Sage Journals: Discover world-class research

Abstract

Group B streptococcus (GBS) or Streptococcus agalactiae is a beta-hemolytic, Gram-positive coccus that can colonize the genitourinary and gastrointestinal tract of pregnant people. GBS can transition from asymptomatic colonization to pathogenic bacterium which can then lead to adverse pregnancy, maternal and neonatal outcomes. While much of the literature focuses on outcomes affecting the neonate, such as early- and late-onset neonatal sepsis, GBS is also thought to be associated with specific pregnancy and fetal adverse outcomes including preterm birth, preterm premature rupture of membranes, urinary tract infection, endometritis, and maternal sepsis. The objective of this literature review is to further address the known associations of these maternal and pregnancy outcomes, review the current strategies for GBS screening and preventative strategies, and explore the current maternal GBS vaccine candidates in development that may address the limitations of current prevention strategies with intrapartum antibiotic prophylaxis.

Keywords

GBS GBS in pregnancy GBS vaccine group B streptococcus (GBS)maternal immunization

Introduction

Group B streptococcus (GBS) or Streptococcus agalactiae is a beta-hemolytic, Gram-positive coccus that can colonize the genitourinary (GU) and gastrointestinal (GI) tract of pregnant people.^1,2 GBS in pregnancy can be associated with adverse maternal, fetal, and neonatal outcomes. Much of the published literature focuses on outcomes affecting the neonate such as early- and late-onset neonatal sepsis; however, less is known about direct mechanisms connecting these adverse maternal and pregnancy outcomes and GBS such as preterm delivery, preterm premature rupture of membranes (PPROM), urinary tract infection, endometritis, and maternal sepsis. The objective of this literature review is to further address the known associations of these maternal and pregnancy outcomes, review the current strategies for GBS screening and preventative strategies, and explore the current maternal GBS vaccine candidates in development that may address the limitations of current prevention strategies with intrapartum antibiotic prophylaxis. Given the large amount of literature available on neonatal outcomes associated with GBS, we focused instead specifically on maternal and pregnancy outcomes in our review.

Group B streptococcus in pregnancy

GBS classification is based on capsular polysaccharide (CPS) phenotype, with 10 known GBS serotypes: Ia, Ib, II, III, IV, V, VI, VII, VIII, and IX.^3–7 Some serotypes have been associated with a higher likelihood of maternal and neonatal GBS disease while others have been more associated with asymptomatic carrier status.^4,8 Schindler et al. showed that the dominant serotype in asymptomatic pregnant people was serotype VI (98 out of 240 isolates, 48%), while the dominant serotype in neonates with early onset GBS disease was serotype III (16 out of 19, 84.2%).⁸ Serotype III has also been frequently associated with late onset neonatal GBS disease, neonatal sepsis, and meningitis.⁹ In one South African study serotype III was noted to be more likely to be associated with persistent colonization.¹⁰ In addition, GBS can be even further classified by sequence type (ST), or allelic profile, the majority of GBS human isolates being ST-1, ST-17, ST-19, or ST-23.¹¹ In one study ST-1 and ST-19 were more highly associated with asymptomatic GBS colonization, while ST-17 was more associated with neonatal invasive infections (p < 0.001).¹¹ Interestingly, all the strains of ST-17 were in serotype III.¹¹ The virulence of GBS is dependent on the CPS, thus antibodies against the CPS can provide type-specific protection, an important target for future GBS vaccines.¹²

Prevalence of GBS colonization varies based on global geographic region. In a systematic review from studies published between 1997 and 2015 the prevalence of GBS colonization worldwide in pregnant people was found to be approximately 17.9% overall, with the highest rates noted in Africa (22.4%) followed by the Americas (19.7%) and Europe (19.0%).¹³ The lowest prevalence was seen in southeast Asia (11.1%).¹³ In a more recent meta-analysis, 19.7 million pregnant people were estimated to have been colonized by GBS globally in the year 2020, with the highest rates of colonization found in sub-Saharan Africa (6.1 million) and central and south Asia (4.4 million).¹⁴ A meta-analysis that included 390 articles, 85 countries, and a total of 299,924 pregnant people found that the serotypes Ia, Ib, II, III, and V account for 98% of serotypes globally. The prevalence of serotype III is 25% (95% CI: 23%–28%) and is less often found in Central America (11%) and Asia (Southeast Asia 12% and South Asia 11%). There is a greater prevalence of serotype V in Western Africa and other serotypes (VI–IX) are more commonly found in Southeast Asia (Figure 1).⁴

Figure 1.

Distribution of maternal group B streptococcus colonizing serotype by United Nations subregion.

There are many risk factors that have been associated with GBS colonization in pregnancy, including race, ethnicity, age, socioeconomic factors, and medical conditions. One US study assessed 40,459 cases of GBS colonization and found that Black race was associated with increased maternal GBS colonization (odds ratio 1.54, CI: 1.36–1.74, p < 0.01), while Hispanic ethnicity decreased the risk of GBS colonization (OR 0.88, CI: 0.80–0.96; p = 0.003).^15,16 There is conflicting data on whether maternal age impacts GBS colonization, as both younger and older maternal age have been associated with GBS colonization. One study in Canada found that women greater than 36 years old were eight times more likely to have persistent colonization, in the third trimester and 6 weeks postpartum, when compared to women less than 25 years.¹⁷ While another study in the US found that the mean observed maternal age at delivery was lower among GBS colonized compared to GBS negative people.¹⁶ Socioeconomic factors have also been associated with increased risk of GBS colonization; healthcare occupation, higher income, and greater educational attainment were associated with increased odds ratios for GBS colonization.¹⁵

