Search Results (40)

Background: Inflammatory mechanisms may contribute to persistent ductal patency in preterm infants with hemodynamically significant patent ductus arteriosus (hsPDA). This study evaluated early postnatal temporal patterns of complete blood count (CBC)-derived inflammatory indices in relation to ductal status and pharmacologic treatment response. Methods: This retrospective single-center study included preterm infants born at <34 weeks’ gestation who received pharmacologic treatment for hsPDA. Hematologic parameters and CBC-derived inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), pan-immune inflammation value (PIV), and immature granulocyte (IG) parameters, were assessed on postnatal days 1, 3, and 7. Results: The final cohort included 71 preterm infants with hsPDA. Over the first postnatal week, NLR and PLR peaked on day 3, MLR remained elevated, and PIV increased toward day 7. SII and SIRI showed significant temporal variation, whereas IG parameters did not. Among longitudinal changes, only ΔPIV, calculated as day 3 minus day 7 values, differed by treatment response, with a greater increase in PIV observed among non-responders. ΔPIV yielded limited discrimination for non-response (AUC = 0.646; sensitivity, 92%; specificity, 37%; cut-off, ≤110.4). Birth weight and gestational age were positively correlated with several hematologic parameters and inflammatory indices, whereas ductal status showed inverse associations with IG% on day 1 and with monocyte count and MLR on day 3. After adjustment for maturational factors and treatment type, the ΔPIV–response association was attenuated, without improved discrimination. Conclusions: CBC-derived inflammatory indices demonstrated distinct early postnatal patterns in infants with hsPDA. ΔPIV may serve as a hypothesis-generating longitudinal marker of treatment response rather than a stand-alone predictor and warrants further validation. Full article

Background and Objectives: Lung ultrasound (LUS) has fundamentally transformed neonatal respiratory diagnostics, offering a radiation-free, bedside-applicable modality capable of guiding surfactant therapy, characterizing pulmonary pathology, and monitoring treatment response in real time. While surfactant replacement therapy is firmly established for neonatal respiratory distress syndrome (RDS), its role in acute complications—specifically pulmonary hemorrhage (PH) and pneumothorax (PTX)—remains uncertain and heterogeneous in clinical practice. This review examines how LUS-based phenotyping can improve the diagnostic precision and therapeutic sequencing of surfactant administration in these high-risk scenarios, and how comorbidities such as hemodynamically significant patent ductus arteriosus, persistent pulmonary hypertension, sepsis, and coagulopathy modulate clinical outcomes. Materials and Methods: We conducted a structured narrative review of studies published from 2020 onward, sourced from PubMed, Web of Science, Semantic Scholar, and Mendeley, using PRISMA-inspired selection principles. The search combined terms including “lung ultrasound,” “neonatal POCUS,” “surfactant therapy,” “pulmonary hemorrhage,” “neonatal pneumothorax,” and “LUS score.” Studies focusing on neonatal populations, clinical LUS applications, and surfactant use in PH and PTX were prioritized. Results: Quantitative LUS scoring systems (range 0–18) predict surfactant need and re-dosing with AUC values of 0.85–0.87, outperforming clinical estimates alone. In PH, LUS reveals dense consolidation with alveolar flooding patterns, guiding the timing of rescue surfactant after hemodynamic stabilization; response monitoring via serial LUS is feasible and informative. In PTX, hallmark signs—absent lung sliding, loss of B-lines, and the pathognomonic lung point—allow diagnosis within seconds, guiding immediate thoracentesis and subsequent surfactant administration if underlying RDS is confirmed. Nationally implemented LUS protocols in neonatal intensive care units have demonstrated significant reductions in radiation exposure without compromising diagnostic accuracy. Conclusions: LUS-guided decision algorithms—integrating ultrasonographic phenotyping, quantitative scoring, and hemodynamic assessment—represent the current best framework for individualizing surfactant therapy in neonatal PH and PTX. Standardization of POCUS training and protocol implementation in neonatal units is essential. Prospective multicenter trials are urgently needed to define optimal indications, timing, and dosing in these vulnerable populations. Full article

