Clinical trial NCT03401255: Interest of a Vaginal Swab in Detection of Placental Alpha-Microglobulin-1 in the Prediction of Preterm Birth
Official title: Prospective Multicentric Study Estimating the Interest of a Vaginal Swab in Detection of Placental Alpha-Microglobulin-1 (Partosure®) in the Prediction of Preterm Birth
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Preterm Labor
Preterm Birth
Keywords: Placental alpha microglobulin-1
PAMG-1
preterm labor
preterm delivery
preterm birth
cervical length
transvaginal ultrasound
corticosteroid
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2018-01-17
Enrollment: 341
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients presenting symptoms of preterm labor

Brief summary: Preterm labor is the first cause of hospitalization during the pregnancy, and at the origin of more than 60 000 births before 37 weeks of amenorrhea every year in France. It is however difficult to predict if a patient consulting in emergencies with symptoms of preterm labor, will give birth prematurely or not. Current diagnostic tools to identify patients with high risk of premature delivery in 7 days are insufficient because of their low positive predictive value. Yet the neonatal complications in case of premature delivery are important, with respiratory distress syndrome, hyaline membrane disease, necrotizing enterocolitis, intraventricular hemorrhage and post-natal death. Recent studies suggested that the detection of the placental alpha microglobulin 1 (PAMG-1) in the vaginal secretions, by Partosure® test at the women presenting symptoms of preterm labor with intact membranes would indicate that a premature spontaneous delivery could arise in 7 days with a good positive predictive value.The test is interesting all the more as the repetition of the prenatal cures of corticosteroids, aiming at the fetal lung maturation, is this day more recommended and as the beneficial effect takes place within 24 hours in 7 days following their administration. It seems thus essential to make studies to specify the interest of this test at the patients presenting a preterm labor. This study aims at estimating the diagnostic performance of the test of detection of PAMG-1 in the prediction of a delivery in 7 days, at the patients presenting symptoms of preterm labor.

Detailed description: Preterm labor is the first cause of hospitalization during the pregnancy and complicates of a premature delivery in about 30 % of the cases during single pregnancy. It is about a clinical situation arising between 22 and 36 amenorrhea weeks (SA) + 6 days, which are observed the cervical modifications and the uterine contractions confirmed by an ultrasound measure with cervical length ≤25mm.The main complication of the threat premature delivery (MAP) is the premature birth, which is an essential factor of perinatal morbidity and is the second cause of death before the age of 5 years. The measure of cervical length with ultrasound and the detection of the fetal fibronectin were estimated to identify the patients with risk of spontaneous premature delivery, however their capacity to discriminate these patients is insufficient (predictive value is positive of 20 %). It thus seems necessary to find a diagnostic alternative more relevant.The prenatal corticosteroid therapy is recommended for all the patients at risk of premature delivery in 7 days between 24 and 34 SA. Indeed the maximal profit of corticoids arises when the delivery occurs between 12 hours and 7 days following their administration, with a significant reduction in neonatal period the hyaline membrane diseases (50 %), intraventricular hemorrhage, necrotizing enterocolitis and deaths (40 %). Thus corticosteroids establishes the most important treatment in the prematurity.However, the beneficial effect of the corticosteroid therapy decreases if the birth arises beyond 7 days after the administration. So the efficiency of a complete cure of corticoids in the prevention of the neonatal respiratory morbidity is in connection with deadline between the administration and the delivery. The challenge consists in administering the cure of corticoids in 7 days preceding the birth to benefit from the maximal neonatal profit. Besides, the repetition of the cures of corticoids could be responsible for noxious effects on the future of the future adult by distorting the growth of the child and its cognitive future, by increasing the risk of obesity or insulin resistance, as well as the cardiovascular risk in the adulthood.The capacity to discriminate between the patients who are going to give birth prematurely in 7 days so answers a double objective: allow the implementation of an effective and beneficial preventive treatment for the newborn child and avoid treatments and inconvenient hospitalizations, generators of unwanted effects and useless spending.A recent study estimates the interest of an interesting molecule, the placental alpha microglobulin 1 (PAMG-1), in this diagnostic approach. She concludes that the detection of PAMG-1 by a vaginal taking is the best test to predict spontaneous delivery in 7 days compared with the measure of the cervical length by transvaginal ultrasound and the test of fetal fibronectin. If the performance of the test is validated by the study, the coverage of the patients would be optimized with less frequent and less long hospitalizations, as well as a decrease of treatments pointlessly prescribed at the patients not giving birth finally prematurely (tocolytics, corticoids). For those giving birth prematurely, corticoids could be administered for an optimal deadline to obtain the maximal profit for the newborn child.