Lastly, certain medical conditions and co-morbidities have also been associated with increased risk of GBS colonization. Elevated BMI, including overweight, obese, and severely obese categories, has also been seen as an independent risk factor for GBS colonization.^15,18,19 There is conflicting data on whether preexisting diabetes mellitus (DM) or gestational diabetes mellitus (GDM) increases risk of colonization in pregnancy. Nguyen et al. completed a literature review, including published studies on GBS colonization and diabetes from 1985 to 2016.²⁰ One study that assessed 60,029 pregnant people found that 3.5% versus 2.8% (p < 0.001) of pregnant people colonized with GBS had preexisting diabetes.^16,20 This study additionally noted that there was a higher risk of GDM (RR 1.21, CI: 1.11–1.32). However, another study that evaluated 446 pregnant people with GDM and 1046 without GDM found no difference in colonization rates (12% and 12%, respectively).^20,21 Similarly, a study conducted in Italy of 473 pregnant patients, 127 with DM and 346 without DM did not find a difference in GBS vaginal colonization between the two groups.^20,22

The GI tract is the primary source of GBS colonization of the genitourinary tract. The study by Badri et al. was one of the first to describe the GI tract as the primary site of colonization by GBS. In their study of 789 pregnant patients, 142 (17.9%) rectal cultures tested positive for GBS versus 81 (10.2%) of vaginal cultures,²³ thus illustrating that vaginal colonization may be due to contamination from the GI tract. Colonization in the GU tract can be intermittent, transitory, or persistent.^1,24,25 One Danish study collected GBS samples during early first trimester and late third trimester and found that 53% of participants were permanent non-GBS carriers, 28% were persistent GBS carriers, and 19% were intermittent carriers.²⁴ Another study assessed GBS colonization during each trimester and found that vaginal colonization changed from 24% in the first trimester to 18% in the second trimester, and 17% in the third trimester in their group of 42 pregnant patients.²⁵ Kwatra et al. found that the prevalence of the GBS colonization varied between 20–25 weeks, 26–30 weeks, 31–35 weeks, and greater than 37 weeks of gestational age in South Africa, with 27% of participants acquiring a new serotype.¹⁰ All these studies illustrate the dynamic nature of GBS colonization in the GU tract. There is no evidence that GBS is transmitted sexually. Honing et al. in a case-control study of 432 non-pregnant female patients that attended a STI clinic in Rotterdam had a vaginal swab taken for bacterial culture that showed 12% of patients were colonized with GBS and no significant correlation was seen between sexual behavior variables, including lifetime partners, partners in last 6 months and 1 month, mean number of days since last sexual contact and use of condoms.²⁶ In addition, Jackson et al. collected perineal and anorectal swabs from 92 couples that attended a STI clinic and found that of the 20 patients that were both colonized only three were colonized with the same strains of GBS.²⁷

Association of GBS colonization with adverse maternal and fetal outcomes

GBS can transition from asymptomatic colonization to pathogenic bacterium which can then lead to adverse pregnancy, maternal and neonatal outcomes. Asymptomatic colonization is defined as a commensal bacterium of the microbiota that does not proceed to cause invasive infection.^1,28 The transition from colonization to bacterial pathogen that causes invasive infection is not well understood.²⁸ Some observation studies suggest that a change from acidic to neutral environments can switch on the virulence-related genes of GBS, and that the control of virulence (Cov) regulator (R)-sensor (S) (CovRS) two-component regulatory system (TCS) can switch GBS from mucosal colonization to invasive infection.²⁸

While much of the literature focuses on outcomes affecting the neonate such as early- and late-onset neonatal sepsis, GBS is also thought to be associated with specific pregnancy and fetal adverse outcomes including preterm birth, PPROM, urinary tract infection, endometritis, and maternal sepsis.^14,29–35 However, less is known about direct mechanisms connecting these maternal and pregnancy outcomes and GBS.

- Preterm birth: The evidence on whether GBS maternal rectovaginal colonization or infection increases risk of preterm delivery is unclear. The suspected mechanism by which GBS colonization and/or infection may lead to preterm birth is through: (a) degradation of extracellular matrix of the fetal membranes through the secretion of proteases, (b) cytokine production and stimulation of prostaglandin and protease synthesis. Both of these mechanisms then lead to increase in uterine contractility which can then result in preterm birth.³⁶

There are conflicting findings on associations between preterm birth and GBS colonization in the published literature. A global landscape review of GBS prevalence found an estimated odds ratio for an association between GBS and prematurity to be 1.30 (1.02–1.71), with an estimated 518,100 preterm birth associated with GBS colonization globally, corresponding to 3.5% of preterm births globally.¹⁴ A systematic review and meta-analysis by Valkenburg-van den Berg et al. showed conflicting findings; an association was seen between maternal GBS colonization and preterm birth in cross-sectional and case-control studies when the GBS culture was completed at the time of delivery. However, this association was not seen in longitudinal cohort studies, when the GBS culture was collected earlier in pregnancy.^29,30 A more recent systematic review and meta-analysis by Bianchi-Jassir et al. found a consistent increase in risk of preterm birth with maternal GBS colonization, with a strong association if GBS bacteriuria was present.³⁰

- PPROM and premature rupture of membranes (PROM): Similarly, the evidence on whether GBS colonization increases risk of PPROM or PROM is unclear. GBS inflammation and infection have been shown to weaken and reduce the tissue integrity of the membranes of the chorion and amnion through the use of matrix metalloproteinases, apoptosis, oxidative stress, and other neutrophil proteases, which can then lead to PPROM or PROM.^31,37,38

GBS colonization has been associated with a greater risk of PPROM and PROM in the published literature. A single-center retrospective cohort study from Japan of 1079 singleton pregnancies found that the incidence of PPROM (3.3% vs 1.9%, p = 0.335) and PROM (23% vs 14.2%, p = 0.062) was higher in GBS positive groups. However it was not statistically significant.³² Older studies also show a statistically significant increase incidence of PROM in patients colonized with GBS. One prospective study of 6706 patients found PROM occurred in 15.3% of colonized patients compared to 8.1% not colonized (p = 0.0005).³⁹ Another study found that patients with GBS bacteriuria were at increased risk of PROM and premature delivery.⁴⁰

