Supplementary Material for: Proactive diagnosis and tailor-made treatment of patent ductus arteriosus in very preterm infants with routine echocardiography in Japan: a post-hoc analysis of the PLASE study

Introduction
A feature of the management of extremely preterm infants in Japan is proactive circulatory management using early routine echocardiography performed by neonatologists.
Methods
This study was a post-hoc analysis of the Patent ductus arteriosus and Left Atrial Size Evaluation in preterm infants (PLASE) study, which is a prospective cohort study including preterm infants admitted to 34 tertiary neonatal intensive care units in Japan between October 2015 and December 2016. We described the details of the treatment strategy of patent ductus arteriosus (PDA) based on early routine echocardiography.
Results
In total 613 preterm infants were included into the analysis. Twenty percent of infants with prophylactic indomethacin were switched to therapeutic cyclooxygenase inhibitor (COX-I) before the completion of the full prophylactic indomethacin course. Therapeutic COX-I was mostly administered based on echocardiographic findings before PDA became symptomatic or hemodynamically significant. Therapeutic COX-I was frequently discontinued after one or two doses before the full course (three doses) was completed. The proportion of infants requiring additional treatment (additional therapeutic COX-I course or surgical PDA closure) after discontinued COX-I courses (< 3 doses) compared to infants after completed 3 doses course was significantly lower (after the first therapeutic COX-I course 46% vs. 68%, p < 0.001) or without a significant difference (after the second or third course).
Conclusions
The clinical management of PDA in Japan featured: 1) COX-I administration based on echocardiographic findings before symptomatic or hemodynamically significant PDA appeared, and 2) frequent discontinuation of therapeutic COX-I before completing the standard three doses course.