Abstract
Background
Erythropoietin has an angiogenic effect on the retina and might increase the risk of retinopathy of prematurity (ROP).
Methods
This retrospective cohort study included infants born at 22 to 27 weeks’ gestation between 2008 and 2018 who were admitted to neonatal intensive care units (NICUs). We compared mortality and morbidities between infants who received erythropoietin and those who did not.
Results
Among 18,955 livebirth infants, this study included 16,031 infants, among which 14,373 infants received erythropoietin. The risk of ROP requiring treatment was significantly higher in the erythropoietin group than in the control group (33% vs. 26%; aOR 1.50 [95% CI 1.28–1.76]). On the other hand, the erythropoietin group had lower risks of death and necrotizing enterocolitis.
Conclusions
This study with a large sample size found that erythropoietin use was associated with increased risk of ROP requiring treatment, while being associated with reductions in deaths and NEC.
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Data availability
The data that support the findings of this study are available from the corresponding author, upon reasonable request.
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Acknowledgements
This study was supported in part by a grant from the Ministry of Health, Labor and Welfare, Japan. Institutions and representative physicians enrolled in the database for NRNJ include: The NRNJ consisted of the following institutions: Sapporo City General Hospital, Asahikawa Kosei General Hospital, Engaru-Kosei General Hospital, Kushiro Red Cross Hospital, Obihiro-Kosei General Hospital, Tenshi Hospital, NTT Higashinihon Sapporo Hospital, Nikko Memorial Hospital, Nayoro City General Hospital, Sapporo Medical University, Asahikawa Medical University, Aomori Prefectural Central Hospital, Iwate Medical University, Iwate Prefectural Ofunato Hospital, Iwate Prefectural Kuji Hospital, Iwate Prefectural Ninohe Hospital, Sendai Red Cross Hospital, Tohoku University, Akita Red Cross Hospital, Akita University, Tsuruoka Municipal Shonai Hospital, Yamagata University, Yamagata Prefectural Central Hospital, Fukushima Medical University, Takeda General Hospital, Fukushima National Hospital, Tsukuba University, Tsuchiura Kyodo Hospital, Ibaraki Children’s Hospital, Dokkyo Medical University, Jichi Medical University, Ashikaga Red Cross Hospital, Gunma Children’s Medical Center, Kiryu Kosei General Hospital, Fuji Heavy Industries Health Insurance Society Ota Memorial Hospital, Gunma University, Saitama Medical University, Saitama Children’s Medical Center, Nishisaitama-chuo National Hospital, Saitama Medical University Saitama Medical Center, Kawaguchi Municipal Medical Center, Jichi Medical University Saitama Medical Center, Asahi General Hospital, Chiba Kaihin Municipal Hospital, Kameda Medical Center, Tokyo Women’s Medical University Yachiyo Medical Center, Juntendo University Urayasu Hospital, Narita Red Cross Hospital, Tokyo Metropolitan Children’s Medical Center, Tokyo Women’s Medical University, Aiiku Hospital, Nihon University Itabashi Hospital, National Center for Global Health and Medicine, Tokyo Medical University, Teikyo University, Showa University, Japan Red Cross Medical Center, National Center for Child Health and Development, Tokyo Metropolitan Otsuka Hospital, Tokyo University, Toho University, Tokyo Metropolitan Bokuto Hospital, Tokyo Jikei Medical University, Tokyo Medical and Dental University, Saint Luke’s International Hospital, Juntendo University, Sanikukai Hospital, Katsushika Red Cross Hospital, Yokohama Rosai Hospital, Yokohama City University Medical Center, St. Marianna University School of Medicine Hospital, Kanagawa Children’s Medical Center, Tokai University, Kitazato University, Odawara Municipal Hospital, Nippon Medical School Musashi Kosugi Hospital, Yokohama City Hospital, Saiseikai Yokohamashi Tobu Hospital, National Hospital Organization Yokohama Medical Center, Yamanashi Prefectural Central Hospital, Nagano Children’s Hospital, Shinshu University, Iida Municipal Hospital, National Hospital Organization Shinshu Ueda Medical Center, Saku General Hospital, Niigata University, Niigata Prefectural Central Hospital, Niigata Municipal Hospital, Nagaoka Red Cross Hospital, Koseiren Takaoka Hospital, Toyama Prefectural Central Hospital, Toyama University, Ishikawa Medical Center for Maternal and Child Health, Kanazawa Medical University, Kanazawa Medical