- Stillbirth: Infection, including GBS infection, is an important contributor to stillbirths worldwide each year. GBS infection is estimated to contribute to stillbirth in 1% in developed countries and 4% in African countries.³³ This is approximately 45,000 and 50,000 deaths per year.^14,34 In 2020 an estimated 46,200 stillbirths likely resulted from “in utero” GBS infection.¹⁴ The direct causative mechanism is not fully understood. One study conducted in Kenya suggest that the ascending infection from the maternal GU tract to “in utero” may be the cause, given that GBS isolated from neonatal post-mortem blood cultures was genetically identical to the maternal GBS isolates.^33,41

- Urinary tract infection: GBS is thought to be responsible for 2%–7% of lower urinary tract infections in pregnant people.^35,42 Bacteriuria with GBS is a sign of higher levels of overall GBS colonization in the GU tract.^30,43 This infection, whether treated or not, can then lead to adverse pregnancy complications such as PPROM and preterm delivery, as discussed above. At this time it is recommended to treat GBS bacteriuria if counts are greater than 100,000 CFU/mL.⁴⁴ Treatment is recommended for asymptomatic bacteriuria with 10⁵ CFU/mL as it has been shown to reduce the risk of pyelonephritis, preterm birth, and birth weight of less than 2500 g.^45,46 Lower colony counts do not require treatment as there is no evidence that prenatal treatment improves maternal or neonatal outcomes. However, they are an indication for GBS prophylaxis at the time of delivery.^1,44

- Endometritis: GBS is one the major causes of intra-amniotic infection (IAI) and postpartum endometritis. Ascending bacterial infections of the vagina can often lead to IAI, placing pregnant individuals with GBS colonization at increased risk of infection. In approximately 15% of patients with IAI, GBS was isolated in the amniotic fluid, with an increase seen in patients with prolonged rupture of membranes and preterm labor.³⁵ In early postpartum endometritis, diagnosed within the first 48 h following delivery, GBS is often identified. In one study it was isolated as the only pathogen for 2%–14% of cases, and was more frequently associated in vaginal deliveries.³⁵ The incidence of GBS IAI and endometritis has declined since the introduction of GBS intrapartum prophylaxis.^35,47

- Maternal sepsis: Although rare, GBS infection can lead to maternal sepsis. A large systematic review and meta-analysis found that incidence of maternal sepsis due to GBS infection was anywhere from 0.17 to 0.38 per 1000 pregnancies, which accounts for 40,500 cases per year.^14,34,48 This constitutes 20%–25% of clinically significant bacteremia in pregnant individuals that are hospitalized with an overall case fatality risk of 0.20%.^14,34

Current screening and preventive strategies

GBS can also be identified in pregnancy either through culture- or molecular-based methods. Culture-based screening is the gold standard for GBS detection as it maximizes GBS identification through the incubation of the specimen in enrichment broth prior to inoculation on the agar culture plates.^1,49 In addition, the culture-based methods allow for antibiotic susceptibility testing to be completed. Molecular-based methods, such as nucleic acid amplification testing (NAAT), have been shown to offer similar or better rates of detection to culture-based screening if the incubation step precedes the NAAT analysis; however, it does not allow for antibiotic susceptibility testing.^50–54 The benefit of NAAT methods is the rapid turnaround time which can be used in the intrapartum management of pregnant people with unknown or unavailable GBS status. However, due to swift turnaround time and lack of full enrichment broth incubation, sensitivity of the assay may be compromised.⁵² Thus, at this time the Centers for Disease Control and Prevention (CDC) recommends that specimens undergo both the appropriate incubation time of 18–24 h at 35–37°C in the appropriate enrichment broth medium, to ensure accurate results over rapid turnaround times, regardless of the method used.⁵⁵

Earlier CDC guidelines had recommended the use of culture-based or risk-based screening as acceptable approaches to identify pregnant people that should receive intrapartum prophylaxis.⁵⁶ The risk-based approach used the presence of any of the following intrapartum risk factors: delivery prior to 37 weeks’ gestation, intrapartum temperature of greater than or equal to 100.4°F (38.0°C), or rupture of membranes greater than or equal to 18 h.⁵⁶ However, a large retrospective cohort study in 1998–1999 found that culture-based screening significantly lowered the risk of early onset GBS disease among infant when compared to the risk-based approach (adjusted related risk, 0.46; 95% CI: 0.36–0.60).⁵⁷ These findings led the CDC to change its guidelines.

Starting in 2002 the CDC has recommended universal antepartum culture-based screening of all pregnant people between 36 weeks and 37 weeks 6 days of gestation, regardless of mode ofdelivery.^51,58 The screening goal is to collect the cultures within 5 weeks of birth, as studies have shown this time period to have the highest degree of accuracy in predicting GBS colonization at the time of delivery.^59,60 The specimen should be collected from the lower vagina and rectum to increase the culture yield, as sampling from each location alone decreases the positive predictive value of the test.⁶¹ Multiple studies have shown that self-obtained samples and clinician-obtained samples result in similar GBS culture yields.^62–65 The results from the antepartum screening culture then dictate eligibility to receive intrapartum antibiotics to prevent early onset GBS disease. For pregnant patients with unknown GBS screening at the onset of labor, intrapartum prophylaxis is recommended with the presence of any of the risk factors discussed above, including a prior neonate with invasive GBS disease, known GBS positive status in previous pregnancy, or GBS bacteriuria during any trimester of the current pregnancy.¹

Given loose associations of maternal and pregnancy outcomes and limited knowledge of pathophysiological mechanisms between GBS colonization and these outcomes, the focus on preventive therapy and treatment has been to decrease the risk of early-onset neonatal sepsis in the infant with intrapartum antibiotic prophylaxis. The efficacy of intravenous intrapartum antibiotic prophylaxis has been shown to be anywhere from 85% to 100% to prevent EOD among pregnant patients colonized with GBS.^66–69 Intravenous penicillin is the preferred first-line antibiotic for intrapartum prophylaxis, with intravenous ampicillin as an acceptable alternative to penicillin.^1,67,70 However, penicillin is preferred due to its narrower antimicrobial activity against Gram-positive bacteria and decreased possibility of development of resistance in other vaginal organisms.^1,55

