Search Results (152)

This research aims to offer a deep learning-based diagnostic approach for hemorrhagic complications linked to patent ductus arteriosus (PDA) in preterm infants. Utilizing the You Only Look Once (YOLO) algorithm, this research analyzed five key cardiac parameters derived from echocardiographic ultrasonic waves: the left ventricular ejection time (LVET), left ventricular internal dimension at diastole (LVIDd), left ventricular internal dimension at systole (LVIDs), posterior wall thickness at end-systole (HES), and RR interval between two successive R-waves. The proposed ensemble model achieved best-in-class detection accuracies for each parameter, with rates of 97.56% (LVET), 88.69% (LVIDd), 99.50% (LVIDs), 82.29% (HES), and 81.15% (RR interval). Furthermore, assessment of cardiac function using derived indices—end-systolic wall stress (ESWS) and rate-corrected mean velocity of circumferential fiber shortening (mVcfc)—achieved mean accuracy rates of 82.33% and 90.16%, respectively. This approach enables physicians to accurately evaluate cardiac function in preterm infants and facilitates the diagnosis of PDA-related hemorrhagic complications. Full article

Background and Objectives: Neonatal respiratory distress syndrome (NRDS), resulting from a deficiency of pulmonary surfactant (PS), can cause alveoli to collapse. Glucocorticoids reduce inflammation and are effective in reducing pulmonary swelling. This study aims to assess the effectiveness of the combination of PS and budesonide in the management of NRDS. Materials and Methods: Publications between 21 May and 24 November were screened through PubMed, Cochrane and Embase. Data analysis was performed on RevMan 5.3 software. Subgroup analysis was performed to evaluate the routes of administrations. Results: The use of budesonide along with pulmonary surfactant for treating NRDS revealed the following results: (1) a reduced duration of invasive mechanical ventilation (standardized mean difference (SMD) = −1.06, 95% confidence interval (CI) = −1.55 to −0.56, p < 0.0001); (2) reduced rate of bronchopulmonary dysplasia (BPD) occurrence (relative risk (RR) = 0.72, 95% CI = 0.60 to 0.86, p = 0.0003); (3) reduced duration for hospital admittance (SMD = −0.38, 95% CI = −0.64 to −0.11, p = 0.005). The occurrence of complications, i.e., sepsis, pneumothorax, retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), rate of mortality, hyperglycemia and intraventricular hemorrhage (IVH), was not significantly different among the intervention and comparison group except for patent ductus arteriosus (PDA) and pulmonary hemorrhage, with their incidence being higher in the control group (p = 0.002 and p = 0.05, respectively). Conclusions: The combination of pulmonary surfactant and budesonide decreases the occurrence of BPD, duration of mechanical ventilation, length of hospital stay and risk of pulmonary hemorrhage and PDA. It does not increase the risk of complications and death and is clinically safe. Full article

Pulmonary hemorrhage (PH) is a life-threatening complication predominantly affecting preterm infants, particularly those with very low birth weight (VLBW) and fetal growth restriction (FGR). Typically occurring within the first 72 h of life, PH is characterized by acute respiratory deterioration and significant morbidity and mortality. This review synthesizes current evidence on the multifactorial pathogenesis of PH, highlighting the roles of immature pulmonary vasculature, surfactant-induced hemodynamic shifts, and left ventricular diastolic dysfunction. Key risk factors include respiratory distress syndrome (RDS), hemodynamically significant patent ductus arteriosus (hsPDA), sepsis, coagulopathies, and genetic predispositions. Diagnostic approaches incorporate clinical signs, chest imaging, lung ultrasound, and echocardiography. Management strategies are multifaceted and include ventilatory support—particularly high-frequency oscillatory ventilation (HFOV)—surfactant re-administration, blood product transfusion, and targeted hemostatic agents. Emerging therapies such as recombinant activated factor VII and antifibrinolytics show promise but require further investigation. Preventive measures like antenatal corticosteroids and early indomethacin prophylaxis may reduce incidence, particularly in high-risk populations. Despite advancements in neonatal care, PH remains a major contributor to neonatal mortality and long-term neurodevelopmental impairment. Future research should focus on individualized risk stratification, early diagnostic tools, and optimized treatment protocols to improve outcomes. Multidisciplinary collaboration and innovation are essential to advancing care for this vulnerable population. Full article

