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Congenital Heart Disease Jan 2019Even though up to 60% of premature infants less than 28 weeks gestation develop persistent patent ductus arteriosus (PDA), there remains controversy regarding if, when,... (Review)
Review
Even though up to 60% of premature infants less than 28 weeks gestation develop persistent patent ductus arteriosus (PDA), there remains controversy regarding if, when, and how to close the PDA. Failure to close the PDA has been associated with significant morbidity but no cause-and-effect has been proven for short-term or long-term outcomes in modern times. Surgical closure has the advantage of eliminating the PDA, but short-term complications and long-term adverse outcomes are worrisome. Intravenous indomethacin has been the "gold standard" for pharmacologic treatment over the past 40 years with high closure rates and decreased incidence of severe intraventricular hemorrhage (IVH) and pulmonary hemorrhage with early treatment but without improvement in long-term outcomes and with risk of renal toxicity. Intravenous ibuprofen has less vasoconstrictive toxicity than indomethacin with comparable closure rates but without improvement in IVH and with hyperbilirubinemia risks. Earlier this decade, acetaminophen (paracetamol) was discovered to effectively close the PDA with good short-term safety profile. Although promising, acetaminophen treatment requires further studies regarding long-term safety as well as ideal dosing and route of administration.
Topics: Acetaminophen; Administration, Oral; Antipyretics; Cyclooxygenase Inhibitors; Ductus Arteriosus, Patent; Humans; Ibuprofen; Indomethacin; Infant, Newborn; Infant, Premature; Infusions, Intravenous; Treatment Outcome
PubMed: 30536827
DOI: 10.1111/chd.12715 -
The Cochrane Database of Systematic... Feb 2020Indomethacin is used as standard therapy to close a patent ductus arteriosus (PDA) but is associated with reduced blood flow to several organs. Ibuprofen, another... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Indomethacin is used as standard therapy to close a patent ductus arteriosus (PDA) but is associated with reduced blood flow to several organs. Ibuprofen, another cyclo-oxygenase inhibitor, may be as effective as indomethacin with fewer adverse effects.
OBJECTIVES
To determine the effectiveness and safety of ibuprofen compared with indomethacin, other cyclo-oxygenase inhibitor(s), placebo, or no intervention for closing a patent ductus arteriosus in preterm, low-birth-weight, or preterm and low-birth-weight infants.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 10), MEDLINE via PubMed (1966 to 30 November 2017), Embase (1980 to 30 November 2017), and CINAHL (1982 to 30 November 2017). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials of ibuprofen for the treatment of a PDA in preterm, low birth weight, or both preterm and low-birth-weight newborn infants.
DATA COLLECTION AND ANALYSIS
Data collection and analysis conformed to the methods of the Cochrane Neonatal Review Group. We used the GRADE approach to assess the quality of evidence.
MAIN RESULTS
We included 39 studies enrolling 2843 infants. Ibuprofen (IV) versus placebo: IV Ibuprofen (3 doses) reduced the failure to close a PDA compared with placebo (typical relative risk (RR); 0.62 (95% CI 0.44 to 0.86); typical risk difference (RD); -0.18 (95% CI -0.30 to -0.06); NNTB 6 (95% CI 3 to 17); I = 65% for RR and I = 0% for RD; 2 studies, 206 infants; moderate-quality the evidence). One study reported decreased failure to close a PDA after single or three doses of oral ibuprofen compared with placebo (64 infants; RR 0.26, 95% CI 0.11 to 0.62; RD -0.44, 95% CI -0.65 to -0.23; NNTB 2, 95% CI 2 to 4; I test not applicable). Ibuprofen (IV or oral) compared with indomethacin (IV or oral): Twenty-four studies (1590 infants) comparing ibuprofen (IV or oral) with indomethacin (IV or oral) found no significant differences in failure rates for PDA closure (typical RR 1.07, 95% CI 0.92 to 1.24; typical RD 0.02, 95% CI -0.02 to 0.06; I = 0% for both RR and RD; moderate-quality evidence). A reduction in NEC (necrotising enterocolitis) was noted in the ibuprofen (IV or oral) group (18 studies, 1292 infants; typical RR 0.68, 95% CI 0.49 to 0.94; typical RD -0.04, 95% CI -0.07 to -0.01; NNTB 25, 95% CI 14 to 100; I = 0% for both RR and RD; moderate-quality evidence). There was a statistically significant reduction in the proportion of