{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T13:23:08Z","timestamp":1778505788702,"version":"3.51.4"},"reference-count":32,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Caffeine has been commonly used for prevention and treatment of apnea-related symptoms in premature infants. However, its side effects have not been thoroughly studied. We investigated whether caffeine affects gastric motility in very-preterm (VP) neonates. Methods: The study is a randomized crossover clinical trial. Twenty-two neonates with mean birth weight (BW) (standard deviation\u2014SD) 1077 (229) g and mean gestational age (GA) (SD) 28.6 (2.1) weeks were recruited. Each neonate had its gastric emptying time checked twice with ultrasound assessment of changes in antral cross sectional area (ACSA). All neonates were sequentially allocated to the caffeine group (A) and the control group (B). Complications from the gastrointestinal tract were documented throughout the study. Results: Statistically significant difference was found with regards to the gastric emptying time [median, (range)] between caffeine and control group (p = 0.040). Additionally, in the neonates with BW 1000\u20131500 g and GA \u2265 28 weeks, the gastric emptying time (minutes) was significantly longer during caffeine treatment [44.5 (36\u201368.2)] and [40 (34.5\u201366.5)] respectively, as compared to the gastric emptying time during no caffeine treatment [27 (24.2\u201330)] (p = 0.002) and [27 (24.5\u201330)] (p = 0.001). The incidence of gastrointestinal (GI) complications was significantly greater in neonates receiving caffeine [6 (27.%)] as compared with those without caffeine treatment [1 (4.6%)] (p = 0.039). Conclusions: During caffeine treatment, a significantly delayed gastric emptying time was noted in all study neonates, especially in these with BW 1000\u20131500 g and those with GA \u2265 28 weeks. Further larger studies are necessary in order to confirm this interesting finding.<\/jats:p>","DOI":"10.3390\/jcm9061676","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T09:19:27Z","timestamp":1591089567000},"page":"1676","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Caffeine and Gastric Emptying Time in Very Preterm Neonates"],"prefix":"10.3390","volume":"9","author":[{"given":"Antonios K.","family":"Gounaris","sequence":"first","affiliation":[{"name":"Neonatal Clinic-NICU, University General Hospital, 413 34 Larissa, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioanna N.","family":"Grivea","sequence":"additional","affiliation":[{"name":"Neonatal Clinic-NICU, University General Hospital, 413 34 Larissa, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Baltogianni","sequence":"additional","affiliation":[{"name":"Neonatal Clinic-NICU, University General Hospital, 451 10 Ioannina, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleni","family":"Gounari","sequence":"additional","affiliation":[{"name":"NICU, Royal Alexandra Children\u2019s Hospital Brighton, Eastern Road, Brighton, East Sussex BN2 5BE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0515-7256","authenticated-orcid":false,"given":"George","family":"Antonogeorgos","sequence":"additional","affiliation":[{"name":"Neonatal Clinic-NICU, General Hospital \u201cAgios Panteleimon\u201d, 18454 Piraeus, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fedra","family":"Kokori","sequence":"additional","affiliation":[{"name":"Department of Radiology, General Hospital \u201cAgios Panteleimon\u201d, 18454 Piraeus, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Polytimi","family":"Panagiotounakou","sequence":"additional","affiliation":[{"name":"Neonatal Clinic-NICU, General Hospital \u201cAgios Panteleimon\u201d, 18454 Piraeus, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martha","family":"Theodoraki","sequence":"additional","affiliation":[{"name":"Neonatal Clinic-NICU, General Hospital \u201cAgios Panteleimon\u201d, 18454 Piraeus, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4966-6826","authenticated-orcid":false,"given":"Aikaterini","family":"Konstantinidi","sequence":"additional","affiliation":[{"name":"Neonatal Clinic-NICU, General Hospital \u201cAgios Panteleimon\u201d, 18454 Piraeus, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rozeta","family":"Sokou","sequence":"additional","affiliation":[{"name":"Neonatal Clinic-NICU, General Hospital \u201cAgios Panteleimon\u201d, 18454 Piraeus, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S377","DOI":"10.1016\/S1526-0542(04)90067-X","article-title":"Apnoea of prematurity","volume":"5","author":"Martin","year":"2004","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1056\/NEJMoa054065","article-title":"Caffeine Therapy for Apnea of Prematurity","volume":"354","author":"Schmidt","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1007\/BF00442697","article-title":"Does caffeine prevent hypoxaemic episodes in premature infants? A randomized controlled trial","volume":"147","author":"Bucher","year":"1988","journal-title":"Eur. J. Pediatr."},{"key":"ref_4","first-page":"Cd000140","article-title":"Methylxanthine treatment for apnoea in preterm infants","volume":"12","year":"2010","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1056\/NEJMoa073679","article-title":"Long-Term Effects of Caffeine Therapy for Apnea of Prematurity","volume":"357","author":"Schmidt","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1001\/jama.2011.2024","article-title":"Survival Without Disability to Age 5 Years After Neonatal Caffeine Therapy for Apnea of Prematurity","volume":"307","author":"Schmidt","year":"2012","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2734","DOI":"10.1080\/14767058.2016.1261400","article-title":"Caffeine combined with sedative\/anesthetic drugs triggers widespread neuroapoptosis in a mouse model of prematurity","volume":"30","author":"Cabrera","year":"2017","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.expneurol.2017.05.013","article-title":"Early-life exposure to caffeine affects the construction and activity of cortical networks in mice","volume":"295","author":"Fazeli","year":"2017","journal-title":"Exp. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/pr.2015.65","article-title":"Caffeine impairs gastrointestinal function in newborn rats","volume":"78","author":"Welsh","year":"2015","journal-title":"Pediatr. