Early prediction of spontaneous patent ductus arteriosus (PDA) closure and pdaassociated outcomes: A prospective cohort investigation

Jonathan L. Slaughter, Clifford L. Cua, Jennifer L. Notestine, Brian K. Rivera, Laura Marzec, Erinn M. Hade, Nathalie L. Maitre, Mark A. Klebanoff, Megan Ilgenfritz, Vi T. Le, Dennis J. Lewandowski, Carl H. Backes

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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.

Original languageEnglish (US)
Article number33
JournalBMC pediatrics
Volume19
Issue number1
DOIs
Publication statusPublished - Jan 1 2019

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All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health

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Slaughter, J. L., Cua, C. L., Notestine, J. L., Rivera, B. K., Marzec, L., Hade, E. M., ... Backes, C. H. (2019). Early prediction of spontaneous patent ductus arteriosus (PDA) closure and pdaassociated outcomes: A prospective cohort investigation. BMC pediatrics, 19(1), [33]. https://doi.org/10.1186/s12887-019-1708