Significant Patent Ductus Arteriosus Research Articles

Furosemide and Ductus Arteriosus Closure in Very-Low-Birth-Weight Preterm Infants: A Comprehensive Retrospective Study.

Ductus arteriosus closure may be delayed in preterm infants, and prostaglandin, a vasodilator, can affect ductal patency. Furosemide can increase renal prostaglandin synthesis, so its net effect on patent ductus arteriosus (PDA) is uncertain. Our goal is to explore the relationship between furosemide and spontaneous ductal closure in very-low-birth-weight preterm infants. Our treatment for PDA involves fluid restriction initially and furosemide administration for hemodynamically significant PDA until closure is confirmed by the echocardiogram. We enrolled 105 infants from 1 January 2019 to 30 June 2022 and evaluated the impact of furosemide on ductal closure, including exposure duration and cumulative dose. There is no correlation between furosemide exposure and spontaneous ductal closure (p = 0.384). Furosemide exposure does not delay the postmenstrual age at which spontaneous ductal closure occurs (p = 0.558). The time for spontaneous ductal closure is positively associated with furosemide prescription days (coefficient value = 0.547, p = 0.026) and negatively with gestational age (coefficient value = -0.384, p = 0.062). The prescription of furosemide does not impact the probability or time duration of ductus arteriosus spontaneous closure. The cumulative dose of furosemide has minimal impact on ductal closure. The correlation between furosemide exposure duration and ductal patency duration is likely due to our treatment protocol, with gestational age being a significant factor.

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.

Doppler Ultrasonographic Assessment of Abdominal Aortic Flow to Evaluate the Hemodynamic Relevance of Left-to-Right Shunting Patent Ductus Arteriosus in Dogs.

In this multicenter, prospective, observational study, abdominal aortic flow was examined with pulsed-wave Doppler ultrasound in dogs with a left-to-right shunting patent ductus arteriosus (PDA) and in apparently healthy dogs. Forty-eight dogs with a PDA and 35 controls were included. In the dogs with a PDA, 37/48 had hemodynamically significant PDAs (hsPDAs) while 11/48 had non-hsPDAs, based on the presence or absence of echocardiographic signs of left-sided volume overload, respectively. In 12 dogs (4/35 control dogs, 7/37 dogs with an hsPDA and 1/11 dogs with a non-hsPDA), the diastole was too short to visualize the end-diastolic flow. Antegrade end-diastolic flow was observed in 30/35 controls and 6/11 dogs with a non-hsPDA. Absent end-diastolic flow was observed in 1/35 control dogs and 3/11 dogs with a non-hsPDA. Retrograde end-diastolic flow was observed in 30/37 dogs with an hsPDA and 1/11 dogs with a non-hsPDA. Twenty-one dogs (15 with an hsPDA and 6 with a non-hsPDA) were reassessed after PDA closure, and, in 19/21, end-diastolic flow was visualized: 17/19 showed an antegrade flow, 1/19 an absent flow and 1/19 a retrograde flow. Sensitivity and specificity of retrograde end-diastolic flow for detection of hsPDAs were 100% and 90%, respectively. In conclusion, ultrasonographic assessment of abdominal aortic flow was feasible in dogs with PDA. However, end-diastolic flow was not always visualized. The presence of a retrograde end-diastolic flow was an accurate finding for discriminating hsPDAs and non-hsPDAs.

Risk factors for the failure of ibuprofen treatment in preterm infants with hemodynamically significant patent ductus arteriosus

To investigate the risk factors for the failure of ibuprofen treatment in preterm infants with hemodynamically significant patent ductus arteriosus (hsPDA). A retrospective collection of clinical data was conducted on preterm infants with a gestational age of <34 weeks who were diagnosed with hsPDA and treated at the Department of Neonatology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, from January 2018 to June 2023. The subjects were divided into two groups based on the treatment approach: the ibuprofen group (95 cases) and the ibuprofen plus surgery group (44 cases). The risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA were identified by binary logistic regression analysis. The binary logistic regression analysis revealed that an increased diameter of the ductus arteriosus, a resistance index (RI) value of the middle cerebral artery ≥0.80, and prolonged total invasive mechanical ventilation time were risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA (P<0.05). Receiver operating characteristic curve analysis showed that a ductus arteriosus diameter >2.85 mm, a middle cerebral artery RI value ≥0.80, and a total invasive mechanical ventilation time >16 days had significant predictive value for the failure of ibuprofen treatment in preterm infants with hsPDA (P<0.05). The combined predictive value of these three factors was the highest, with an area under the curve of 0.843, a sensitivity of 86.5%, and a specificity of 75.0% (P<0.05). A ductus arteriosus diameter >2.85 mm, a middle cerebral artery RI value ≥0.80, and a total invasive mechanical ventilation time >16 days are risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA, and they are of significant predictive value for the necessity of surgical treatment following the failure of ibuprofen treatment.