infants with oliguria in the ibuprofen group (6 studies, 576 infants; typical RR 0.28, 95% CI 0.14 to 0.54; typical RD -0.09, 95% CI -0.14 to -0.05; NNTB 11, 95% CI 7 to 20; I = 24% for RR and I = 69% for RD; moderate-quality evidence). The serum/plasma creatinine levels 72 hours after initiation of treatment were statistically significantly lower in the ibuprofen group (11 studies, 918 infants; MD -8.12 µmol/L, 95% CI -10.81 to -5.43). For this comparison, there was high between-study heterogeneity (I = 83%) and low-quality evidence. Ibuprofen (oral) compared with indomethacin (IV or oral): Eight studies (272 infants) reported on failure rates for PDA closure in a subgroup of the above studies comparing oral ibuprofen with indomethacin (IV or oral). There was no significant difference between the groups (typical RR 0.96, 95% CI 0.73 to 1.27; typical RD -0.01, 95% CI -0.12 to 0.09; I = 0% for both RR and RD). The risk of NEC was reduced with oral ibuprofen compared with indomethacin (IV or oral) (7 studies, 249 infants; typical RR 0.41, 95% CI 0.23 to 0.73; typical RD -0.13, 95% CI -0.22 to -0.05; NNTB 8, 95% CI 5 to 20; I = 0% for both RR and RD). There was low-quality evidence for these two outcomes. There was a decreased risk of failure to close a PDA with oral ibuprofen compared with IV ibuprofen (5 studies, 406 infants; typical RR 0.38, 95% CI 0.26 to 0.56; typical RD -0.22, 95% CI -0.31 to -0.14; NNTB 5, 95% CI 3 to 7; moderate-quality evidence). There was a decreased risk of failure to close a PDA with high-dose versus standard-dose of IV ibuprofen (3 studies 190 infants; typical RR 0.37, 95% CI 0.22 to 0.61; typical RD - 0.26, 95% CI -0.38 to -0.15; NNTB 4, 95% CI 3 to 7); I = 4% for RR and 0% for RD); moderate-quality evidence). Early versus expectant administration of IV ibuprofen, echocardiographically-guided IV ibuprofen treatment versus standard IV ibuprofen treatment, continuous infusion of ibuprofen versus intermittent boluses of ibuprofen, and rectal ibuprofen versus oral ibuprofen were studied in too few trials to allow for precise estimates of any clinical outcomes.
AUTHORS' CONCLUSIONS
Ibuprofen is as effective as indomethacin in closing a PDA. Ibuprofen reduces the risk of NEC and transient renal insufficiency. Therefore, of these two drugs, ibuprofen appears to be the drug of choice. The effectiveness of ibuprofen versus paracetamol is assessed in a separate review. Oro-gastric administration of ibuprofen appears as effective as IV administration. To make further recommendations, studies are needed to assess the effectiveness of high-dose versus standard-dose ibuprofen, early versus expectant administration of ibuprofen, echocardiographically-guided versus standard IV ibuprofen, and continuous infusion versus intermittent boluses of ibuprofen. Studies are lacking evaluating the effect of ibuprofen on longer-term outcomes in infants with PDA.
Topics: Cyclooxygenase Inhibitors; Ductus Arteriosus, Patent; Enzyme Inhibitors; Humans; Ibuprofen; Indomethacin; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Randomized Controlled Trials as Topic
PubMed: 32045960
DOI: 10.1002/14651858.CD003481.pub8 -
Oxygen-induced faults in bottled white wine: A review of technological and chemical characteristics.Food Chemistry Jun 2021Several changes can take place in wine after blotting. Some of them lead to the desired evolution of wine being more complex, round and pleasant. However, unexpected... (Review)
Review
Several changes can take place in wine after blotting. Some of them lead to the desired evolution of wine being more complex, round and pleasant. However, unexpected changes can also occur ascribable to the premature wine oxidation (PremOx) arising when a wine, presumably with aging potential, results oxidized and often undrinkable. The complexity of PremOx, where aromas are also involved, makes difficult to identify all the oxidation products, and to predict its occurrence in wines. Despite most studies have been focused on the effect of time after wine bottling on PremOx as well as pinking phenomena, identification of pinking markers, reliable methods for their detection in wine, and correlations between markers and the wine-bottle-closure system are still unknown. This review aimed to highlight aspects PremOx-related, including wine-bottle-closure system, color change, with particular emphasis on pinking, and aroma decay based on the current knowledge becoming the bases for future perspectives.
