Oral Probiotic Supplementation in Pregnancy to Reduce Group B Streptococcus Colonisation (OPSiP trial): study protocol for a double-blind parallel group randomised placebo trial

Abstract

Introduction: Group B streptococcus (GBS), or Streptococcus agalactiae, remains a leading cause of neonatal morbidity and mortality. Canadian guidelines advise universal maternal screening for GBS colonisation in pregnancy in conjunction with selective antibiotic therapy. This results in over 1000 pregnant individuals receiving antibiotic therapy to prevent one case of early-onset neonatal GBS disease, and over 20 000 pregnant individuals receiving antibiotic therapy to prevent one neonatal death. Given the growing concern regarding the risk of negative sequela from antibiotic exposure, it is vital that alternative approaches to reduce maternal GBS colonisation are explored.Preliminary studies suggest some probiotic strains could confer protection in pregnancy against GBS colonisation.

Methods and analysis: This double-blind parallel group randomised trial aims to recruit 450 pregnant participants in Vancouver, BC, Canada and will compare GBS colonisation rates in those who have received a daily oral dose of three strains of probiotics with those who have received a placebo. The primary outcome will be GBS colonisation status, measured using a vaginal/rectal swab obtained between 35 weeks' gestation and delivery. Secondary outcomes will include maternal antibiotic exposure and urogenital infections. Analysis will be on an intention-to-treat basis.

Patient or public involvement: There was no patient or public involvement in the design of the study protocol.

Ethics and dissemination: This study protocol received ethics approval from the University of British Columbia's Clinical Research Ethics Board, Dublin City University and Health Canada. Findings will be presented at research rounds, conferences and in peer-reviewed publications.

Trial registration number: NCT03407157.

Keywords: BACTERIOLOGY; Clinical Trial; INFECTIOUS DISEASES; Infections disease; Microbiology; NEONATOLOGY; OBSTETRICS; Pregnancy; Streptococcus agalactiae; probiotics.

Figure 1

Study flow chart. For those assessed eligible, consent will be obtained between 23 and 25 weeks gestation. Participants will be blindly randomised via a computer-generated programme to either probiotic (n=225) or placebo (n=225). Participants will take their daily study supplements from 25 weeks gestation until infant delivery. Study swabs will be obtained between 23 and 25 weeks gestation (1 vaginal/rectal, 1 oral), 29–33 weeks gestation (1 vaginal/rectal) and 35 weeks gestation and delivery (1 vaginal/rectal, 1 oral). Participant questionnaires will be completed between 23 and 25 weeks gestation, 29–33 weeks gestation and 4–6 weeks postnatal. A telephone check-in with participants will take place at 27 weeks. Data will be collected from participant questionnaires and medical charts. Analysis will be by intention to treat. ITT, intention to treat; PP, per protocol.