OBJECTIVE: Acetaminophen for patent ductus arteriosus (PDA) closure has gained popularity over the last decade; however, therapeutic drug monitoring for this indication remains uncertain. The exact timing and goal trough serum acetaminophen concentration ranges are not well defined. The purpose of our study is to evaluate the impact of therapeutic drug monitoring on both PDA closure rates and identify real-world risk of hepatotoxicity.
METHODS: Retrospective single-center chart review of neonates admitted to the neonatal intensive care unit (NICU) between April 2016 and August 2022 with at least 1 serum acetaminophen concentration to monitor for PDA closure. Acetaminophen was initiated at 15 mg/kg administered intravenously every 6 hours and a trough serum concentration was obtained prior to the sixth or seventh dose. PDA closure was confirmed radiographically with corresponding provider documentation. Associations of efficacy to closure were -analyzed using descriptive statistics.
RESULTS: Thirty-eight neonates were included in the analysis, of which 18 (47%) achieved PDA closure. First serum acetaminophen trough concentration was obtained before the seventh dose [IQR, 6-8] and ranged from undetectable (< 5 mg/L) to 30.8 mg/L. Subgroup analysis of first concentrations revealed therapeutic trough, defined as 10 to 20 mg/L, did not correlate to PDA closure (no closure median concentration = 14.7 [IQR, 13-15.6] vs closure median concentration = 15.4 [IQR, 11.4-18.5], p = 0.42), or duration of treatment. No neonate experienced acetaminophen-associated toxicity.
CONCLUSIONS: PDA closure did not correlate to serum acetaminophen trough concentration. The regimen of 15 mg/kg every 6 hours appears safe as no neonate experienced acetaminophen toxicity or discontinued treatment early.

UNASSIGNED: Patent ductus arteriosus (PDA) stent placement and systemic-pulmonary surgical shunt procedure can both be performed as palliation for infants with duct-dependent pulmonary circulation. The aim of this meta-analysis and literature review was to compare outcomes and study populations between the 2 methods as well as review the technical considerations and complications of PDA stenting.
UNASSIGNED: A systematic search was conducted using the PubMed database and meta-analysis was performed. Risk ratio and mean difference were used to compare the reported outcomes of studies across patients receiving PDA stent and surgical shunt.
UNASSIGNED: In total, 1094 patients from 8 comparative observational studies were included. The PDA stent group had a lower mortality rate and a shorter hospital length of stay than the systemic-pulmonary surgical shunt group, although at the expense of increased reintervention rates. There were higher proportions of patients with single-ventricle physiology and single-source pulmonary blood flow in the surgical shunt group.
UNASSIGNED: PDA stenting appears to be a noninferior or possibly superior method of palliation for duct-dependent pulmonary circulation compared with systemic-pulmonary surgical shunt, recognizing, however, that patients receiving surgical shunt more often had single-ventricle physiology or single-source pulmonary blood flow in this meta-analysis.

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

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

[This corrects the article DOI: 10.1016/j.jscai.2022.100392.][This corrects the article DOI: 10.1016/j.jscai.2023.101051.].

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

UNASSIGNED: We sought to investigate the impact of stenting on native patent ductus arteriosus (PDA) length, curvature, and pulsatile deformations in patients with ductal-dependent pulmonary circulations.
UNASSIGNED: Patients with PDA stents who received contrast-enhanced 3-dimensional computed tomography with a view of the PDA, thoracic aorta, and pulmonary arteries were retrospectively included in this study. Geometric models of the prestented and poststented PDA were constructed from the computed tomography images, and PDA arclength, curvature, and pulsatile deformations were quantified.
UNASSIGNED: A total of 12 patients with cyanotic congenital heart disease were included, 10 of whom received 1 stent in the PDA and 2 received multiple overlapping stents. From prestenting to poststenting, the PDA shortened by 26 ± 18% (P = .004) and decreased in mean and peak curvature by 60 ± 21% and 68 ± 15%, respectively (both P < .001). Pulsatile deformations varied highly for the native PDA, stented PDA, and stents themselves.
UNASSIGNED: The shortening and straightening of the PDA after stenting are significant and substantial, and their quantitative characterization will enable interventionalists to select stent lengths that span the entire PDA without encroaching on the aortic or pulmonary artery, which could cause hemodynamic interference, stent kink, and fatigue. Pulsatile PDA deformations can be used to design and evaluate devices tailored to congenital heart disease in neonates.

