Prolonged Tracheal Intubation and the Association Between Patent Ductus Arteriosus and Bronchopulmonary Dysplasia: A Secondary Analysis of the PDA-TOLERATE trial.
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ABSTRACT:
SUBMITTER: Clyman RI
PROVIDER: S-EPMC7855529 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAn increased risk for bronchopulmonary dysplasia (BPD) exists when moderate-to-large patent ductus arteriosus shunts (hsPDA) persist beyond 14 days.GoalTo examine the interaction between prolonged exposures to tracheal ventilation (≥10 days) and hsPDA on the incidence of BPD in infants <28 weeks gestation.Study designPredefined definitions of prolonged ventilation (≥10 days), hsPDA (≥14 days), and BPD (room air challenge test at 36 weeks) were used to analyze deidentified data from the multicenter TRIOCAPI RCT in a secondary analysis of the trial.ResultsAmong 307 infants who survived >14 days, 41 died before 36 weeks. Among survivors, 93/266 had BPD. The association between BPD and hsPDA depended on the length of intubation. In multivariable analyses, prolonged hsPDA shunts were associated with increased BPD (odds ratio (OR) (95% confidence interval (CI)) = 3.00 (1.58-5.71)) when infants required intubation for ≥10 days. In contrast, there was no significant association between hsPDA exposure and BPD when infants were intubated <10 days (OR (95% CI) = 1.49 (0.98-2.26)). A similar relationship between prolonged hsPDA and length of intubation was found for BPD/death (n = 307): infants intubated ≥10 days: OR (95% CI) = 2.41 (1.47-3.95)); infants intubated <10 days: OR (95% CI) = 1.37 (0.86-2.19)).ConclusionsModerate-to-large PDAs were associated with increased risks of BPD and BPD/death-but only when infants required intubation ≥10 days.ImpactInfants with a moderate-to-large hsPDA that persist beyond 14 days are only at risk for developing BPD if they also receive prolonged tracheal ventilation for ≥10 days. Infants who receive less ventilatory support (intubation for <10 days) have the same incidence of BPD whether the ductus closes shortly after birth or whether it persists as a moderate-to-large shunt for several weeks. Early PDA closure may be unnecessary in infants who require short durations of intubation since the PDA does not seem to alter the incidence of BPD in infants who require intubation for <10 days.
| S-EPMC8904244 | biostudies-literature
Project description:Patent ductus arteriosus (PDA) is a frequent, complex, and difficult to treat clinical syndrome among preterm infants in the neonatal intensive care unit. In addition to known clinical risk factors, there are emerging data about genetic predisposition to PDA in both animal and human models. Clinical response and toxicity from drugs used to treat PDA are highly variable. Developmental and genetic aspects of pharmacokinetics and pharmacodynamics influence exposure and response to pharmacologic therapies. Given the variable efficacy and toxicity of known drug therapies, novel therapeutic targets for PDA treatment offer the promise of precision medicine. This review addresses the known genetic contributions to prolonged ductal patency, variability in response to drug therapy for PDA, and potential novel drug targets for future PDA treatment discovery.
| S-EPMC6098727 | biostudies-literature
Project description:The ductus arteriosus (DA) is a unique fetal vascular shunt, which allows blood to bypass the developing lungs in utero. After birth, changes in complex signaling pathways lead to constriction and permanent closure of the DA. The persistent patency of the DA (PDA) is a common disorder in preterm infants, yet the underlying causes of PDA are not fully defined. Although limits on the availability of human DA tissues prevent comprehensive studies on the mechanisms of DA function, mouse models have been developed that reveal critical pathways in DA regulation. Over 20 different transgenic models of PDA in mice have been described, with implications for human DA biology. Similarly, we enumerate 224 human single-gene syndromes that are associated with PDA, including a small subset that consistently feature PDA as a prominent phenotype. Comparison and functional analyses of these genes provide insight into DA development and identify key regulatory pathways that may serve as potential therapeutic targets for the management of PDA.