Patients with a penicillin allergy are recommended (1) to be assessed for severity of reaction and (2) to assess the susceptibility of GBS isolate to clindamycin to determine the optimal intrapartum antibiotic therapy.¹ A high-risk penicillin allergy is defined as the development of anaphylaxis, recurrent reactions, reactions to multiple beta-lactam antibiotics, positive penicillin allergy test, or severe delayed-onset reactions (e.g., eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome, Stevens-Johnson syndrome, or toxic epidermal necrolysis).^1,71 In patients without a high-risk penicillin allergy, cefazolin, a first-generation cephalosporin, is recommended as intrapartum prophylaxis, as GBS has a high susceptibility to this antibiotic, and cefazolin has been shown to have high amniotic fluid and fetal blood levels.^1,72–75 In patients identified as high-risk, either clindamycin or vancomycin are recommended as intrapartum prophylaxis.¹ Erythromycin is no longer recommended as an alternative given the high rates of GBS resistance to this antibiotic and its poor ability to cross the placenta which leads to low drug levels in amniotic fluid and fetal blood.^75–77 Clindamycin is recommended as an alternative if the GBS isolate is known to be susceptible to clindamycin.^1,76 If the GBS isolate is not susceptible to clindamycin, intravenous vancomycin is recommended.^1,78–80

Other preventative modalities such as intramuscular intrapartum antibiotic prophylaxis, antenatal antibiotics, chlorhexidine vaginal wipes, or douches have not been proven to be as effective in the prevention of EOD.^55,81–84 There is some concern regarding the development of antibiotic resistance of some GBS isolates.⁵⁷ There are no preventative strategies in place that address the prevention of many of the adverse pregnancy and maternal outcomes described above.

GBS vaccine in pregnancy

There are several maternal GBS vaccine candidates in development that may address the limitations of current prevention strategies with intrapartum antibiotic prophylaxis. As previously discussed, while intrapartum prophylaxis can prevent early-onset disease in infants it is not effective in the prevention of late-onset disease and adverse maternal and pregnancy outcomes. Furthermore, a GBS vaccine would reduce antibiotic use intrapartum, thereby reducing risk of antibiotic resistance and possible interference with the infant microbiota. Lastly, a vaccine would have an impact on a global scale, particularly in areas where pregnant patients do not have access to screening or intrapartum antibiotic prophylaxis.⁸⁵

Progress toward a GBS vaccine has been slow despite the fact that as early as 1976 Baker et al. demonstrated that transplacental transfer of maternal antibody of CPS type III could protect the infant from invasive GBS infection from CPS type III strains.⁸⁶ It was not until 2015 and 2016 that the World Health Organization (WHO) in the Product Development for Vaccines Advisory Committee prioritized the development of GBS vaccine.⁸⁷ In addition, the WHO has included milestones in its “Defeating Meningitis roadmap” for the GBS vaccine, including to have at least one GBS vaccine licensed by 2026 and have introduced the vaccine to at least 10 countries by 2030.⁸⁸ There have thus far been three GBS vaccine candidates (Figure 2):

1. Two polysaccharide conjugate vaccines that target multiple GBS serotypes.

a. The hexavalent conjugate vaccine that targets the serotypes Ia, Ib, II, III, IV, and V.

b. The trivalent conjugate vaccine that target serotypes Ia, Ib, and III.

2. One protein vaccine, an alpha-like protein fusion with recombinant protein.^{12,85,89–92}

The trivalent conjugate vaccine which underwent several phase I and II trials has now been discontinued due to limited disease coverage and variable immunogenicity in human trials.^89,90,93

Figure 2.

Group B streptococcus (GBS) vaccine development pipeline.

The single dose hexavalent CPS-cross reactive material 197 glycoconjugate vaccine (GBS6) is designed using surveillance data from global whole-genome sequencing of recovered GBS isolates that are responsible for invasive neonatal GBS disease.⁹³ In phase I/II, placebo-controlled, observer-blinded, dose-escalation trial in healthy, non-pregnant adults in the US the vaccine was found to be well tolerated with a good immune response that persisted for 6 months after vaccination.⁹² As of 2025, a phase II randomized clinical trial utilizing GBS6 is underway.¹² Part of phase II was conducted in South Africa where the vaccine was given in six formulations, which included three dose groups (5-, 10-, or 20-μg CPS per serotype) each with and without aluminum. There were 360 pregnant people that underwent randomization, 40 assigned to each of the six formulations and 120 assigned to the placebo. The primary outcome was to assess safety and immunogenicity of a single dose GBS6. No safety concerns, including local and systemic reactions, were associated with the GBS6 compared to placebo in the study. An IgG response was noted for all six serotypes that continued through delivery and was transferred to the infant.¹² Transplacental antibody transfer was noted at levels postulated to be associated with reduced risk of invasive GBS disease, specifically cord blood ST-specific antibody levels were mostly above the protective thresholds identified in the accompanying epidemiological study of natural antibodies, making this a promising vaccine for prevention of GBS disease in the neonate and possibly to reduce risk of adverse maternal and pregnancy outcomes.⁹⁵ A final formulation is being evaluated in the US, UK, and South Africa to complete phase II of the clinical trial and inform a planned phase III clinical trial development program.

The protein vaccine, GBS-NN, contains structural components of GBS alpha-like proteins (Alps), fused N-terminal domains of GBS Alpha C and Rib proteins.^96,97 It has been shown that low occurring Alpha C or Rib specific titers in maternal and neonatal serum can correlate with GBS disease which influenced the creation of the GBS-NN vaccine.^96,98 Phase I clinical trial in non-pregnant individuals of this vaccine was overall well tolerated, with mainly mild injection site reactions observed. The GBS-NN vaccine showed a high immunogenic response after two doses of 50 µg.⁹⁷ The vaccine has also been tested in murine models where an increase in GBS-NN IgG specific titers has been shown to lead to reduced burden of systemic GBS and improved fetal and neonatal survival.⁹⁶ As of 2025, phase II clinical trial in pregnant patients is ongoing.

