Risk And Molecular Characteristics Of Group B Streptococcus Mother-baby Transmission:A Prospective Cohort Study

ObjectiveTo understand the prevalence of maternal and neonatal Group B Streptococcus(GBS)and the vertical transmission rate of GBS between mother and baby,and to analyze the influencing factors of vertical transmission to provide important theoretical basis for effective prevention and control measures for vertical transmission of GBS?To understand the antibiotic resistance spectrum and drug resistance mechanism of maternal and infant GBS strains,and to provide data support for the treatment of clinical GBS infectious diseases and rational use of antibiotics.To explore the molecular characteristics of GBS,and to provide new ideas for the research and development of GBS multi-valent joint vaccine.To analyze the consistency of the molecular characteristics of maternal and infant matched strains and to enrich the research on the vertical transmission of GBS,and to provide important molecular evidence for the confirmation of GBS mother-to-infant transmission risks,and to explore the phenomenon of vertical mutation in molecular characteristics.MethodIn this study,a prospective cohort study was conducted in Longhua New District,Shenzhen,with a questionnaire survey,vaginal swabs sampling and follow-up in the pregnant women who were recruited.According to the result of vaginal swabs,pregnant women who GBS positive were divided into exposure group,pregnant women without vaginal GBS were divided into control group.The infant was born with GBS as the observation outcome.The incidence of outcomes in the two groups was compared and the relative risk ratio was calculated.The antibiotic susceptibility test of GBS isolates were carried out by disk diffusion method.The sequence of GBS was identified by Multilocus Sequence Typing.The serotypes,resistance and virulence genes,and pilus island of GBS were identified by simple or multiple polymerase chain reaction.Quantitative data were compared using t test and qualitative data were compared using?~2 test or Fisher's exact test to compare the differences between the two groups.Univariable and multivariable generalized linear models were used to analyze the influencing factors of vertical transmission and relative risk(RR).The relationship between two or multiple molecular characteristics of GBS isolates was tested by correspondence analysis.Kappa test was used to analyze the consistency of the molecular characteristics of GBS isolates from mother and her infant.Results1.Demographics characteristicA total of 1815 pregnant women were recruited,including 92 pregnant women were colonized GBS with a carriage rate of 5.1%.A total of 1815newborns and 24 neonates were colonized GBS with a carriage rate of 1.3%.Of the 92 GBS-positive mothers,the neonatal GBS-positive rate was 14.1%;among the 1723 GBS-negative mothers,the neonatal GBS-positive was 0.6%.2.Influencing factors of GBS vertical transmission(1)To all neonate:GBS colonization in all neonates was significantly associated with maternal GBS colonization,delivery types,perineal tear,number of prenatal vaginal exams,parity,and gestational hypertension,and maternal GBS positive,vaginal delivery,mother perineal tear,vaginal birth and perineal tear,maternal examination?10 times and parity?4 times increase the risk of neonatal GBS.(2)To neonates born to GBS-positive mothers,GBS vertical transmission was associated with delivery type,perineal tear,fetal membrane integrity,and sexually transmitted diseases,and vaginal delivery,perineal tearing,vaginal birth and perineum tear,maternal fetal membrane integrity and pregnancy sexually transmitted diseases increase the risk of neonatal GBS.3.Antibiotic susceptibility testGBS isolates were mainly resistant against tetracycline(75.9%),erythromycin(71.6%)and clindamycin(64.7%),and all isolates were sensitive to penicillin,linezolid,ceftriaxone and vancomycin.A total 69.8%of GBS isolates were multidrug resistance,of which co-resistance to erythromycin,clindamycin and tetracycline was the most common multidrug resistance pattern.The major erythromycin resistance genes were erm(B)and mef(A/E),and 16 isolates were carried both erm(B)and mef(A/E);the major tetracycline resistance genes were tet(M)and tet(O),and 21 isolates were carried both tet(M)and tet(O).4.Molecular characteristicsA total of 17 ST types were identified in this study,the