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How close are we to intrapartum molecular testing for GBS status in Australia and New Zealand?

Current strategies for reducing neonatal Group B Streptococcal disease

Group B Streptococcus (GBS) is still the most common pathogen responsible for early-onset sepsis in neonates in developed countries.Early-onset GBS (EOGBS) disease, including sepsis, meningitis and pneumonia, is a leading cause of infant morbidity and mortality.¹

Prevention strategies of EOGBS disease in neonates rely on reducing or eliminating vertical transmission of GBS to the newborn with systemic administration of intrapartum antibiotic prophylaxis (IAP). IAP for at least four hours during labour has reduced, but not eliminated, the incidence of EOGBS disease in neonates.^{1 2 3}

There are currently two strategies in established practice for identifying women eligible for IAP. This entails either performing universal culture-based screening for GBS colonisation (for term deliveries) or identifying the presence of clinical risk factors for GBS transmission.^{1 2} Both strategies are deemed acceptable for reducing EOGBS disease as per the current RANZCOG Statement.⁴

GBS carriage detection by bacterial culture

The current gold standard test for maternal GBS carriage detection is bacterial culture of a specimen obtained by vaginal-rectal swab, which is typically performed at 35–37 weeks gestation. The culture method for GBS detection has several disadvantages: limited sensitivity, a high turnaround time of 36–72hrs, the need for an experienced technician to perform the test, and the low predictive value of antenatal culture findings for GBS colonisation at delivery.^{5 6} Evidence has shown that approximately 10% of women screened negative using antenatal culture screening were found to be GBS positive at the time of delivery.⁷

Due to the variability of GBS colonisation, the widespread use of antibiotics may not always be warranted.^{3 8} Concerns exist about antibiotic resistance in the community and the influence of early antibiotics on dysbiosis of the infant’s microbiome which may lead to adverse health effects in later life.⁹

Real-time polymerase chain reaction (PCR) testing for GBS at the onset of labour is a potential solution to these problems.¹⁰

Intrapartum molecular testing for GBS status

Point-of-care intrapartum testing, based on nucleic acid amplification, can provide qualitative analysis of the presence of GBS in the genitourinary and gastrointestinal tract at the time of delivery, both before and after rupture of membranes.¹¹

Intrapartum PCR testing has been shown to be both highly sensitive (84–99%) and specific (76–99%) for detection of GBS and comparable to GBS culture.^{3 6 6 12 13} Out of many testing systems globally, the GeneXpert® GBS test (Cepheid, Sunnyvale, CA,USA) is approved by TGA Australia and is promising because it can yield a result in 30–50 minutes with high diagnostic accuracy, and is characterised by a low workload.^{3 8 14}

A 2015 European consensus conference recommended IAP based on universal intrapartum GBS screening using a rapid real-time PCR-testing method.⁸ Use of PCR testing for GBS at the time of preterm rupture of membranes has shown a 50% reduction in IAP usage.^{14 15} A 2019 French study compared EOGBS rates in a hospital prior to and after introduction of an intrapartum PCR screening protocol and demonstrated a significant reduction in the rate of proven EOGBS disease cases from 1.01/1000 live births to 0.21/1000 live births. Intrapartum PCR testing also reduced the number of days of antibiotic usage for EOGBS by 60%.⁷

One disadvantage to the use of the intrapartum PCR testing is the absence of information about antimicrobial susceptibility. This is particularly important in the setting of maternal beta-lactam allergy. The recommended use of clindamycin in this setting is problematic in that clindamycin resistance continues to increase in Australia, with resistance rates of up to 40% reported in Western Australia.^{16 17} Therefore, antimicrobial susceptibility testing remains essential for penicillin-allergic women with a high anaphylaxis risk. Future improvements to the PCR test may be the combined detection of GBS and of mutations likely to confer resistance to clindamycin.⁸

The cost of a GBS PCR test is more expensive compared to antenatal culture.^{3 18} Costs involving implementation of the test into routine care are also significant, relating to equipment, clinical and laboratory staff training and availability. An option to deal with the increasing demand on laboratory staff is to train midwifery staff to use a point-of-care machine on the labour ward (this has been done successfully in some European centres).^{7 10 18} One study showed a higher number of invalid tests when performed by midwifery staff compared to trained laboratory staff. This highlights that adequate training of non-laboratory staff is important to achieve sensitivity required for point-of-care testing in labour wards.¹⁹ The point-of-care tests are simple to perform but require an administrative burden of quality control, training and result entry, which may be difficult for the midwifery workforce to absorb.

Table 1 summarises the potential benefits and limitations of the intrapartum PCR test.

Table 1. Summary of potential benefits and limitations of the routine use of intrapartum GBS PCR testing.

Introducing intrapartum PCR testing into routine obstetric care in Australia and New Zealand

National Australian and New Zealand guidelines do not yet recommend the use of intrapartum PCR testing. The RANZCOG guideline on Maternal GBS in Pregnancy, last updated 2019, expresses concerns about the cost of the test and laboratory accessibility for PCR analysis after-hours.⁴ Available evidence in recent publications is convincing in terms of overall benefits and safety of the test, and validates current technology. However, there are human and hospital infrastructure requirements still being navigated in an Australian and New Zealand context before routine implementation is possible. The 2019 guideline also states concerns about the timeliness of the PCR test to provide IAP within four hours of delivery. However, studies have addressed this showing that most test results are available four hours prior to delivery allowing for timely IAP.^{3 8 19}

Cost effectiveness still needs to be evaluated in the Australian and New Zealand healthcare systems. European studies have demonstrated intrapartum GBS PCR testing to be cost-effective or at least cost-neutral.^{7 20} The additional cost of PCR testing is balanced against the cost of routine intrapartum antibiotics, the significant reduction in early onset GBS disease and costs associated with treatment and admission of neonatal EOGBS sepsis.^{7 8 20} If the test is introduced into clinical practice, the cost of the test will likely decrease and be similar or lower than the cost of antepartum culture.³

There is no available published data on the stages of implementation of this test across Australia and New Zealand. It is likely that pilot studies and cost analyses are being conducted at an institutional level at this stage.