There are several published studies seeking to quantify the impact of a future GBS vaccine on maternal and neonatal morbidity and mortality. One paper summarized the estimated health impact of GBS vaccine using Seale et al.’s global estimates of incidence and case fatality of GBS in 2017 and Gonçalves et al.’s estimates of global burden of GBS in 2020 using Bayesian modelling.^14,33,85 The potential health impacts are summarized in Tables 1 and 2. The effect a GBS vaccine may have on adverse maternal and pregnancy outcomes associated with GBS colonization and disease is less clear. More studies in this area are warranted to address this knowledge gap.

Table 1.

Health impacts of a GBS vaccine using previously published 2017 global estimates of incidence and case fatality of GBS, assuming a GBS vaccine with an 80% efficacy rate and reaching 90% coverage.

Reduction of infant and maternal GBS	229,000 (UR: 114,000–507,000)
Prevention of GBS-related stillbirths	41,000 (UR: 8000–75,000)
Prevention of GBS-related infant fatalities	67,000 (UR: 12,000–123,000)

Source: Estimates from Trotter et al.^85,99

GBS, Group B streptococcus; UR, uncertainty range.

Table 2.

Health impacts of a GBS vaccine using 2020 previously published estimates of global burden of GBS in 2020 using Bayesian modelling, assuming a GBS vaccine with an 80% efficacy rate and reaching 90% coverage.

Prevention of early-onset GBS disease	126,800 (UR: 63,300–247,700)
Prevention of late-onset GBS disease	87,300 (UR: 38,100–209,400)
Prevention of GBS-related deaths	31,100 (UR: 14,400–66,400)
Prevention of GBS-related stillbirths	23,000 (UR: 10,000–56,400)

Source: Estimates from Trotter et al.^14,85,100

GBS, Group B streptococcus; UR, uncertainty range.

Conclusion

GBS in pregnancy can transition from asymptomatic colonization to pathogenic bacterial infection which can then lead to adverse pregnancy, maternal, and neonatal outcomes. Literature on associations of GBS with neonatal outcomes such as early- and late-onset neonatal sepsis is more robust compared to associations with maternal outcomes. More research is needed to better understand the impact of GBS colonization in pregnancy and adverse maternal and pregnancy events. The development of a GBS vaccine emerges as a promising avenue that not only will address the risk of adverse neonatal outcomes but may also mitigate adverse pregnancy and maternal outcomes.

Footnotes

Acknowledgements

None.

Declarations

ORCID iDs

Monica Sosa

Linda O. Eckert

Alisa Kachikis

References

Prevention of group B streptococcal early-onset disease in newborns: ACOG committee opinion, number 797. Obstet Gynecol 2020; 135(2): e51–e72. Erratum in: Obstet Gynecol. 2020; 135(4): 978–979.

Armistead

Oler

Adams Waldorf

, et al. The double life of group B streptococcus: asymptomatic colonizer and potent pathogen. J Mol Biol 2019; 431(16): 2914–2931.

Slotved

Kong

Lambertsen

, et al. Serotype IX, a proposed new Streptococcus agalactiae serotype. J Clin Microbiol 2007; 45(9): 2929–2936.

Russell

Seale

O’Driscoll

, et al. Maternal colonization with group B streptococcus and serotype distribution worldwide: systematic review and meta-analyses. Clin Infect Dis 2017; 65(Suppl. 2): S100–S111.

Ferrieri

Flores

AE.

Surface protein expression in group B streptococcal invasive isolates. Adv Exp Med Biol 1997; 418: 635–637.

Afshar

Broughton

Creti

, et al. International external quality assurance for laboratory identification and typing of Streptococcus agalactiae (Group B streptococci). J Clin Microbiol 2011; 49(4): 1475–1482.

Lancefield

Freimer

EH.

Type-specific polysaccharide antigens of group B streptococci. J Hyg (Lond) 1966; 64(2): 191–203.

Schindler

Rahav

Nissan

, et al. Group B streptococcus serotypes associated with different clinical syndromes: asymptomatic carriage in pregnant women, intrauterine fetal death, and early onset disease in the newborn. PLoS One 2020; 15(12): e0244450.

Gudjónsdóttir

Hentz

Berg

, et al. Serotypes of group B streptococci in western Sweden and comparison with serotypes in two previous studies starting from 1988. BMC Infect Dis 2015; 15: 507.

10.

Kwatra

Adrian

Shiri

, et al. Serotype-specific acquisition and loss of group B streptococcus recto-vaginal colonization in late pregnancy. PLoS One 2014; 9(6): e98778.

11.

Jones

Bohnsack

Takahashi

, et al. Multilocus sequence typing system for group B streptococcus. J Clin Microbiol 2003; 41(6): 2530–2536.

12.

Madhi

Anderson

Absalon

, et al. Potential for maternally administered vaccine for infant Group B streptococcus. N Engl J Med 2023; 389(3): 215–227.

13.

Kwatra

Cunnington

Merrall

, et al. Prevalence of maternal colonisation with group B streptococcus: a systematic review and meta-analysis. Lancet Infect Dis 2016; 16(9): 1076–1084.

14.

Gonçalves

Procter

Paul

, et al. Group B streptococcus infection during pregnancy and infancy: estimates of regional and global burden. Lancet Glob Health 2022; 10(6): e807–e819.

15.

Stapleton

Kahn

Evans

, et al. Risk factors for group B streptococcal genitourinary tract colonization in pregnant women. Obstet Gynecol 2005; 106(6): 1246–1252.

16.

Edwards

Watson

Focht

, et al. Group B streptococcus (GBS) colonization and disease among pregnant women: a historical cohort study. Infect Dis Obstet Gynecol 2019; 2019: 5430493.

17.

Manning

Lewis

Springman

, et al. Genotypic diversity and serotype distribution of group B streptococcus isolated from women before and after delivery. Clin Infect Dis 2008; 46(12): 1829–1837.

18.