Topics: Color; Food Quality; Odorants; Oxidation-Reduction; Oxygen; Wine
PubMed: 33581681
DOI: 10.1016/j.foodchem.2020.128922 -
The Cleft Palate-craniofacial Journal :... Apr 2023Rickets results from defective bone mineralization, leading to skeletal deformities. Among those deformities, rickets has been associated with craniosynostosis, the...
Rickets results from defective bone mineralization, leading to skeletal deformities. Among those deformities, rickets has been associated with craniosynostosis, the premature closure of cranial sutures. Most of these patients have fusion of major sutures. Rarely, squamosal craniosynostosis in association with rickets has been described. Squamosal craniosynostosis is noted as lacking a definitive head abnormality and difficult visualization on standard imaging modalities, leading to poor recognition. Careful attention should be given to rickets patients to monitor for these unusual suture closures. Additionally, craniosynostosis could be a presenting feature of rickets, and further rickets evaluation of the patient is indicated.
PubMed: 37062955
DOI: 10.1177/10556656231170138 -
Journal of Cardiovascular Development... Sep 2023Transcatheter device closure of patent ductus arteriosus (PDA) in preterm infants has been proven to be a feasible and safe technique with promising results when... (Review)
Review
Transcatheter device closure of patent ductus arteriosus (PDA) in preterm infants has been proven to be a feasible and safe technique with promising results when compared to surgical ligation. However, managing transport and anaesthesia in extremely premature infants with haemodynamically significant PDA and limited reserves presents unique challenges. This review article focuses on the key considerations throughout the clinical pathway for the PDA device closure, including referral hospital consultation, patient selection, intra- and inter-hospital transport, and anaesthesia management. The key elements encompass comprehensive patient assessment, meticulous airway management, optimised ventilation strategies, precise thermoregulation, patient-tailored sedation protocols, vigilant haemodynamic monitoring, and safe transport measures throughout the pre-operative, intra-operative, and post-operative phases. A multidisciplinary approach enhances the chances of procedure success, improves patient outcomes, and minimises the risk of complications.
PubMed: 37754806
DOI: 10.3390/jcdd10090377 -
International Journal of Molecular... Jun 2018The ductus arteriosus (DA) connects the main pulmonary artery and the aorta in fetal circulation and closes spontaneously within days after birth in normal infants.... (Review)
Review
The ductus arteriosus (DA) connects the main pulmonary artery and the aorta in fetal circulation and closes spontaneously within days after birth in normal infants. Abnormal patent DA (PDA) causes morbidities and mortality, especially in preterm infants. Closure of the DA is a complex interactive process involving two events: functional and anatomic closure. Functional closure by smooth muscle contraction was achieved through the regulatory factors of vaso-reactivity. These factors include oxygen sensing system, glutamate, osmolality, prostaglandin E₂, nitric oxide, and carbon monoxide. Anatomic closure by vascular remodeling involved several vascular components including endothelium, extracellular matrix, smooth muscle cells, and intraluminal blood cells. Despite advances in understanding of PDA pathogenesis, the molecular mechanism for regulation of DA closure is complex and not fully understood. In this article we review recent evidence regarding the molecular mechanisms of DA closure.
