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International Journal of Molecular... Mar 2021The ductus arteriosus (DA) is a physiologic vessel crucial for fetal circulation. As a major regulating factor, the prostaglandin pathway has long been the target for DA... (Review)
Review
The ductus arteriosus (DA) is a physiologic vessel crucial for fetal circulation. As a major regulating factor, the prostaglandin pathway has long been the target for DA patency maintenance or closure. However, the adverse effect of prostaglandins and their inhibitors has been a major unsolved clinical problem. Furthermore, a significant portion of patients with patent DA fail to respond to cyclooxygenase inhibitors that target the prostaglandin pathway. These unresponsive medical patients ultimately require surgical intervention and highlight the importance of exploring pathways independent from this well-recognized prostaglandin pathway. The clinical limitations of prostaglandin-targeting therapeutics prompted us to investigate molecules beyond the prostaglandin pathway. Thus, this article introduces molecules independent from the prostaglandin pathway based on their correlating mechanisms contributing to vascular remodeling. These molecules may serve as potential targets for future DA patency clinical management.
Topics: Animals; Biomarkers; Cell Movement; Cell Proliferation; Ductus Arteriosus; Ductus Arteriosus, Patent; Extracellular Matrix; Humans; Myocytes, Smooth Muscle; Prostaglandins; Signal Transduction; Vascular Remodeling
PubMed: 33810164
DOI: 10.3390/ijms22063238 -
Pediatric Cardiology Mar 2022Symptomatic patent ductus arteriosus (sPDA) is common among preterm infants, and can lead to several complications. This is particularly true for extremely preterm...
Symptomatic patent ductus arteriosus (sPDA) is common among preterm infants, and can lead to several complications. This is particularly true for extremely preterm infants, as closure of the ductus arteriosus using cyclooxygenase inhibitors is often difficult. A recent study using a preterm sheep model showed that intimal thickening-required for anatomical closure of the ductus arteriosus-is less developed in twins than in singletons. Therefore, this study primarily aimed to prove that the ductus arteriosus of extremely preterm twins is more resistant to cyclooxygenase inhibitors than those of extremely preterm singletons. Its secondary aim was to assess whether the resistance against cyclooxygenase inhibitors differed according to chorionicity. In this retrospective case-control study, medical records of 162 extremely preterm infants (gestational age < 28 weeks) were reviewed, and the treatment course of sPDA was subsequently compared between singletons (n = 131) and twins (n = 31). The median indomethacin doses for sPDA and the necessity for surgical ligation were significantly higher in twins than in singletons (5 vs 2 [p < 0.001] and 42% vs 21% [p = 0.018], respectively). No significant differences in sPDA treatment, including the number of indomethacin doses and the necessity for surgical ligation, were observed between monochorionic diamniotic and dichorionic diamniotic twins. This study confirms that the ductus arteriosus of extremely preterm twins is more resistant to cyclooxygenase inhibitors than those of singletons. However, there was no significant difference in sPDA treatment by chorionicity.
Topics: Animals; Case-Control Studies; Cyclooxygenase Inhibitors; Ductus Arteriosus; Ductus Arteriosus, Patent; Humans; Infant, Extremely Premature; Infant, Newborn; Retrospective Studies; Sheep
PubMed: 34716772
DOI: 10.1007/s00246-021-02765-0 -
Pediatrics Apr 2017To examine yearly trends of patent ductus arteriosus (PDA) diagnosis and treatment in very low birth weight infants.
OBJECTIVE
To examine yearly trends of patent ductus arteriosus (PDA) diagnosis and treatment in very low birth weight infants.
METHODS
In this retrospective cohort study of very low birth weight infants (<1500 g) between 2008 and 2014 across 134 California hospitals, we evaluated PDA diagnosis and treatment by year of birth. Infants were either inborn or transferred in within 2 days after delivery and had no congenital abnormalities. Intervention levels for treatment administered to achieve ductal closure were categorized as none, pharmacologic (indomethacin or ibuprofen), both pharmacologic intervention and surgical ligation, or ligation only. Multivariable logistic regression was used to assess risk factors for PDA diagnosis and treatment.
RESULTS
PDA was diagnosed in 42.8% (12 002/28 025) of infants, with a decrease in incidence from 49.2% of 4205 infants born in 2008 to 38.5% of 4001 infants born in 2014. Pharmacologic and/or surgical treatment was given to 30.5% of patients. Between 2008 and 2014, the annual rate of infants who received pharmacologic intervention (30.5% vs 15.7%) or both pharmacologic intervention and surgical ligation (6.9% vs 2.9%) decreased whereas infants who were not treated (60.5% vs 78.3%) or received primary ligation (2.2% vs 3.0%) increased.
