{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T06:15:12Z","timestamp":1778652912988,"version":"3.51.4"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Methylxanthines are the first-line medication in apnea of prematurity. However, serum concentrations exhibit marked variability due to immature hepatic metabolism and drug\u2013drug interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aimed to evaluate premature newborns diagnosed with apnea of prematurity and highlight the role of therapeutic drug monitoring in preventing complications related to overaccumulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This prospective observational clinical study was conducted on 325 premature neonates, divided into high caffeine citrate study group with serum titer &amp;gt;50\u202f\u03bcg\/mL (HC,\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f25) and normal caffeine group with serum titer &amp;lt;50\u202f\u03bcg\/mL (NC,\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f50) and a comparison group that did not receive caffeine citrate (CoG,\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f250). CoG required pulmonary ventilation, while HC and NC received both pulmonary ventilation and standard caffeine citrate. Serum caffeine citrate concentrations were monitored dynamically.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Major complications in caffeine group were intracranial hemorrhage (5.33%) and convulsions followed by death (4.00%) as, while the CoG demonstrated fewer adverse outcomes and more favorable clinical evolution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Intermittent administration of standard methylxanthine doses or adjustment of therapeutic doses, guided by serial monitoring of serum caffeine citrate titer, may improve clinical outcomes in critical cases, reduce adverse drug effects, and support safer and individualized therapeutic management of apnea of prematurity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1808401","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T05:56:17Z","timestamp":1778651777000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and biological impact of caffeine therapy in premature infants with apnea of prematurity: a prospective observational study"],"prefix":"10.3389","volume":"13","author":[{"given":"Adela-Valeria","family":"Neam\u021bu","sequence":"first","affiliation":[{"name":"Department of Anesthesia and Intensive Care, Doctoral School, University of Medicine and Pharmacy of Craiova","place":["Craiova, Romania"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ovidiu Mircea","family":"Zlatian","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova","place":["Craiova, Romania"]},{"name":"Medical 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Romania"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana-Maria","family":"P\u0103tra\u0219cu","sequence":"additional","affiliation":[{"name":"Department of Hematology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova","place":["Craiova, Romania"]},{"name":"Clinic of Hematology, \u201cFilantropia\u201d Clinical Municipal Hospital","place":["Craiova, Romania"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramona","family":"Cioboat\u0103","sequence":"additional","affiliation":[{"name":"Department of Pneumology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova","place":["Craiova, Romania"]},{"name":"Clinic of Pneumology, \u201cVictor Babes\u201d Infectious Diseases Hospital","place":["Craiova, Romania"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliana","family":"Stanca","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, University of Medicine and Pharmacy of Craiova","place":["Craiova, Romania"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivia Garofi\u021ba","family":"Mateescu","sequence":"additional","affiliation":[{"name":"Department of Histology, University of Medicine and Pharmacy of Craiova","place":["Craiova, Romania"]},{"name":"Laboratory of Pathology, \u201cFilantropia\u201d Clinical Municipal Hospital","place":["Craiova, Romania"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u0218tefan","family":"P\u0103tra\u0219cu","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Medicine and Pharmacy of Craiova","place":["Craiova, Romania"]},{"name":"Clinic of Surgery, Clinical Emergency County Hospital","place":["Craiova, Romania"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia","family":"Radu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Botany, University of Medicine and Pharmacy of Craiova","place":["Craiova, Romania"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona-Daniela","family":"Neam\u021bu","sequence":"additional","affiliation":[{"name":"Department of Immunology and Hematology, University of Medicine and Pharmacy of Craiova","place":["Craiova, Romania"]},{"name":"Medical Laboratory, \u201cFilantropia\u201d Clinical Municipal Hospital","place":["Craiova, Romania"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2011.02.011","article-title":"Longitudinal assessment of hemoglobin oxygen saturation in preterm and term infants in the first six months of life","volume":"159","author":"Hunt","year":"2011","journal-title":"J Pediatr"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1542\/peds.84.5.785","article-title":"Periodic breathing in preterm infants: incidence and 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