Antibiotics for amniotic-fluid colonization by Ureaplasma and/or Mycoplasma spp. to prevent preterm birth: A randomized trial

doi:10.1371/journal.pone.0206290

Randomized Controlled Trial

. 2018 Nov 7;13(11):e0206290.

doi: 10.1371/journal.pone.0206290. eCollection 2018.

Antibiotics for amniotic-fluid colonization by Ureaplasma and/or Mycoplasma spp. to prevent preterm birth: A randomized trial

Gilles Kayem^{1

2

3}, Alexandra Doloy⁴, Thomas Schmitz^{5

6}, Yvon Chitrit⁷, Philippe Bouhanna⁸, Bruno Carbonne^{2

9}, Jean Marie Jouannic^{2

10}, Laurent Mandelbrot^{5

7

11}, Alexandra Benachi¹², Elie Azria^{1

13}, Francoise Maillard¹, Florence Fenollar¹⁴, Claire Poyart^{4

15}, Cécile Bebear^{16

17}, François Goffinet^{1

15

18}

Affiliations

¹ Inserm UMR 1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team (Epopé), Center for Epidemiology and Statistics Sorbonne Paris Cité, DHU Risks in pregnancy, Paris Descartes University, Paris, France.
² Sorbonne University, Université Pierre et Marie Curie, Paris, France.
³ Department of Obstetrics and Gynecology, CHI Créteil Hospital, Créteil, France.
⁴ Department of Microbiology, Cochin, Broca, Hôtel Dieu Hospital, AP-HP, Paris, France.
⁵ Paris Diderot-Paris VII University, Paris, France.
⁶ Department of Gynecology and Obstetrics, Robert Debré Hospital, APHP, Paris, France.
⁷ Department of Gynecology and Obstetrics, Louis Mourier Hospital, APHP, Paris, France.
⁸ Department of Gynecology and Obstetrics, CHI Poissy, Poissy, France.
⁹ Department of Obstetrics and Gynecology, Saint Antoine Hospital, APHP, Paris, France.
¹⁰ Department of Obstetrics and Gynecology, Trousseau Hospital, APHP, Paris, France.
¹¹ Inserm IAME-UMR1137, Paris, France.
¹² Department of Obstetrics and Gynecology, Antoine Beclère Hospital, Clamart, APHP, Paris, France.
¹³ Department of Gynecology and Obstetrics, Bichat Hospital, APHP, Paris, France.
¹⁴ Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes CNRS UMR 6236 IRD 198, Marseille, France.
¹⁵ Paris Descartes University, Paris, France.
¹⁶ INRA, USC EA 3671, Mycoplasmal and Chlamydial Infections in Humans, Bordeaux, France.
¹⁷ University of Bordeaux, USC EA 3671, Mycoplasmal and Chlamydial Infections in Humans, Bordeaux, France.
¹⁸ Department of Obstetrics and Gynecology, Cochin, Broca, Hôtel Dieu Hospital, AP-HP, Paris, France.

PMID: 30403730
PMCID: PMC6221323
DOI: 10.1371/journal.pone.0206290

Randomized Controlled Trial

Antibiotics for amniotic-fluid colonization by Ureaplasma and/or Mycoplasma spp. to prevent preterm birth: A randomized trial

Gilles Kayem et al. PLoS One. 2018.

. 2018 Nov 7;13(11):e0206290.

doi: 10.1371/journal.pone.0206290. eCollection 2018.

