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Exclusion criteria were contraindication to expectant management or indication for antibiotic therapy other than preterm premature rupture of membranes. Antibiotic prophylaxis was categorised as amoxicillin (<jats:italic>n<\/jats:italic>\u00a0=\u00a0345), macrolide (<jats:italic>n<\/jats:italic>\u00a0=\u00a030), third\u2010generation cephalosporin (<jats:italic>n<\/jats:italic>\u00a0=\u00a045) or any combinations covering <jats:italic>Streptococcus agalactiae<\/jats:italic> and &gt;90% of <jats:italic>Escherichia coli<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u00a072), initiated within 24\u00a0hours after preterm premature rupture of membranes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Population\u2010averaged robust Poisson models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcome Measures<\/jats:title><jats:p>Survival at discharge without severe neonatal morbidity, 2\u2010year neurodevelopment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>With amoxicillin, macrolide, third\u2010generation cephalosporin and combinations, 78.5%, 83.9%, 93.6% and 86.0% of neonates were discharged alive without severe morbidity. The administration of third\u2010generation cephalosporin or any <jats:italic>E<\/jats:italic>.\u00a0<jats:italic>coli<\/jats:italic>\u2010targeting combinations was associated with improved survival without severe morbidity (adjusted risk ratio 1.25 [95% confidence interval 1.08\u20131.45] and 1.10 [95 % confidence interval 1.01\u20131.20], respectively) compared with amoxicillin. We evidenced no increase in neonatal sepsis related to third\u2010generation cephalosporin\u2010resistant pathogen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In preterm premature rupture of membranes at 24\u201331\u00a0weeks, antibiotic prophylaxis based on third\u2010generation cephalosporin may be associated with improved survival without severe neonatal morbidity when compared with amoxicillin, with no evidence of increase in neonatal sepsis related to third\u2010generation cephalosporin\u2010resistant pathogen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Tweetable Abstract<\/jats:title><jats:p>Antibiotic prophylaxis after PPROM at 24\u201331\u00a0weeks: 3rd\u2010generation cephalosporins associated with improved neonatal outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1471-0528.17081","type":"journal-article","created":{"date-parts":[[2021,12,26]],"date-time":"2021-12-26T15:29:40Z","timestamp":1640532580000},"page":"1560-1573","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Antibiotic prophylaxis in preterm premature rupture of membranes at 24\u201331\u00a0weeks\u2019 gestation: Perinatal and 2\u2010year outcomes in the EPIPAGE\u20102 cohort"],"prefix":"10.1111","volume":"129","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9654-8104","authenticated-orcid":false,"given":"Elsa","family":"Lorthe","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Paris, Epidemiology and Statistics Research Center\/CRESS, INSERM, INRA  Paris France"},{"name":"Unit of Population Epidemiology, Department of Primary Care Medicine Geneva University Hospitals  Geneva 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