| S-EPMC8814064 | biostudies-literature
Project description:ObjectiveTo evaluate the effectiveness of drugs used to constrict patent ductus arteriosus (PDA) in newborns < 28 weeks.MethodsWe performed a secondary analysis of the multi-center PDA-TOLERATE trial (NCT01958320). Infants with moderate-to-large PDAs were randomized 1:1 at 8.1 ± 2.1 days to either Drug treatment (n = 104) or Conservative management (n = 98). Drug treatments were assigned by center rather than within center (acetaminophen: 5 centers, 27 infants; ibuprofen: 7 centers, 38 infants; indomethacin: 7 centers, 39 infants).ResultsIndomethacin produced the greatest constriction (compared with spontaneous constriction during Conservative management): RR (95% CI) = 3.21 (2.05-5.01)), followed by ibuprofen = 2.03 (1.05-3.91), and acetaminophen = 1.33 (0.55-3.24). The initial rate of acetaminophen-induced constriction was 27%. Infants with persistent moderate-to-large PDA after acetaminophen were treated with indomethacin. The final rate of constriction after acetaminophen ± indomethacin was 60% (similar to the rate in infants receiving indomethacin-alone (62%)).ConclusionIndomethacin was more effective than acetaminophen in producing ductus constriction.
| S-EPMC6561645 | biostudies-literature
Project description:ObjectiveTo compare early routine pharmacologic treatment of moderate-to-large patent ductus arteriosus (PDA) at the end of week 1 with a conservative approach that requires prespecified respiratory and hemodynamic criteria before treatment can be given.Study designA total of 202 neonates of <28 weeks of gestation age (mean, 25.8 ± 1.1 weeks) with moderate-to-large PDA shunts were enrolled between age 6 and 14 days (mean, 8.1 ± 2.2 days) into an exploratory randomized controlled trial.ResultsAt enrollment, 49% of the patients were intubated and 48% required nasal ventilation or continuous positive airway pressure. There were no differences between the groups in either our primary outcome of ligation or presence of a PDA at discharge (early routine treatment [ERT], 32%; conservative treatment [CT], 39%) or any of our prespecified secondary outcomes of necrotizing enterocolitis (ERT, 16%; CT, 19%), bronchopulmonary dysplasia (BPD) (ERT, 49%; CT, 53%), BPD/death (ERT, 58%; CT, 57%), death (ERT,19%; CT, 10%), and weekly need for respiratory support. Fewer infants in the ERT group met the rescue criteria (ERT, 31%; CT, 62%). In secondary exploratory analyses, infants receiving ERT had significantly less need for inotropic support (ERT, 13%; CT, 25%). However, among infants who were ≥26 weeks gestational age, those receiving ERT took significantly longer to achieve enteral feeding of 120 mL/kg/day (median: ERT, 14 days [range, 4.5-19 days]; CT, 6 days [range, 3-14 days]), and had significantly higher incidences of late-onset non-coagulase-negative Staphylococcus bacteremia (ERT, 24%; CT,6%) and death (ERT, 16%; CT, 2%).ConclusionsIn preterm infants age <28 weeks with moderate-to-large PDAs who were receiving respiratory support after the first week, ERT did not reduce PDA ligations or the presence of a PDA at discharge and did not improve any of the prespecified secondary outcomes, but delayed full feeding and was associated with higher rates of late-onset sepsis and death in infants born at ≥26 weeks of gestation.Trial registrationClinicalTrials.gov: NCT01958320.
| S-EPMC6502709 | biostudies-literature
Project description:Percutaneous closure of patent ductus arteriosus (PDA) in term neonates is established, but data regarding outcomes in infants born very preterm (<32 weeks of gestation) are minimal, and no published criteria exist establishing a minimal weight of 4 kg as a suitable cutoff. We sought to analyze outcomes of percutaneous PDA occlusion in infants born very preterm and referred for PDA closure at weights <4 kg.Retrospective analysis (January 2005-January 2014) was done at a single pediatric center. Procedural successes and adverse events were recorded. Markers of respiratory status (need for mechanical ventilation) were determined, with comparisons made before and after catheterization. A total of 52 very preterm infants with a median procedural weight of 2.9 kg (range 1.2-3.9 kg) underwent attempted PDA closure. Twenty-five percent (13/52) of infants were <2.5 kg. Successful device placement was achieved in 46/52 (88%) of infants. An adverse event occurred in 33% of cases, with an acute arterial injury the most common complication. We observed no association between weight at time of procedure and the risk of an adverse event. No deaths were attributable to the PDA closure. Compared to precatheterization trends, percutaneous PDA closure resulted in improved respiratory status, including less exposure to mechanical ventilation (mixed effects logistic model, P<0.01).Among infants born very preterm, percutaneous PDA closure at weights <4 kg is generally safe and may improve respiratory health, but risk of arterial injury is noteworthy. Randomized clinical trials are needed to assess clinically relevant differences in outcomes following percutaneous PDA closure versus alternative (surgical ligation) management strategies.
