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.

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