Objective: We evaluated how pre-treatment clinical and echocardiographic findings influence treatment decisions for patent ductus arteriosus (PDA) in preterm neonates. Study Design: Preterm neonates weighing < 1500 g and diagnosed with PDA were enrolled. They were categorized into conservative, medical, and surgical groups based on treatment. Results: A total of 242 preterm neonates (120 boys and 122 girls) participated, with a mean gestational age of 27.9 ± 2.2 weeks and a birth weight of 1034.3 ± 239.3 g. Multivariate logistic regression revealed that oliguria (p < 0.001), inotropic drug use (p = 0.049), low PDA flow velocity (p = 0.039), and left atrial enlargement (p = 0.002) were significantly associated with medical or surgical treatment decisions. Additionally, a low base deficit prior to medical therapy was associated with the decision to proceed with surgical intervention after medical treatment failure (p = 0.006). Conclusions: Oliguria, inotropic drug use, low PDA flow velocity, and left atrial enlargement were significantly associated with aggressive treatment decisions in preterm neonates with PDA. Furthermore, a low base deficit influenced the need for surgery following medical therapy failure. Our findings suggest that comprehensive monitoring of both clinical and echocardiographic factors may support treatment decision-making in PDA management in preterm neonates. Full article

Objectives: Pulmonary hypertension and hemodynamically significant PDA (hsPDA) involve seemingly opposite physiological features—decreased pulmonary blood flow and pulmonary overcirculation, respectively—but the literature demonstrates variable respiratory consequences in association with each of these morbidities. The aim of this study is to evaluate whether the two factors representing pulmonary circulation provide different contributions to respiratory outcomes in preterm infants with and without pulmonary hypoplasia. Methods: The medical records of preterm very low birth weight (VLBW) infants admitted to our unit during the study period from January 2013 to December 2020 were retrospectively reviewed. Preterm VLBW infants were divided into groups according to the presence of presumed pulmonary hypoplasia (PPH). Multivariable logistic regression analysis was performed to assess the association of PPH and pulmonary hypertension or delayed PDA closure with in-hospital outcomes. Results: Postnatal age at final treatment for PDA was significantly later [median 33 vs. 19 days, p = 0.025] in the PPH group. Multivariable analysis indicated that early pulmonary hypertension was significantly associated with neonatal death [aOR (95%CI) 11.575 (2.988–44.833) for no-PPH vs. 9.981 (1.334–74.647) for PPH]. Delayed PDA closure was associated with increased odds of adverse respiratory and composite outcomes [aOR (95%CI) 4.929 (1.613–15.055) and 3.320 (1.048–10.515), respectively] but decreased odds of neonatal death in the no-PPH group. However, Cox proportional hazards models did not demonstrate statistically significant associations for PPH, early pulmonary hypertension, or delayed PDA closure with mortality, likely due to time-varying effects and the absence of death events in the subgroup of infants with both PPH and delayed PDA closure. Conclusions: PPH is associated with a higher prevalence of air leak syndrome and pulmonary hypertension. Delayed PDA closure exerts different effects on respiratory outcomes in preterm VLBW infants with and without PPH. Although early pulmonary hypertension appears to be a key circulatory factor contributing to neonatal death, its effect may vary over time. These findings underscore the importance of accounting for time-dependent effects when interpreting pulmonary circulatory risk factors in clinical practice. Full article

Background and Clinical Significance: The incidence of persistent ductus arteriosus (PDA) in preterm infants is the highest and depends on their birth weight (BW) and respiratory condition after birth. Previously, after the unsuccessful drug treatment, surgical ligation was the primary treatment option. However, according to clinical studies, the Amplatzer Piccolo Occluder was approved for PDA closure for patients ≥700 g. In our country, percutaneous PDA embolization has not been performed yet. Case Presentation: We present three premature infants with hemodynamically significant patent ductus arteriosus (hsPDA) in whom percutaneous occlusion was performed using the Amplatzer Piccolo Occluder (APO). The average gestational week (GW) was 27 ± 1, while body weight was 1030 ± 60 g. All patients had respiratory deterioration, with dilatation of the left heart chambers, and renal failure. The second developed a severe form of broncho-pulmonary dysplasia. Transthoracic echocardiography (TTE) examinations revealed a hemodynamically significant PDA (LA/Ao 1.8–2.2) and medical closure was unsuccessfully carried out. Due to the hemodynamically significant PDA maintenance in all neonates, transvenous PDA closure was performed using the APO (APO 9-PDAP-04-02-L, 9-PDAP-04-04-L, 9-PDAP-05-054L, respectively). The entire devices, with both retention discs, are implanted within the duct. TTE pointed out adequate device position without descending aorta, left pulmonary artery obstruction, residual shunt, and reverse remodelling of the left ventricle and left atrium. The first newborn was weaned from mechanical ventilation three days after the procedure and discharged three weeks after. The second patient was extubated 2 weeks after the procedure, and even the severe BPD, X-ray showed improvement. The third patient’s renal failure completely resolved, weaned from inotropic drug support and mechanical ventilation. Conclusions: Due to a significantly lower complication rate than surgical ligation, we will strive to make percutaneous PDA occlusion a new standard for treatment in newborns, especially preterm newborns, in our country. Full article