| S-EPMC4802484 | biostudies-other
Project description:BackgroundPatent ductus arteriosus (PDA), the most commonly diagnosed cardiovascular condition in preterm infants, is associated with increased mortality and harmful long-term outcomes (chronic lung disease, neurodevelopmental delay). Although pharmacologic and/or interventional treatments to close PDA likely benefit some infants, widespread routine treatment of all preterm infants with PDA may not improve outcomes. Most PDAs close spontaneously by 44-weeks postmenstrual age; treatment is increasingly controversial, varying markedly between institutions and providers. Because treatment detriments may outweigh benefits, especially in infants destined for early, spontaneous PDA closure, the relevant unanswered clinical question is not whether to treat all preterm infants with PDA, but whom to treat (and when). Clinicians cannot currently predict in the first month which infants are at highest risk for persistent PDA, nor which combination of clinical risk factors, echocardiographic measurements, and biomarkers best predict PDA-associated harm.MethodsProspective cohort of untreated infants with PDA (n=450) will be used to predict spontaneous ductal closure timing. Clinical measures, serum (brain natriuretic peptide, N-terminal pro-brain natriuretic peptide) and urine (neutrophil gelatinase-associated lipocalin, heart-type fatty acid-binding protein) biomarkers, and echocardiographic variables collected during each of first 4 postnatal weeks will be analyzed to identify those associated with long-term impairment. Myocardial deformation imaging and tissue Doppler imaging, innovative echocardiographic techniques, will facilitate quantitative evaluation of myocardial performance. Aim1 will estimate probability of spontaneous PDA closure and predict timing of ductal closure using echocardiographic, biomarker, and clinical predictors. Aim2 will specify which echocardiographic predictors and biomarkers are associated with mortality and respiratory illness severity at 36-weeks postmenstrual age. Aim3 will identify which echocardiographic predictors and biomarkers are associated with 22 to 26-month neurodevelopmental delay. Models will be validated in a separate cohort of infants (n=225) enrolled subsequent to primary study cohort.DiscussionThe current study will make significant contributions to scientific knowledge and effective PDA management. Study results will reduce unnecessary and harmful overtreatment of infants with a high probability of early spontaneous PDA closure and facilitate development of outcomes-focused trials to examine effectiveness of PDA closure in "high-risk" infants most likely to receive benefit.Trial registrationClinicalTrials.gov NCT03782610. Registered 20 December 2018.
| S-EPMC6743099 | biostudies-literature
Project description: Not available
| S-EPMC8617388 | biostudies-literature
Project description:BackgroundPatent ductus arteriosus (PDA) is a common complication in very preterm infants. It is known that there is an association between PDA and development of bronchopulmonary dysplasia (BPD) or death before the postmenstrual age (PMA) of 36 weeks, but this association remains one of the most controversial aspects of the problem. The study aimed to evaluate the relationship between PDA, serum NT-proBNP levels at 2-3 and 8-9 days of life, and BPD/death in very preterm infants.MethodsData of 52 preterm infants with a gestational age < 32 weeks, chronological age < 72 h, and PDA diameter > 1.5 mm, enrolled in a randomized controlled trial, were used for the retrospective analysis. All patients underwent daily echocardiographic and two serum NT-proBNP measurements within the first 10 days after birth. Two groups of infants were formed retrospectively at PMA of 36 weeks depending on the outcome, BPD (n = 18)/death (n = 7) or survival without BPD (n = 27). Receiver operator characteristic (ROC) curve was used to evaluate the predictive performance of serum NT-proBNP levels for BPD/death occurrence.ResultsThe percentage of infants who received pharmacological treatment for PDA did not differ between the groups. Based on the area under the ROC curve, serum NT-proBNP levels on the 2-3 day of life (AUC = 0.71; 95% confidence interval (CI): 0.56-0.9; p = 0.014)) and on the 8-9 day of life (AUC = 0.76; 95% CI: 0.6-0.9; p = 0.002) could reliably predict BPD/death in very preterm infants who had PDA diameter > 1.5 mm in the first 72 h of life. Hemodynamically significant PDA (hsPDA) was significantly more often detected in newborns with BPD/death, however, treatment of infants with hsPDA did not reduce the incidence of BPD/death.ConclusionsIn very preterm infants with PDA > 1.5 mm at the age of 24-48 h, serum NT-proBNP concentration could reliably predict the development of BPD or death, regardless of the persistence of PDA, with the highest diagnostic value at 8-9 days.Trial registrationThis study is registered in ClinicalTrials.gov - NCT03860428 on March 4, 2019.
| S-EPMC8214290 | biostudies-literature
Project description: Not available
| S-EPMC3014131 | biostudies-literature