Effect of Probiotics on the Preterm Delivery Rate in Pregnant Women at High Risk for Preterm Birth (PROPEV)

Effect of Probiotics on the Preterm Delivery Rate (< 37 Weeks) in Pregnant Women at High Risk for Preterm Birth (Pregnant Women With Threatened Preterm Labour): PROPEV TRIAL Protocol

Preterm birth (PB) continues to be the main cause of perinatal morbidity and mortality, with emotional and economic consequences. Despite improvements in health, PB prevalence remains stable, possibly due to complex causes such as maternal age, stress, multiparity, etc. Shortening of the uterine cervix in early stages of gestation is a risk factor for PB. The presence of abnormal vaginal microbiota in the early stages of pregnancy is als a risk factor for PB. However, no studies have analysed the impact of probiotics (live microorganisms which, in adequate amounts, confer a health benefit on the host) on the PB in high-risk PB patients (pregnant women with threatened preterm delivery, i.e., uterine contractions and cervical shortening, with a 30% PB risk before 34 weeks, and 50% PB prior to 37 weeks (> 6-10% PB). Similarly, the effect of probiotics on vaginal flora dominated by lactic acid-producing bacteria could be analysed.

Study Overview

• Status: Completed
• Conditions: Preterm Birth
• Intervention / Treatment: Other: Placebo; Dietary supplement: Probiotic

Detailed Description

Hypothesis

• Pregnant women with threatened preterm labour (TPL) will present vaginal microbiome different from those without TPL.
• Treatment with probiotics will modify the vaginal microbioma of pregnant women with TPL.
• The PB rate before 37 weeks in pregnant women with TPL who have received probiotics since their diagnosis will be reduced by at least 30%.

Goals

• To correlate the use of probiotics of pregnant women with TPL with the PB rate before 37 weeks.
• To ascertain the PB rate before 28, 30, 32 and 34 weeks in both groups.
• To assess neonatal morbidity between both groups.

Methods

Prospective, randomised, longitudinal, prospective, double-blind study.

Relevance

This study will determine whether the use of probiotics in pregnant women with TPL is associated with a lower risk of PB before 37 weeks. If so, it would allow us to act on the tertiary prevention of PB and treatment of TPL, the main cause of perinatal morbidity and mortality in our setting. It will also facilitate understanding of the pathophysiology of PB, influence of vaginal microbiota and the mechanism of action of probiotics.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital Vall d'Herbron

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion criteria

• Threatened preterm labour: regular clinical and cardiotography-registered uterine dynamics, and cervical modifications (cervical shortening ≤ 25 mm between 24 and 29 weeks, and ≤ 15 mm between 30 and 34 weeks) according to our care protocol.
• Single gestation.
• Echographically-normal foetal morphology.
• Minimum age 18 years.
• Ability to understand informed consent.
• Signed informed consent.

Exclusion criteria

• Multiple gestations.
• Pregnant women with diagnosis of chorioamnionitis.
• Cervical dilation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Probiotics group; Probiotic drug	Dietary supplement: Probiotic; Reduce preterm birth with this dietary supplement
Placebo Comparator: Control group; This group will receive placebo	Other: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preterm birth rate <37 weeks	To evaluate the percentage of preterm birth in each group (in days of gestation)	From 24 to 37 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preterm birth rate <34 weeks	To evaluate the percentage of preterm birth in each group (in days of gestation)	From 24 to 34 weeks
Preterm birth rate <32 weeks	To evaluate the percentage of preterm birth in each group (in days of gestation)	From 24 to 32 weeks
Preterm birth rate <30 weeks	To evaluate the percentage of preterm birth in each group (in days of gestation)	From 24 to 30 weeks
Preterm birth rate <28 weeks	To evaluate the percentage of preterm birth in each group (in days of gestation)	From 24 to 38 weeks
Intergroup neonatal morbidity	To assess neonatal morbidity	First year of life of newborns

Collaborators and Investigators

• Sponsor: Maternal-Infantil Vall d´Hebron Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2017
• Primary Completion (Actual): June 16, 2022
• Study Completion (Actual): June 16, 2022

Study Registration Dates

• First Submitted: February 11, 2018
• First Submitted That Met QC Criteria: September 27, 2018
• First Posted (Actual): September 28, 2018

Study Record Updates

• Last Update Posted (Actual): September 16, 2022
• Last Update Submitted That Met QC Criteria: September 15, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Probiotics; Preterm birth; Threatened preterm labour
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: PR(AMI)236/2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: This study will allow us to determine whether the use of probiotics in pregnant women with TPL is associated with an increased risk of PB. If so, it would allow us to act on the tertiary prevention of PB and treatment of TPL, the main cause of perinatal morbidity and mortality in our setting. Similarly, it will facilitate understanding of the pathophysiology of PB, influence of vaginal microbiota and the mechanism of action of probiotics.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No