A comparison of different dosing regimen of intravenous paracetamol for hemodynamically significant patent ductus arteriosus closure in premature neonates

To compare the efficacy of low vs conventional dose intravenous paracetamol in early closure of haemodynamically significant patent ductus arteriosus within 7 days of life. Preterm infants (<32 weeks of gestation) having echocardiographic evidence of hsPDA were given low dose (15 mg/kg initially followed by 7.5 mg/kg every 6 hourly) vs conventional dose (15 mg/kg every 6 hourly) for 5-7 days. In total, 56 infants (28 in each group) were enrolled. Ductal closure was achieved in 96% infants in the low-dose group and 100% infants in the conventional group (P = 1.00). Secondary outcomes, including ductal reopening and need for the second course of medical treatment (21% vs 3.5%, P = 0.1), median duration of hospital stay [30 (15, 43.5) vs 27 (18.5,45), P = 0.64], cumulative oxygen requirement [17.5 (7, 25) vs 14 (8.5, 25), P = 0.89], mortality (10.7% vs 25%, P = 0.29) and other morbidities, were comparable in both the groups. Median paracetamol levels were comparable in both the groups [53.4 μg/L (47, 2,70) vs 62.5 (55.6, 81.2), P = 0.67]. Low-dose paracetamol was non-inferior to conventional dose paracetamol for early ductal closure in preterm infants.

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.

Serial tissue Doppler imaging in the evaluation of bronchopulmonary dysplasia-associated pulmonary hypertension among extremely preterm infants: a prospective observational study.

To evaluate serial tissue Doppler cardiac imaging (TDI) in the evolution of bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) among extremely preterm infants. Prospective observational study. Single-center, tertiary-level neonatal intensive care unit. Infant born <28 weeks gestation. Utility of TDI in the early diagnosis and prediction of BPD-PH and optimal timing for screening of BPD-PH. A total of 79 infants were included. Of them, 17 (23%) had BPD-PH. The mean gestational age was 25.9 ± 1.1 weeks, and mean birth weight was 830 ± 174 g. The BPD-PH group had a high incidence of hemodynamically significant patent ductus arteriosus (83% vs. 56%, p < 0.018), longer oxygen days (96.16 ± 68.09 vs. 59.35 ± 52.1, p < 0.008), and prolonged hospital stay (133.8 ± 45.9 vs. 106.5 ± 37.9 days, p < 0.005). The left ventricular eccentricity index (0.99 ± 0.1 vs. 1.1 ± 0.7, p < 0.01) and the ratio of acceleration time to right ventricular ejection time showed a statistically significant trend from 33 weeks (0.24 ± 0.05 vs. 0.28 ± 0.05, p < 0.05). At 33 weeks, the BPD-PH group showed prolonged isovolumetric contraction time (27.84 ± 5.5 vs. 22.77 ± 4, p < 0.001), prolonged isovolumetric relaxation time (40.3 ± 7.1 vs. 34.9 ± 5.3, p < 0.003), and abnormal myocardial performance index (0.39 ± 0.05 vs. 0.32 ± 0.03, p < 0.001). These differences persisted at 36 weeks after conceptional gestational age. TDI parameters are sensitive in the early evolution of BPD-PH. Diagnostic accuracy can be increased by combining the TDI parameters with conventional echocardiographic parameters. BPD-PH can be recognizable as early as 33-34 weeks of gestation.

Patent Ductus Arteriosus and Lung MRI Phenotype in Moderate and Severe Bronchopulmonary Dysplasia-Pulmonary Hypertension.

