Reduction of Spontaneous Prematurity by Antibiotic Treatment (Josamycin) (PREMYC)

• Antenatal :occurence of a miscarriage late [ Time Frame: between 16 and 22 weeks of amenorrhoea ] [ Designated as safety issue: Yes ]
• Antenatal : premature delivery [ Time Frame: at week of amenorrhea <= 34, 32, 28 ] [ Designated as safety issue: Yes ]
• Antenatal : hospitalisation for risk of premature delivery [ Time Frame: antenatal period ] [ Designated as safety issue: Yes ]
• antenatal : Number of day of hospitalisation for risk of premature delivery [ Time Frame: antenatal period ] [ Designated as safety issue: Yes ]
• Antenatal : premature rupture of membranes [ Time Frame: before 37 week of amenorrhea ] [ Designated as safety issue: Yes ]
• Antenatal : occurence of chorioamnionitis defined by 2 of the following criteria :maternal temperature > 38°C, uterine contractions, Fetid leucorrhoeas, foetal tachycardia > 160bpm, C reactive protein >10mg/l [ Time Frame: antenatal period ] [ Designated as safety issue: Yes ]
• During childbirth : Hyperthermia > 38°C [ Time Frame: Childbirth period ] [ Designated as safety issue: Yes ]
• During childbirth : fetal tachycardia > 160 bpm [ Time Frame: childbirth period ] [ Designated as safety issue: Yes ]
• Post-partum : Hyperthermia > 38°C for more than 24hours [ Time Frame: post partum period ] [ Designated as safety issue: Yes ]
• Post partum :need an antibiotic treatment for more than 48 hours [ Time Frame: post partum period ] [ Designated as safety issue: Yes ]
• Neonatal : neonatal mortality late [ Time Frame: from day 7 to day 28 ] [ Designated as safety issue: Yes ]
• Neonatal : early neonatal mortality [ Time Frame: from day 0 to day 6 ] [ Designated as safety issue: Yes ]
• Neonatal morbidity : immediate neonatal state [ Time Frame: neonatal period ] [ Designated as safety issue: Yes ]
• Neonatal morbidity : infection [ Time Frame: neonatal period ] [ Designated as safety issue: Yes ]
• Neonatal morbidity : respiratory disease [ Time Frame: neonatal period ] [ Designated as safety issue: Yes ]
• Neonatal morbidity : digestive disease [ Time Frame: neonatal period ] [ Designated as safety issue: Yes ]

• Antenatal :occurence of a miscarriage late [ Time Frame: between 16 and 22 weeks of amenorrhoea ] [ Designated as safety issue: Yes ]
• Antenatal : premature delivery [ Time Frame: at week of amenorrhea <= 34, 32, 28 ] [ Designated as safety issue: Yes ]
• Antenatal : hospitalisation for risk of premature delivery [ Time Frame: antenatal period ] [ Designated as safety issue: Yes ]
• antenatal : Number of day of hospitalisation for risk of premature delivery [ Time Frame: antenatal period ] [ Designated as safety issue: Yes ]
• Antenatal : premature rupture of membranes [ Time Frame: before 37 week of amenorrhea ] [ Designated as safety issue: Yes ]
• Antenatal : occurence of chorioamnionitis defined by 2 of the following criteria :maternal temperature > 38°C, uterine contractions, Fetid leucorrhoeas, foetal tachycardia > 160bpm, C reactive protein >10mg/l [ Time Frame: antenatal period ] [ Designated as safety issue: Yes ]
• During childbirth : Hyperthermia > 38°C [ Time Frame: Childbirth period ] [ Designated as safety issue: Yes ]
• During childbirth : fetal tachycardia > 160 bpm [ Time Frame: childbirth period ] [ Designated as safety issue: Yes ]
• post-partum : • Hyperthermia > 38°C for more than 24hours [ Time Frame: post partum period ] [ Designated as safety issue: Yes ]
• Post partum :need an antibiotic treatment for more than 48 hours [ Time Frame: post partum period ] [ Designated as safety issue: Yes ]
• Neonatal : neonatal mortality late [ Time Frame: from day 7 to day 28 ] [ Designated as safety issue: Yes ]
• neonatal : early neonatal mortality [ Time Frame: from day 0 to day 6 ] [ Designated as safety issue: Yes ]
• Neonatal morbidity : immediate neonatal state [ Time Frame: neonatal period ] [ Designated as safety issue: Yes ]
• Neonatal morbidity : infection [ Time Frame: neonatal period ] [ Designated as safety issue: Yes ]
• Neonatal morbidity : respiratory disease [ Time Frame: neonatal period ] [ Designated as safety issue: Yes ]
• Neonatal morbidity : digestive disease [ Time Frame: neonatal period ] [ Designated as safety issue: Yes ]

The purpose of this study is to test the effectiveness of an antibiotic treatment (Josamycin) in the case of positive PCR for Ureaplasma spp. and/or Mycoplasma hominis in the second quarter on the risk of premature birth.

Infection would be the cause of 40 % of spontaneous premature deliveries. The physiopathological hypothesis accepted is a premature ascent of present bacteria in the low genital ways towards the decidual, the foetal membranes then the amniotic liquid. These bacteria are responsible for an inflammatory reaction to the interface feto-maternal characterized by the production of proinflammatory cytokines and pro-contractants agents (prostaglandins, oxytocin) by the decidual and the membranes.

These mediators cause uterine contractions, a maturation of the uterine collar, a rupture of the membranes then a premature birth.

Several recent publications show on the one hand that Mycoplasma hominis and Ureaplasma spp. are the bacteria most frequently found in the amniotic liquid in the second quarter of the pregnancy and that a positive PCR for these bacteria is associated with a premature birth.

A probable assumption would be that Mycoplasma hominis or Ureaplasma spp. cause a premature birth by infecting the fetal membranes and the decidual, then activating the immune system and the pro-inflammatory production of cytokines. These bacteria are sensitive to antibiotic treatment.

Nevertheless, no randomized controlled trials have been carried out to determine wether an antibiotic treatment would decrease spontaneous prematurity in the case of positive PCR in the amniotic liquid.

• Drug: Josamycin
  josamycin with posology of 2 grams per day by oral way during 10 days
  Other Name: Josamycin
• Drug: Placebo
  Placebo with posology of 2 grams per day by oral way during 10 days
  Other Name: Placebo

• Experimental: 1
  josamycin
  Intervention: Drug: Josamycin
• Placebo Comparator: 2
  Placebo
  Intervention: Drug: Placebo

Inclusion Criteria:

• Patient older ≥ 18 years
• French speaking
• Women who have an amniocentesis between 15 and 20 weeks of amenorrhoea for an antenatal diagnosis
• Affiliated to social security or an equivalent system
• Karyotype analysis and ultrasound morphological normal (apart from minor signs of trisomy 21)
• Clear amniotic fluid (not contaminated by the mother's blood)
• Gestational age is between 15 WA(day+0) and 20 WA(day+6)
• Patient have not allergy to macrolides
• Do not have cure underway by macrolide
• Patient followed during her pregnancy in an investigator site
• Informed consent and signed

Exclusion Criteria:

• No speaking french
• Having an allergy to macrolides
• Having a multiple pregnancy
• Morphological Anomaly
• Patient no consented
• Lactose Intolerance
• Not agreed to participate