Background and Clinical Significant: Patent ductus arteriosus (PDA) is a common cardiovascular disorder in extremely low-birth-weight (ELBW) infants, for which surgical ligation is indicated when pharmacologic closure fails. Sudden increases in afterload combined with immature myocardial contractility can lead to post-ligation cardiac syndrome (PLCS), which usually occurs within hours after surgery. However, acute intraoperative hemodynamic collapse during PDA ligation has rarely been described. Case Presentation: A preterm infant born at 24 weeks and 3 days of gestation with a birth weight of 890 g underwent emergency PDA ligation for a hemodynamically significant PDA (hs-PDA) refractory to pharmacological treatment. Fifteen minutes after skin incision, the infant developed desaturation, bradycardia, and non-measurable noninvasive blood pressure, which required immediate hemodynamic resuscitation with manual ventilation, fluid administration, and dopamine and dobutamine infusions. Hemodynamics gradually recovered after completion of ductal ligation, whereas oxygen saturation did not fully recover. Postoperative chest radiography revealed a left-sided pneumothorax, and oxygen saturation stabilized after pleural air aspiration. The subsequent clinical course was uneventful, and typical PLCS did not develop. Conclusions: This case suggests that intraoperative hemodynamic collapse during PDA ligation may share pathophysiologic features with PLCS, and that concomitant pneumothorax can further aggravate hemodynamic instability by worsening hypoxemia and reducing venous return. Full article

Very preterm infants with immature kidneys exhibit high vulnerability to acute kidney injury (AKI). While AKI is associated with adverse outcomes, serum-creatinine-based diagnostics prove unreliable in early risk assessment of kidney damage. This pilot study investigated ¹H-NMR spectroscopy-based metabolomics for the identification of very-low-birth-weight (VLBW < 1500 g) infants at risk of AKI before and during indomethacin treatment for patent ductus arteriosus (PDA). Longitudinal urine samples (0 h, 12 h, 36 h, 84 h, 120 h, 14 d, 28 d) from 12 VLBW infants receiving indomethacin for hemodynamically significant PDA were analyzed by ¹H-NMR spectroscopy. In total, 150 urinary metabolites were annotated and single-metabolite and multivariate analyses were performed. At 36 h after treatment initiation, three patients (25%) developed AKI (KDIGO criteria). Principal component analysis (PCA) revealed significant differences in urinary metabolic profiles between the AKI and non-AKI groups 12 h after indomethacin initiation. Before treatment, five metabolites were significantly lower in the AKI group: adenine, creatine, dimethylglycine, 1-methylnicotinamide, and methylmalonic acid. Urinary creatine/creatinine (AUC 0.97) and 1-methylnicotinamide/creatinine (AUC 0.93) exhibited promising prognostic accuracy for the prediction of AKI. 1-methylnicotinamide/creatinine concentrations remained persistently reduced during the study. In conclusion, urinary metabolomics, particularly creatine and 1-methylnicotinamide levels, may serve as valuable non-invasive biomarkers for identifying VLBW infants at risk of AKI. Full article

Background: Patent ductus arteriosus (PDA) is a common congenital heart defect. While closure of hemodynamically significant PDAs is well established, closure of small, hemodynamically insignificant PDAs for prevention of infective endocarditis or endarteritis (IEE) remains controversial and is supported only by low-level evidence. Methods: A systematic PubMed search was performed in May 2025 to identify published case reports of PDA-associated IEE. Data on PDA characteristics, audibility, vegetation location, and causative pathogens were extracted. In addition, the annual national number of percutaneous PDA closures in The Netherlands was determined using data from the Dutch Society of Pediatrics. Finally, the literature was searched for the incidence of complications of percutaneous ductal closure. Results: Seventy-two PDA-IEE cases were identified, of which fifty-five reported PDA audibility. Most cases involved audible PDAs with high-velocity turbulent flow and vegetations at sites exposed to shear stress, particularly the main pulmonary artery. Silent PDAs demonstrated similar vegetation locations and flow characteristics, suggesting that they had comparable pathophysiology. National data showed an average of 76.6 percutaneous PDA closures annually, of which 61% were hemodynamically insignificant. Adverse events during percutaneous ductal closure occur in 23.3% of procedures and clinically significant complications are reported in 10.1%. Both audible and silent PDAs appear capable of promoting IEE through similar hemodynamic mechanisms. Conclusions: Given the low incidence of PDA IEE relative to procedural risks, the high number needed to treat and the associated costs, routine closure of non-hemodynamically significant PDAs solely for IEE prevention is not clearly justified, and no distinction should be made between audible and silent PDAs. The current guidelines warrant critical reassessment. Full article