Changes to established protocols, that have significant resource and logistical implications, will take time. The process of implementing intrapartum PCR testing for GBS status into routine care is in its infancy and it will likely be years before this is routine practice. Collaboration between units may be useful to fully appreciate the current state of implementing intrapartum PCR testing for GBS status across Australia and New Zealand.

1. Hasperhoven GF, AlNasiry S, Bekker V, et al. Universal screening versus risk-based protocols for antibiotic prophylaxis during childbirth to prevent early-onset group B stretococcal disease: a systemic review and meta-analysis. BJOG. 2020;126(6):680-91.
2. Li Q, Wang D, Li H, Liu J. Screening-based and Risk-based Strategy for the Prevention of Early-onset Group B Streptococcus/Non-group B Streptococcus Sepsis in the Neonate: A Systematic Review and Meta-analysis. Pediatr Infect Dis. 2020;39(8):740-8.
3. Pichiassi E, Coata G, Babucci G, et al. Intrapartum test for detection of Group B Streptococcus colonization during labour. J Matern Fetal Neonatal Med. 2018;31(24):3303-10.
4. RANZCOG. Maternal Group B Streptococcus in pregnancy: screening and management. 2013, updated 2019. Available from: https://ranzcog.edu.au/statements-guidelines/obstetrics/maternal-group-b-streptococcus-(gbs)-in-pregnancy
5. Verani JR, McGee L, Schrag SJ. Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC). Prevention of perinatal group B streptococcal disease – revised guidelines from CDC. MMWR Recomm Rep. 2010;59(RR-10):1-36.
6. El Helali N, Nguyen JC, Giovangrandi Y, Trinquart L. Diagnostic accuracy of a rapid real-time polymerase chain reaction assay for universal intrapartum group B streptococcus screening. Clin Infect Dis. 2009 49(3):417-23.
7. El Helali N, Habibi F, Azria E, et al. Point-of-Care Intrapartum Group B Streptococcus Molecular Screening: Effectiveness and Costs. Obstet Gynaecol. 2019;00:1-6.
8. Di Renzo GC, Melin P, Berardi A. Intrapartum GBS screening and antibiotic prophylaxis: a European consensus conference. J Matern Fetal Neonatal Med. 2015;28(7):766-82.
9. Neuman H, Forsythe P, Uzan A, et al. Antibiotics in early life: dysbiosis and the damage done. FEMS Microbiol Rev. 2018;42(4):489-99.
10. Dakin A, Ferguson W, Drew R, et al. Assessing standards for prevention of early onset group B streptococcal (GBS) disease in Ireland. Ir J Med Sci. 2021;14:1-7.
11. Bergeron M, Danbig K, Menard C, et al. Rapid Detection of Group B Streptococci in Pregnant Women at Delivery. N Engl J Med. 2000;343:175-9.
12. Feuerschuette O, Silveira S, Cancelier A, et al Diagnostic yield of real-time polymerase chain reaction in the diagnosis of intrapartum maternal rectovaginal colonization by group B streptococcus: a systematic review with meta-analysis. Diagn Microbiol Infect Dis. 2018;91(2):99-104.
13. Nielson SY, Moller JK, Khalil MR. A comparison of GenomEra GBS PCR and GeneXpert GBS PCR assays with culture of GBS performed with and without broth pre-enrichment. Eur J Clin Microbiol Infect Dis. 2020;39(10):1945-50.
14. Helmig RB, Gertsen JB. Intrapartum PCR-assay for detection of Group B Streptococci (GBS) European Journal of Obstetrics and Gynaecology and Reproductive Biology: X. 2019;4:1-4.
15. Bourgeois-Nicolaos N, Cordier AG, Guillet-Caruba C. Evaluation of the Cepheid Xpert GBS assay for rapid detection of group B streptococci in amniotic fluids from pregnant women with premature rupture of membranes. J Clin Microbiol. 2013;51(4):1305-6.
16. Chang LW, Gardland S, Daley ARC. Increasing clindamycin resistance among Austarlian group B streptococcus isolates. Intern Med J. 2015;45(4):456-6.
17. King Edward Memorial Hospital Antibiogram January to December 2019. Available from: https://wnhs-healthpoint.hdwa.health.wa.gov.au/directory/CES/MedicalServices/AntimicrobialStewardship/Documents/Antibiogram%202019.pdf.
18. National Institute for Health and Care Excellence (NICE). Xpert GBS test for the intrapartum detection of group B streptococcus. Medtech innocation briefing. 2015. Available from: www.nice.org.uk/advice/mib28/resources/xpert-gbs-test-for-the-intrapartum-detection-of-group-b-streptococcus-63499051847365.
19. Plainvert C, El Alaoui F, Tazi A, et al. Intrapartum group B Streptococcus screening in the labor ward by Xpert GBS real-time PCR. Eur J Clin Microbiol Infect Dis. 2018;37:265-70.
20. El Helali N, Giovangrandi Y, Guyot K, et al. Cost and effectiveness of intrapartum group B streptococcus polymerase chain reaction screening for term deliveries. Obstet Gynaecol. 2012;119(4):822-9.