Early-onset group B streptococcal disease: Rethinking intrauterine and intrapartum transmission pathways

Roghayeh  Sadeghzadeh; Fereshteh  Afkar; Negar Sadat  Parviz Farzam; Sara  Nezhadi; Ebrahim  Kharazinejad; Reza  Khorasani; Ehsan  Moradi-Joo; Sara Kooti

doi:10.66224/jcbior.7.3.366

Authors

Roghayeh Sadeghzadeh Department of Obstetrics and Gynecology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran https://orcid.org/0009-0001-7966-6483
Fereshteh Afkar Department of Nursing and Midwifery, Faculty of Paramedical Sciences, Islamic Azad University, Kermanshah Branch, Kermanshah, Iran
Negar Sadat Parviz Farzam Department of Developmental Biology, Islamic Azad University, Tehran, Iran
Sara Nezhadi Department of Obstetrics and Gynecology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
Ebrahim Kharazinejad Department of Anatomical Sciences, School of Medicine, Abadan University of Medical Sciences, Abadan, Iran
Reza Khorasani Department of Toxicology and Pharmacology, School of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
Ehsan Moradi-Joo Department of Public Health, School of Health, Abadan University of Medical Sciences, Abadan, Iran
Sara Kooti Infectious Ophthalmologic Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran https://orcid.org/0000-0001-8153-4239

DOI:

https://doi.org/10.66224/jcbior.7.3.366

Keywords:

Group B Streptococcus, Early-onset disease, Intrauterine infection, Intrapartum transmission, Neonatal sepsis

Abstract

Early-onset group B streptococcal disease (EOGBS) remains an important cause of invasive neonatal infection and is traditionally attributed predominantly to vertical transmission occurring during labor or following rupture of membranes. Although this model provides the basis for current screening and intrapartum antibiotic prophylaxis strategies, increasing clinical, pathological, experimental, and molecular observations have raised the possibility that fetal exposure to Group B Streptococcus (GBS) may occur before the onset of labor in a subset of pregnancies. In this narrative review, the biological and clinical pathways linking maternal GBS colonization to neonatal infection are examined, with particular attention to the temporal distinction between intrauterine and intrapartum transmission. Evidence concerning ascending infection, intraamniotic exposure, placental and fetal inflammatory responses, and molecular characterization of matched maternal, intraamniotic, placental, and neonatal isolates is considered. The established intrapartum transmission model and the evidence supporting its prevention through intrapartum antibiotic prophylaxis are also reviewed. The strengths and limitations of the available evidence for intrauterine acquisition are discussed, with emphasis on the difficulty of distinguishing antenatal infection from exposure occurring immediately before or during delivery. Finally, the potential implications of a broader temporal model for prevention are considered, including the complementary roles of intrapartum prophylaxis, antenatal risk recognition, and maternal vaccination. By integrating these perspectives, this review aims to provide a framework for understanding EOGBS as a potentially heterogeneous process in which maternal colonization, ascending infection, peripartum exposure, and neonatal invasion may occur along a continuum rather than as mutually exclusive transmission pathways.

References

1. Delara M, Vadlamudi NK, Sadarangani M. Strategies to Prevent Early and Late-Onset Group B Streptococcal Infection via Interventions in Pregnancy. Pathogens. 2023;12(2):229.

DOI: 10.3390/pathogens12020229 PMID: 36839501

2. Lee KW, Yap SF, Murdan S, Zainudin Z, Abdul Hamid H, Emamjomeh M, et al. Maternal and neonatal group B streptococcus colonisation: A systematic review and the meta-analysis of matched-pair studies. Acta Paediatr. 2024;113(5):892-911. DOI: 10.1111/apa.17152 PMID: 38351491

3. Prevention of Group B Streptococcal Early-Onset Disease in Newborns: ACOG Committee Opinion, Number 797. Obstet Gynecol. 2020;135(4):978-979.

DOI: 10.1097/AOG.0000000000003824 PMID: 31977795

4. Campbell P, Broderick C, Fenton C, Davis B, Xu W, Todhunter-Brown A, et al. Benefits and Harms of Antenatal/Intrapartum Screening for Maternal Group B Streptococcus and Use of Intrapartum Antibiotic Prophylaxis Versus Risk-Based Protocols or No Intervention: A Rapid Review. Acta Paediatr. 2026;115(8):1598-1610.

DOI: 10.1111/apa.70568 PMID: 42060466

5. Consonni S, Salmoiraghi E, Vaglio Tessitore I, Pintucci A, Vitale V, Calzi P, et al. Intra-Amniotic Inflammation or Infection: Suspected and Confirmed Diagnosis of "Triple I" at Term. Children (Basel). 2023;10(7):1110.

DOI: 10.3390/children10071110 PMID: 37508607

6. Manuel G, Twentyman J, Noble K, Eastman AJ, Aronoff DM, Seepersaud R, et al. Group B streptococcal infections in pregnancy and early life. Clin Microbiol Rev. 2025;38(1):e0015422.