Manzanares

Zamorano

Naveiro-Fuentes

, et al. Maternal obesity and the risk of group B streptococcal colonisation in pregnant women. J Obstet Gynaecol 2019; 39(5): 628–632.

19.

Alvareza

Subramaniam

Tang

, et al. Obesity as an independent risk factor for group B streptococcal colonization. J Matern Fetal Neonatal Med 2017; 30(23): 2876–2879.

20.

Nguyen

Omage

Noble

, et al. Group B streptococcal infection of the genitourinary tract in pregnant and non-pregnant patients with diabetes mellitus: an immunocompromised host or something more? Am J Reprod Immunol 2021; 86(6): e13501.

21.

Piper

Georgiou

Xenakis

, et al. Group B streptococcus infection rate unchanged by gestational diabetes. Obstet Gynecol 1999; 93(2): 292–296.

22.

Lukic

Napoli

Santino

, et al. Cervicovaginal bacteria and fungi in pregnant diabetic and non-diabetic women: a multicenter observational cohort study. Eur Rev Med Pharmacol Sci 2017; 21(10): 2303–2315.

23.

Badri

Zawaneh

Cruz

, et al. Rectal colonization with group B streptococcus: relation to vaginal colonization of pregnant women. J Infect Dis 1977; 135(2): 308–312.

24.

Hansen

Uldbjerg

Kilian

, et al. Dynamics of Streptococcus agalactiae colonization in women during and after pregnancy and in their infants. J Clin Microbiol 2004; 42(1): 83–89.

25.

Brzychczy-Włoch

Pabian

Majewska

, et al. Dynamics of colonization with group B streptococci in relation to normal flora in women during subsequent trimesters of pregnancy. New Microbiol 2014; 37(3): 307–319.

26.

Honig

Mouton

van der Meijden

WI.

The epidemiology of vaginal colonisation with group B streptococci in a sexually transmitted disease clinic. Eur J Obstet Gynecol Reprod Biol 2002; 105(2): 177–180.

27.

Jackson

Hinder

Stringer

, et al. Carriage and transmission of group B streptococci among STD clinic patients. Br J Vener Dis 1982; 58(5): 334–337.

28.

Shabayek

Spellerberg

Group B streptococcal colonization, molecular characteristics, and epidemiology. Front Microbiol 2018; 9: 437.

29.

Valkenburg-van den Berg

Sprij

Dekker

, et al. Association between colonization with Group B Streptococcus and preterm delivery: a systematic review. Acta Obstet Gynecol Scand 2009; 88(9): 958–967.

30.

Bianchi-Jassir

Seale

Kohli-Lynch

, et al. Preterm birth associated with group B streptococcus maternal colonization worldwide: systematic review and meta-analyses. Clin Infect Dis 2017; 65(Suppl. 2): S133–S142.

31.

Romero

Dey

Fisher

SJ.

Preterm labor: one syndrome, many causes. Science 2014; 345(6198): 760–765.

32.

Tano

Ueno

Mayama

, et al. Relationship between vaginal group B streptococcus colonization in the early stage of pregnancy and preterm birth: a retrospective cohort study. BMC Pregnancy Childbirth 2021; 21(1): 141.

33.

Seale

Blencowe

Bianchi-Jassir

, et al. Stillbirth with group B streptococcus disease worldwide: systematic review and meta-analyses. Clin Infect Dis 2017; 65(Suppl. 2): S125–S132.

34.

Stephens

Charnock-Jones

Smith

GCS

. Group B streptococcus and the risk of perinatal morbidity and mortality following term labor. Am J Obstet Gynecol 2023; 228(5S): S1305–S1312.

35.

Muller

Oostvogel

Steegers

, et al. Morbidity related to maternal group B streptococcal infections. Acta Obstet Gynecol Scand 2006; 85(9): 1027–1037.

36.

Surve

Anil

Kamath

, et al. Membrane vesicles of group B streptococcus disrupt feto-maternal barrier leading to preterm birth. PLoS Pathog 2016; 12(9): e1005816.

37.

Brokaw

Furuta

Dacanay

, et al. Bacterial and host determinants of group B streptococcal vaginal colonization and ascending infection in pregnancy. Front Cell Infect Microbiol 2021; 11: 720789.

38.

Lannon

Vanderhoeven

Eschenbach

, et al. Synergy and interactions among biological pathways leading to preterm premature rupture of membranes. Reprod Sci 2014; 21(10): 1215–1227.

39.

Regan

Chao

James

LS.

Premature rupture of membranes, preterm delivery, and group B streptococcal colonization of mothers. Am J Obstet Gynecol 1981; 141(2): 184–186.

40.

Møller

Thomsen

Borch

, et al. Rupture of fetal membranes and premature delivery associated with group B streptococci in urine of pregnant women. Lancet 1984; 2(8394): 69–70.

41.

Seale

Koech

Sheppard

, et al. Maternal colonization with Streptococcus agalactiae and associated stillbirth and neonatal disease in coastal Kenya. Nat Microbiol 2016; 1(7): 16067.

42.

Landon

MB.

Gabbe’s obstetrics: normal and problem pregnancies. 8th ed. Philadelphia, PA: Elsevier, 2021, p.1257.

43.

Mei

Silverman

NS.

Group B streptococcus in pregnancy. Obstet Gynecol Clin North Am 2023; 50(2): 375–387.

44.

Urinary tract infections in pregnant individuals. Obstet Gynecol 2023; 142(2): 435–445.

45.

Nicolle

Gupta

Bradley

, et al. Clinical practice guideline for the management of asymptomatic bacteriuria: 2019 update by the Infectious Diseases Society of America. Clin Infect Dis 2019; 68(10): e83–e110.

46.

Smaill

Vazquez

JC.

Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev 2007 A; (2): CD000490. Update in: Cochrane Database Syst Rev 2015; (8): CD000490.

47.

Schrag

Zywicki

Farley

, et al. Group B streptococcal disease in the era of intrapartum antibiotic prophylaxis. N Engl J Med 2000; 342(1): 15–20.

48.