Authors

Affiliations

¹ Inserm UMR 1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team (Epopé), Center for Epidemiology and Statistics Sorbonne Paris Cité, DHU Risks in pregnancy, Paris Descartes University, Paris, France.
² Sorbonne University, Université Pierre et Marie Curie, Paris, France.
³ Department of Obstetrics and Gynecology, CHI Créteil Hospital, Créteil, France.
⁴ Department of Microbiology, Cochin, Broca, Hôtel Dieu Hospital, AP-HP, Paris, France.
⁵ Paris Diderot-Paris VII University, Paris, France.
⁶ Department of Gynecology and Obstetrics, Robert Debré Hospital, APHP, Paris, France.
⁷ Department of Gynecology and Obstetrics, Louis Mourier Hospital, APHP, Paris, France.
⁸ Department of Gynecology and Obstetrics, CHI Poissy, Poissy, France.
⁹ Department of Obstetrics and Gynecology, Saint Antoine Hospital, APHP, Paris, France.
¹⁰ Department of Obstetrics and Gynecology, Trousseau Hospital, APHP, Paris, France.
¹¹ Inserm IAME-UMR1137, Paris, France.
¹² Department of Obstetrics and Gynecology, Antoine Beclère Hospital, Clamart, APHP, Paris, France.
¹³ Department of Gynecology and Obstetrics, Bichat Hospital, APHP, Paris, France.
¹⁴ Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes CNRS UMR 6236 IRD 198, Marseille, France.
¹⁵ Paris Descartes University, Paris, France.
¹⁶ INRA, USC EA 3671, Mycoplasmal and Chlamydial Infections in Humans, Bordeaux, France.
¹⁷ University of Bordeaux, USC EA 3671, Mycoplasmal and Chlamydial Infections in Humans, Bordeaux, France.
¹⁸ Department of Obstetrics and Gynecology, Cochin, Broca, Hôtel Dieu Hospital, AP-HP, Paris, France.

PMID: 30403730
PMCID: PMC6221323
DOI: 10.1371/journal.pone.0206290

Abstract

Objective: To assess whether antibiotics used for treatment in asymptomatic second-trimester women positive for Mycoplasma or Ureaplasma spp. detected by amniotic-fluid PCR prevents preterm delivery.

Design: A randomized, double-blind, placebo-controlled trial.

Setting: 10 maternal fetal medicine centers in France.

Population: Women with a singleton pregnancy who underwent amniocentesis between 16 and 20 weeks' gestation (weeks) for Down syndrome screening. A sample of 238 women with PCR-positive findings per treatment group was needed to show a 50% reduction in the preterm delivery rate.

Methods: Amniotic fluid was tested. Women with positive findings on real-time PCR of amniotic fluid for Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma urealyticum and Ureaplasma parvum were randomized to receive josamycin or placebo. Amniotic fluid was also tested for 16S PCR.

Main outcome measures: The primary outcome was delivery before 37 weeks.

Results: In total, 1043 women underwent amniotic-fluid screening with specific PCR detection between July 2008 and July 2011: PCR detection failed in 27 (2.6%), and 20 (1.9%) underwent termination of pregnancy. Among the 1016 women with PCR results, 980 had available data for the primary outcome (delivery before 37 weeks) and 29 (3.0%) were positive for Ureaplasma and/or Mycoplasma spp. Because of the low rate of women with PCR-positive findings, the trial was stopped prematurely. In total, 19 women were randomized to receive placebo (n = 8) or josamycin (n = 11) and their characteristics were comparable, as was the rate of preterm delivery and secondary outcomes. In comparing all PCR-positive and -negative women regardless of treatment, PCR positivity for Ureaplasma and/or Mycoplasma spp. was not associated with any adverse pregnancy or neonatal outcome. Amniotic-fluid screening by 16S PCR showed no other bacterial colonization associated with preterm birth.

Conclusions: Because of a low amniotic fluid colonization rate, the trial was interrupted. Maternal amniotic-fluid colonization by Mycoplasma and/or Ureaplasma spp. at 16-20 weeks in asymptomatic women is rare and not associated with adverse pregnancy outcomes.

Trial registration: ClinicalTrials.gov NCT00718705.