DOI: 10.1128/cmr.00154-22 PMID: 39584819

7. Pongchaikul P, Romero R, Wongsurawat T, Jenjaroenpun P, Kruasuwan W, Mongkolsuk P, et al. Molecular evidence that GBS early neonatal sepsis results from ascending infection: comparative hybrid genomics analyses show that microorganisms in the vaginal ecosystem, amniotic fluid, chorioamniotic membranes, and neonatal blood are the same. J Perinat Med. 2024;52(9):977-990.

DOI: 10.1515/jpm-2024-0310 PMID: 39405032

8. Mei JY, Silverman NS. Group B Streptococcus in Pregnancy. Obstet Gynecol Clin North Am. 2023;50(2):375-387.

DOI: 10.1016/j.ogc.2023.02.009 PMID: 37149317

9. Tavares T, Pinho L, Bonifácio Andrade E. Group B Streptococcal Neonatal Meningitis. Clin Microbiol Rev. 2022;35(2):e0007921. DOI: 10.1128/cmr.00079-21 PMID: 35170986

10. Heath PT, Jardine LA. Neonatal infections: group B streptococcus. BMJ Clin Evid. 2014;2014:0323.

PMID: 24580886

11. Tudela CM, Stewart RD, Roberts SW, Wendel GD Jr, Stafford IA, McIntire DD, et al. Intrapartum evidence of early-onset group B streptococcus. Obstet Gynecol. 2012;119(3):626-9.

DOI: 10.1097/AOG.0b013e31824532f6 PMID: 22353962

12. Afsari M, White A, Adhikari EH. Group B Streptococcus and Intraamniotic Inflammation and Infection. Clin Obstet Gynecol. 2024;67(3):576-588.

DOI: 10.1097/GRF.0000000000000884 PMID: 39061126

13. Vornhagen J, Adams Waldorf KM, Rajagopal L. Perinatal Group B Streptococcal Infections: Virulence Factors, Immunity, and Prevention Strategies. Trends Microbiol. 2017;25(11):919-931. DOI: 10.1016/j.tim.2017.05.013 PMID: 28633864

14. Fairlie T, Zell ER, Schrag S. Effectiveness of intrapartum antibiotic prophylaxis for prevention of early-onset group B streptococcal disease. Obstet Gynecol. 2013;121(3):570-577. DOI: 10.1097/AOG.0b013e318280d4f6 PMID: 23635620

15. Jung E, Romero R, Suksai M, Gotsch F, Chaemsaithong P, Erez O, et al. Clinical chorioamnionitis at term: definition, pathogenesis, microbiology, diagnosis, and treatment. Am J Obstet Gynecol. 2024;230(3S):S807-S840.

DOI: 10.1016/j.ajog.2023.02.002 PMID: 38233317

16. Dhudasia MB, Flannery DD, Pfeifer MR, Puopolo KM. Updated Guidance: Prevention and Management of Perinatal Group B Streptococcus Infection. Neoreviews. 2021;22(3):e177-e188. DOI: 10.1542/neo.22-3-e177 PMID: 33649090

17. Greenfield KG, Harlow OS, Witt LT, Dziekan EM, Tamar CR, Meier J, et al. Neonatal intestinal colonization of Streptococcus agalactiae and the multiple modes of protection limiting translocation. Gut Microbes. 2024;16(1):2379862.

DOI: 10.1080/19490976.2024.2379862 PMID: 39042143

18. Daskalakis G, Psarris A, Koutras A, Fasoulakis Z, Prokopakis I, Varthaliti A, et al. Maternal Infection and Preterm Birth: From Molecular Basis to Clinical Implications. Children (Basel). 2023;10(5):907.

DOI: 10.3390/children10050907 PMID: 37238455

19. Benitz WE, Gould JB, Druzin ML. Risk factors for early-onset group B streptococcal sepsis: estimation of odds ratios by critical literature review. Pediatrics. 1999;103(6):e77.

DOI: 10.1542/peds.103.6.e77 PMID: 10353974

20. Chen X, Zhang X, Xue R, Mi L, Liu Y, Zhang G, et al. Intrauterine inflammation exposure may increase the risk of late-onset sepsis in premature infants: a retrospective cohort study. Ital J Pediatr. 2025;51(1):218. DOI: 10.1186/s13052-025-02040-5 PMID: 40640885

21. Allard MJ, Brochu ME, Bergeron JD, Segura M, Sébire G. Causal role of group B Streptococcus-induced acute chorioamnionitis in intrauterine growth retardation and cerebral palsy-like impairments. J Dev Orig Health Dis. 2019;10(5):595-602.

DOI: 10.1017/S2040174418001083 PMID: 30626456

22. Kobayashi M, Vekemans J, Baker CJ, Ratner AJ, Le Doare K, Schrag SJ. Group B Streptococcus vaccine development: present status and future considerations, with emphasis on perspectives for low and middle income countries. F1000Res. 2016;5:2355. DOI: 10.12688/f1000research.9363.1 PMID: 27803803

23. Schrag SJ, Verani JR. Intrapartum antibiotic prophylaxis for the prevention of perinatal group B streptococcal disease: experience in the United States and implications for a potential group B streptococcal vaccine. Vaccine. 2013;31 Suppl 4:D20-6.

DOI: 10.1016/j.vaccine.2012.11.056 PMID: 23219695