PREvention of Preterm birth with Oral Probiotics

INTERVENTION: Study randomisation will be conducted by a research statistician not involved in the trial. Using computer software, the statistician will generate three blocks of randomly allocated sequential study numbers for the two groups of capsules. Participants will be assigned to receive either intervention (probiotics) and placebo (control). Participants randomised to the intervention arm will be asked to take two capsules (each containing 5 billion CFU) orally, once daily. This is a total daily dose of 10 billion CFU. Participants randomised to the control arm will be asked to take two capsules (containing no probiotics) orally, once daily. Study capsules will be packed based on group allocation, with only the study number denoted on the plain packaging. Participants will be consecutively assigned to each study number upon recruitment. Neither investigators nor participants will know the study group designation, thus ensuring the trial is double‐blinded. Study supplements will be provided to the participant in clinic upon successful recruitment and randomisation to the study. Identical capsules containing either the intervention (a total of 10 billion colony forming units of Lactobacillus crispatus LBV 88, Lactobacillus jensenii LBV116, Lactobacillus gaseseri LBV 150N and Lactobacillus rhamnosus LBV96 per capsule) or placebo (maltodextrin and no probiotics) will be supplemented throughout pregnancy from recruitment (at around 12 weeks gestation) until 1 month postpartum. CONDITION: Pregnant women at high risk of preterm birth ; Pregnancy and Childbirth ; Preterm labor with preterm delivery PRIMARY OUTCOME: 25% increase in the relative abundance of L. Crispatus measured using high‐throughput DNA sequencing and/or qPCR after at least 12 weeks of oral supplementation SECONDARY OUTCOME: ; 1. Cervical length at 26‐34 weeks gestation measured using transvaginal ultrasound after at least 12 weeks of oral supplementation; 2. Compliance with the intervention measured by counting remaining capsules at 1 month postpartum; 3. Preterm premature rupture of membranes measured from patient notes at the time of birth; 4. Histological chorioamnionitis measured using placental histopathology at the time of birth; 5. Gestational age at delivery measured from patient notes at the time of birth; 6. NICU admissions measured from patient notes at 1 month postpartum; 7. Neonatal complications measured from patient notes at 1 month postpartum; INCLUSION CRITERIA: 1. Previous preterm birth (<34 weeks gestation) 2. Previous second‐trimester loss (14‐24 weeks gestation) 3. =2 large loop excision of the transformation zone (LLETZ) procedures 4. =1 cone biopsy 5. Uterine anomaly