PubMed Disclaimer

Conflict of interest statement

Bayer has provided the treatment (josamycin) only. Bayer did not provide any financial support for the study or to any investigator. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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References

1. MacDorman MF, Matthews TJ, Mohangoo AD, Zeitlin J. International comparisons of infant mortality and related factors: United States and Europe, 2010. Natl Vital Stat Rep. 2014;63(5):1–6. Epub 2014/09/25. . - PubMed
1. Larroque B, Breart G, Kaminski M, Dehan M, Andre M, Burguet A, et al. Survival of very preterm infants: Epipage, a population based cohort study. Arch Dis Child Fetal Neonatal Ed. 2004;89(2):F139–44. 10.1136/adc.2002.020396 . - DOI - PMC - PubMed
1. Goldenberg RL, Hauth JC, Andrews WW. Intrauterine infection and preterm delivery. N Engl J Med. 2000;342(20):1500–7. 10.1056/NEJM200005183422007 - DOI - PubMed
1. Goncalves LF, Chaiworapongsa T, Romero R. Intrauterine infection and prematurity. Ment Retard Dev Disabil Res Rev. 2002;8(1):3–13. 10.1002/mrdd.10008 . - DOI - PubMed
1. Gerber S, Vial Y, Hohlfeld P, Witkin SS. Detection of Ureaplasma urealyticum in second-trimester amniotic fluid by polymerase chain reaction correlates with subsequent preterm labor and delivery. J Infect Dis. 2003;187(3):518–21. 10.1086/368205 . - DOI - PubMed

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[1] MacDorman MF, Matthews TJ, Mohangoo AD, Zeitlin J. International comparisons of infant mortality and related factors: United States and Europe, 2010. Natl Vital Stat Rep. 2014;63(5):1–6. Epub 2014/09/25. . - PubMed

[2] MacDorman MF, Matthews TJ, Mohangoo AD, Zeitlin J. International comparisons of infant mortality and related factors: United States and Europe, 2010. Natl Vital Stat Rep. 2014;63(5):1–6. Epub 2014/09/25. . - PubMed

[3] Larroque B, Breart G, Kaminski M, Dehan M, Andre M, Burguet A, et al. Survival of very preterm infants: Epipage, a population based cohort study. Arch Dis Child Fetal Neonatal Ed. 2004;89(2):F139–44. 10.1136/adc.2002.020396 . - DOI - PMC - PubMed

[4] Larroque B, Breart G, Kaminski M, Dehan M, Andre M, Burguet A, et al. Survival of very preterm infants: Epipage, a population based cohort study. Arch Dis Child Fetal Neonatal Ed. 2004;89(2):F139–44. 10.1136/adc.2002.020396 . - DOI - PMC - PubMed

[5] Goldenberg RL, Hauth JC, Andrews WW. Intrauterine infection and preterm delivery. N Engl J Med. 2000;342(20):1500–7. 10.1056/NEJM200005183422007 - DOI - PubMed

[6] Goldenberg RL, Hauth JC, Andrews WW. Intrauterine infection and preterm delivery. N Engl J Med. 2000;342(20):1500–7. 10.1056/NEJM200005183422007 - DOI - PubMed

[7] Goncalves LF, Chaiworapongsa T, Romero R. Intrauterine infection and prematurity. Ment Retard Dev Disabil Res Rev. 2002;8(1):3–13. 10.1002/mrdd.10008 . - DOI - PubMed

[8] Goncalves LF, Chaiworapongsa T, Romero R. Intrauterine infection and prematurity. Ment Retard Dev Disabil Res Rev. 2002;8(1):3–13. 10.1002/mrdd.10008 . - DOI - PubMed

[9] Gerber S, Vial Y, Hohlfeld P, Witkin SS. Detection of Ureaplasma urealyticum in second-trimester amniotic fluid by polymerase chain reaction correlates with subsequent preterm labor and delivery. J Infect Dis. 2003;187(3):518–21. 10.1086/368205 . - DOI - PubMed

[10] Gerber S, Vial Y, Hohlfeld P, Witkin SS. Detection of Ureaplasma urealyticum in second-trimester amniotic fluid by polymerase chain reaction correlates with subsequent preterm labor and delivery. J Infect Dis. 2003;187(3):518–21. 10.1086/368205 . - DOI - PubMed

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Antibiotics for amniotic-fluid colonization by Ureaplasma and/or Mycoplasma spp. to prevent preterm birth: A randomized trial

Affiliations

Antibiotics for amniotic-fluid colonization by Ureaplasma and/or Mycoplasma spp. to prevent preterm birth: A randomized trial

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Abstract

Conflict of interest statement

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