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

Seiichi Tomotaki; Tetsuya Isayama; Tohru Kobayashi; Satoshi Masutani; Hidenori Kawasaki; Atsushi Nakayama; Toshifumi Ikeda; Katsuaki Toyoshima; PLASE Study Group Investigators

doi:10.1159/000538363

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

Neonatology. 2024 Apr 9:1-9. doi: 10.1159/000538363. Online ahead of print.

Authors

Seiichi Tomotaki^{1

2}, Tetsuya Isayama³, Tohru Kobayashi⁴, Satoshi Masutani⁵, Hidenori Kawasaki⁵, Atsushi Nakayama⁶, Toshifumi Ikeda⁷, Katsuaki Toyoshima¹; PLASE Study Group Investigators

Affiliations

¹ Department of Neonatology, Kanagawa Children's Medical Center, Yokohama, Japan.
² Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
³ Department of Neonatology, National Center for Child Health and Development, Setagaya, Japan.
⁴ Department of Data Science, Clinical Research Center, National Center for Child Health and Development, Setagaya, Japan.
⁵ Department of Pediatrics, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan.
⁶ Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital, Nagoya, Japan.
⁷ Aomori Prefectural Central Hospital, Aomori, Japan.

PMID: 38593757
DOI: 10.1159/000538363

Abstract

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.

Keywords: Cyclooxygenase inhibitor; Ductus arteriosus; Echocardiography; Indomethacin; Preterm infant.