prophylactic indomethacin (PIND) to promote closure of patent ductus arteriosus (PDA) and reduce morbidity and mortality. This study investigated the predictive factors of a non-response to PIND for PDA in preterm-birth infants. Consecutive preterm-birth infants (gestational age: < 28 weeks) who received PIND between 2009 and 2019 were retrospectively enrolled. Seventy-six eligible participants were classified as PIND responders (N=42) or non-responders (N=34). Information on potential confounders in maternal obstetric and perinatal data were collected from medical records. Multiple logistic regression analysis was carried out to identify the prognostic factors of a PIND response in preterm-birth infants. The prevalence of intrauterine infection and multiple births was significantly different between responders and non-responders to PIND (intrauterine infection: 2 [4.8%] vs. 8 [23.5%], P=0.036; twins: 3 [7.1%] vs. 9 [ 26.5%], P=0.029, respectively). In multivariate logistic regression analysis after adjustment for multiple births, intrauterine infection was a significant and independent predictive factor of a non-response to PIND (odds ratio [OR] 5.54, 95% confidence interval [CI] 1.05-29.2, P=0.044). A remarkable association was also noted for multiple births with a non-response to PIND (OR 4.22, 95% CI 0.99-17.8, P=0.050). Intrauterine infection and multiple births were identified as potential risk factors of a non-response to PIND for PDA in preterm infants.

Effect of Maternal Coronavirus Disease on Preterm Morbidities.

Coronavirus disease (COVID-19) during pregnancy may have an impact on preterm morbidities due to the inflammatory nature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Exposure to intrauterine inflammation could result in adverse consequences in preterm infants. We aimed to determine the effect of maternal coronavirus disease on preterm morbidities at a tertiary neonatal intensive care unit. This observational cohort study compared the clinical outcomes of preterm infants < 37 gestational weeks with and without maternal COVID-19. The study was conducted in a tertiary-level neonatal intensive care unit between March 2020 and December 2021. Demographics and clinical data of the study groups were collected from the medical files. A total of 254 infants (127 in the maternal COVID-19 group and 127 in the control group) were included in the study. Respiratory distress syndrome, early and late neonatal sepsis, intraventricular hemorrhage, patent ductus arteriosus (PDA), necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity rates were similar between groups. In the subgroup analysis, the rate of PDA was significantly higher in preterm infants ≤1,500 g with maternal SARS-CoV-2 infection (38 vs. 15% p = 0.023). Presence of maternal COVID-19 was found to be an independent predictor for PDA in very low birthweight infants, as revealed by multivariate analyses (odds ratio: 3.4; 95% confidence interval: 1.12-10.4; p = 0.031). Mortality rates and duration of hospitalization were similar in both groups. Our results suggest that COVID-19 infection during pregnancy seems to have no adverse effect on preterm morbidities and mortality. However, maternal COVID-19 was found to be a risk factor for PDA in preterm infants ≤1,500 g. · The effect of maternal COVID-19 on preterm morbidities still has not well defined.. · Maternal COVID-19 seems to have no adverse effect on preterm morbidities and mortality.. · The exact impact of the COVID-19 on fetal/neonatal health is yet to be clarified..

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.

Identifying two distinct subphenotypes of patent ductus arteriosus in preterm infants using machine learning.

To use unsupervised machine learning to identify potential subphenotypes of preterm infants with patent ductus arteriosus (PDA). The study was conducted retrospectively at a neonatal intensive care unit in Brazil. Patients with a gestational age < 28weeks who had undergone at least one echocardiogram within the first two weeks of life and had PDA size > 1.5 or LA/AO ratio > 1.5 were included. Agglomerative hierarchical clustering on principal components was used to divide the data into different clusters based on common characteristics. Two distinct subphenotypes of preterm infants with hemodynamically significant PDA were identified: "inflamed," characterized by high leukocyte, neutrophil, and neutrophil-to-lymphocyte ratio, and "respiratory acidosis," characterized by low pH and high pCO2 levels. Conclusions: This study suggests that there may be two distinct subphenotypes of preterm infants with hemodynamically significant PDA: "inflamed" and "respiratory acidosis." By dividing the population into different subgroups based on common characteristics, it is possible to get a more nuanced understanding of the effectiveness of PDA interventions. What is Known: • Treatment of PDA in preterm infants has been controversial. • Stratification of preterm infants with PDA into subgroups is important in order to determine the best treatment. What is New: • Unsupervised machine learning was used to identify two subphenotypes of preterm infants with hemodynamically significant PDA. • The 'inflamed' cluster was characterized by higher values of leukocyte, neutrophil, and neutrophil-to-lymphocyte ratio. The 'respiratory acidosis' cluster was characterized by lower pH values and higher pCO2 values.

Comparison of Therapeutic Effect and Safety of Oral and Rectal Use of Acetaminophen on Patent Ductus Arteriosus in Preterm Infants: Clinical Randomized Trial.