A hemodynamically significant patent ductus arteriosus (hsPDA) in premature infants has been associated with bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH). However, these associations remain incompletely understood. The aim was to assess the association between hsPDA duration with clinical outcomes, PH, and phenotypic differences on lung MRI. This retrospective cohort study identified all infants with BPD <32 weeks gestation who also underwent a research lung MRI <48 weeks postmenstrual age (PMA) from 2014-2022. Clinical echocardiograms were reviewed for hsPDA, and categorized into no hsPDA, hsPDA 1-60 days, and hsPDA >60 days. Outcome variables included BPD severity, PH at 36 weeks PMA, PH after 36 weeks PMA in the absence of shunt (PH-PVD), tracheostomy or death, and lung phenotype by MRI via modified Ochiai score, indexed total lung volume (TLVI), and whole lung hyperdensity (WLH). Logistic regression and ANOVA analysis were used. In total, 133 infants born at 26.2 ± 1.9 weeks and 776 ± 276g were reviewed (47 no hsPDA, 44 hsPDA 1-60 days, 42 hsPDA >60 days). hsPDA duration >60 days was associated with BPD severity (p<0.01), PH at 36 weeks PMA (aOR 9.7 [95% CI: 3.3-28.4]), PH-PVD (aOR 6.5 [95% CI: 2.3-18.3]), and tracheostomy or death (aOR 3.0 [95% CI: 1.0-8.8]). Duration of hsPDA > 60 days was associated with higher Ochiai score (p=0.03) and TLVI (p=0.01), but not WLH (p=0.91). In infants with moderate or severe BPD, prolonged exposure to hsPDA is associated with BPD severity, PH-PVD, and increased parenchymal lung disease by MRI.

Exposure to persistent hemodynamically significant patent ductus arteriosus is associated with retinopathy of prematurity

BackgroundHemodynamically significant patent ductus arteriosus (hsPDA) shunt may predispose infants to retinopathy of prematurity (ROP) because of its higher preductal cardiac output and blood oxygen content, which may augment ocular oxygen delivery. MethodsA retrospective cohort study of preterm infants, born at <27 weeks’ gestation and admitted at <24h postnatal age to a large quaternary referral was conducted. The primary composite outcome was death at <32 weeks or moderate-to-severe ROP (≥stage 2 or requiring treatment) in either eye. Secondary outcomes included ROP requiring treatment, and any ROP. Univariate analysis of patient characteristics and outcomes was performed as well as logistic regression. A receiver operating characteristics curve was generated for the outcome of ROP ≥stage 2 or requiring treatment. ResultsA total of 91 patients were screened, of whom 86 (54 hsPDA, 32 controls) were eligible for inclusion. hsPDA patients were younger and lighter at birth and had a higher burden of hyperglycemia and respiratory illness. The rates of the composite outcome (death <32 weeks or moderate-to-severe ROP) and of any ROP were more frequent in the hsPDA group. hsPDA shunt exposure was independently associated with development of any ROP among survivors to assessment (P = 0.006). PDA cumulative exposure score of 78 (clinical equivalent = 7 days high-volume shunt exposure) predicts moderate-to-severe ROP with 80% sensitivity and 78% specificity. ConclusionsAmong infants <27 weeks, hsPDA shunt is associated with increased risks of a composite outcome of death or moderate-to-severe ROP, as well as ROP of any stage. Shunt modulation as a strategy to reduce ROP represents a biologically plausible avenue for investigation.

Risk factors for severe bronchopulmonary dysplasia in a Chinese cohort of very preterm infants.