Background/Objective: Patent Ductus Arteriosus (PDA) is a common congenital heart defect causing high morbidity and mortality in preterm neonates. IV ibuprofen is the standard treatment, with acetaminophen as a potential alternative when ibuprofen is contraindicated. However, evidence for acetaminophen’s effectiveness is inconclusive. This study aimed to compare the efficacy and safety of IV acetaminophen versus IV ibuprofen as the initial treatment for PDA closure in preterm neonates. Methods: A retrospective cohort study was conducted at a tertiary Saudi hospital. This study included preterm neonates with a gestational age of ≤32 weeks diagnosed with PDA and treated with IV ibuprofen or IV acetaminophen. The primary outcome was to evaluate the efficacy of ibuprofen versus acetaminophen for treating PDA. Results: A total of 95 courses were included. Of these, 49 neonates received ibuprofen, and 18 neonates received acetaminophen as first therapy. The mean age at the initial course was 5.47 ± 10.30 days for the ibuprofen group and 5.22 ± 6.43 days for the acetaminophen group. In most neonates, the hemodynamic significance of the PDA was confirmed by ultrasound examination. As a result, 35 of 49 neonates treated with ibuprofen experienced successful full PDA closure, with a rate of 71.4%, compared to 10 of 18 in the acetaminophen group, which had a rate of 55.6%. However, this difference was not statistically significant (p-value = 0.35). Conclusions: A trend toward higher PDA closure with ibuprofen was observed compared to acetaminophen, without a statistically significant difference. Both treatments showed comparable safety. Further studies are needed to confirm these findings and optimize acetaminophen dosing. Full article

Background/Objectives: Near-infrared spectroscopy measures regional oxygen saturation (RSO₂) in target tissues. Cerebral and renal RSO₂ are associated with hemodynamically significant patent ductus arteriosus (PDA) in preterm infants. The aim of this study was to determine whether liver RSO₂ is associated with PDA status. Methods: Preterm infants born before 32 weeks of gestation and/or weighing <1.5 kg were enrolled. Cerebral, renal, and liver RSO₂ values were recorded on day 2 (D2; 48–72 h), day 7 (D7; 7 ± 2 days), and day 14 (D14; 14 ± 3 days), along with the corresponding point-of-care echocardiographic findings. Results: Of the forty preterm infants enrolled (mean ± SD gestational age, 28.8 ± 2.2 weeks; birthweight, 1209.9 ± 364.2 g), 22 (55.0%) had spontaneous PDA closure, 18 (45.0%) underwent pharmacological closure, and 4 (10.0%) required surgical closure. Cerebral, renal, and liver RSO₂ values were significantly lower in infants with PDA than those without. Liver RSO₂ was significantly lower in the presence of PDA at D7 (68.19 ± 13.24 vs. 82.14 ± 5.58, p < 0.001) and D14 (59.33 ± 12.06 vs. 80.0 ± 6.48, p < 0.001). Liver RSO₂ showed a strong inverse association with a higher LA/Ao ratio (β −38.71, 95%CI −55.03 to −22.40, p <0.001) in the linear mixed model analysis. Conclusions: Liver RSO₂ was associated with different PDA statuses. Future studies exploring the potential utility of liver RSO₂ as an adjunct parameter for detecting and guiding the management of hemodynamically significant PDA in preterm infants may be warranted. Full article

This study uses a pointwise statistical approach to analyze Near-Infrared Spectroscopy (NIRS) signals in preterm infants with and without Patent Ductus Arteriosus (PDA). The analysis focuses on three signals: blood oxygenation (SpO₂), cerebral oxygenation (rSO₂-1), and renal oxygenation (rSO₂-2), across three newborn groups: without PDA (no-PDA), with hemodynamically insignificant PDA (PDA), and with hemodynamically significant PDA (hsPDA). While NIRS is widely used in medicine, its research, featuring statistical analysis, has been limited. Smoothed signals were tested using pointwise ANOVA and Tukey HSD to detect significant group differences. Results showed distinct patterns in rSO₂-1 and rSO₂-2, with the hsPDA group standing out in rSO₂-1 and the no-PDA group in rSO₂-2, demonstrating the value of this method in biomedical signal analysis. Pointwise ANOVA shows more time periods with significant differences compared to the SpO₂ signal. The time period with the most significant differences is between 2 and 6 h, with additional peaks of p-values below 0.05 occurring before 2 h. These findings demonstrate the value of FDA in improving statistical analysis of biomedical NIRS signals and support its use in future research. Full article