Hall

Adams

Bartlett

, et al. Maternal disease with group B streptococcus and serotype distribution worldwide: systematic review and meta-analyses. Clin Infect Dis 2017; 65(Suppl. 2): S112–S124.

49.

Church

Baxter

Lloyd

, et al. Evaluation of StrepB carrot broth versus Lim broth for detection of group B streptococcus colonization status of near-term pregnant women. J Clin Microbiol 2008; 46(8): 2780–2782.

50.

Curry

Bookless

Donaldson

, et al. Evaluation of hibergene loop-mediated isothermal amplification assay for detection of group B streptococcus in recto-vaginal swabs: a prospective diagnostic accuracy study. Clin Microbiol Infect 2018; 24(10): 1066–1069.

51.

Alfa

Sepehri

De Gagne

, et al. Real-time PCR assay provides reliable assessment of intrapartum carriage of group B Streptococcus. J Clin Microbiol 2010; 48(9): 3095–3099.

52.

Couturier

Weight

Elmer

, et al. Antepartum screening for group B Streptococcus by three FDA-cleared molecular tests and effect of shortened enrichment culture on molecular detection rates. J Clin Microbiol 2014; 52(9): 3429–3432.

53.

Silbert

Rocchetti

Gostnell

, et al. Detection of group B streptococcus directly from collected ESwab samples by use of the BD max GBS assay. J Clin Microbiol 2016; 54(6): 1660–1663.

54.

Young

Dodge

Gupta

, et al. Evaluation of a rapid, real-time intrapartum group B streptococcus assay. Am J Obstet Gynecol 2011; 205(4): 372.e1–372.e6.

55.

Verani

McGee

Schrag

, et al. Prevention of perinatal group B streptococcal disease—revised guidelines from CDC, 2010. MMWR Recomm Rep 2010; 59(RR-10): 1–36.

56.

Prevention of perinatal group B streptococcal disease: a public health perspective. Centers for disease control and prevention. MMWR Recomm Rep 1996; 45(RR-7): 1–24. Erratum in: MMWR Morb Mortal Wkly Rep 1996; 45(31): 679.

57.

Schrag

Zell

Lynfield

, et al. A population-based comparison of strategies to prevent early-onset group B streptococcal disease in neonates. N Engl J Med 2002; 347(4): 233–239.

58.

Schrag

Gorwitz

Fultz-Butts

, et al. Prevention of perinatal group B streptococcal disease: Revised guidelines from CDC. MMWR Recomm Rep 2002; 51(Rr-11): 1–22.

59.

Virranniemi

Raudaskoski

Haapsamo

, et al. The effect of screening-to-labor interval on the sensitivity of late-pregnancy culture in the prediction of group B streptococcus colonization at labor: a prospective multicenter cohort study. Acta Obstet Gynecol Scand 2019; 98(4): 494–499.

60.

Yancey

Schuchat

Brown

, et al. The accuracy of late antenatal screening cultures in predicting genital group B streptococcal colonization at delivery. Obstet Gynecol 1996; 88(5): 811–815.

61.

Boyer

Gadzala

Kelly

, et al. Selective intrapartum chemoprophylaxis of neonatal group B streptococcal early-onset disease. II. Predictive value of prenatal cultures. J Infect Dis 1983; 148(5): 802–809.

62.

Price

Shaw

Howard

, et al. Self-sampling for group B streptococcus in women 35 to 37 weeks pregnant is accurate and acceptable: a randomized cross-over trial. J Obstet Gynaecol Can 2006; 28(12): 1083–1088.

63.

Odubamowo

Garcia

Muriithi

, et al. Self-collected versus health-care professional taken swab for identification of vaginal-rectal colonisation with group B streptococcus in late pregnancy: a systematic review. Eur J Obstet Gynecol Reprod Biol 2023; 286: 95–101.

64.

Arya

Cryan

O'Sullivan

, et al. Self-collected versus health professional-collected genital swabs to identify the prevalence of group B streptococcus: a comparison of patient preference and efficacy. Eur J Obstet Gynecol Reprod Biol 2008; 139(1): 43–45.

65.

Torok

Dunn

. Self-collection of antepartum anogenital group B streptococcus cultures. J Am Board Fam Pract 2000; 13(2): 107–110.

66.

Lin

Brenner

Johnson

, et al. The effectiveness of risk-based intrapartum chemoprophylaxis for the prevention of early-onset neonatal group B streptococcal disease. Am J Obstet Gynecol 2001; 184(6): 1204–1210.

67.

Boyer

Gotoff

SP.

Prevention of early-onset neonatal group B streptococcal disease with selective intrapartum chemoprophylaxis. N Engl J Med 1986; 314(26): 1665–1669.

68.

Lim

Morales

Walsh

, et al. Reduction of morbidity and mortality rates for neonatal group B streptococcal disease through early diagnosis and chemoprophylaxis. J Clin Microbiol 1986; 23(3): 489–492.

69.

Matorras

García-Perea

Omeñaca

, et al. Intrapartum chemoprophylaxis of early-onset group B streptococcal disease. Eur J Obstet Gynecol Reprod Biol 1991; 40(1): 57–62.

70.

Garland

Fliegner

. Group B streptococcus (GBS) and neonatal infections: the case for intrapartum chemoprophylaxis. Aust N Z J Obstet Gynaecol 1991; 31(2): 119–122.

71.

Shenoy

Macy

Rowe

, et al. Evaluation and management of penicillin allergy: a review. JAMA 2019; 321(2): 188–199.

72.

Silverman

Morgan

Nichols

WS.

Antibiotic resistance patterns of group B streptococcus in antenatal genital cultures. J Reprod Med 2000; 45(12): 979–982.

73.

Fiore Mitchell

Pearlman

Chapman

, et al. Maternal and transplacental pharmacokinetics of cefazolin. Obstet Gynecol 2001; 98(6): 1075–1079.

74.

Allegaert

van Mieghem

Verbesselt

, et al. Cefazolin pharmacokinetics in maternal plasma and amniotic fluid during pregnancy. Am J Obstet Gynecol 2009; 200(2): 170.e1–170.e7.