To examine the risk factors for severe bronchopulmonary dysplasia (BPD) in a cohort of very preterm infants (VPIs) in China, as BPD is common among VPIs and associated with a high mortality rate. In this multicenter retrospective study, medical records from infants with BPD born at gestation age (GA) of <32 weeks with birth weight (BW) of <1,500 grams (g) in 7 regions of China were included. The cohort was stratified into different BPD severity groups based on their fraction of inspired oxygen requirement at a modified GA of 36 weeks or post discharge. Risk factors were identified using logistic regression analysis. A significant inverse correlation was revealed between BPD severity and both GA and BW (p<0.001). Independent risk factors for severe BPD (sBPD) were identified as invasive mechanical ventilation (≥7d), multiple blood transfusion (≥3), nosocomial infection (NI), hemodynamically significant patent ductus arteriosus (hsPDA), delayed initiation of enteral nutrition, and longer time to achieve total caloric intake of 110kcal/kg. Conversely, administration of antenatal steroids was associated with reduced risk of sBPD. Our study not only reaffirmed the established risk factors of low GA and BW for sBPD in VPIs, but also identified additional, potentially modifiable risk factors. Further research is warranted to explore whether intervention in these modifiable factors might reduce the risk of sBPD.Clinical Trial Reg. No.: ChiCTR1900023418.

Perfusion Index as a Predictor of Hemodynamically Significant Patent Ductus Arteriosus in Preterm Newborns

Aim: To assess the value of perfusion index (PI) and arrive at the ideal cut-off value of delta PI (DPI) (pre and postductal difference in PI) in identifying hemodynamically significant patent ductus arteriosus (HsPDA). Methods: Prospective observational study was conducted on 156 preterm newborns of &lt;37 weeks in the NICU of tertiary care center, from August 2019 to March 2020 after ethical clearance. 156 preterm babies were classified into noPDA, HsPDA and Non-HsPDA based on echocardiogram findings and compared with DPI value on Day 1 to 3 of life. Receiver operating characteristic (ROC) curve was constructed to establish cut-offs for DPI in diagnosing HsPDA. A P value &lt;.05 is considered for statistical significance. Results: There was a significantly lower PI in both preductal and post ductal limbs with HsPDA compared to other groups. A DPI Cut-off of 0.75 on day 2 of life has a sensitivity of 75%, specificity of 100% and positive predictive value (PPV) of 100% and a negative predictive value of 89%. Conclusion: PI is a simple non-invasive bedside index predict the presence of a HsPDA in preterm newborns and DPI of &gt;0.75 indicates for presence of HsPDA.

Lung and diaphragm ultrasound as predictors of successful weaning from nasal continuous positive airway pressure in preterm infants.

Assessment of the utility of lung and diaphragm ultrasound in the prediction of successful weaning from nasal continuous positive airway pressure (NCPAP) in preterm infants. This prospective cohort study was conducted on preterm infants who were considered ready for weaning off NCPAP. Lung and diaphragm ultrasound were performed just before and 3 h after weaning off NCPAP. The primary outcome was to evaluate the accuracy of lung ultrasound (LUS) in predicting successful weaning from NCPAP. Out of 65 enrolled preterm infants, 30 (46.2%) were successfully weaned from NCPAP to room air. The successful weaning group had higher gestational ages, lower incidences of previous invasive mechanical ventilation, and treated hemodynamically significant patent ductus arteriosus before the trial weaning. A LUS score of ≤6, measured before discontinuation of NCPAP, exhibited a predictive sensitivity of 80% and specificity of 75% for successful weaning (Area under the curve (AUC) = 0.865, ≤.001). When the LUS score was assessed 3 h after weaning from NCPAP, a cutoff point of ≤7 predicted successful weaning with a sensitivity and specificity of 90% and 60% respectively (AUC = 0.838, p ≤ .001). The diaphragmatic thickness fraction (DTF) was significantly lower in the successful weaning group. After adjustment for various factors, LUS score remained the only independent predictor of successful weaning. LUS score before weaning from NCPAP has a good sensitivity and specificity for predicting successful weaning from NCPAP in preterm infants. Diaphragmatic excursion and DTF were not good predictors.

Comparative Analysis of Machine Learning Algorithms Evaluating the Single Nucleotide Polymorphisms of Metabolizing Enzymes with Clinical Outcomes Following Intravenous Paracetamol in Preterm Neonates with Patent Ductus Arteriosus.