Background: Despite substantial advances in neonatology, the management of patent ductus arteriosus (PDA) in preterm infants continues to pose a major clinical challenge. The presence of PDA may exacerbate circulatory instability, contribute to tissue hypoxia, and significantly increase the risk of prematurity-related complications. Risk factors for patent ductus arteriosus (PDA), including its hemodynamically significant form (HsPDA), have been consistently associated with lower gestational age, low birth weight, the requirement for invasive mechanical ventilation, and lack of antenatal corticosteroid exposure. With the advent of novel diagnostic approaches, growing attention has been directed toward the genetic determinants of various neonatal conditions. Genetic variability has been extensively documented as a factor influencing drug metabolism, thereby modulating dose-dependent responses and resistance to standard pharmacological interventions. Methods: The study population comprised neonates delivered before 32 completed weeks’ gestation to assess the potential impact of polymorphisms in genes associated with the prostaglandin pathway on the response to pharmacological treatment of HsPDA. Results: Among the identified polymorphisms, one demonstrated a statistically significant association with treatment success. Additional analyses were performed to determine whether therapeutic efficacy differed according to the drug administered. Conclusions: We propose that further research, particularly studies incorporating diverse ethnic populations, may provide valuable insights into the underlying the pathophysiology of PDA and contribute to the development of more effective treatment strategies. Full article

Background: Persistency of patent ductus arteriosus is the main cardiac condition in the preterm population born before 32 completed weeks of gestation with possible short- and long-term hemodynamic disturbances leading to vast morbidity. Jaundice is present in the majority of very preterms needing phototherapy, that also may have an influence on immature hemodynamics. The objectives of this review and meta-analysis were to find relevant evidence of whether chest shielding during phototherapy does or does not have an impact on the ductus arteriosus patency and hemodynamics. Methods: we reviewed the literature and performed a meta-analysis of five randomized controlled trials regarding chest shielding effect on the ductus arteriosus closure. Results: A total of 452 infants, with a mean gestational age of 28.04 weeks and mean birth weight of 1004.8 g were included in our meta-analysis, where we found an RR of 0.6 for developing PDA during phototherapy and chest shielding (95% CI: 0.37; 0.96. prediction interval: 0.18; 1.99) while development of hemodynamically significant PDA had RR = 0.57, within 95% CI: 0.3; 1.06, and a predictive interval between: 0.11; 2.93. Conclusions: Although the estimated RR may suggest a possible moderate protective role of the chest shield regarding development of PDA during phototherapy, the wideness of the predictive intervals, that include no effect, as well as the small number of eligible trials with heterogeneity between them, make the available data insufficient to evaluate the effectiveness of chest shielding during phototherapy. For more conclusive evidence there is a need for well-designed, blinded, multicenter randomized controlled trials with standardized assessment addressing to a more compact target population, knowing the large physiological differences among preterm infants of different gestational ages. Full article

Background and Objectives: Patent ductus arteriosus (PDA) is one of the most common cardiovascular conditions affecting preterm infants, with incidence rates reaching 60% in neonates born before 28 weeks gestation. Traditional clinical assessment alone often proves inadequate for accurate diagnosis, potentially leading to both overtreatment and undertreatment. Targeted neonatal echocardiography (TnECHO) has emerged as a powerful bedside tool that enables neonatologists to perform focused cardiac evaluations, providing real-time assessment of ductal significance and systemic hemodynamics. This systematic review aimed to comprehensively evaluate the clinical utility of TnECHO in the management of PDA in preterm infants, with specific focus on its diagnostic accuracy, impact on treatment decisions, and influence on clinical outcomes. Materials and Methods: Following PRISMA guidelines, we conducted a systematic search of PubMed, Web of Science, and Scopus from inception (earliest available date of each database) through February 2025. The search strategy combined terms for “Targeted Neonatal Echocardiography” and “Patent Ductus Arteriosus.” We included observational studies and randomized controlled trials (RCTs) evaluating TnECHO in PDA management, while excluding reviews and case reports. Data extraction focused on study design, population characteristics, TnECHO protocols, and clinical outcomes. Results: From 173 initial records, 11 studies met inclusion criteria. Eight studies were rated as high-quality (NOS score ≥ 7). TnECHO implementation was associated with a 49% reduction in PDA ligation rates and decreased need for multiple treatment courses. Studies demonstrated improved diagnostic precision in assessing shunt significance and myocardial function, leading to more tailored therapeutic approaches. The establishment of dedicated TnECHO services enhanced interdisciplinary collaboration between neonatologists and cardiologists. However, limitations included operator dependence, variable institutional protocols, and occasional missed minor cardiac anomalies. Conclusions: TnECHO represents a transformative approach to PDA management in preterm infants, enabling physiology-guided decision-making that reduces unnecessary interventions while maintaining patient safety. Current evidence supports its role in improving diagnostic accuracy and optimizing treatment timing. Future research should prioritize multicenter RCTs to establish standardized protocols and evaluate long-term neurodevelopmental outcomes. The integration of TnECHO into routine neonatal practice requires investment in training programs and quality assurance measures to maximize its clinical potential. 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

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: 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