Center, Fukui Prefectural Hospital, Fukui University, Gifu Prefectural General Medical Center, Oogaki City Hospital, National Hospital Organization Nagara Medical Center, Takayama Red Cross Hospital, Seirei Hamamatsu Hospital, Shizuoka Saiseikai Hospital, Shizuoka Children’s Hospital, Hamamatsu Medical University, Numazu Municipal Hospital, Yaizu City Hospital, Fujieda Municipal General Hospital, Nagoya Red Cross Daini Hospital, Nagoya University, Nagoya Red Cross Daiichi Hospital, Toyohashi Municipal Hospital, Nagoya City West Medical Center, Fujita Health University, Anjo Kosei Hospital, Tosei General Hospital, Komaki Municipal Hospital, TOYOTA Memorial Hospital, Okazaki Municipal Hospital, Handa City Hospital, Konan Kosei Hospital, Aichi Medical University, National Mie Central Medical Center, Ise Red Cross Hospital, Yokkaichi Municipal Hospital, Otsu Red Cross Hospital, Shiga University of Medical Science Hospital, Nagahama Red Cross Hospital, Uji Tokushukai Hospital, The Japan Baptist Hospital, Kyoto University, Kyoto Red Cross Daiichi Hospital, National Maizuru Medical Center, Fukuchiyama City Hospital, Kyoto Prefectural University of Medicine Hospital, Kyoto City Hospital, Mitsubishi Kyoto Hospital, Yodogawa Christian Hospital, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka University, Takatsuki General Hospital, Kansai Medical University, Osaka City General Hospital, Osaka City Sumiyoshi Hospital, Aizenbashi Hospital, Toyonaka Municipal Hospital, National Cerebral and Cardiovascular Center, Kitano Hospital, Saiseikai Suita Hospital, Chifune Hospital, Bellland General Hospital, Rinku General Medical Center, Osaka Red Cross Hospital, Yao Municipal Hospital, Hannan Central Hospital, Osaka General Medical Center, Osaka City University, Hyogo Prefectural Kobe Children’s Hospital, Kobe University, Kakogawa West City Hospital, Saiseikai Hyogoken Hospital, Kobe City Medical Center General Hospital, Hyogo College of Medicine Hospital, Himeji Red Cross Hospital, Toyooka Public Hospital, Hyogo Prefectural Awaji Medical Center, Nara Medical University, Wakayama Medical University, Tottori Prefectural Central Hospital, Tottori University, Shimane Prefectural Central Hospital, Matsue Red Cross Hospital, Kurashiki Central Hospital, Tsuyama Central Hospital, Kawasaki Medical School Hospital, National Hospital Organization Okayama Medical Center, Okayama Red Cross Hospital, Hiroshima City Hiroshima Citizens Hospital, Hiroshima Prefectural Hospital, Hiroshima University, Tsuchiya General Hospital, National Hospital Organization Kure Medical Center, Yamaguchi University, Yamaguchi Grand Medical Center, Tokushima University, Tokushima Municipal Hospital, Kagawa University, Shikoku Medical Center for Children and Adults, Matsuyama Red Cross Hospital, Ehime Prefectural Central Hospital, Kochi Health Science Center, St. Mary’s Hospital, National Kyushu Medical Center, Kurume University, Kitakyushu Municipal Medical Center, University of Occupational and Environmental Health, Fukuoka University, Kyushu University, Iizuka Hospital, National Hospital Organization Kokura Medical Center, Fukuoka City Children’s Hospital, National Hospital Organization Saga Hospital, Nagasaki University, National Hospital Organization Nagasaki Medical Center, Sasebo City Hospital, Kumamoto City Hospital, Kumamoto University, Oita Prefectural Hospital, Almeida Memorial Hospital, Nakatsu Municipal Hospital, Miyazaki University, National Hospital Organization Miyakonojo Medical Center, Kagoshima City Hospital, Imakiire General Hospital, Okinawa Prefectural Nanbu Medical Center & Children’s Medical Center, Okinawa Prefectural Chubu Hospital, Naha City Hospital, Okinawa Red Cross Hospital.
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Kana Fukui, Yushi Ito and Tetsuya Isayama designed the data collection instruments, collected data, conducted analyses, and critically reviewed and revised the manuscript. Kana Fukui, Masayo Kokubo, Hidehiko Nakanishi, Shinya Hirano, Satoshi Kusuda, and Shuichi Ito reviewed and revised the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for the work.
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Fukui, K., Ito, Y., Kokubo, M. et al. Erythropoietin and retinopathy of prematurity: a retrospective cohort study in Japan, 2008–2018. J Perinatol (2024). https://doi.org/10.1038/s41372-024-01929-z
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DOI: https://doi.org/10.1038/s41372-024-01929-z