The prevalence of patent ductus arteriosus (PDA) in preterm infants is high. There is little information about the therapeutic effect and safety of rectal acetaminophen in the treatment of PDA. We aimed to compare the therapeutic effect and safety of oral and rectal acetaminophen on PDA in preterm infants. This study was a single-blind randomized clinical trial using 40 preterm infants. The cases were hospitalized in the neonatal intensive care unit of Mohammad Kermanshahi and Imam Reza hospitals of Kermanshah. Subjects were randomly divided into 2 groups, the first group was treated with oral acetaminophen and the second group was treated with rectal acetaminophen. The presence of PDA and response to treatment was assessed based on pre- and post-treatment echocardiographic criteria. The likelihood of complications or prohibition of acetaminophen use was assessed with paraclinical tests before and after treatment. The neonates were in the age range of 30 to 35 weeks. Twenty-one cases (52.5%) were boys and 19 cases (47.5%) were girls. Two cases in the oral-acetaminophen group and 1 case in the rectal-acetaminophen group needed the second round of treatment. There was no difference between the success of treatment and the type of treatment. The study showed that there was no difference between PDA treatment of preterm infants with oral and rectal acetaminophen. Also, no side effects were observed in treatment with any of the treatments. Therefore, it could be suggested that in infants who are intolerant to oral acetaminophen, the rectal form can be used.

The Association of Patent Ductus Arteriosus with Inflammation: A Narrative Review of the Role of Inflammatory Biomarkers and Treatment Strategy in Premature Infants.

Patent ductus arteriosus (PDA) is a common cardiovascular complication that complicates clinical care in the intensive care of premature infants. Prenatal and postnatal infections and the inflammation process can contribute to PDA, and intrauterine inflammation is a known risk factor of PDA. A variety of inflammatory biomarkers have been reported to be associated with PDA. Chorioamnionitis induces the fetal inflammatory process via several cytokines that have been reported to be associated with the presence of PDA and may have a role in the vascular remodeling process or vessel dilation of the ductus. On the other hand, anti-inflammatory agents, such as antenatal steroids, decrease PDA incidence and severity in patients born to those with chorioamnionitis. Proinflammatory cytokines, which are expressed more significantly in preterm neonates and chorioamnionitis, are associated with the presence of PDA. In this review, we focus on the pathogenesis of PDA in preterm infants and the role of biomarkers associated with the perinatal inflammatory process.

High-sensitivity troponin T in preterm infants with a hemodynamically significant patent ductus arteriosus

Background: The incidence of patent ductus arteriosus (PDA) is inversely related to gestational age. Cardiac troponin T (cTnT) is a specific marker for myocardial ischemic injury. The aim of this work was to investigate if a hemodynamically significant patent ductus arteriosus leads to elevated high- sensitivity troponin T (hsTnT) levels in serum. Methods: This prospective observational research included 60 preterm infants &lt;34 weeks’ gestation, weighing &lt;1500 g with PDA. Patients were classified into two groups according to the ECHO findings: Group A: preterm infants who had hs.PDA (PDA &gt;1.5 mm and LA: Ao &gt;1.2 and group B: preterm infants without hs.PDA. All cases were subjected to clinical examination, echocardiogram and hsTnT assay. Results: Serum hsTnT levels was significantly elevated in patients with hs PDA compared to patients without hs PDA. High sensitive T-troponin can significantly detect hsPDA with AUC of 0.986, P value &lt;0.001. At cut off &gt;100 pg/ml, it’s a significant detector with sensitivity of 93.33%, specificity of 90%, PPV of 90.3, NPV of 93.1 and diagnostic accuracy of 91.5%. PDA had a significant positive correlation with hsTnT (r=0.803, P&lt;0.001). Conclusions: HsTnT can significantly detect hemodynamically significant PDA in preterm infants with high sensitivity and specificity.

Efficacy and safety of high versus standard dose ibuprofen for patent ductus arteriosus treatment in preterm infants: A systematic review and meta-analysis.

Several small randomized controlled trials (RCTs) and observational studies have compared high (15-20/7.5-10/7.5-10 mg/kg/dose) versus standard dose (10/5/5 mg/kg/dose) ibuprofen for patent ductus arteriosus (PDA) closure, with limited evidence on efficacy and safety. To systematically review and meta-analyze studies of high versus standard dose ibuprofen for the closure of PDA in preterm infants. Databases were searched for RCTs and observational studies assessing high compared to standard dose of ibuprofen for PDA closure for preterm infants until August 2021. The primary outcome was failure of PDA closure after the first course of ibuprofen. The secondary outcomes were the failure of PDA closure after a second course of ibuprofen, rates of PDA ligation, all-cause mortality prior to hospital discharge, bronchopulmonary dysplasia, necrotizing enterocolitis, bleeding disorders, oliguria, and serum creatinine after treatment. There were 6 studies with 369 patients (3 RCT, N = 190; 3 observational studies, N = 179). Compared to standard dose, high dose ibuprofen did not significantly decrease the failure rate of PDA closure in preterm infants after the first course (Relative risk (RR) 0.74, 95% confidence interval (CI) 0.53 -1.03, 6 studies, N = 369). High dose ibuprofen significantly decreased the rates of PDA ligation compared to standard dose (RR 0.33, 95% CI 0.16 -0.70, 5 studies, N = 309). Based on low-grade evidence, high dose ibuprofen may more effectively reduce rates of PDA ligation compared to standard dose with no increase in adverse effects, neonatal morbidities and mortality.