Eligibility criteria: Inclusion Criteria:

* patients presenting for emergency obstetrical care with signs suggestive of preterm labor
* single pregnancy
* gestational age between 24 + 0 and 33SA + 6 weeks of gestation
* cervical length ≤ 25mm measurement on transvaginal ultrasound with or without uterine contraction
* informed consent
* consenting to be part of the trial

Exclusion Criteria:

* \< 18 years old or patient under guardianship / curators
* multiple pregnancy
* gestational term less than 24 SA or greater than or equal to 34 SA
* heavy vaginal bleeding- antecedent of conisation
* uterine malformation ( bicervical-bicorn uterus, unicervical bicorn uterus, unicorn uterus, septate uterus)
* Cervical dilatation \>3 cm.
* cervical length with transvaginal ultrasound \>25mm
* presence of a hydramnios with a superior amniotic fluid index 25
* premature rupture of manifest membranes (PROM)
* clinical or biological chorioamnionitis
* hooping cervical
* intercurrent obstetric pathology that can induce premature birth
* patient hospitalized for more than 24 hours in another hospital or service for preterm labor diagnosis

Primary outcomes:
measure: diagnostic performance of detection test of PAMG-1 for the prediction of imminent spontaneous preterm delivery within 7 days in patients presenting with symptoms of preterm labor
timeFrame: time to delivery
Secondary outcomes:
measure: sensitivity of detection test of PAMG-1
timeFrame: time to delivery
measure: positive predictive of detection value test of PAMG-1
timeFrame: time to delivery
measure: negative predictive of detection value test of PAMG-1
timeFrame: time to delivery
measure: diagnostic performance of detection test of PAMG-1 in the prediction of imminent spontaneous preterm delivery within 48 hours in patients presenting with symptoms of preterm labor.
timeFrame: time to delivery
measure: cervical length at inclusion
timeFrame: within 48 hours after delivery
measure: cervical length at inclusion
timeFrame: within 7days after delivery
measure: gestational age at inclusion
timeFrame: within 48hours after delivery
measure: gestational age at inclusion
timeFrame: 7 days within after delivery
measure: False positives.
timeFrame: time to delivery
measure: hospital stays
timeFrame: time to delivery
measure: PAMG-1 tests consumption
timeFrame: time to delivery
measure: corticosteroid treatments consumption
timeFrame: time to delivery
measure: tocolytic treatments consumption
timeFrame: time to delivery
Other outcomes:
Locations:
city: La Roche-sur-Yon
country: France
facility: La Roche-sur-yon University Hospital
city: Nantes
country: France
facility: Nantes University Hospital
Study officials:
affiliation: Nantes University Hospital
name: Vincent Dochez, PH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Marie E, Ducarme G, Boivin M, Badon V, Pelerin H, Le Thuaut A, Lamoureux Z, Riche VP, Winer N, Thubert T, Dochez V. The value of a vaginal sample for detecting PAMG-1 (Partosure(R)) in women with a threatened preterm delivery (the MAPOSURE Study): protocol for a multicenter prospective study. BMC Pregnancy Childbirth. 2020 Aug 3;20(1):442. doi: 10.1186/s12884-020-03129-x.