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, 3) , Héloïse Torchin (4, 1) , Laurence Foix L'Helias (1) , Christèle Gras-Le Guen (5) , Valérie Benhammou (6) , Pascal Boileau (2, 3) , Caroline Charlier (7) , Gilles Kayem (8) , Pierre‐yves Ancel (6) , Catherine Arnaud (9, 10) , Julie Blanc (11, 12) , Thierry Debillon (13, 14) , Pierre Delorme (6) , Claude D’ercole (15) , Thomas Desplanches (16, 6) , Caroline Diguisto (1) , Géraldine Gascoin (17, 10) , Catherine Gire (18, 19) , François Goffinet (20) , Bruno Langer (21) , Emeline Maisonneuve , Stéphane Marret , Isabelle Monier , Andrei Morgan , Jean‐christophe Rozé (22, 5) , Thomas Schmitz , Loïc Sentilhes , Damien Subtil , Barthélémy Tosello , Christophe Vayssière (10) , Norbert Winer (22, 5) , 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 (10) , 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 , 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 , Jean Gondry (23, 24, 25) , 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

1 CRESS (U1153 / UMR_A 1125) - Centre for Research in Epidemiology and Statistics | Centre de Recherche Épidémiologie et Statistiques
2 Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy]
3 UVSQ Santé - Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil
4 AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris]
5 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
6 EPOPé [CRESS - U1153 / UMR_A 1125] - Obstetrical, Perinatal and Pediatric Epidemiology | Épidémiologie Obstétricale, Périnatale et Pédiatrique
7 Unité de Parasitologie-Mycologie, Service de Microbiologie [Hôpital Necker-Enfants-Malades, Paris]
8 CHU Trousseau [APHP]
9 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
10 Equipe SPHERE (CERPOP)
11 EFTS - Education, Formation, Travail, Savoirs
12 ENSFEA - École Nationale Supérieure de Formation de l'Enseignement Agricole de Toulouse-Auzeville
13 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
14 TIMC-MESP - Modélisation et Évaluation des données complexes en Santé Publique
15 Service de gynécologie-obstétrique [Hôpital Nord - APHM]
16 CHU Dijon
17 CHU Angers - Centre Hospitalier Universitaire d'Angers
18 Hôpital Nord [CHU - APHM]
19 CEReSS - Centre d'études et de recherche sur les services de santé et la qualité de vie
20 Recherches épidémiologiques en santé périnatale et santé des femmes
21 Department of Obstetrics and Gynecology
22 PhAN - Physiopathologie des Adaptations Nutritionnelles
23 CHU Amiens-Picardie
24 GRAMFC - Groupe de Recherche sur l'Analyse Multimodale de la Fonction Cérébrale - UMR INSERM_S 1105
25 EPIPAGE-2 Study Group

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.

Keywords: amoxicillin; antenatal management; cephalosporins; latency; macrolides; neurodevelopment; obstetric intervention; perinatal outcome; prematurity

Domains: Life Sciences [q-bio]

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, 2022, 129 (9), pp.1560-1573. ⟨10.1111/1471-0528.17081⟩. ⟨hal-03979342⟩