Pharmacogenomics has been identified to play a crucial role in determining drug response. The present study aimed to identify significant genetic predictor variables influencing the therapeutic effect of paracetamol for new indications in preterm neonates. Paracetamol has recently been preferred as a first-line drug for managing Patent Ductus Arteriosus (PDA) in preterm neonates. Single Nucleotide Polymorphisms (SNPs) in CYP1A2, CYP2A6, CYP2D6, CYP2E1, and CYP3A4 have been observed to influence the therapeutic concentrations of paracetamol. The purpose of this study was to evaluate various Machine Learning Algorithms (MLAs) and bioinformatics tools for identifying the key genotype predictor of therapeutic outcomes following paracetamol administration in neonates with PDA. Preterm neonates with hemodynamically significant PDA were recruited in this prospective, observational study. The following SNPs were evaluated: CYP2E1*5B, CYP2E1*2, CYP3A4*1B, CYP3A4*2, CYP3A4*3, CYP3A5*3, CYP3A5*7, CYP3A5*11, CYP1A2*1C, CYP1A2*1K, CYP1A2*3, CYP1A2*4, CYP1A2*6, and CYP2D6*10. Amongst the MLAs, Artificial Neural Network (ANN), C5.0 algorithm, Classification and Regression Tree analysis (CART), discriminant analysis, and logistic regression were evaluated for successful closure of PDA. Generalized linear regression, ANN, CART, and linear regression were used to evaluate maximum serum acetaminophen concentrations. A two-step cluster analysis was carried out for both outcomes. Area Under the Curve (AUC) and Relative Error (RE) were used as the accuracy estimates. Stability analysis was carried out using in silico tools, and Molecular Docking Studies (MDS) were carried out for the above-mentioned enzymes. Two-step cluster analyses have revealed CYP2D6*10 and CYP1A2*1C to be the key predictors of the successful closure of PDA and the maximum serum paracetamol concentrations in neonates. The ANN was observed with the maximum accuracy (AUC = 0.53) for predicting the successful closure of PDA with CYP2D6*10 as the most important predictor. Similarly, ANN was observed with the least RE (1.08) in predicting maximum serum paracetamol concentrations, with CYP2D6*10 as the most important predictor. Further MDS confirmed the conformational changes for P34A and P34S compared to the wildtype structure of CYP2D6 protein for stability, flexibility, compactness, hydrogen bond analysis, and the binding affinity when interacting with paracetamol, respectively. The alterations in enzyme activity of the mutant CYP2D6 were computed from the molecular simulation results. We have identified CYP2D6*10 and CYP1A2*1C polymorphisms to significantly predict the therapeutic outcomes following the administration of paracetamol in preterm neonates with PDA. Prospective studies are required for confirmation of the findings in the vulnerable population.