most prevalent ST were ST19(19.8%),ST17(12.9%),ST10(12.1%)and ST12(10.3%),and the main clonal complexs were CC19(25.0%),CC103(13.8%),CC17(12.9%)and CC10(12.9%).Six serotypes were identified,the predominant serotypes were III(48.3%),Ia(25.0%)and V(13.8%).ScpB and hylB genes were detected in all the isolates.109 isolates carried alpha-like proteins(alp)genes,the most prevalent alp genes were rib(37.9%),epsilon(27.6%)and alphaC(25.0%).All isolates carried at least one pilus island(PI).The most common combination of PIs were PI-2b alone(38.8%),PI-1+PI-2a(35.3%)and PI-2a alone(25.0%).5.Vaccine coverage based on molecular characteristics of GBS isolatesThe overall coverage rates of serotype-based vaccines were 83.6%for the3-valent conjugate vaccine(serotypes Ia,Ib,and III)and 97.4%for the 4-valent conjugate vaccine(serotypes Ia,Ib,III,and V);the coverage rates were 62.9%for the 2-valent surface protein-based vaccine(rib and alphaC)and 90.5%for the 3-valent vaccine(rib,alphaC,and epsilon);the coverage rates were 74.1%for the 2-valent pilus-based vaccine(PI-2b and PI-1+PI-2a)and 99.1%for the3-valent vaccine(PI-2b,PI-1+PI-2a,and PI-2a).6.The relationship of mutiple molecular characteristicsMultiple correspondence analysis of multiple molecular characteristics reveals that ST17 associated with serotype-III/Rib/PI-2b,ST19 with serotype-III/Rib/PI-1+PI-2a,and ST485 with serotype-Ia/Epsilon/PI-2b.7.The agreement between GBS-positive mother-neonate paired data in molecular characteristicsThere was complete agreement in the carriage of virulence genes and PI,and excellent or good agreement in the distribution of STs(Kappa=0.913,p<0.001)and serotypes(Kappa=0.577,p<0.001).Among them,the molecular characteristics of four pairs of mother-neonate paired GBS were inconsistent,including three pairs of maternal GBS serotypes were all type V,while neonatal GBS were type Ib and type Ia,and a pair of maternal GBS was ST86and neonatal GBS was ST176.Conclusion1.The vertical transmission rate of mother-to-child GBS was 14.1%,maternal GBS colonization is the most important factor for vertical transmission.Therefore,it is recommended to use risk assessment or prenatal GBS screening to provide antibiotic prevention for pregnant women who is risk of carry GBS-positive or screen-positive GBS.And what's interesting is,GBS vertical transmission from GBS-colonized mothers was also associated with perineal situation and delivery type,suggesting that cesarean section and perineal intactness may effectively prevent GBS vertical transmission.2.GBS isolates were mainly resistant to tetracycline,erythromycin and clindamycin.The most prevalent resistance genes were tetracycline-resistant genes[tet(M)and tet(O)]and erythromycin-resistant genes[erm(B)and mef(A/E)].The most common multidrug resistance pattern was co-resistance to erythromycin,clindamycin and tetracycline.The above results indicate the importance of continuous monitoring of antibiotic resistance,and the use of antibiotics in clinical treatment and prevention of GBS disease should be combined with GBS antibiotic spectrum.3.The predominant STs were ST19,ST17,ST10 and ST12,and the predominant serotypes were III,Ia and V.ScpB and hylB genes were detected in all the isolates.The most prevalent alp genes were rib,epsilon and alphaC.All isolates carried at least one pilus island,the most common combination of PIs were PI-2b alone,PI-1+PI-2a and PI-2a alone.Multiple correspondence analysis revealed that there was a high dimensional correlation between ST type,serotype,virulence gene,and PI of strains,and to provide new ideas for the discovery of new clones of GBS,and to provide an important theoretical basis for the development of GBS multivalent combined vaccine.4.This study used a prospective cohort study to examine the consistency of virulence gene,PI,serotype,and ST type of mother-neonate paired GBS strains,and to reveal the vertical transmission based on the high degree of consistency of paired GBS multiple molecular characteristics.At the same time,it was found that there may be a vertical mutation in the molecular characteristics of GBS strains during vertical transmission.Therefore,it is necessary to carry out continuous dynamic monitoring of GBS strains to verify the vertical transmission process of GBS strains and to dynamically analyze the switchs in the genetic characteristics of the vertical transmission process of GBS strains.