Background/Objectives: Prenatal adverse events may influence the development of complications of prematurity, including patent ductus arteriosus (PDA). We conducted a systematic review and Bayesian model-averaged (BMA) meta-analysis of observational studies exploring the association between hypertensive disorders of pregnancy (HDP) and the risk of PDA in preterm infants. Methods: PubMed/Medline and Embase databases were searched. We used BMA analysis to calculate Bayes factors (BFs). The BF₁₀ is the ratio of the probability of the data under the alternative hypothesis (H₁, presence of association) over the probability of the data under the null hypothesis (H₀, absence of association). Results: We included 41 studies (58,004 infants). BMA analysis showed moderate evidence in favour of H₀ for the association between HDP and any PDA (BF₁₀ = 0.20) as well as for the association between HDP and hemodynamically significant PDA (BF₁₀ = 0.27). Subgroup analyses based on the subtype of HDP showed that the moderate evidence in favour of H₀ was only conclusive (i.e., BF₁₀ < 0.33) for the associations of any PDA with preeclampsia (BF₁₀ = 0.30) and hemodynamically significant PDA with preeclampsia (BF₁₀ = 0.17). Conclusions: The currently available evidence suggests a lack of association between HDP and the risk of developing PDA. Full article

Background/Objectives: Retinopathy of prematurity (ROP) is a significant cause of childhood blindness, particularly among preterm infants. Patent ductus arteriosus (PDA) is commonly observed in neonates and may contribute to the development of ROP through increased oxygen delivery to the retina. However, the association between PDA and the severity of ROP remains unclear. This study aims to evaluate the relationship between PDA and the development of treatment-requiring ROP in preterm infants. Methods: A retrospective cohort study was conducted on preterm infants born between 2014 and 2020 at Izmir Private Medical Park Hospital. Infants with a birth weight of less than 2000 g and a gestational age of ≤36 + 6 weeks were included. Data on demographics, prematurity-related complications, PDA status, ROP severity, and treatment requirements were collected. Statistical analysis was performed using univariate and multivariate logistic regression models to identify predictors of ROP. Results: Of 516 infants, 328 did not have PDA, 117 had spontaneous PDA closure, and 71 required PDA treatment. Neonates requiring PDA treatment had significantly lower gestational age and birth weight, as well as longer respiratory support duration. PDA presence was associated with increased ROP incidence in univariate analysis (p < 0.001); however, it was not an independent predictor of treatment-requiring ROP in multivariate models. Significant predictors for treatment-requiring ROP included longer non-invasive ventilation duration (OR = 1.029) and total respiratory support (OR = 1.009). Conclusions: The findings of this study highlight the central role of respiratory morbidity in ROP pathogenesis and suggest that optimal respiratory management may be more critical for ROP prevention than PDA treatment alone. Full article

The complications observed in preterm infants are largely attributable to underdeveloped organ systems and inadequate nutritional stores at birth. Insufficient nutritional support can further exacerbate persistent sequelae, such as bronchopulmonary dysplasia (BPD), metabolic bone disease of prematurity (MBDP), and retinopathy of prematurity (ROP). As a result, clinicians have collaborated to develop optimal nutrition strategies for preterm neonates. However, these clinical nutrition plans may be hindered by several factors, including fluid restrictions due to patent ductus arteriosus (PDA) and delayed enteral nutrition following necrotizing enterocolitis (NEC). Modified strategies for specific conditions can help prevent further deterioration, but inadequate nutritional support may limit organ growth and contribute to additional complications. Achieving an optimal balance between nutritional support and managing specific medical conditions varies across institutions. In addition to fluid balance and energy intake, supplementary nutrition—such as vitamins and probiotics—plays a crucial role in disease prevention. Drawing on recent evidence and our clinical experiences with neonatal nutritional strategies, this review article summarizes the specialized nutritional management required for preterm neonates with conditions such as BPD, NEC, MBDP, PDA, and ROP. Full article

