. 2022 Aug;129(9):1560-1573.

doi: 10.1111/1471-0528.17081. Epub 2022 Jan 13.

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

2}, Mathilde Letouzey^{1

3}, Héloïse Torchin^{1

4}, Laurence Foix L'Helias^{1

5}, Christèle Gras-Le Guen⁶, Valérie Benhammou¹, Pascal Boileau^{3

7}, Caroline Charlier⁸, Gilles Kayem^{1

9}; EPIPAGE-2 Obstetric Writing Group

Collaborators, Affiliations

Collaborators

EPIPAGE-2 Obstetric Writing Group:
Pierre-Yves Ancel, Catherine Arnaud, Julie Blanc, Thierry Debillon, Pierre Delorme, Claude D'Ercole, Thomas Desplanches, Caroline Diguisto, Géraldine Gascoin, Catherine Gire, François Goffinet, 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, M J Costedoat, A Leguen, B Lecomte, D Lemery, F Vendittelli, G Beucher, M Dreyfus, B Guillois, Y Toure, A Burguet, S Couvreur, J B Gouyon, P Sagot, N Colas, J Sizun, A Beuchée, P Pladys, F Rouget, R P 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, P H 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, M H Binet, J Fresson, J M Hascoët, A Milton, O Morel, R Vieux, L Hilpert, C Alberge, M Baron, M L 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, J C Picaud, S Rubio-Gurung, C Cans, A Ego, H Patural, A Rannaud, E Janky, A Poulichet, J M Rosenthal, E Coliné, A Favre, N Joly, S Châlons, J Pignol, P L Laurence, P Y 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, M J Saurel-Cubizolles, D Tran

Affiliations

¹ Université de Paris, Epidemiology and Statistics Research Center/CRESS, INSERM, INRA, Paris, France.
² Unit of Population Epidemiology, Department of Primary Care Medicine, Geneva University Hospitals, Geneva, Switzerland.
³ Department of Neonatal Paediatrics, Poissy Saint Germain Hospital, Versailles Saint Quentin en Yvelines University, Poissy, France.
⁴ Department of Neonatal Paediatrics, Cochin Port Royal Hospital, APHP, Paris, France.
⁵ Department of Neonatal Paediatrics, Trousseau Hospital, APHP, Sorbonne University, Paris, France.
⁶ Department of Paediatrics, Paediatrics Emergency Unit and General Paediatrics, Nantes University Hospital, Hôpital Mère-Enfant, CHU de Nantes, Nantes, France.
⁷ UFR des Sciences de la Santé Simone Veil, Versailles St Quentin en Yvelines University, Montigny le Bretonneux, France.
⁸ Université de Paris, Hôpital Universitaire Necker-Enfants Malades, Biology of Infection Unit, Division of Infectious Diseases and Tropical Medicine, Assistance Publique-Hôpitaux de Paris, Institut Pasteur, French National Reference Centre and WHO Collaborating Centre for Listeria U1117, Inserm U1117, Paris, France.
⁹ Department of Gynaecology and Obstetrics, Trousseau Hospital, APHP, Sorbonne University, Paris, France.

PMID: 34954867
PMCID: PMC9546066
DOI: 10.1111/1471-0528.17081

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 et al. BJOG. 2022 Aug.

. 2022 Aug;129(9):1560-1573.

doi: 10.1111/1471-0528.17081. Epub 2022 Jan 13.

Authors

Collaborators

EPIPAGE-2 Obstetric Writing Group:
Pierre-Yves Ancel, Catherine Arnaud, Julie Blanc, Thierry Debillon, Pierre Delorme, Claude D'Ercole, Thomas Desplanches, Caroline Diguisto, Géraldine Gascoin, Catherine Gire, François Goffinet, 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, M J Costedoat, A Leguen, B Lecomte, D Lemery, F Vendittelli, G Beucher, M Dreyfus, B Guillois, Y Toure, A Burguet, S Couvreur, J B Gouyon, P Sagot, N Colas, J Sizun, A Beuchée, P Pladys, F Rouget, R P 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, P H 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, M H Binet, J Fresson, J M Hascoët, A Milton, O Morel, R Vieux, L Hilpert, C Alberge, M Baron, M L 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, J C Picaud, S Rubio-Gurung, C Cans, A Ego, H Patural, A Rannaud, E Janky, A Poulichet, J M Rosenthal, E Coliné, A Favre, N Joly, S Châlons, J Pignol, P L Laurence, P Y 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, M J Saurel-Cubizolles, D Tran

Affiliations

¹ Université de Paris, Epidemiology and Statistics Research Center/CRESS, INSERM, INRA, Paris, France.
² Unit of Population Epidemiology, Department of Primary Care Medicine, Geneva University Hospitals, Geneva, Switzerland.
³ Department of Neonatal Paediatrics, Poissy Saint Germain Hospital, Versailles Saint Quentin en Yvelines University, Poissy, France.
⁴ Department of Neonatal Paediatrics, Cochin Port Royal Hospital, APHP, Paris, France.
⁵ Department of Neonatal Paediatrics, Trousseau Hospital, APHP, Sorbonne University, Paris, France.
⁶ Department of Paediatrics, Paediatrics Emergency Unit and General Paediatrics, Nantes University Hospital, Hôpital Mère-Enfant, CHU de Nantes, Nantes, France.
⁷ UFR des Sciences de la Santé Simone Veil, Versailles St Quentin en Yvelines University, Montigny le Bretonneux, France.
⁸ Université de Paris, Hôpital Universitaire Necker-Enfants Malades, Biology of Infection Unit, Division of Infectious Diseases and Tropical Medicine, Assistance Publique-Hôpitaux de Paris, Institut Pasteur, French National Reference Centre and WHO Collaborating Centre for Listeria U1117, Inserm U1117, Paris, France.
⁹ Department of Gynaecology and Obstetrics, Trousseau Hospital, APHP, Sorbonne University, Paris, France.

PMID: 34954867
PMCID: PMC9546066
DOI: 10.1111/1471-0528.17081

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.

Tweetable abstract: Antibiotic prophylaxis after PPROM at 24-31 weeks: 3rd-generation cephalosporins associated with improved neonatal outcomes.

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

PubMed Disclaimer

Conflict of interest statement

None declared. Completed disclosure of interest forms are available to view online as supporting information.

Figures

**FIGURE 1**
Flow chart. Summarises how sample size of analysis was obtained. PPROM, preterm premature rupture of membranes

See this image and copyright information in PMC

References

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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

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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

Authors

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Abstract

Conflict of interest statement

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