CONCLUSIONS
There is an increasing trend toward not treating patients diagnosed with PDA compared with more intensive treatments: pharmacologic intervention or both pharmacologic intervention and surgical ligation. Possible directions for future study include the impact of these trends on hospital-based and long-term outcomes.
Topics: California; Cohort Studies; Cyclooxygenase Inhibitors; Ductus Arteriosus, Patent; Female; Humans; Ibuprofen; Indomethacin; Infant, Newborn; Infant, Very Low Birth Weight; Ligation; Logistic Models; Male; Retrospective Studies
PubMed: 28562302
DOI: 10.1542/peds.2016-2390 -
Arquivos Brasileiros de Cardiologia Sep 2022The presence of patent ductus arteriosus can be as high as 50% in preterm babies. Hemodynamically significant patent ductus arteriosus is a common cause of delayed...
BACKGROUND
The presence of patent ductus arteriosus can be as high as 50% in preterm babies. Hemodynamically significant patent ductus arteriosus is a common cause of delayed weaning of respiratory support and an important risk factor of necrotizing enterocolitis, intraventricular hemorrhage, and bronchopulmonary dysplasia in this population.
OBJECTIVE
The aim of this study is to describe an initial experience of percutaneous closure of the ductus arteriosus in preterm infants weighing less than 2 kg.
METHODS
This was a prospective study, comprised of 14 consecutive patients submitted to percutaneous closure of ductus arteriosus between March 2020 and February 2021 in 6 institutions in Brazil.
RESULTS
Mean gestational age was 28.45±3.14 weeks, mean age at the procedure was 38.85±17.35 days and mean weight was 1.41 ±0.41 kg; 79% of the patients were under mechanical ventilation, and 79% had been submitted, on average, to a 1.5 cycle of non-steroidal anti-inflammatory drugs. Most patients were weaned off of mechanical ventilation in a mean of 12.6 ±7.24 days after the procedure. Success rate was 100%. No procedure-related mortality was observed.
CONCLUSION
This study concluded that percutaneous closure of ductus arteriosus in premature babies below 2 kg has satisfactory results and a low complication rate in this study sample.
Topics: Brazil; Ductus Arteriosus; Ductus Arteriosus, Patent; Humans; Ibuprofen; Infant; Infant, Newborn; Infant, Premature; Prospective Studies
PubMed: 36074378
DOI: 10.36660/abc.20210818 -
Italian Journal of Pediatrics Nov 2023Ductal patency of preterm infants is potentially associated with long term morbidities related to either pulmonary overflow or systemic steal. When an interventional... (Review)
Review
Ductal patency of preterm infants is potentially associated with long term morbidities related to either pulmonary overflow or systemic steal. When an interventional closure is needed, it can be achieved with either surgical ligation or a catheter-based approach.Transcatheter PDA closure is among the safest of interventional cardiac procedures and it is the first choice for ductal closure in adults, children, and infants weighing more than 6 kg. In preterm and very low birth weight infants, it is increasingly becoming a valid and safe alternative to ligation, especially for the high success rate and the minor invasiveness and side effects. Nevertheless, being it performed at increasingly lower weights and gestational ages, hemodynamic complications are possible events to be foreseen.Procedural steps, timing, results, possible complications and available monitoring systems, as well as future outlooks are here discussed.
Topics: Infant; Child; Infant, Newborn; Humans; Infant, Premature; Ductus Arteriosus, Patent; Hemodynamic Monitoring; Feasibility Studies; Gestational Age; Treatment Outcome
PubMed: 37932790
DOI: 10.1186/s13052-023-01552-2 -
Pediatrics and Neonatology Jan 2021Patent Ductus Arteriosus (PDA) is a common condition, affecting nearly half of infants born before 28 weeks' of gestation, and it has been associated with poor growth.... (Comparative Study)
Comparative Study
BACKGROUND
Patent Ductus Arteriosus (PDA) is a common condition, affecting nearly half of infants born before 28 weeks' of gestation, and it has been associated with poor growth. It is not known if different treatment modalities are associated with more profound growth impairment. Our aim was to compare differences in weight gain at 36 weeks' corrected gestational age (CGA) in premature infants that received medical, surgical or conservative management for PDA.
