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Paediatric Drugs Mar 2022The hemodynamic impact of persistent patent ductus arteriosus (PDA) is associated with neonatal morbidities and mortality in preterm newborns. While there has been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The hemodynamic impact of persistent patent ductus arteriosus (PDA) is associated with neonatal morbidities and mortality in preterm newborns. While there has been considerable debate about optimal management of PDA and its impact on clinical outcomes, there is widespread variation in practice, such as using different pharmacotherapies to achieve closure of hemodynamically significant PDA during the first week of life in very low birth weight infants.
AIMS
The objective was to estimate the efficacy of acetaminophen, ibuprofen, and indomethacin with regard to ductal closure and to compare the costs of these three commonly used medications to treat PDA in preterm infants.
METHODS
PubMed, Embase, and Cochrane Registry were searched for trials from the years 2010-2020. We identified 17 randomized clinical trials (RCTs) and 14 case series that enrolled preterm infants < 37 weeks gestational age for inclusion. Pooled estimates of closure rates for acetaminophen (n = 630), ibuprofen (n = 694), and indomethacin (n = 312) were analyzed using the weighted proportion ratio using a Mantel‑Haenszel random effects model. The chi-squared test of proportions was used to determine significance between groups. We accessed cost estimates of pharmacotherapy from the Lexi-Comp average wholesale price database and utilized a decision tree model to appraise cost benefits for the outcome measure of successful PDA closure.
RESULTS
The pooled proportional point estimates of closure rates from RCTs for acetaminophen, ibuprofen, and indomethacin were 70.1% (95% confidence interval [CI] 60-80), 63.4% (95% CI 52.8-74.1), and 71.5% (95% CI 62.3-80.7), respectively. There was no significant statistical difference in closure rates when RCTs and uncontrolled case series were combined. Pairwise comparisons showed both acetaminophen and indomethacin were each more effective in closing PDA than ibuprofen (acetaminophen vs indomethacin: p = 0.01; ibuprofen vs indomethacin: p = 0.02; acetaminophen vs indomethacin: p = 0.93). Comparing costs for successful closure of PDA, at the average wholesale price of different medications, suggested that treatment with acetaminophen costs significantly less, with a mean of $1487 (95% CI 1300-1737), compared to ibuprofen, with a mean of $2585 (95% CI 2214-3104), and indomethacin, with a mean of $2661 (95% CI 2358-3052), per course of treatment.
CONCLUSIONS
Our meta-analysis suggests acetaminophen is non-inferior to both indomethacin and ibuprofen, and costs relatively less for successful PDA constriction in premature infants. Further clinical trials are warranted to compare acetaminophen's safety, along with short- and long-term effects, to help resolve the clinical conundrum of the necessity of early treatment in the management of PDA, and the optimal pharmacological course, if indicated.
Topics: Ductus Arteriosus, Patent; Humans; Ibuprofen; Indomethacin; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight
PubMed: 35229248
DOI: 10.1007/s40272-022-00495-1 -
Pediatric Research Jun 2020
Topics: Acetaminophen; Animals; Animals, Newborn; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Rats
PubMed: 32218515
DOI: 10.1038/s41390-020-0864-z -
Clinical Pharmacology and Therapeutics Oct 2021In preterm infants, a high risk of hemodynamically significant patent ductus arteriosus (PDA) exists and its persistence is associated with an increased risk of severe...
In preterm infants, a high risk of hemodynamically significant patent ductus arteriosus (PDA) exists and its persistence is associated with an increased risk of severe morbidity. Current pharmacological options include ibuprofen or indomethacin. However, treatment by indomethacin or ibuprofen of a large PDA was shown to reduce early pulmonary hemorrhage and later medical treatment but had no effect on neonatal death or morbidity. Early prophylactic treatment of ductus arteriosus by paracetamol seems to be an attractive opportunity to reduce life-threatening morbidity. However, there are currently no data regarding the pharmacokinetics (PK) and pharmacodynamics of paracetamol in preterm neonates in this potential new indication. In this study, we aimed to develop a population PK model for paracetamol and investigate the relationship between paracetamol exposure levels and time to contraction of the ductus. Data were modeled using Monolix software. A one-compartment model adequately described the paracetamol concentration-time course. A Weibull model adequately described the time to contraction of the ductus. Our results suggest that the dosage used in this study (i.e., first day 42.5 mg/kg, then 30 mg/kg/day) allows for reaching the maximum inhibition response from paracetamol regarding the time to close the ductus. However, this study pointed out a lower effect of paracetamol on extremely preterm neonates (below 27 weeks). Therefore, a dose-finding study focusing specifically on extremely preterm neonates with treatment efficacy and toxicity is strongly needed.
Topics: Acetaminophen; Administration, Intravenous; Analgesics, Non-Narcotic; Ductus Arteriosus, Patent; Echocardiography; Female; Humans; Infant, Extremely Premature; Infant, Newborn; Infant, Premature; Male; Time Factors
PubMed: 34314519
DOI: 10.1002/cpt.2380 -
International Journal of Cardiology Jul 2020Patent ductus arteriosus (PDA) is common in preterm infants and can contribute to morbidity and mortality. We aimed to compare results and outcome of transcatheter...
