201 - Predicting the Probability of Spontaneous Patent Ductus Arteriosus Closure and Closure Timing using Clinical and Echocardiographic Predictors from the First Postnatal Month: A large prospective cohort

Publication Number: 201.6115

Jonathan L. Slaughter, Nationwide Children's Hospital and The Ohio State University, Columbus, OH, United States; Erinn M. Hade, NYU Grossman School of Medicine, New York, NY, United States; Sara Conroy, Nationwide Children's Hospital, Columbus, OH, United States; Clifford L. Cua, Nationwide Children's Hospital, Columbus, OH, United States; Mark Klebanoff, Nationwide Children's Hospital, Columbus, OH, United States; Katherine Siu, New York University Grossman School of Medicine, New York, NY, United States; Himangini singh Dixit, Nationwide Children's Hospital, Columbus, OH, United States; Chance Alvarado, Nationwide Children's Hospital, Columbus, OH, United States; Cara B.. Boyle, Nationwide Children's Hospital, COLUMBUS, OH, United States; Joanie Randle, Nationwide Childrens Hospital Center for Perinatal Research, Division of Neonatology Nationwide Children's Hospital, Columbus, OH, United States; Brian Rivera, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States; Lesley A. Freel, Nationwide Children's Hospital, Dublin, OH, United States; Michele Kappeler, Nationwide Children's Hospital, Dublin, OH, United States; Tanvi Naik, Nationwide Children's Hospital, Columbus, OH, United States; Kelly R. T.. Schmidt, Nationwide Children's Hospital, Columbus, OH, United States; Kacy Taylor, Nationwide Children's Hospital, Columbus, OH, United States; Carl Backes, Nationwide Children's Hospital, Col, OH, United States

Background: All forms of deliberate patent ductus arteriosus (PDA) closure potentially have adverse effects. Detriments of treatment may outweigh benefits, especially for infants destined for early, spontaneous closure. Identifying highly predictive characteristics of spontaneous closure may reduce unnecessary treatment.

Objective: To estimate the risk of spontaneous PDA closure across a robust set of clinical and echocardiographic covariates, and to predict ductal closure timing in extremely preterm infants.

Design/Methods: We prospectively enrolled a cohort of < 30-week gestational age (GA) preterm infants without life-threatening congenital anomalies from April 2019-September 2023. An open PDA was required on initial screening echocardiography (echo) at age < 72 hours. Clinical, echo, and biomarker variables were collected on the same day weekly for each participant during the first 4-weeks postnatal. Serial echos continued every 2-weeks until documented PDA-closure or discharge. Fine-Gray subdistribution hazard models estimate the probability of PDA closure over time, while accommodating competing risks of death, PDA-closure drug treatment, or catheter-closure prior to spontaneous closure. LASSO penalization was used in building multivariable prediction models.

Our primary outcome was time of documented spontaneous PDA closure through 36-weeks postmenstrual age. Maternal and infant demographics, clinical measures including illness severity markers, weekly biomarker measurements, and weekly echo-derived predictors collected the first 4 postnatal weeks were candidate predictors.

Results: We enrolled 365 eligible preterm infants (=1738 total echos), of whom 274 had spontaneous PDA closure (75%). Median time to closure from enrollment was 15 days (IQR: 42 days). Twenty-nine infants were observed to have PDA treatment prior to spontaneous closure; 21 died before closure or treatment. PDA size at < 72-hours, birth GA, history of maternal infection, and ventilator use at NICU admission were strong predictors of spontaneous PDA closure in our multivariable model (Table 3).

Conclusion(s): In this initial model from our large, prospective cohort, PDA size at 72-hours postnatal, birth GA, history of maternal infection, and ventilator use at NICU admission remained strong predictors of spontaneous PDA closure. Additional planned modeling within the cohort, using more precise measured echocardiographic predictors of PDA magnitude and intensity during the first postnatal month, may improve our ability to identify markers of spontaneous PDA closure.

Table 1
Demographic and clinical characteristics of infants by outcomes

Table 2
Unadjusted Fine-Gray sub-distribution Hazard model estimate for risk of spontaneous closure

Table 3
Multivariable Fine-Gray sub-distribution hazard model estimates for risk of spontaneous closure

Table 1
Demographic and clinical characteristics of infants by outcomes

Table 2
Unadjusted Fine-Gray sub-distribution Hazard model estimate for risk of spontaneous closure

Table 3
Multivariable Fine-Gray sub-distribution hazard model estimates for risk of spontaneous closure