A 33-year-old patient presented with a chief complaint of patent ductus arteriosus (PDA) persisting for over 30 years. Physical examination revealed bilateral facial angiofibromas, multiple nail fibromas, intraoral fibromas, and a \'shagreen patch\' on the left lumbar region. Genetic testing was performed using a peripheral venous blood sample, which confirmed the diagnosis of Tuberous Sclerosis Type 2 (TSC2). Subsequently, the patient underwent cardiac color Doppler ultrasound and chest computed tomography angiography, which confirmed the presence of PDA. Tuberous sclerosis complex (TSC) is associated with cardiovascular diseases. The initial clinical manifestation of TSC is usually cardiac rhabdomyoma in children, and it is rarely reported in adults with PDA. In this case, the patient was diagnosed with PDA when he was young, and the genetic test showed heterozygous variation of TSC2 gene. The purpose of this article is to explore the correlation between TSC and PDA at the gene level through literature review.

UNASSIGNED: In cases of atrial septal defect with pulmonary arterial hypertension (PAH), a treat-and-repair strategy that adopts pulmonary vasodilator therapy and subsequent defect closure is postulated to be effective. However, this strategy has not been applied to the large patent ductus arteriosus (PDA) with PAH.
UNASSIGNED: A 10-year-old girl with trisomy 21 was referred to our hospital for the treatment of a large PDA with PAH. Cardiac catheterization and angiography revealed a type C tubular PDA with a minimal diameter of 8.1 mm, an increase in mean pulmonary artery pressure (mPAP) of 60 mmHg, a ratio of pulmonary to systemic blood flow (Qp/Qs) of 2.7, and pulmonary artery resistance (Rp) of 7.1 U/m2. Because she was categorized in the grey zone for operability, we adopted a hybrid treat-and-repair strategy in which palliative surgical duct banding was performed before pulmonary vasodilator therapy to prevent excessive pulmonary blood flow and was followed by transcatheter closure of the PDA. Postoperatively, we confirmed the flow-restricted duct with a minimal diameter of 3.3 mm, decreased Qp/Qs 1.38, high mPAP 40 mmHg, and Rp 7.3 U/m2. Six months after treatment with macitentan and tadalafil, we confirmed a decrease in Rp 4.1 U/m2 as well as low Qp/Qs 1.12, which was low enough for the duct occlusion. The transcatheter occlusion of the surgically created type A conical duct was easily and safely performed. In the mid-term follow-up, favourable haemodynamics and improved exercise were confirmed.
UNASSIGNED: This is the first proof-of-concept case report to show the successful hybrid treat-and-repair strategy for large PDA, which warrants further investigation.

UNASSIGNED: Excessive fluid intake is a predictor of the development of patent ductus arteriosus (PDA) in preterm infants. Previous studies have examined the relationship between fluid intake and outcomes following ibuprofen for PDA. However, there is a lack of data to determine whether fluid balance has an effect on ibuprofen treatment for PDA. Therefore, this study sought to determine the relationship between fluid balance and outcomes following treatment with ibuprofen for PDA.
UNASSIGNED: We conducted a retrospective study of 110 infants admitted to the Children\'s Hospital of Chongqing Medical University between January 2017 and April 2022, who were treated with ibuprofen for hemodynamically significant PDA (hsPDA). We calculated the average fluid balance before and during the two courses of ibuprofen treatment and whether they were significantly associated with outcomes in hsPDA patients.
UNASSIGNED: In the first course of ibuprofen treatment (FIT), responders had lower fluid balance before FIT compared to non-responders [median 31.82 (18.01, 39.66) vs 34.68 (25.31, 43.56) mL/kg/day; p = 0.049], while the fluid balance during FIT [median 40.61 (33.18, 63.06) vs 42.65 (30.02, 57.96) mL/kg/day; p = 0.703] did not differ between responders and non-responders. Fluid balance before the second course of ibuprofen treatment (SIT) (mean 41.58 ± 14.26 vs 35.74 ± 10.99 mL/kg/day; p = 0.322) and during SIT (mean 39.21 ± 12.65 vs 37.00 ± 21.38 mL/kg/day; p = 0.813) was not found to have a significant association with SIT outcome. Multivariate logistic regression analysis showed fluid balance before FIT was a predictor for FIT success [Odds ratio (OR): 0.967; 95% confidence interval (CI): 0.935-0.999; p = 0.042]. Fluid balance within the first week of life had a greater association with the FIT outcome (OR: 0.967, 95% CI: 0.939-0.996, p = 0.027). Gestational diabetes mellitus and higher Apgar scores decreased the possibility of PDA closure after FIT.
UNASSIGNED: Lower fluid balance before FIT, especially within the first week of life appeared to be a predictor for closure of hsPDA after FIT in preterm infants.