Neonatal Intensive Care Unit-Level Patent Ductus Arteriosus Treatment Rates and Outcomes in Infants Born Extremely Preterm

Tetsuya Isayama, Satoshi Kusuda, Brian Reichman, Shoo K. Lee, Liisa Lehtonen, Mikael Norman, Mark Adams, Dirk Bassler, Kjell Helenius, Stellan Hakansson, Junmin Yang, Amish Jain, Prakesh S. Shah*, Adele Harrison, Anne Synnes, Joseph Ting, Zenon Cieslak, Rebecca Sherlock, Wendy Yee, Khalid AzizJennifer Toye, Carlos Fajardo, Zarin Kalapesi, Koravangattu Sankaran, Sibasis Daspal, Mary Seshia, Ruben Alvaro, Amit Mukerji, Orlando Da Silva, Chuks Nwaesei, Kyong Soon Lee, Michael Dunn, Brigitte Lemyre, Kimberly Dow, Ermelinda Pelausa, Keith Barrington, Christine Drolet, Bruno Piedboeuf, Martine Claveau, Marc Beltempo, Valerie Bertelle, Edith Masse, Roderick Canning, Hala Makary, Cecil Ojah, Luis Monterrosa, Akhil Deshpandey, Jehier Afifi, Andrzej Kajetanowicz, Sture Andersson, Outi Tammela, Ulla Sankilampi, Timo Saarela, Eli Heymann, Shmuel Zangen, Tatyana Smolkin, Francis Mimouni, David Bader, Avi Rothschild, Zipora Strauss, Clari Felszer, Hussam Omari, Smadar Even Tov-Friedman, Benjamin Bar-Oz, Michael Feldman, Nizar Saad, Orna Flidel-Rimon, Meir Weisbrod, Daniel Lubin, Ita Litmanovitz, Amir Kugelman, Eric Shinwell, Gil Klinger, Yousif Nijim, Alona Bin-Nun, Agneta Golan, Dror Mandel, Vered Fleisher-Sheffer, David Kohelet, Lev Bakhrakh, Satoshi Hattori, Masaru Shirai, Toru Ishioka, Toshihiko Mori, Takasuke Amizuka, Toru Huchimukai, Hiroshi Yoshida, Ayako Sasaki, Junichi Shimizu, Toshihiko Nakamura, Mami Maruyama, Hiroshi Matsumoto, Shinichi Hosokawa, Atsuko Taki, Machiko Nakagawa, Kyone Ko, Azusa Uozumi, Setsuko Nakata, Akira Shimazaki, Tatsuya Yoda, Osamu Numata, Hiroaki Imamura, Azusa Kobayashi, Shuko Tokuriki, Yasushi Uchida, Takahiro Arai, Mitsuhiro Ito, Kuniko Ieda, Toshiyuki Ono, Masashi Hayashi, Kanemasa Maki, Mie Toru Yamakawa, Masahiko Kawai, Noriko Fujii, Kozue Shiomi, Koji Nozaki, Hiroshi Wada, Taho Kim, Yasuyuki Tokunaga, Akihiro Takatera, Toshio Oshima, Hiroshi Sumida, Yae Michinomae, Yoshio Kusumoto, Seiji Yoshimoto, Takeshi Morisawa, Tamaki Ohashi, Yukihiro Takahashi, Moriharu Sugimoto, Noriaki Ono, Shinichiro Miyagawa, Takahiko Saijo, Takashi Yamagami, Kosuke Koyano, Shoko Kobayashi, Takeshi Kanda, Yoshihiro Sakemi, Mikio Aoki, Koichi Iida, Mitsushi Goshi, Yuko Maruyama, Jiri Kofron, Katarina Strand Brodd, Andreas Odlind, Lars Alberg, Sofia Arwehed, Ola Hafström, Anna Kasemo, Karin Nederman, Lars Åhman, Fredrik Ingemarsson, Henrik Petersson, Pernilla Thurn, Eva Albinsson, Bo Selander, Thomas Abrahamsson, Ingela Heimdahl, Kristbjorg Sveinsdottir, Erik Wejryd, Anna Hedlund, Maria Katarina Söderberg, Lars Navér, Thomas Brune, Jens Bäckström, Johan Robinson, Aijaz Farooqi, Erik Normann, Magnus Fredriksson, Anders Palm, Urban Rosenqvist, Bengt Walde, Cecilia Hagman, Andreas Ohlin, Rein Florell, Agneta Smedsaas Löfvenberg, Philipp Meyer, Rachel Kusche, Sven Schulzke, Mathias Nelle, Bendicht Wagner, Thomas Riedel, Grégoire Kaczala, Riccardo E. Pfister, Jean François Tolsa, Matthias Roth, Martin Stocker, Bernhard Laubscher, Andreas Malzacher, John P. Micallef, Lukas Hegi, Romaine Arlettaz, Vera Bernet

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: To assess associations between neonatal intensive care unit (NICU)-level patent ductus arteriosus (PDA) treatment rates (pharmacologic or surgical) and neonatal outcomes. Study design: This cohort study included infants born at 24-28 weeks of gestation and birth weight <1500 g in 2007-2015 in NICUs caring for ≥100 eligible infants in 6 countries. The ratio of observed/expected (O/E) PDA treatment rates was derived for each NICU by estimating the expected rate using a logistic regression model adjusted for potential confounders and network. The primary composite outcome was death or severe neurologic injury (grades III-IV intraventricular hemorrhage or periventricular leukomalacia). The associations between the NICU-level O/E PDA treatment ratio and neonatal outcomes were assessed using linear regression analyses including a quadratic effect (a square term) of the O/E PDA treatment ratio. Results: From 139 NICUs, 39 096 infants were included. The overall PDA treatment rate was 45% in the cohort (13%-77% by NICU) and the O/E PDA treatment ratio ranged from 0.30 to 2.14. The relationship between the O/E PDA treatment ratio and primary composite outcome was U-shaped, with the nadir at a ratio of 1.13 and a significant quadratic effect (P<.001). U-shaped relationships were also identified with death, severe neurologic injury, and necrotizing enterocolitis. Conclusions: Both low and high PDA treatment rates were associated with death or severe neurologic injury, whereas a moderate approach was associated with optimal outcomes.

Original languageEnglish
Pages (from-to)34-39.e5
JournalJournal of Pediatrics
Volume220
DOIs
StatePublished - May 2020

Funding

FundersFunder number
Israel Center for Disease Control
Israel Neonatal Network
National Institute for Health and Welfare
Swedish Neonatal Quality Register
Swiss Neonatal Network
THL
Canadian Institutes of Health ResearchCTP 87518
Canadian Institutes of Health Research
Ontario Ministry of Health and Long-Term Care
Ministry of Health, Labour and Welfare
Socialdepartementet
Ministeriet Sundhed Forebyggelse

    Keywords

    • morbidity
    • mortality
    • neonatal intensive care
    • patent ductus arteriosus
    • preterm infants

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