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Antibiotic prophylaxis in preterm premature rupture of membranes at 24–31 weeks’ gestation: Perinatal and 2‐year outcomes in the EPIPAGE‐2 cohort

Elsa Lorthe 1 Mathilde Letouzey 2, 1 Héloïse Torchin 3, 1 Laurence Foix l'Helias 1 Christèle Gras‐le Guen 4 Valérie Benhammou 5 Pascal Boileau 2 Caroline Charlier 6 Gilles Kayem 7 Pierre‐yves Ancel 5 Catherine Arnaud 8 Julie Blanc 9 Thierry Debillon 10 Pierre Delorme 5 Claude D’ercole 11 Thomas Desplanches 12 Caroline Diguisto 1 Géraldine Gascoin 13 Catherine Gire 14 François Goffinet 15 Bruno Langer Emeline Maisonneuve Stéphane Marret Isabelle Monier Andrei Morgan Jean‐christophe Rozé Thomas Schmitz Loïc Sentilhes Damien Subtil Barthélémy Tosello Christophe Vayssière Norbert Winer Jennifer Zeitlin D Astruc P Kuhn J Matis C Ramousset X Hernandorena P Chabanier L Joly‐pedespan Mj Costedoat A Leguen B Lecomte D Lemery F Vendittelli G Beucher M Dreyfus B Guillois Y Toure A Burguet S Couvreur Jb Gouyon P Sagot N Colas J Sizun A Beuchée P Pladys F Rouget Rp Dupuy D Soupre F Charlot S Roudaut A Favreau E Saliba L Reboul N Bednarek P Morville V Verrière G Thiriez C Balamou L Marpeau C Barbier X Durrmeyer M Granier M Ayoubi O Baud B Carbonne Ph Jarreau D Mitanchez C Duffaut L Cornu R Moras P Boulot G Cambonie 16, 17 H Daudé A Badessi N Tsaoussis A Bédu F Mons C Bahans Mh Binet J Fresson Jm Hascoët A Milton O Morel R Vieux L Hilpert C Alberge M Baron Ml Charkaluk V Pierrat P Truffert S Akowanou U Simeoni A Bongain M Deschamps B Branger V Rouger C Dupont J Gondry G Krim B Baby M Debeir O Claris Jc Picaud S Rubio‐gurung C Cans A Ego H Patural A Rannaud E Janky A Poulichet Jm Rosenthal E Coliné A Favre N Joly S Châlons J Pignol Pl Laurence Py Robillard S Samperiz D Ramful B Blondel M Bonet A Brinis A Coquelin M Durox M Kaminski K Khemache B Khoshnood C Lebeaux L Marchand‐martin J Rousseau Mj Saurel‐cubizolles D Tran
Abstract : Objective To compare different antibiotic prophylaxis administered after preterm premature rupture of membranes to determine whether any were associated with differences in obstetric and/or neonatal outcomes and/or neurodevelopmental outcomes at 2 years of corrected age. Design Prospective, nationwide, population-based EPIPAGE-2 cohort study of preterm infants. Setting France, 2011. Sample We included 492 women with a singleton pregnancy and a diagnosis of preterm premature rupture of membranes at 24–31 weeks. 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 (n = 345), macrolide (n = 30), third-generation cephalosporin (n = 45) or any combinations covering Streptococcus agalactiae and >90% of Escherichia coli (n = 72), initiated within 24 hours after preterm premature rupture of membranes. Methods Population-averaged robust Poisson models. Main Outcome Measures Survival at discharge without severe neonatal morbidity, 2-year neurodevelopment. Results With amoxicillin, macrolide, third-generation cephalosporin and combinations, 78.5%, 83.9%, 93.6% and 86.0% of neonates were discharged alive without severe morbidity. The administration of third-generation cephalosporin or any E. coli-targeting combinations was associated with improved survival without severe morbidity (adjusted risk ratio 1.25 [95% confidence interval 1.08–1.45] and 1.10 [95 % confidence interval 1.01–1.20], respectively) compared with amoxicillin. We evidenced no increase in neonatal sepsis related to third-generation cephalosporin-resistant pathogen. Conclusion In preterm premature rupture of membranes at 24–31 weeks, antibiotic prophylaxis based on third-generation 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-generation cephalosporin-resistant pathogen.
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Elsa Lorthe, Mathilde Letouzey, Héloïse Torchin, Laurence Foix l'Helias, Christèle Gras‐le Guen, et al.. Antibiotic prophylaxis in preterm premature rupture of membranes at 24–31 weeks’ gestation: Perinatal and 2‐year outcomes in the EPIPAGE‐2 cohort. BJOG: An International Journal of Obstetrics and Gynaecology, Wiley, 2022, ⟨10.1111/1471-0528.17081⟩. ⟨hal-03538872⟩

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