Topics: Animals; Animals, Newborn; Aorta; Ductus Arteriosus; Glutamic Acid; Humans; Infant, Premature; Morphogenesis; Myocytes, Smooth Muscle; Osmolar Concentration; Oxygen; Pulmonary Artery; Vascular Remodeling
PubMed: 29941785
DOI: 10.3390/ijms19071861 -
Expert Review of Gastroenterology &... Apr 2018Gastroschisis is the commonest developmental defect of the anterior abdominal wall in both developed and developing countries. The past 30 years have seen... (Review)
Review
Gastroschisis is the commonest developmental defect of the anterior abdominal wall in both developed and developing countries. The past 30 years have seen transformational improvements in outcome due to advances in neonatal intensive care and enhanced integration between the disciplines of maternal fetal medicine, neonatology and pediatric surgery. A review of gastroschisis, which emphasizes its epidemiology, multidisciplinary care strategies and contemporary outcomes is timely. Areas covered: This review discusses the current state of knowledge related to prevalence and causation, and postulated embryopathologic mechanisms contributing to the development of gastroschisis. Using relevant, current literature with an emphasis on high level evidence where it exists, we review modern techniques of prenatal diagnosis, pre and postnatal risk stratification, preferred timing and method of delivery, options for abdominal wall closure, nutritional management, and short and long term clinical and neurodevelopmental follow-up. Expert commentary: This section explores controversies in contemporary management which contribute to practice and cost variation and discusses the benefits of novel nutritional therapies and care standardization that target unnecessary practice variation and improve overall cost-effectiveness of gastroschisis care. The commentary concludes with a review of fertile areas of gastroschisis research, which represent opportunities for knowledge synthesis and further outcome improvement.
Topics: Age Factors; Child Development; Digestive System Surgical Procedures; Female; Fetal Death; Gastroschisis; Gestational Age; Humans; Infant; Infant Nutritional Physiological Phenomena; Infant, Newborn; Male; Nutritional Status; Parenteral Nutrition; Premature Birth; Prenatal Diagnosis; Prevalence; Risk Factors; Time Factors; Treatment Outcome
PubMed: 29419329
DOI: 10.1080/17474124.2018.1438890 -
Translational Pediatrics Dec 2020The role of oxygen, reactive oxygen species (ROS), and isoprostanes (IsoPs) in regulating patency and closure of patent ductus arteriosus (PDA) have been studied in... (Review)
Review
The role of oxygen, reactive oxygen species (ROS), and isoprostanes (IsoPs) in regulating patency and closure of patent ductus arteriosus (PDA) have been studied in preterm infants. Also the possible correlation between a hemodynamically significant PDA and its pharmacological treatment with oxidative stress has been investigated. The National Library of Medicine (MEDLINE) database was searched without time limits. Available data demonstrate that free radicals are not always harmful and that ROS and IsoPs play a relevant role in DA closure. On the other hand, a hemodynamically significant PDA can cause oxidative stress and this can partially explain its association with other complications of prematurity related to oxidative stress, such as bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH), and necrotizing enterocolitis (NEC). Some drugs used for pharmacological closure, such as ibuprofen, also have antioxidant effects, and the closure of PDA can restore a proper tissue oxygenation and the balance between pro-oxidant and antioxidant factors. These data support the importance of the relationship between PDA and oxidative stress whose understanding increase our awareness when we approach this prematurity complication in the clinical practice. Further studies might assess the reliability of ROS as possible biomarkers of the risk of developing a hsPDA.
PubMed: 33457306
DOI: 10.21037/tp-20-121 -
Seminars in Perinatology Mar 2023While cyclooxygenase inhibitors have been the most common medications used to facilitate earlier closure of patent ductus arteriosus in preterm infants, adverse effects... (Review)
Review
While cyclooxygenase inhibitors have been the most common medications used to facilitate earlier closure of patent ductus arteriosus in preterm infants, adverse effects and low efficacy in extremely low gestational age neonates (ELGANs) have highlighted a need for alternative options. Combination therapy with acetaminophen and ibuprofen is a novel strategy for PDA treatment in ELGANs, as it may facilitate higher ductal closure rates via additive action on two separate pathways inhibiting prostaglandin production. Initial small observational studies and pilot randomized clinical trials indicate potentially higher efficacy of the combination regime to induce ductal closure in comparison to treatment with ibuprofen alone. In this review, we examine the potential clinical impact of treatment failure in ELGANs with significant PDA, highlight the biological rationale in support of studying combination therapy, and review the randomized and non-randomized studies to date. With the rising number of ELGANs receiving neonatal intensive care, who are vulnerable to PDA-related morbidities, there is an urgent need for adequately powered clinical trials to systematically investigate the efficacy and safety of combination therapy for PDA treatment.
Topics: Infant, Newborn; Humans; Ductus Arteriosus, Patent; Infant, Premature; Ibuprofen; Indomethacin; Infant, Low Birth Weight
PubMed: 36914507
DOI: 10.1016/j.semperi.2023.151720