Rapid Intrapartum Test for Maternal Group B Streptococcal Colonisation and its Effect on Antibiotic Use in Labouring Women with Risk Factors for Early Onset Neonatal Infection (GBS2): Cluster Randomised Trial with Nested Test Accuracy Study

Background: We evaluated whether use of point-of-care rapid intrapartum test to detect maternal GBS colonisation reduces maternal antibiotics exposure compared with usual care, where antibiotics are administered due to clinical risk factors. We assessed the accuracy of the rapid test in diagnosing maternal GBS colonisation, against the reference standard of selective enrichment culture. Methods: Parallel-group cluster randomised trial with nested test accuracy study and microbiological sub-study in 20 maternity units in UK randomised to a strategy of rapid test (GeneXpert GBS system, Cepheid) or usual care. The main outcomes were maternal intrapartum antibiotics administered to prevent neonatal early-onset GBS infection, accuracy of the rapid test, and antibiotic resistance profiles in maternal and infant samples. The trial was registered ISRCTN74746075 Findings: 722 mothers (749 babies) participated in rapid test units; 906 mothers (951 babies) in usual care units. There was no evidence of a difference in the primary outcome (Risk ratio 1.16, 95% CI 0.83 to 1.64) between the rapid test (41%, 297/716) and usual care (36%, 328/906) units. The sensitivity and specificity measures of the rapid test were 86% (95% CI 81 to 91%) and 89% (95% CI 85 to 92%) respectively. Interpretation: Use of intrapartum rapid test to diagnose maternal GBS colonisation did not reduce the rates of antibiotics administered for preventing neonatal early-onset GBS infection than usual care, although with considerable uncertainty. The accuracy of the rapid test is within acceptable limits. Trial Registration: ISRCTN74746075 Funding: National Institute for Health Research Health Technology Assessment programme (13/82/04). Declaration of Interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf. JP is the Chief Executive of Group B Strep Support, a Charity working to stop GBS in babies. JP received support from Cepheid to attend an academic conference in 2016, from Pfizer to attend a summit for vaccine advocacy stakeholders in the USA in 2019 and from i-CONSENT to attend workshops in London in 2018 and Brussels in 2019 regarding consent for vaccine trials. JP was a member of the Department of Health research prioritisation expert group in 2016. JP and JG are members of the NICE guideline update committee for Neonatal infection: antibiotics for prevention and treatment (update). JG was a member of the NICE Diagnostics Advisory Committee that produced DG38 Rapid tests for group A streptococcal infections in people with a sore throat (which included assessment of the Cepheid GeneXpert Xpert® Xpress Strep A test) (Published November 2019). JPD, JP, JG are grant holders for HTA 17/86/06 (GBS3), a cluster randomised trial of routine screening for GBS. JPD and JP are grant applicants for a study to determine a serocorrelate of immune protection against GBS. All other authors declare no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. JJD is supported by the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham. Ethics Approval Statement: This study was approved by the West Midlands – Edgbaston Multi centre Research Ethics Committee (16/WM/0036), including waiver of individual research consent.