Clinical trial NCT02225717: Identification of Spontaneous Delivery Markers
Official title: Markers of Fetal Membranes Remodelling in Cervicovaginal Fluid and Delivery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Preterm Labor (24 GA - 32 GA)
Keywords: Preterm labor
cervicovaginal secretions
markers of fetal membranes remodelling
Multiplex test
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2014-08-26
Enrollment: 238
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: The investigators project aims to identify, in pregnant women, discriminating molecules to allow an early detection of women who will spontaneously deliver prematurely, suitable in routine clinical practice.

Human parturition is tightly correlated with hormonal changes at the maternal-fetal interface during pregnancy, that may control cell interactions and fetal membranes (the water bag) remodelling. Precocious remodelling may lead to a premature onset of labor, associated or not with premature rupture of membrane whether the cause is infectious or not.

In this regard, remodelled fetal membranes overlying the cervix may discharge signals that could be detectable in cervico-vaginal fluids and serve as biomarkers of the imminence of delivery. Such information on delivery timing may be of great importance for an adequate prediction that would change drastically the management of threatening preterm delivery.

Detailed description: Prematurity is a major Public Health concern in developed countries, since it is the first cause of perinatal morbi-mortality and of cerebral palsy in early childhood. Premature birth rate has risen by 36 percent over the last 25 years to reach 7.2% in 2010 in France. Antenatal corticosteroids administration before 34 weeks and in utero transfer in high-qualified maternity wards are ones of the rare antenatal therapies recommended to improve neonatal complications of preterm delivery. Early identification of women with high risk of preterm birth should be helpful to implement those prophylactic measures. Moreover discriminating true preterm labor (PTL) vs. symptoms of PTL in women, who will finally deliver at term, would reduce unnecessary hospitalizations and prescriptions.

During human gestation, fetal membranes (the "water bag") encompass the amnion, facing the amniotic cavity, and the chorion, lining the maternal decidua and comprising trophoblast cells. Membranes usually remain intact until their spontaneous rupture, close to the first stage of labor at term. Often seen as a simple inert shell, with a role of "airbag" for the developing fetus, the membranes provide yet a large surface of interaction between maternal and fetal tissues and function as a transient endocrine organ with immune properties.

Specific remodelling of the membranes is observed at term prior to delivery. During this remodelling, drastic changes in extracellular matrix occur, with the secretion of specific molecules. The investigators hypothesize that premature fetal membranes remodelling occurs weeks prior to actual birth and may be able to be detected in women at risk for preterm birth, i.e. presenting signs of PTL. This study investigates if the detection of fetal membranes remodelling in cervico-vaginal fluids can accurately identify those women at greatest risk for preterm birth. A prospective cohort of pregnant women will before 32 weeks of gestation with symptoms of preterm labor be enrolled. As negative controls, healthy pregnant women at 12-15 or 35-36 weeks of gestation or non-pregnant women will be recruited. As positive controls, healthy pregnant woman at term (over 38 weeks of gestation) will be enrolled. The main outcome assessed is preterm delivery.

Eligibility criteria: Inclusion Criteria:

- Singleton pregnancy, monitored in Port Royal or secondarily transferred, between 24 and 32 GA. Hospitalization for preterm labor (cervix \< 25 mm at transvaginal cervical ultrasound) or -Singleton pregnancy, monitered in Port Royal between 15-16 weeks of gestation, without complication.

or - Singleton pregnancy, monitered in Port Royal between 35-36 weeks of gestation, without complication.

or - Healthy woman, no pregnancy.

Exclusion Criteria:

* Minor
* Not affiliated to health insurance
* Persons under guardianship or judicial protection
* Infection with HIV, Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV)
* Diabetes or chronic inflammatory disease
* Carrier of B streptococcus
* Cervical strapping
* Fetus with chromosomal abnormalities
* Infections
* Premature rupture of membrane

Primary outcomes:
measure: Delivery
timeFrame: until Day 14
Secondary outcomes:
measure: Delivery before 34 GA
timeFrame: until Day 14
measure: composite Prenatal maternal care
timeFrame: until Delivery
measure: composite Neonatal outcome
timeFrame: At Birth
measure: composite Obstetric outcome
timeFrame: At Delivery
Other outcomes:
Locations:
city: Paris
country: France
facility: Maternité Port Royal-Cochin
Study officials:
affiliation: INSERM U1016 - Cochin Hospital Public Hospitals of Paris
name: Celine MEHATS, PhD
role: STUDY_DIRECTOR
References:
citation: Larroque B, Ancel PY, Marret S, Marchand L, Andre M, Arnaud C, Pierrat V, Roze JC, Messer J, Thiriez G, Burguet A, Picaud JC, Breart G, Kaminski M; EPIPAGE Study group. Neurodevelopmental disabilities and special care of 5-year-old children born before 33 weeks of gestation (the EPIPAGE study): a longitudinal cohort study. Lancet. 2008 Mar 8;371(9615):813-20. doi: 10.1016/S0140-6736(08)60380-3.
citation: McLaren J, Malak TM, Bell SC. Structural characteristics of term human fetal membranes prior to labour: identification of an area of altered morphology overlying the cervix. Hum Reprod. 1999 Jan;14(1):237-41. doi: 10.1093/humrep/14.1.237.
citation: Malak TM, Bell SC. Structural characteristics of term human fetal membranes: a novel zone of extreme morphological alteration within the rupture site. Br J Obstet Gynaecol. 1994 May;101(5):375-86. doi: 10.1111/j.1471-0528.1994.tb11908.x.