75.

Castor

Whitney

Como-Sabetti

, et al. Antibiotic resistance patterns in invasive group B streptococcal isolates. Infect Dis Obstet Gynecol 2008; 2008: 727505.

76.

Teatero

Ferrieri

Martin

, et al. Serotype distribution, population structure, and antimicrobial resistance of group B streptococcus strains recovered from colonized pregnant women. J Clin Microbiol 2017; 55(2): 412–422.

77.

Bulska

Szcześniak

Pięta-Dolińska

, et al. The placental transfer of erythromycin in human pregnancies with group B streptococcal infection. Ginekol Pol 2015; 86(1): 33–39.

78.

Hamel

Has

Datkhaeva

, et al. The effect of intrapartum vancomycin on vaginal group B streptococcus colony counts. Am J Perinatol 2019; 36(6): 555–560.

79.

Onwuchuruba

Towers

Howard

, et al. Transplacental passage of vancomycin from mother to neonate. Am J Obstet Gynecol 2014; 210(4): 352.e1–352.e4.

80.

Towers

Weitz

Transplacental passage of vancomycin. J Matern Fetal Neonatal Med 2018; 31(8): 1021–1024.

81.

Baecher

Grobman

Prenatal antibiotic treatment does not decrease group B streptococcus colonization at delivery. Int J Gynaecol Obstet 2008; 101(2): 125–128.

82.

Bland

Vermillion

Soper

DE.

Late third-trimester treatment of rectovaginal group B streptococci with benzathine penicillin G. Am J Obstet Gynecol 2000; 183(2): 372–376.

83.

Facchinetti

Piccinini

Mordini

, et al. Chlorhexidine vaginal flushings versus systemic ampicillin in the prevention of vertical transmission of neonatal group B streptococcus, at term. J Matern Fetal Neonatal Med 2002; 11(2): 84–88.

84.

Stade

Shah

Ohlsson

Vaginal chlorhexidine during labour to prevent early-onset neonatal group B streptococcal infection. Cochrane Database Syst Rev 2004; (3): CD003520.

85.

Trotter

Alderson

Dangor

, et al. Vaccine value profile for Group B streptococcus. Vaccine 2023; 41(Suppl. 2): S41–S52.

86.

Baker

Kasper

DL.

Correlation of maternal antibody deficiency with susceptibility to neonatal group B streptococcal infection. N Engl J Med 1976; 294(14): 753–756.

87.

Giersing

Vekemans

Nava

, et al. Committee WPDfVA. Report from the World Health Organization's third product development for vaccines advisory committee (PDVAC) meeting, Geneva, 8–10th June 2016. Vaccine 2019; 37(50): 7315–7327.

88.

Venkatesan

Defeating meningitis by 2030: the WHO roadmap. Lancet Infect Dis 2021; 21(12): 1635.

89.

Swamy

Metz

Edwards

, et al. Safety and immunogenicity of an investigational maternal trivalent group B streptococcus vaccine in pregnant women and their infants: results from a randomized placebo-controlled phase II trial. Vaccine 2020; 38(44): 6930–6940.

90.

Madhi

Cutland

Jose

, et al. Safety and immunogenicity of an investigational maternal trivalent group B streptococcus vaccine in healthy women and their infants: a randomised phase 1b/2 trial. Lancet Infect Dis 2016; 16(8): 923–934.

91.

Donders

Halperin

Devlieger

, et al. Maternal immunization with an investigational trivalent group B streptococcal vaccine: a randomized controlled trial. Obstet Gynecol 2016; 127(2): 213–221.

92.

Absalon

Segall

Block

, et al. Safety and immunogenicity of a novel hexavalent group B streptococcus conjugate vaccine in healthy, non-pregnant adults: a phase 1/2, randomised, placebo-controlled, observer-blinded, dose-escalation trial. Lancet Infect Dis 2021; 21(2): 263–274.

93.

Buurman

Timofeyeva

, et al. A novel hexavalent capsular polysaccharide conjugate vaccine (GBS6) for the prevention of neonatal group B streptococcal infections by maternal immunization. J Infect Dis 2019; 220(1): 105–115.

94.

World Health Organization. Vaccine pipeline. who.int, 2022. https://www.who.int/teams/immunization-vaccines-and-biologicals/diseases/group-b-streptococcus-%28gbs%29

95.

Kobayashi

Vekemans

Baker

, et al. Group B. F1000Res 2016; 5: 2355.

96.

Brokaw

Nguyen

Quach

, et al. A recombinant alpha-like protein subunit vaccine (GBS-NN) provides protection in murine models of group B streptococcus infection. J Infect Dis 2022; 226(1): 177–187.

97.

Fischer

Pawlowski

Cao

, et al. Safety and immunogenicity of a prototype recombinant alpha-like protein subunit vaccine (GBS-NN) against group B streptococcus in a randomised placebo-controlled double-blind phase 1 trial in healthy adult women. Vaccine 2021; 39(32): 4489–4499.

98.

Larsson

Lindroth

Nordin

, et al. Association between low concentrations of antibodies to protein alpha and Rib and invasive neonatal group B streptococcal infection. Arch Dis Child Fetal Neonatal Ed 2006; 91(6): F403–F408.

99.

Seale

Bianchi-Jassir

Russell

, et al. Estimates of the burden of group b streptococcal disease worldwide for pregnant women, stillbirths, and children. Clin Infect Dis 2017; 65(Suppl. 2): S200–S219.

100.

World Health Organization. Group B streptococcus vaccine: full value of vaccine assessment. Geneva: World Health Organization, 2021.

Understanding GBS infection in pregnancy: exploring adverse maternal and pregnancy outcomes and the prospect of a GBS vaccine

Abstract

Keywords

Introduction

Group B streptococcus in pregnancy

Association of GBS colonization with adverse maternal and fetal outcomes

Current screening and preventive strategies

GBS vaccine in pregnancy

Conclusion

Footnotes

Acknowledgements

Declarations

ORCID iDs

References