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"F297","DOI":"10.1136\/adc.2003.027565","article-title":"Theophylline and gastric emptying in very low birthweight neonates: A randomised controlled trial","volume":"89","author":"Gounaris","year":"2004","journal-title":"Arch. Dis. Child Fetal. Neonatal Ed."},{"key":"ref_11","first-page":"1129","article-title":"Comparison of caffeine citrate and aminophylline for treating primary apnea in premature infants","volume":"16","author":"Xu","year":"2014","journal-title":"Zhongguo Dang Dai Er Ke Za Zhi"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1136\/archdischild-2015-309396","article-title":"Adverse drug reactions in neonates: A prospective study","volume":"101","author":"Arruza","year":"2016","journal-title":"Arch. Dis. Child."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"243","DOI":"10.5935\/MedicalExpress.2014.05.06","article-title":"Clinical Pharmacology of Caffeine Citrate in Preterm Infants","volume":"1","author":"Pacifici","year":"2014","journal-title":"Med. Express"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"00330","DOI":"10.1183\/23120541.00330-2019","article-title":"Caffeine in preterm infants: Where are we in 2020?","volume":"6","author":"Moschino","year":"2020","journal-title":"ERJ Open Res."},{"key":"ref_15","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":"Shrestha","year":"2017","journal-title":"Pediatrics Neonatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1542\/peds.2006-2986","article-title":"Therapeutic Drug Monitoring for Caffeine in Preterm Neonates: An Unnecessary Exercise?","volume":"119","author":"Natarajan","year":"2007","journal-title":"Pediatrics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1038\/s41390-019-0514-5","article-title":"Very preterm neonates receiving \u201caggressive\u201d nutrition and early nCPAP had similar long-term respiratory outcomes as term neonates","volume":"86","author":"Panagiotounakou","year":"2019","journal-title":"Pediatric Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Gounaris, A., Sokou, R., Panagiotounakou, P., and Grivea, I.N. (2020). It is Time for a Universal Nutrition Policy in Very Preterm Neonates during the Neonatal Period? Comment on: \u201cApplying Methods for Postnatal Growth Assessment in the Clinical Setting: Evaluation in a Longitudinal Cohort of Very Preterm Infants\u201d. Nutrients, 12.","DOI":"10.3390\/nu12040980"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/bdd.1937","article-title":"Does age affect gastric emptying time? A model-based meta-analysis of data from premature neonates through to adults","volume":"36","author":"Bonner","year":"2015","journal-title":"Biopharm. Drug Dispos."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1136\/adc.69.1_Spec_No.32","article-title":"Ultrasonic assessment of gastric emptying in the preterm infant","volume":"69","author":"Newell","year":"1993","journal-title":"Arch. Dis. Child."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.3109\/14767058.2014.885941","article-title":"Early caffeine therapy for prevention of bronchopulmonary dysplasia in preterm infants","volume":"27","author":"Taha","year":"2014","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"339","DOI":"10.3233\/NPM-15814059","article-title":"Evaluation of caffeine and the development of necrotizing enterocolitis","volume":"8","author":"Cox","year":"2015","journal-title":"J. Neonatal Perinat. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.3109\/14767058.2012.746303","article-title":"Feeding tolerance of preterm infants appropriate for gestational age (AGA) as compared to those small for gestational age (SGA)","volume":"26","author":"Bozzetti","year":"2013","journal-title":"J. Matern Fetal Neonatal. Med."},{"key":"ref_24","first-page":"797","article-title":"Clinical characteristics and risk factors for feeding intolerance in preterm infants","volume":"43","author":"Huang","year":"2018","journal-title":"Zhong Nan Da Xue Xue Bao Yi Xue Ban"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1089\/jcr.2016.0012","article-title":"Early High-Dose Caffeine Increases Seizure Burden in Extremely Preterm Neonates: A Preliminary Study","volume":"6","author":"Vesoulis","year":"2016","journal-title":"J. Caffeine Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1089\/caff.2018.0005","article-title":"Caffeine Treatment for Apnea of Prematurity and the Influence on Dose-Dependent Postnatal Weight Gain Observed Over 15 Years","volume":"8","author":"Philip","year":"2018","journal-title":"J. Caffeine Adenosine Res."},{"key":"ref_27","first-page":"16","article-title":"Effect of erythromycin on gastroduodenal contractile activity in developing neonates","volume":"34","author":"Jadcherla","year":"2002","journal-title":"J. Pediatric Gastroenterol. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/sj.jp.7211618","article-title":"Erythromycin and feeding intolerance in premature infants: A randomized trial","volume":"27","author":"Aly","year":"2007","journal-title":"J. Perinatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1097\/MPG.0000000000000596","article-title":"Influences of breast milk composition on gastric emptying in preterm infants","volume":"60","author":"Perrella","year":"2015","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e13233","DOI":"10.1111\/nmo.13233","article-title":"The newborn rat gastric emptying rate is volume and not developmentally dependent","volume":"30","author":"Ferreira","year":"2018","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.jpeds.2006.05.028","article-title":"Factors regulating gastric emptying in preterm infants","volume":"149","author":"Ramirez","year":"2006","journal-title":"J. Pediatr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1038\/pr.2017.292","article-title":"Gastric emptying of different meal volumes of identical composition in preterm infants: A time series analysis","volume":"83","author":"Perrella","year":"2018","journal-title":"Pediatr. Res."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/6\/1676\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:34:43Z","timestamp":1760175283000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/6\/1676"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,1]]},"references-count":32,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["jcm9061676"],"URL":"https:\/\/doi.org\/10.3390\/jcm9061676","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,1]]}}}