BRIDGING GAPS: ADDRESSING TREATMENT CHALLENGES WITH ORAL PGE2 IN DUCTUS-DEPENDENT CONGENITAL HEART DEFECTS

circulation. During fetal development, it diverts approximately 90% of the right ventricular output from the high-resistance pulmonary circulation to the umbilical-placental circulation for gas exchange with maternal blood. After birth, the ductus arteriosus usually shuts within 72 hours to help with lung circulation. Failure to close leads to a persistent left-to-right shunt known as patent ductus arteriosus (PDA). PDA affects up to 80% of premature infants and constitutes 5–10% of all congenital cardiac abnormalities in term infants. Hemodynamically significant PDA is associated with various morbidities, including neurodevelopmental impairment and respiratory distress syndrome (Slaughter et al., 2019). Conversely, in ductus-dependent heart lesions, which account for 20–25% of all congenital heart defects, it is crucial to maintain patency of the neonatal DA to uphold life-saving pulmonary or systemic circulation before corrective surgery (Subramaniam and Solomon, 2013). Treatment for closing patent ductus arteriosus (PDA) mostly involves nonsteroidal anti-inflammatory medicines (NSAIDs) such as indomethacin and ibuprofen, which block cyclooxygenase enzymes necessary for prostaglandin production. Although effective, NSAIDs carry dangers such as renal impairment and intestinal problems. Acetaminophen is considered a safer option, although its effectiveness in premature infants is unclear because it may not fully inhibit prostaglandin synthesis. However, few medications exist for preserving ductus arteriosus (DA) patency, with prostaglandin E1 (PGE1) being the sole pharmacological option despite its associated side effects, such as peripheral vasodilation, apnea, fever, and physiological disturbances (Sear, 2019). Furthermore, the shortage of PGE1 in certain countries like Pakistan highlights the urgent need for alternate solutions. In such situations, adopting other available choices like PGE2, which is accessible in Pakistan as an oral drug, becomes crucial for the efficient management of ductus-dependent congenital heart anomalies. Prostaglandin E2 (PGE2) has been successfully utilized orally in newborns with ductus-dependent cyanotic congenital heart disease. In research by Silove et al., PGE2 was supplied orally in doses ranging from 12 to 65 micrograms/kg at 1 to 4 hours intervals. This treatment regimen resulted in consistent increases in oxygen saturation (SaO2) and plasma PGE2 concentrations within 15-30 minutes after administration, equivalent to those achieved with intravenous infusions. Treatment lasted for durations ranging from 5 days to 4 months, during which the ductus remained open for extended periods, allowing for delayed surgical intervention to support the growth of the infants and their pulmonary arteries. While adverse effects during oral medication were similar to those found with intravenous administration, they were generally less severe in this series, underlining the effectiveness and simplicity of oral PGE2 administration for long-term treatment (Nabavi et al., 2019). Furthermore, a 1987 study by B.D. Thanopoulos et al. supported the effectiveness of oral PGE2 in the treatment of neonates with cyanotic congenital heart disease, which primarily depends on the ductus. The data from this investigation revealed that oral PGE2 treatment, while less productive than intravenous infusions, nonetheless proved useful for long-term therapy, affording more convenience and lower morbidity (Fernández-Francos et al., 2021). It is crucial to highlight that side effects such as apnea and hypotension may occur in newborns following PGE2 therapy and require close monitoring during treatment. In conclusion, oral PGE2 offers a viable alternative for addressing congenital heart defects in resource-limited countries like Pakistan. Its effectiveness and convenience make it a viable choice, especially if access to injectable drugs is limited. This underlines the necessity to investigate alternative treatments for appropriate care in such circumstances.

Lung ultrasound score in the decision of patent ductus arteriosus closure in neonates.

We aimed to investigate the role of lung ultrasound (LUS) score in the closure of hemodynamically insignificant patent ductus arteriosus (PDA) and the clinical findings of the patients before and after closure. The study groups (107 preterm neonates under 34 gestational weeks) were classified as hemodynamically significant PDA (group 1), hemodynamically insignificant PDA with closure therapy (group 2), hemodynamically insignificant PDA without closure therapy (group 3), and no PDA group (group 4) based on the echocardiography. 6- and 10-region LUS scores were compared for each group. There was a significant difference between groups 1 and 3 on first, third, and seventh days. In contrast, groups 1 and 2 had similar LUS scores on the first, third, and seventh days. There was a negative correlation between LUS scores on the first and third days and gestational age, birth weight, the first- and fifth-minute APGAR scores, and there was a positive correlation between aortic root to left atrium ratio, and PDA diameter/weight ratio. We observed that LUS scores in patients with hemodynamically insignificant PDA treated with closure therapy were similar to in patients with hemodynamically significant PDA. Thus, LUS score can have role in PDA closure in preterm neonates. However, more comprehensive studies are needed.

Early Echocardiographic Predictors of Eventual Need for Patent Ductus Arteriosus Treatment: A Retrospective Study.

Hemodynamically significant patent ductus arteriosus (hsPDA) in preterm neonates is associated with end-organ injury including intraventricular hemorrhage. Early treatment may reduce morbidities but may result in overtreatment. This study aimed to examine the association between commonly obtained echocardiographic markers within the first 12 hours of life and eventual treatment of an hsPDA. Patients with <32 weeks' gestational age had blinded echocardiograms done within the first 12 hours of life as part of research protocols. Subsequent treatment of the patent ductus arteriosus (PDA) was determined by the clinical team independent of echocardiogram results. t-tests and chi-square tests were done for continuous data and categorical outcomes. A receiver operating curve was created to optimize cutoff values. Among 199 neonates studied (mean time of echocardiogram 6.7 h after birth), those needing PDA treatment had higher left ventricular output (LVO), right ventricular output (RVO), and superior vena cava (SVC) flow (p-values 0.007, 0.044, and 0.012, respectively). Cutoffs for predicting PDA treatment were LVO > 204 mL/kg/min (63% sensitivity, 66% specificity), RVO > 221 mL/kg/min or SVC flow > 99 mL/kg/min (sensitivities 70 and 43%, specificities 48 and 73%, respectively). Preterm neonates with higher markers of cardiac output in the first 12 hours of birth later required PDA treatment. These data are the first to use standard cardiac output measures in the first 12 hours of life to predict the need for future PDA treatment. Further prospective studies will need to be performed to corroborate these associations between echocardiographic markers and clinical outcomes/morbidities. · Early diagnosis of hsPDA may prevent severe morbidity and death.. · There are echocardiographic markers beyond duct size and flow direction that may aid early diagnosis.. · Cardiac output markers within the first 12 hours of life may predict need for treatment of hsPDA..