AIMS
Patent ductus arteriosus (PDA) is common in preterm infants and can contribute to morbidity and mortality. We aimed to compare results and outcome of transcatheter closure using the Amplatzer Piccolo Occluder versus surgical closure in 2 matched groups of preterm infants weighing <3000 g.
METHODS AND RESULTS
A total of 147 babies from three tertiary centres were retrospectively analysed. Sixty-four babies undergoing catheter closure were compared with 83 matched surgical cases. Patent ductus arteriosus closure was successful in all cases. During neonatal unit course, mortality was 6.3% (n = 4) after catheterization and 12% (n = 10) after surgery (p = 0.24). Median duration of mechanical ventilation was shorter after catheterisation than after surgery (3 vs 5 days, p = 0.035). Before 4 weeks of age the difference between transcatheter and surgical closure for mechanical ventilation was even more pronounced (3 vs 9 days, p = 0.022). Additionally, when catheterisation was performed before 4 weeks, babies were discharged home earlier as compared to those who underwent closure later in life (39 vs. 42 weeks, p = 0.021). Such difference was not found in the surgical group.
CONCLUSIONS
Transcatheter closure of patent ductus arteriosus is safe, effective and is associated with shorter mechanical ventilation than after surgery. Hospital stay might be shorter when performed earlier in life.
Topics: Cardiac Catheterization; Ductus Arteriosus, Patent; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Retrospective Studies; Treatment Outcome
PubMed: 32253052
DOI: 10.1016/j.ijcard.2020.03.040 -
Seminars in Perinatology Jun 2018Risks associated with drug therapy and surgical ligation have led health care providers to consider alternative strategies for patent ductus arteriosus (PDA) closure.... (Review)
Review
Risks associated with drug therapy and surgical ligation have led health care providers to consider alternative strategies for patent ductus arteriosus (PDA) closure. Catheter-based PDA closure is the procedure of choice for ductal closure in adults, children, and infants ≥6kg. Given evidence among older counterparts, interest in catheter-based closure of the PDA in lower weight (<6kg) infants is growing. Among these smaller infants, the goals of this review are to: (1) provide an overview of the procedure; (2) review the types of PDA closure devices; (3) review the technical success (feasibility); (4) review the risks (safety profile); (5) discuss the quality of evidence on procedural efficacy; (6) consider areas for future research. The review provided herein suggests that catheter-based PDA closure is technically feasible, but the lack of comparative trials precludes determination of the optimal strategy for ductal closure in this subgroup of infants.
Topics: Cardiac Catheterization; Ductus Arteriosus, Patent; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Patient Selection; Risk Assessment; Treatment Outcome
PubMed: 29909074
DOI: 10.1053/j.semperi.2018.05.009 -
Journal of Neonatal-perinatal Medicine 2023There is no consensus on managing pregnancy when the fetus is diagnosed with idiopathic premature constriction or closure of the ductus arteriosus (PCDA). Knowing...
BACKGROUND
There is no consensus on managing pregnancy when the fetus is diagnosed with idiopathic premature constriction or closure of the ductus arteriosus (PCDA). Knowing whether the ductus reopens is valuable information for managing idiopathic PCDA. We conducted a case-series study to investigate the natural perinatal course of idiopathic PCDA and examined factors associated with ductal reopening.
METHODS
We retrospectively collected information about the perinatal course and echocardiographic findings at our institution, which, on principle, does not determine delivery timing based on fetal echocardiographic results. We also examined perinatal factors related to the reopening of the ductus arteriosus.
RESULTS
Thirteen cases of idiopathic PCDA were included in the analysis. The ductus reopened in 38% of cases. Among cases diagnosed in < 37 weeks of gestation, 71% reopened, which was confirmed seven days after diagnosis (interquartile range 4-7). Diagnosis earlier in gestation was associated with ductal reopening (p = 0.006). Two cases (15%) developed persistent pulmonary hypertension. No fetal hydrops or death occurred.
CONCLUSIONS
The ductus is likely to reopen when prenatally diagnosed before 37 weeks gestation. There were no complications due to our pregnancy management policy. In idiopathic PCDA, especially if the prenatal diagnosis is made before 37 weeks of gestational age, continuing the pregnancy with careful monitoring of the fetus's well-being is recommended.
Topics: Pregnancy; Female; Humans; Ductus Arteriosus; Retrospective Studies; Constriction; Ductus Arteriosus, Patent; Prenatal Diagnosis; Premature Birth
PubMed: 36872790
DOI: 10.3233/NPM-221013 -
Clinical Obstetrics and Gynecology Dec 2022Increasing hospital and labor & delivery (L&D) closures have led to declining access to hospital obstetric care in rural areas across the country. These closures...
