Cervicovaginal Microbial-Immune State and Group B Streptococcus Colonization in Pregnancy

Objective Maternal colonization with Group B Streptococcus (GBS) is a significant risk factor for serious neonatal morbidity. There are limited data on how the cervicovaginal (CV) microbiota and host immune factor β-defensin-2 might influence GBS colonization in pregnant individuals. This study sought to determine if the CV microbiota is associated with GBS colonization in pregnant individuals, and if β-defensin-2 modifies this relationship. Study Design This was a secondary analysis of a prospective cohort study of pregnant individuals with singleton pregnancies who had CV microbiota specimens analyzed at 16 to 20, 20 to 24, and 24 to 28 weeks' gestation, along with a third trimester GBS rectovaginal (RV) culture (n = 492). Microbiota data were analyzed with 16S rRNA gene sequencing and classified into community state types (CSTs). Log-binomial multivariable regression was used to model associations between CST and GBS RV status and to calculate risk ratios. β-defensin-2, an immune factor known to modulate the relationship between CST and pregnancy outcomes, was examined as an effect modifier. Results of 492 individuals, 34.3% were GBS RV +. Compared with individuals with CST I at 16 to 20 weeks, individuals with CST IV-A and CST II had a significantly elevated relative risk of subsequent GBS RV+ status. When stratified by high and low β-defensin-2 levels, β-defensin-2 was found to be an effect modifier of the association between CST IV-A and GBS RV+ status. In individuals with low β-defensin-2 levels, CST VI-A was associated with GBS RV+ status, but among individuals with high β-defensin-2 levels, there was no such association (interaction p -value = 0.03). Conclusion Pregnant individuals with CV microbiota characterized by CST IV-A and CST II had significantly elevated risk of GBS RV colonization in the third trimester compared with those with CST I, and β-defensin-2 was an effect modifier of the association between CST IV-A and GBS RV+ status. Future research should investigate if manipulation of the CV microbiota can prevent GBS colonization, thereby reducing intrapartum antibiotic prophylaxis and the risks of neonatal GBS infection. Key Points The relationship between the CV microbiota and GBS RV colonization is unknown. A Lactobacillus-deficient, anaerobic rich vaginal community, CST IV-A, is associated with increased risk of GBS RV colonization. β-defensin-2 is an effect modifier of the association between CST IV-A and GBS RV+ status.