Effect of Antenatal Magnesium Sulfate Exposure on Patent Ductus Arteriosus in Premature Infants.

Magnesium sulfate (MgSO4) provides effective fetal neuroprotection. However, there is conflicting evidence regarding the association between antenatal MgSO4 exposure and patent ductus arteriosus (PDA). Thus, herein, we aimed to evaluate the association between antenatal MgSO4 exposure and PDA. Preterm infants born between 240/7 and 316/7 weeks of gestation were included in this retrospective study. Infants who died within the first 72 hours of life and those with significant congenital anomalies were excluded from the study. Echocardiographic and clinical assessment parameters were used to define PDA and hemodynamically significant PDA (hsPDA). Treatments were planned according to the standard protocols of the unit. The following data were collected from hospital medical records: perinatal characteristics, neonatal outcomes, detailed PDA follow-up findings, and maternal characteristics including MgSO4 exposure and doses. Of the 300 included infants, 98 (32.6%) were exposed to antenatal MgSO4. hsPDA rates were similar in the infants exposed and not exposed to antenatal MgSO4, when adjusted for antenatal steroid administration, gestational age, and birth weight (OR: 1.6, 95% CI: 0.849-3.118, p = 0.146). The rates of PDA ligation and open PDA at discharge were similar between the groups. A cumulative MgSO4 dose of >20 g was associated with an increased risk of hsPDA (crude OR: 2.476, 95% CI: 0.893-6.864, p = 0.076; adjusted OR: 3.829, 95% CI: 1.068-13.728, p = 0.039). However, the cumulative dose had no effect on the rates of PDA ligation or open PDA at discharge. Rates of prematurity-related morbidities and mortality were similar between the groups. Although antenatal MgSO4 exposure may increase the incidence of hsPDA, it may not affect the rates of PDA ligation or open PDA at discharge. Further studies are required to better evaluate the dose-dependent outcomes and identify the MgSO4 dose that not only provides neuroprotection but also has the lowest risk of adverse effects. · Antenatal exposure of MgSO4 may cause PDA.. · Antenatal MgSO4 exposure may not increase the rates of PDA ligation or open PDA at discharge.. · Further studies are required to better evaluate the dose-dependent outcomes and optimal MgSO4 dose..

Establishment and efficiency test of a clinical prediction model of bronchopulmonary dysplasia associated pulmonary hypertension in very premature infants

