{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T20:04:42Z","timestamp":1773086682234,"version":"3.50.1"},"reference-count":43,"publisher":"BMJ","issue":"6","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Arch Dis Child Fetal Neonatal Ed"],"accepted":{"date-parts":[[2024,4,12]]},"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Caffeine is widely used in preterm infants to prevent or treat apnoea of prematurity. Adverse gastrointestinal effects of caffeine have not been thoroughly researched in preterm infants. With this systematic review and meta-analysis, we aim to summarise the results of trials on the gastrointestinal effects of caffeine in preterm infants.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>We searched MEDLINE, Web of Science, Scopus and ClinicalTrials.gov up to 21 April 2023. We included randomised controlled trials assessing caffeine versus placebo in preterm neonates and reporting gastrointestinal side effects. Risk of bias was assessed using the Cochrane Risk of Bias tool. A Bayesian meta-analysis was performed to estimate the pooled OR of gastrointestinal side effects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Nine trials involving 2746 preterm infants were analysed. Seven trials assessing necrotising enterocolitis and four trials assessing feeding intolerance in our meta-analysis found no differences between caffeine and placebo (OR=1.007 (95% credible interval 0.021, 5.462), I<jats:sup>2<\/jats:sup>=97.4%, and OR=1.266 (95% credible interval 0.064, 28.326), I<jats:sup>2<\/jats:sup>=84.8%, respectively). Four trials assessed the outcomes spontaneous intestinal perforation, constipation, gastrointestinal disorder (composite outcome: gastro-oesophageal regurgitation or dilated bowel loops), age at oral feeding and cholestasis syndrome and found no differences between groups. One trial assessed the outcomes gastro-oesophageal symptoms and duration of tube feeding and found that caffeine was associated with a reduced burden of gastro-oesophageal reflux symptoms at 2\u2009weeks (p&lt;0.05), but not at term.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>According to this systematic review and meta-analysis, the use of caffeine at usual doses in preterm infants does not seem to be associated with significant gastrointestinal adverse effects.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/archdischild-2024-327075","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T13:20:40Z","timestamp":1713792040000},"page":"670-676","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Gastrointestinal effects of caffeine in preterm infants: a systematic review and Bayesian meta-analysis"],"prefix":"10.1136","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6300-8469","authenticated-orcid":false,"given":"Beatriz","family":"Gama","sequence":"first","affiliation":[{"name":"Department of Gynecology-Obstetrics and Pediatrics, Universidade do Porto Faculdade de Medicina, Porto, Portugal"}]},{"given":"Madalena","family":"von Hafe","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, Porto, Portugal"}]},{"given":"Rafael","family":"Vieira","sequence":"additional","affiliation":[{"name":"Department of Community Medicine, Information and Health Decision Sciences (MEDCIDS), Universidade do Porto Faculdade de Medicina, Porto, Portugal"},{"name":"Center for Health Technology and Services Research, Health Research Network (CINTESIS@RISE), Universidade do Porto Faculdade de Medicina, Porto, Portugal"}]},{"given":"Henrique","family":"Soares","sequence":"additional","affiliation":[{"name":"Department of Gynecology-Obstetrics and Pediatrics, Universidade do Porto Faculdade de Medicina, Porto, Portugal"},{"name":"Department of Neonatology, Centro Hospitalar Universitario de Sao Joao, Porto, Portugal"}]},{"given":"In\u00eas","family":"Azevedo","sequence":"additional","affiliation":[{"name":"Department of Gynecology-Obstetrics and Pediatrics, Universidade do Porto Faculdade de Medicina, Porto, Portugal"},{"name":"Department of Pediatrics, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, Porto, Portugal"}]},{"given":"Gustavo","family":"Rocha","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Centro Hospitalar Universitario de Sao Joao, Porto, Portugal"}]}],"member":"239","published-online":{"date-parts":[[2024,4,22]]},"reference":[{"key":"2025090513044720000_109.6.670.1","doi-asserted-by":"publisher","DOI":"10.1542\/neo.8-5-e214"},{"key":"2025090513044720000_109.6.670.2","doi-asserted-by":"publisher","DOI":"10.5409\/wjcp.v4.i4.81"},{"key":"2025090513044720000_109.6.670.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.pedneo.2016.10.003"},{"key":"2025090513044720000_109.6.670.4","doi-asserted-by":"crossref","DOI":"10.1016\/j.siny.2021.101227","article-title":"Are we over-treating hypoxic spells in Preterm infants","volume":"26","author":"Conlon","year":"2021","journal-title":"Semin Fetal Neonatal Med"},{"key":"2025090513044720000_109.6.670.5","doi-asserted-by":"publisher","DOI":"10.1159\/000014200"},{"key":"2025090513044720000_109.6.670.6","doi-asserted-by":"publisher","DOI":"10.1542\/peds.109.5.784"},{"key":"2025090513044720000_109.6.670.7","doi-asserted-by":"publisher","DOI":"10.1136\/fn.80.2.F128"},{"key":"2025090513044720000_109.6.670.8","doi-asserted-by":"publisher","DOI":"10.2146\/ajhp120457"},{"key":"2025090513044720000_109.6.670.9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa054065"},{"key":"2025090513044720000_109.6.670.10","doi-asserted-by":"publisher","DOI":"10.1592\/phco.20.7.644.35167"},{"key":"2025090513044720000_109.6.670.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-018-0089-6"},{"key":"2025090513044720000_109.6.670.12","doi-asserted-by":"publisher","DOI":"10.1055\/s-0041-1727157"},{"key":"2025090513044720000_109.6.670.13","doi-asserted-by":"crossref","DOI":"10.3390\/jcm9061676","article-title":"Caffeine and gastric emptying time in very Preterm neonates","volume":"9","author":"Gounaris","year":"2020","journal-title":"J Clin Med"},{"key":"2025090513044720000_109.6.670.14","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"2025090513044720000_109.6.670.15","unstructured":"Higgins JPT , Chandler J , Cumpston M , et al . 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