Increasing hospital and labor & delivery (L&D) closures have led to declining access to hospital obstetric care in rural areas across the country. These closures increase the burden on women and families living in rural communities, who often must drive long distances for prenatal visits and delivery. The lack of maternal health care in rural America can also result in several adverse maternal and infant outcomes including premature birth, low birth weight, out of hospital births, maternal and infant morbidity and mortality, and increased risk of postpartum depression. The reasons for these closures are multifactorial, and include, workforce shortages, financial viability, low volume of patients, concerns over maintaining the knowledge base and skill sets of the obstetrical health care team required to provide high quality and safe care, as well as medical-legal concerns. The problems of providing and accessing quality maternal and obstetrical care in rural America have not happened overnight, Likewise, the solutions to these problems will also not occur overnight and must also address the multifactorial nature of the problem. However, there are several opportunities to improve access to maternal health care in rural communities. Programs, policies, and funding need to be designed and provided to make these opportunities a reality.
Topics: Pregnancy; Infant; Humans; Female; Rural Population; Maternal Health; Maternal Health Services; Prenatal Care; Pregnancy Complications; Maternal Mortality
PubMed: 36162090
DOI: 10.1097/GRF.0000000000000754 -
Frontiers in Pediatrics 2020The patent ductus arteriosus (PDA) is the most commonly found cardiac condition in neonates. While there have been several studies and thousands of publications on the... (Review)
Review
The patent ductus arteriosus (PDA) is the most commonly found cardiac condition in neonates. While there have been several studies and thousands of publications on the topic, the decision to treat the PDA is still strongly debated among cardiologists, surgeons, and neonatologists. This is in part due to the shortage of long-term benefits with the interventions studied. Practice variations still exist within sub-specialties and centers. This article briefly summarizes the history, embryology and histology of the PDA. It also succinctly discusses the hemodynamic significance of a PDA which builds the framework to review all the available literature on PDA closure in premature infants, though not a paradigm shift just yet; it introduces transcatheter PDA closure (TCPC) as a possible armament to the clinician for this age-old problem.
PubMed: 33643964
DOI: 10.3389/fped.2020.590578 -
Cardiovascular Journal of AfricaThis is a report on percutaneous closure of patent ductus arteriosus (PDA) using Amplatzer Duct Occluder type two additional sizes (ADO II AS) in patients under 6 kg.
BACKGROUND
This is a report on percutaneous closure of patent ductus arteriosus (PDA) using Amplatzer Duct Occluder type two additional sizes (ADO II AS) in patients under 6 kg.
METHODS
Prospective data were collected and a review of Patients' records was conducted. Demographics, and angiographic and clinical outcomes are reported in this article.
RESULTS
During the period June 2011 to June 2017, of the 92 patients who underwent closure of the PDA using the ADO II AS device, 59 were under 6 kg. The median weight of the cohort at closure was 3.6 kg (range: 900 g - 5.8 kg). The median ductal diameter was 1.9 mm (range: 1.0-3.4 mm). Three embolisations in the cohort were all retrieved percutaneously. Two PDAs were closed percutaneously and one surgically. Four premature infants required blood transfusions. The closure rate was 96.6% before discharge.
CONCLUSIONS
PDA closure using ADO II AS in small infants is feasible, effective and has few complications.
Topics: Age Factors; Birth Weight; Cardiac Catheterization; Child Development; Ductus Arteriosus, Patent; Feasibility Studies; Female; Gestational Age; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Male; Prospective Studies; Prosthesis Design; Septal Occluder Device; South Africa; Treatment Outcome
PubMed: 31469384
DOI: 10.5830/CVJA-2019-044 -
Anatolian Journal of Cardiology Feb 2017Our hypothesis was that percutaneous PDA closure in babies less than 2 kg was a safe and effective method. The aim of this study is to share our experience in...
OBJECTIVE
Our hypothesis was that percutaneous PDA closure in babies less than 2 kg was a safe and effective method. The aim of this study is to share our experience in transcatheter PDA closure in infants whose body weight is less than 2 kg in order to support our hypothesis.
METHODS
Between July 1997 and October 2014, 382 percutaneous PDA closures were done in our center. Nineteen patients who weighed less than 2 kg were included in this retrospectively study. The other inclusion criteria were 1) being symptomatic and PDA was thought as a possible contributor of medical state and 2) persistence of PDA after medical closure treatment. Patients who had sepsis and bleeding diathesis were excluded. According to size and shape of PDA, different types of devices were used such as detachable coils and Amplatzer duct occluders. Data was expressed as mean (SD) or median (minimum-maximum). Comparisons of means and medians were performed with Student's t-test and with Mann-Whitney U test, respectively.
RESULTS
The median patient age and weight were 32 days and 1603 g (range 910-2000 g) respectively. Mean PDA diameter was 3.2±1.3 mm. Morphology of PDA was type A in 7 patients, type C in 10, type E in 1, and type B in 1 patient. There were no reported major complications. Stenosis of left pulmonary artery was detected in four patients, all of which resolved in 6 months follow-up.
CONCLUSION
Percutaneous PDA closure in babies less than 2 kg is a safe and effective method that can be an alternative to surgery. Main distinguishing feature of this study is that it includes the largest cohort of patients less than 2 kg whose PDA closed percutaneously.
Topics: Cardiac Catheterization; Cohort Studies; Ductus Arteriosus, Patent; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Male; Retrospective Studies; Treatment Outcome
PubMed: 27599665
DOI: 10.14744/AnatolJCardiol.2016.6847