Objective: To develop a risk prediction model for identifying bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH) in very premature infants. Methods: This was a retrospective cohort study. The clinical data of 626 very premature infants whose gestational age <32 weeks and who suffered from BPD were collected from October 1st, 2015 to December 31st, 2021 of the Seventh Medical Center of the People's Liberation Army General Hospital as a modeling set. The clinical data of 229 very premature infants with BPD of Hunan Children's Hospital from January 1 st, 2020 to December 31st, 2021 were collected as a validation set for external verification. The very premature infants with BPD were divided into PH group and non PH group based on the echocardiogram after 36 weeks' corrected age in the modeling set and validation set, respectively. Univariate analysis was used to compare the basic clinical characteristics between groups, and collinearity exclusion was carried out between variables. The risk factors of BPD associated PH were further screened out by multivariate Logistic regression, and the risk assessment model was established based on these variables. The receiver operating characteristic (ROC) area under curve (AUC) and Hosmer-Lemeshow goodness-of-fit test were used to evaluate the model's discrimination and calibration power, respectively. And the calibration curve was used to evaluate the accuracy of the model and draw the nomogram. The bootstrap repeated sampling method was used for internal verification. Finally, decision curve analysis (DCA) to evaluate the clinical practicability of the model was used. Results: A total of 626 very premature infants with BPD were included for modeling set, including 85 very premature infants in the PH group and 541 very premature infants in the non PH group. A total of 229 very premature infants with BPD were included for validation set, including 24 very premature infants in the PH group and 205 very premature infants in the non PH group. Univariate analysis of the modeling set found that 22 variables, such as artificial conception, fetal distress, gestational age, birth weight, small for gestational age, 1 minute Apgar score ≤7, antenatal corticosteroids, placental abruption, oligohydramnios, multiple pulmonary surfactant, neonatal respiratory distress syndrome (NRDS)>stage Ⅱ, early pulmonary hypertension, moderate-severe BPD, and hemodynamically significant patent ductus arteriosus (hsPDA) all had statistically significant influence between the PH group and the non PH group (all P<0.05). Antenatal corticosteroids, fetal distress, NRDS >stage Ⅱ, hsPDA, pneumonia and days of invasive mechanical ventilation were identified as predictive variables and finally included to establish the Logistic regression model. The AUC of this model was 0.86 (95%CI 0.82-0.90), the cut-off value was 0.17, the sensitivity was 0.77, and the specificity was 0.84. Hosmer-Lemeshow goodness-of-fit test showed that P>0.05. The AUC for external validation was 0.88, and the Hosmer-Lemeshow goodness-of-fit test suggested P>0.05. Conclusions: A high sensitivity and specificity risk prediction model of PBD associated PH in very premature infants was established. This predictive model is useful for early clinical identification of infants at high risk of BPD associated PH.

Clinical and echocardiography predictors of response to first-line acetaminophen treatment in preterm infants with hemodynamically significant patent ductus arteriosus.

To assess clinical and echocardiography predictors of acetaminophen response for the treatment of patent ductus arteriosus (PDA) in preterm neonates. Retrospective cohort study of preterm infants born <30 weeks, with a diagnosis of hemodynamically significant PDA, who received 1st line treatment with intravenous acetaminophen during the first 2 postnatal weeks. Response was defined by PDA closure or improvement in PDA score of >50%. A total of 100 infants were included whose median weight and gestational age at birth were 663 grams and 24.6 weeks respectively. In total, 66 infants were classified as responders and were more likely to have intrauterine growth restriction, exposure to maternal hypertension and chorioamnionitis. Non-response was more common among infants with thrombocytopenia and anemia. Responders were more likely to be IUGR with echocardiography indices of lower preload. Response to 1st line intravenous acetaminophen therapy is comparable to non-steroidal drugs in preterm infants. Relationship of response to acetaminophen to perinatal characteristics requires further characterization.

Comparison of efficacy of paracetamol and ibuprofen for treatment of hemodynamically significant patent ductus arteriosus in preterm infants

Background: Indomethacin and ibuprofen (IBU) have been approved for the pharmacological closure of hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. Recent works have demonstrated that paracetamol (PCM) can also be used but more research is required regarding efficacy and safety. Objectives: The objective is to compare the efficacy and safety of PCM and IBU for the treatment of hsPDA in preterm infants. Methodology: An observational study was designed with ethical clearance and parental consent. Patients were evaluated for hsPDA by clinical and 2 D echo findings. After inclusion and exclusion criteria, consecutive 100 patients were assigned between PCM and IBU and were given a 3-day course. After echocardiographic and clinical evaluation, if required, a second course with same drug was given. The outcome measures were the rate of ductal closure, the safety of drugs, and adverse events. Results: The PCM group had a closure rate of 76.25% and the IBU group had 75%. IBU had a significantly higher rate of closure in the first course (45% vs. 16.25%). The mean closure time observed was 4.54 days and 4 days for PCM and IBU, respectively. PCM gave a higher closure rate in the low-birth-weight group and where platelet counts were below normal. Regarding the safety aspect also no significant difference between groups was observed. Conclusion: PCM can be advised as a first-line treatment for hsPDA cases in preterm infants and is a better choice in cases of comorbidities and patients with low platelet count.