METHODS
We retrospectively reviewed notes of 208 infants born under 30 weeks' gestation with a diagnosis of PDA. Gestational age (GA) at birth, birth weight z-score, CGA and weight z-score at 36 weeks' CGA were collected. In our cohort, surgical closure was performed in infants who remained symptomatic after medical or conservative management.
RESULTS
Ninety-four infants had medical, 56 surgical and 58 conservative management. Surgically managed infants had a lower median (IQR) GA [24.4 (24.0-26.1) weeks'] than medically [25.4 (24.6-26.5) weeks'] or conservatively managed [26.4 (25.4-28.1) weeks', p < 0.001] infants. There was no difference in birth weight z-scores across the groups. Surgically managed infants demonstrated a greater decrease in weight z-score [-2.24 (-2.89 to -1.53)] compared to medically [-1.79 (-2.45 to -1.35)] and conservatively [-1.57 (-1.99 to -1.28), p < 0.001] managed infants between birth and 36 weeks' CGA. After adjusting for GA at birth, definitive treatment modality was significantly related to change in weight z-score from birth to 36 weeks' CGA (adjusted p = 0.022).
CONCLUSION
Premature infants with PDA who were managed surgically had a greater degree of faltering growth compared to those who were treated medically or conservatively.
Topics: Cardiac Surgical Procedures; Conservative Treatment; Ductus Arteriosus, Patent; Female; Gestational Age; Growth Disorders; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Postoperative Complications; Retrospective Studies; Weight Gain
PubMed: 32830076
DOI: 10.1016/j.pedneo.2020.08.005 -
Current Problems in Cardiology Feb 2024Adult patent ductus arteriosus (PDA) repair surgery often involves hypothermic cardiopulmonary bypass (CPB) and is associated with postoperative neurological... (Review)
Review
Adult patent ductus arteriosus (PDA) repair surgery often involves hypothermic cardiopulmonary bypass (CPB) and is associated with postoperative neurological complications. Our study evaluates brain function during PDA surgery using regional cerebral oxygen saturation (rSO) and bispectral index (BIS) monitoring to mitigate these complications. Patients were categorized into moderate (26-31 ℃) and mild (32-35 ℃) hypothermia groups. Findings indicate a positive correlation between PDA diameter and pulmonary artery systolic blood pressure, and a strong correlation between delirium and average rSO2-AUC. The mild hypothermia group had longer extubation and hospitalization times. During CPB, rSO levels fluctuated significantly, and EEG analysis revealed changes in brain wave patterns. One case of nerve injury in the mild hypothermia group showed incomplete recovery after a year. Our results advocate for moderate hypothermia during CPB in adult PDA repair, suggesting that combined rSO and BIS monitoring can reduce neurological complications post-surgery.
Topics: Adult; Humans; Brain; Cardiopulmonary Bypass; Ductus Arteriosus, Patent; Hypothermia, Induced
PubMed: 38142948
DOI: 10.1016/j.cpcardiol.2023.102334 -
BMC Pediatrics Jun 2021This study aimed to provide UK data describing the incidence of patent ductus arteriosus (PDA) surgery in the neonatal population, including: pre-ligation management,...
BACKGROUND
This study aimed to provide UK data describing the incidence of patent ductus arteriosus (PDA) surgery in the neonatal population, including: pre-ligation management, and outcomes until discharge. We used British Paediatric Surveillance Unit (BPSU) methodology; collecting data via questionnaires for preterm neonates undergoing PDA ligation (PDAL) between 1st Sept 2012 - 30th Sept 2013. Infants born less than 37 weeks gestation, who underwent PDAL prior to discharge home, with no other structural cardiac abnormality, were included. Information collected included: patient demographics, pre and post-operative clinical characteristics, pre-operative medical management, post-operative complications and outcome.
RESULTS
Over the study, 263 infants underwent PDAL an incidence of 3.07 per 10,000 live births. 88% were born extremely preterm (< 28 weeks) and 60% were male. The commonest reasons for ligation were inability to wean respiratory support (83.7%) and haemodynamically significant PDA (87.8%). Pre-operatively 65.7% received medical therapy. Surgery was performed at a median age of 33 days (range 9-260, IQR 24-48); the corrected age was less than 31 + 6 week in 50.6% babies at PDAL. Most, (90%), of procedures were open ligation; only 9 (3.4%) were catheter occlusions (PDACO). 20.5% of patients had post-operative complications. The 30-day mortality was 3%, with 93.5% surviving to hospital discharge.
CONCLUSION
This study showed there was little consensus over medical and surgical management of the PDA or timing of surgery.
