Early prediction of spontaneous Patent Ductus Arteriosus (PDA) closure and PDA-associated outcomes: a prospective cohort investigation

Abstract

Background Patent 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. Methods Prospective 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. Discussion The 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 registration ClinicalTrials.gov NCT03782610. Registered 20 December 2018.

Management of Patent Ductus Arteriosus in Premature Infants in 2020

“…These markers include B-type natriuretic peptide (BNP), amino-terminal pro-B-type natriuretic peptide (NT-proBNP), and cardiac Troponin T (cTnT) ( 63 , 64 ). There are also urinary markers such as Neutrophil gelatinase-associated lipocalin and heart-type fatty acid binding protein that have been used to predict ductal closure timing ( 65 ). While locally certified BNP or NT-proBNP assays can be useful to trend for appraisal of response to therapy, the variability of assays across institutions prevents universal assertions about their utilization ( 56 ).…”

“…The preferred route of ibuprofen administration has just been clarified by recent studies. A Cochrane review in 2015 observed that ibuprofen administered intravenously was less effective at PDA closure than ibuprofen administered orally (RR 0.37; 95% CI 0.23–0.61) ( 65 ). This was also seen in a large network meta-analysis ( 74 ).…”

Related Factors of Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-Analysis

“…Not only does PDA have a rather high morbidity in preterm infants, but also it has a high severity. The hemodynamic consequence of PDA is a left-to-right shunt (5), resulting in a combination of pulmonary overcirculation and reduced organ perfusion (1,(3)(4)(5), which will further entail a series of harmful clinical outcomes such as intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), feeding intolerance, decreased glomerular filtration rate, and even mortality (1,4,5,(7)(8)(9)(10). Therefore, PDA is one of the major causes of long hospitalization duration and poor prognosis for preterm infants and has a seriously damaging effect on the growth and development of newborns, on account of which the early diagnosis and management of PDA are definitely essential.…”

Echocardiography-Guided Management of Preterms With Patent Ductus Arteriosus Influences the Outcome: A Cohort Study

“…If some infants might benefit from pharmacological therapy, the criteria for PDA treatment remain currently unclear. The American Academy of Pediatrics and Experts on PDA agree that further studies are advocated to evaluate the efficacy of different diagnostic and therapeutic management of newborns with PDA (13)(14)(15)(16). Starting from these considerations, we aimed to compare, in a cohort study, two management options: (1) targeted treatment based on ECHO criteria and (2) treatment based on ECHO criteria in addition to clinical signs and symptoms.…”