Background/Objectives: Congenital heart disease (CHD) occurs in ~1% of all live neonates globally, rendering it the most prevalent developmental anomaly affecting humans; this condition confers substantial infant morbidity and mortality worldwide. Although there is ample evidence to suggest a paramount genetic basis for CHD, the genetic etiologies underpinning the majority of CHD remain elusive. In the present study, SOX4 was selected as a significant candidate gene for human CHD, mainly because SOX4 is abundantly expressed in both human and murine hearts during embryogenesis, and the knockout of Sox4 in mice causes embryonic demise predominantly attributable to cardiovascular developmental defects. Methods: Sequencing analysis of SOX4 was fulfilled in 248 probands affected with various types of CHD and the available relatives of the identified variation carrier as well as 262 unrelated healthy individuals. Functional analysis of the mutant SOX4 protein was conducted by utilizing a dual-reporter gene system. Results: a novel heterozygous SOX4 variation, NM_003107.3:c.331G>T;p.(Glu111*), was discovered in a male proband with Coffin–Siris syndromic CHD. Genetic investigation of the proband’s available relatives revealed that the truncating variation co-segregated with the phenotype in the whole family. The nonsense variation was absent from 262 healthy controls. Functional analysis demonstrated that the Glu111*-mutant SOX4 lost transactivation on NKX2.5 and GATA4, two well-established genes that are causative factors for CHD. Moreover, the Glu111* mutation nullified the synergistic transactivation between SOX4 and TBX20, another CHD-causing gene. Conclusions: These findings support SOX4 as a causative gene accountable for familial Coffin–Siris syndromic CHD in humans. These findings may aid in developing personalized preventive and therapeutic strategies for patients with Coffin–Siris syndromic CHD. Full article

Background: The diagnosis of hemodynamically significant patent ductus arteriosus (hsPDA) occurs in 55% of very low birth weight (VLBW) preterm infants. There is no agreement on the best approach to ensure a quick hsPDA closure. Drug treatment of hsPDA fails in approximately 20% of cases with an increasing risk of prolonged ventilation, BPD, and NEC, as well as the need for surgical duct ligation. This study aims to highlight the efficacy of ibuprofen versus acetaminophen in the case of a second cycle of medical therapy after the failure of the first pharmacological approach for hsPDA closure. Methods: Every VLBW infant admitted to our NICU and treated for hsPDA was included in our retrospective research. Information about the clinical course, hsPDA diagnosis and treatment, and common complications associated with preterm birth was collected. A comparison was made between patients treated with acetaminophen or ibuprofen to assess effectiveness in hsPDA closing. Results: A total of 286 VLBW infants were included. First-course ibuprofen was effective in 87 of 115 infants (75.7%) treated, acetaminophen in 138 of 171 (80.7%). Second-course therapy with ibuprofen was effective in 62.5% of the patients, while acetaminophen was effective in 69.2%. No statistically significant difference was observed in the first-course and second-course success rates. Conclusions: This study confirms that acetaminophen is not inferior to ibuprofen in the closure of hsPDA in VLBW infants. Our data demonstrate that a second course of medical therapy after the failure of the first course could help close the majority of hsPDA cases without surgery. Full article

The survival and health outcomes of extremely preterm neonates (PNs) remain a critical challenge in neonatal intensive care. This 5-year retrospective, observational study evaluated morbidity and mortality trends in PNs born at the limits of viability and identified survival patterns and associated risk factors. It was conducted from 2017 to 2022 on a dataset of PNs born between 22 + 0 and 26 + 0 weeks of gestation in a tertiary public hospital in Greece. A total of 73 PNs were included. The mortality rate was 56.2%. The median gestational age was 24.3 weeks, and the mean birth weight was 603.6 g. Survival improved significantly with a higher gestational age and birth weight. Respiratory distress syndrome was the most prevalent morbidity (71–94%), followed by late-onset sepsis (35.3%) and patent ductus arteriosus (29.4%). The use of antenatal corticosteroids and enteral feeding were associated with improved survival rates. Survivors required prolonged respiratory support and demonstrated better outcomes with early and adequate nutritional support. We conclude that the gestational age, birth weight, and effective respiratory and nutritional interventions are critical determinants of survival in neonates at the limits of viability. Enhancing neonatal care protocols with targeted interventions, such as antenatal corticosteroid use and evidence-based nutritional practices, could significantly improve outcomes in this vulnerable population. Full article

