{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:29:33Z","timestamp":1790875773867,"version":"4.1.0"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T00:00:00Z","timestamp":1663545600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Methylxanthine, including caffeine citrate and aminophylline, is the most common pharmacologic treatment for apnea of prematurity. However, due to the lack of high-quality evidence, there are no clear recommendations or guidelines on how to choose between caffeine and aminophylline.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objective<\/jats:title>\n<jats:p>This meta-analysis aimed to assess the comparative efficacy and safety of caffeine and aminophylline for apnea of prematurity, and provide reliable evidence for clinical medication in the treatment for apnea of prematurity.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>PubMed, Scopus, Embase, EBSCO, Web of Science, and Cochrane databases were systematically searched from May 1975 to June 2022.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>Ten studies including a total of 923 preterm infants were evaluated. Our results showed that there was no significant difference in the effective rate of 1-3days between caffeine and aminophylline (OR 1.05, 95%CI: 0.40\u20132.74, <jats:italic>P<\/jats:italic> = 0.914). However, for side effects such as tachycardia (OR 0.22, 95%CI: 0.13\u20130.37, <jats:italic>P&lt;<\/jats:italic>0.001) and feeding intolerance (OR 0.40, 95%CI: 0.23\u20130.70, <jats:italic>P<\/jats:italic> = 0.001), the incidence rate was lower in the caffeine group compared with the aminophylline group. No significant difference was found in hyperglycemia (OR 0.45, 95%CI: 0.19\u20131.05, <jats:italic>P<\/jats:italic> = 0.064).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>This meta-analysis reveals that caffeine citrate and aminophylline have similar therapeutic effectiveness on respiratory function, but caffeine has fewer side effects and should be considered first for treatment.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0274882","type":"journal-article","created":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T17:32:51Z","timestamp":1663608771000},"page":"e0274882","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Comparative efficacy and safety of caffeine citrate and aminophylline in treating apnea of prematurity: A systematic review and meta-analysis"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6084-3662","authenticated-orcid":true,"given":"Yiqun","family":"Miao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuliang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9144-2805","authenticated-orcid":true,"given":"Aihua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,9,19]]},"reference":[{"key":"pone.0274882.ref001","volume-title":"Infant Apnea. 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Bancalari","year":"2014","journal-title":"Early human development"},{"issue":"1","key":"pone.0274882.ref006","first-page":"e21783","article-title":"Treating Apnea of Prematurity.","volume":"14","author":"J Pergolizzi","year":"2022","journal-title":"Cureus."},{"issue":"6","key":"pone.0274882.ref007","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/jp.2014.226","article-title":"Serum caffeine concentrations and short-term outcomes in premature infants of \u2a7d29 weeks of gestation.","volume":"35","author":"P Alur","year":"2015","journal-title":"Journal of perinatology: official journal of the California Perinatal Association"},{"issue":"5","key":"pone.0274882.ref008","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.pedneo.2016.10.003","article-title":"Caffeine citrate\u2014Is it a silver bullet in neonatology","volume":"58","author":"B Shrestha","year":"2017","journal-title":"Pediatrics and 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infants[J]","volume":"16","author":"JL Xu","year":"2014","journal-title":"Chinese journal of contemporary pediatrics"},{"issue":"5","key":"pone.0274882.ref024","doi-asserted-by":"crossref","first-page":"46","DOI":"10.3892\/etm.2020.9175","article-title":"Caffeine versus aminophylline in combination with oxygen therapy for apnea of prematurity: A retrospective cohort study.","volume":"20","author":"CY Zhang","year":"2020","journal-title":"Exp Ther Med"},{"issue":"3","key":"pone.0274882.ref025","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1159\/000087584","article-title":"Methylxanthine therapy for apnea of prematurity: evaluation of treatment benefits and risks at age 5 years in the international Caffeine for Apnea of Prematurity (CAP) trial.","volume":"88","author":"B. 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Systematic Overview of Meta-Analyses.","volume":"22","author":"E Alhersh","year":"2020","journal-title":"Paediatric drugs."},{"issue":"4","key":"pone.0274882.ref035","doi-asserted-by":"crossref","first-page":"81","DOI":"10.5409\/wjcp.v4.i4.81","article-title":"Caffeine therapy in preterm infants","volume":"4","author":"H Abdel-Hady","year":"2015","journal-title":"World journal of clinical pediatrics"},{"issue":"2","key":"pone.0274882.ref036","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s40272-013-0063-z","article-title":"Use of methylxanthine therapies for the treatment and prevention of apnea of prematurity.","volume":"16","author":"K Schoen","year":"2014","journal-title":"Paediatric drugs."},{"issue":"6","key":"pone.0274882.ref037","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1891\/0730-0832.30.6.408","article-title":"Caffeine citrate therapy for apnea of prematurity.","volume":"30","author":"PJ Johnson","year":"2011","journal-title":"Neonatal 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