Topics: Child; Ductus Arteriosus, Patent; Gestational Age; Humans; Infant; Infant, Newborn; Ligation; Male; Patient Discharge; Retrospective Studies
PubMed: 34107888
DOI: 10.1186/s12887-021-02734-9 -
Early Human Development Mar 2024This study aimed to determine long-term neurodevelopmental outcome and cerebral oxygenation in extremely preterm infants, comparing those with a hemodynamic significant...
OBJECTIVE
This study aimed to determine long-term neurodevelopmental outcome and cerebral oxygenation in extremely preterm infants, comparing those with a hemodynamic significant patent ductus arteriosus (hsPDA) to those without.
STUDY DESIGN
We included infants born before 28 weeks of gestation from 2008 to 2010 with routine echocardiography. Prior to echocardiography, regional cerebral oxygen saturation was measured. At 5 years of age, we evaluated neurodevelopmental outcomes using the Movement Assessment Battery for Children 2nd Dutch edition for motor skills and the Wechsler Preschool and Primary Scale of Intelligence 3rd Dutch edition for cognition.
RESULTS
A total of 66 infants (gestational age 26.6 ± 0.9 weeks, birth weight 912 ± 176 g) were included, 34 infants with a hsPDA (including treatment). The group infants with hsPDA showed lower pre-closure cerebral saturation levels (58.2 % ±7.8 % versus 62.8 % ±7.0 %; p = 0.01). At 5 years, impaired motor outcome occurred more often in infants with hsPDA (17 (53 %) vs. 7 (23 %); p = 0.01). In multivariate analysis existence of hsPDA remained unfavourably related to the motor subdomain "aiming and catching". There were no potential effects of hsPDA on cognitive performance at 5 years of age.
CONCLUSION
Treatment-receiving infants with hsPDA appear to exhibit motor deficits, specifically in "aiming and catching", by the age 5. Persistent ductal patency could be a contributing factor.
Topics: Infant; Child, Preschool; Child; Infant, Newborn; Humans; Ductus Arteriosus, Patent; Birth Weight; Gestational Age; Infant, Extremely Premature; Hemodynamics
PubMed: 38330542
DOI: 10.1016/j.earlhumdev.2024.105953 -
Early Human Development Apr 2024Patent ductus arteriosus (PDA) in premature infants is associated with adverse clinical outcomes. Mode and timing of treatment are still controversial. Data are limited...
Active versus restrictive ligation strategy for patent ductus arteriosus - A retrospective two-center study of extremely preterm infants born between 22 + 0 and 25 + 6 weeks of gestational age.
BACKGROUND
Patent ductus arteriosus (PDA) in premature infants is associated with adverse clinical outcomes. Mode and timing of treatment are still controversial. Data are limited in the most extremely premature infants <26 weeks of gestational age (GA), where clinical problems are most significant and patients are most vulnerable.
AIMS
To investigate whether different approaches to surgical closure of PDA in two large Swedish centers has an impact on clinical outcomes including mortality in extremely preterm infants born <26 weeks GA.
STUDY DESIGN
Retrospective, two-center, cohort study.
SUBJECTS
Infants born at 22-25 weeks GA between 2010 and 2016 at Uppsala University Children's Hospital (UUCH; n = 228) and Queen Silvia Children's Hospital Gothenburg (QSCHG; n = 220).
MAIN OUTCOME MEASURES
Survival, bronchopulmonary dysplasia (BPD), and retinopathy of prematurity (ROP).
RESULTS
Surgical closure of PDA was more common and performed earlier at QSCHG (50 % vs 16 %; median age 11 vs 44 days; p < 0.01). Survival was similar in both centres. There was a higher incidence of severe BPD and longer duration of mechanical ventilation at UUCH (p < 0.01). There was a higher incidence of ROP, IVH and sepsis at QSCH (p < 0.05, p < 0.01 and p < 0.01). A sub-group analysis matching all surgically treated infants at QSCHG with infants at UUCH with the same GA showed similar results as the total cohort.
CONCLUSION
Earlier and higher rate of surgical PDA closure in this cohort of extremely preterms born <26 weeks GA did not impact mortality but was associated with lower rates of severe BPD and higher rates of severe ROP.
Topics: Infant; Female; Child; Infant, Newborn; Humans; Infant, Extremely Premature; Ductus Arteriosus, Patent; Gestational Age; Retrospective Studies; Cohort Studies; Bronchopulmonary Dysplasia; Retinopathy of Prematurity
PubMed: 38452632
DOI: 10.1016/j.earlhumdev.2024.105976