Compartment boundaries divide the embryo into segments with distinct fates and functions. In the vascular system, compartment boundaries organize endothelial cells into arteries, capillaries, and veins that are the fundamental units of a circulatory network. For vascular smooth muscle cells (SMCs), such boundaries produce mosaic patterns of investment based on embryonic origins with important implications for the non-uniform distribution of vascular disease later in life. The morphogenesis of blood vessels requires vascular cell movements within compartments as highly-sensitive responses to changes in fluid flow shear stress and wall strain. These movements underline the remodeling of primitive plexuses, expansion of lumen diameters, regression of unused vessels, and building of multilayered artery walls. Although the loss of endothelial compartment boundaries can produce arterial–venous malformations, little is known about the consequences of mislocalization or the failure to form SMC-origin-specific boundaries during vascular development. We propose that the failure to establish a normal compartment boundary between cardiac neural-crest-derived SMCs of the 6th pharyngeal arch artery (future ductus arteriosus) and paraxial-mesoderm-derived SMCs of the dorsal aorta in mid-gestation embryos leads to aortic coarctation observed at birth. This model raises new questions about the effects of fluid flow dynamics on SMC investment and the formation of SMC compartment borders during pharyngeal arch artery remodeling and vascular development. Full article

Background and Objectives: Patent ductus arteriosus (PDA) is common in newborns, being associated with high morbidity and mortality. While maternal and neonatal conditions are known contributors, few studies use advanced machine learning (ML) as predictive factors. This study assessed how maternal pathologies, medications, and neonatal factors affect the risk of PDA using traditional statistics and ML algorithms: Random Forest (RF) and XGBoost (XGB). Materials and Methods: A retrospective 3-year cohort study of 201 NICU neonates assessed maternal and neonatal factors. Logistic regression (LR) and chi-square analyses identified significant predictors, while ML models enhanced predictive accuracy and pinpointed key PDA factors. Results: LR identified prolonged rupture of membranes (>18 h) as the most significant predictor (OR: 13.03, p < 0.001). The ML models identified gestational age, maternal anemia, prenatal care level, birth weight, prolonged rupture of membranes, medication usage, diabetes, pregnancy-induced hypertension, SARS-CoV-2 infection, and cervical cerclage as key predictors. The RF model had 76.3% accuracy, moderate sensitivity (47.4%), and high specificity (90%). XGB performed better with 81.4% accuracy, an AUC of 0.872, sensitivity of 92.5%, and specificity of 57.9%. Conclusions: This study shows that maternal and neonatal factors significantly influence the risk of PDA. ML, particularly XGBoost, enhances predictive abilities, guiding targeted interventions and improving neonatal outcomes. Full article

Background/Objectives: Premature infants are often referred for the definitive procedural closure of the patent ductus arteriosus (PDA) with the failure of, or contraindication to, pharmacotherapy and the inability to wean respiratory support. However, once this need is identified, the importance of expedited closure is unclear. The objective of this study was to compare the effect of the timing of definitive closure (i.e., surgical ligation or device occlusion) on early respiratory outcomes in premature infants. Method: We first specify a hypothetical randomized trial (the “target trial”) that would estimate the effect on extubation of early (0–4 days from referral) vs. late (5–14 days from referral) definitive PDA closure. We then emulate this target trial using a single-institution registry of premature infants (born <30 weeks or with a birth weight < 1500 g) who underwent the definitive closure of PDA between January 2014 and October 2023. Results: We identify 131 eligible infants. At the end of the follow-up, 70 and 38 infants were adherent to early and late PDA closure strategies, respectively. The cumulative incidence of extubation in the early group was higher than that in the late group until day 40 (maximum risk difference: 22 percentage points at day 13; 95% CI: −11 to 56). Outcomes were similar at the end of the 45-day follow-up period (risk difference: −1 percentage point; 95% CI: −46 to 42). Conclusions: The need for mechanical ventilation was equivalent between early and late PDA closure strategies at the end of a 45-day follow-up period although infants in the early intervention group were extubated sooner. Full article