Synbiotics in Patients at RIsk fOr Preterm Birth

Ziekenhuis Oost-Limburg402 enrolled

Overview

Prematurity remains the main cause of death and serious health problems in new-borns. Besides the need for hospitalization and medical interventions in the first weeks or months of the new-borns' life, prematurity can cause long-lasting health problems (e.g. multiple hospital admissions, developmental delay, learning difficulties, motor delay, hearing or eye problems, ...). Moreover, prematurity places an enormous economic burden on the society. Aside from the medical problems and the financial cost, the emotional stress and psychological impact on the parents, siblings and other family members should not be underestimated. Previous preterm delivery (before 37 weeks of pregnancy) increases the risk for recurrent preterm delivery in a subsequent pregnancy. Therefore, these women should be considered as 'high risk' for preterm birth. Infections ascending from the vagina may be an important cause of preterm delivery in certain cases. Some women have an abnormal vaginal microbiome and are therefore at risk for infections and preterm birth. On the other hand, the vaginal flora is more stable and resistant to infections in healthy pregnant women who deliver at term (after 37 weeks of gestation). Synbiotics are a mixture containing probiotics and prebiotics. Probiotics are living bacteria with potential beneficial effects that can be used safely in pregnancy, while prebiotics are consumed by the bacteria. It is known that probiotics, when used for a long period of time, can maintain a healthy and stable vaginal flora that may protect against infections. In this study, pregnant patients with a history of preterm birth will be included in the first trimester of pregnancy to start with synbiotics or placebo. The investigators will examine the effect of synbiotics on the vaginal flora and on the pregnancy duration. The hypothesis is that synbiotics, when started early in the pregnancy, can change the disturbed vaginal flora into a stable micro-environment.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

QUADRUPLE

Eligibility

Sex: FEMALEMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Signed written informed consent must be obtained before any study assessment is performed; 2. 18 years of age or older; 3. Singleton pregnancy; 4. Pregnancy consultation between 8 and 10 weeks gestation. 5. At least one of the following risk factors for spontaneous preterm birth: * Prior spontaneous preterm birth, defined as delivery between 24 and 36 weeks following PPROM, preterm labor or cervical insufficiency * PPROM ≤36 weeks in previous pregnancy * Prior spontaneous second-trimester pregnancy loss, defined as PPROM, preterm labor or cervical insufficiency with birth between 14 and 24 weeks. Exclusion Criteria: 1. Patients who are already using pro-, pre- or synbiotics and not willing to stop 2. Multiple pregnancy 3. Need for primary (type 1) cerclage 4. Inflammatory bowel disease 5. Known congenital uterine anomaly 6. History of LLETZ conization

Locations (7)

Ziekenhuis Oost-Limburg

Genk, Limburg, Belgium

RECRUITING

Universitaire Ziekenhuizen Leuven

Leuven, Limburg, Belgium

RECRUITING

UZ Gent

Ghent, Oost-Vlaanderen, Belgium

RECRUITING

AZ Sint-Jan

Bruges, West-Vlaanderen, Belgium

RECRUITING

AZ Sint-Lucas

Bruges, West-Vlaanderen, Belgium

RECRUITING

AZ Groeninge

Kortrijk, Belgium

RECRUITING

CHR Citadelle

Liège, Belgium

RECRUITING

Outcomes

Primary Outcomes

Gestational age at delivery

Time frame: Through study completion - at delivery

Secondary Outcomes

Incidence of PTB, defined as GA at delivery < 37 weeks

Time frame: Through study completion - at delivery

Proportion of PTB in different categories

* of patients that deliver \< 28 weeks: extreme PTB * of patients that deliver from 28 until 37 weeks: very PTB * of patients that deliver from 32 until 37 weeks: moderate to late PTB

Time frame: Through study completion - at delivery

PPROM

Incidence

Time frame: Up to 34 weeks from the date of randomization

PPROM

Gestational age at PPROM

Time frame: Up to 34 weeks from the date of randomization

PPROM

Time to delivery

Time frame: Up to 34 weeks from the date of randomization

Composition of the vaginal microbiome

The vaginal microbiome will be assessed throughout pregnancy at 4 well-defined stages of pregnancy (9, 20, 30 weeks and at delivery) and at admission at the MIC unit for preterm labor, PPROM or cervical insufficiency.

Time frame: Assessed 3 times during the study period: at randomization, 11-13 weeks after randomization (at gestational age 19-21 weeks), and 21-23 weeks after randomization (29-31 weeks of gestation)

Incidence of neonatal admissions

Time frame: Neonatal admission at a neonatal intensive care unit (when the neonate is admitted at a neonatal intensive care unit within 7 days of delivery)

Duration of neonatal admissions

Time frame: Neonatal admission at a neonatal intensive care unit (when the neonate is admitted at a neonatal intensive care unit within 7 days of delivery)

Incidence of maternal admissions

Time frame: Up to 34 weeks from the date of randomization

Duration of maternal admissions

Time frame: Up to 34 weeks from the date of randomization

Quality Of Life during pregnancy and during neonatal admission at a neonatal intensive care unit

Using EQ5D questionnaire (5 questions and scale from 1 to 100)

Time frame: Trough study completion, on average 1 year

Neonatal outcome: infectious parameters

Sepsis (early, late and culture negative), number of episodes (min 72 hours) of antibiotic treatment, duration of antibiotic treatment in days