Clinical Study On Vaginal Microecology And Pathogenesis Of Premature Delivery In Pregnant Women With Group B Streptococcus

BackgroundGroup B Hemolytic streptococcus(GBS)is Gram-positive coccus,which is an important pathogen causing maternal and neonatal infections.Clinical observation showed that most of GBS-positive pregnant women in pregnancy were only carriers and did not cause disease,but there were many GBS-positive pregnant women in some cases,especially in preterm infants.The incidence of neonatal pneumonia and sepsis in preterm infants was high and the condition was serious.This situation has attracted great attention to Obstetricians.With the further development of sequencing technology and bioinformatics analysis,more and more studies have been done on microorganisms,pathological pregnancy and adverse pregnancy outcomes.However,the types and locations of microorganisms associated with premature delivery are still unclear or unanimous,and further research is needed.Does GBS interfere with vaginal microenvironment and disturb vaginal flora,or does vaginal inflammatory environment prompt the transformation of GBS from colonization to virulent pathogens,and induce uterine contraction through vaginal and cervical mucosal upward infection,which ultimately leads to premature birth?What is the mechanism of GBS-induced preterm birth?Is the expression of IL-6 and phosphorylated STAT3 in GBS-positive cases related to the pathway of premature delivery?What are the characteristics of serotyping of GBS strains in premature cases?It is also an important subject in obstetric clinical research.Based on the above background,this study explored the vaginal microecology and the pathogenesis of premature delivery in pregnant women with group B Streptococcus positive through the following four parts.ObjectiveTo explore the vaginal microecology and the pathogenesis of premature delivery in pregnant women with group B Streptococcus positive.MethodsWe selected 5862 pregnant women who had been registered in our hospital from outpatient clinic to delivery in recent two years.In addition to leucorrhea examination and vaginal microecology analysis,cervical and lower 1/3 vaginal secretions were taken for GBS test,and then re-examined at 37 weeks of gestation.Amniotic fluid,placental mothers’decent swabs and umbilical cord blood were collected during delivery to detect GBS.Pathological examination of placenta.Using GEO data from public databases,human placental cells infected with GBS,transcriptome chips speculate the pathway of GBS-induced preterm birth.The concentration of IL-6 and IL-10 were detected by ELISA,the expression of phosphorylated STAT3 was detected by Wester blot,and the serotyping of GBS was detected by PCR.Result1.The vaginal microflora imbalance of GBS positive pregnant women was higher than that of negative pregnant women.There was significant difference(P<0.05).It was no difference in vaginal PH value and bacterial species and proportions between early and late pregnancy(P>0.05).The positive rate of GBS in early pregnancy was similar to that at 37 weeks.The rate of abortion was 5.84%,5.80%,2.44%and 1.32%,and the incidence ofpremature birth was 14.52%,13.04%,6.5%and 5.1%,respectively,and the incidence of PROM was 25.81%,25.76%,17.07%and 8.68%,respectively,and the incidence of neonatal infection was 3.23%,3.03%,2.44%and 0.23%,respectively.The incidence of abortion,premature delivery and premature rupture of membranes in pregnant women with GBS positive and abnormal vaginal microccology was higher than that in women with normal vaginal microecology(P<0.05).2.The positive rates of amniotic fluid,placenta and umbilical cord blood of GBS positive mothers at delivery were 3.94%,3.94%and 2.36%respectively.All tests were negative in GBS negative patients.There was no significant difnerence in postpartum fever,puerperal infection and postpartum hemorrhage between GBS positiv mothers and negative mothers.The incidence of chorioamnionitis in placenta pathological examination(69.29%)was significantly higher than that in negative mothers(18.94%).The neonatal infection rate of GBS positive mothers was 2.36%.GBS negative mothers and neonatal GBS negative mothers were all negative.3.R software limma was used to screen differentially expressed genes.The selection criteria of differentially expressed genes were Q-value(FDR)<0.01,FC>2 or FC<0.5.A total of 89 differentially expressed genes were found.Cluster Profiler was used for GO enrichment analysis,and the selection criterion was Q-value(FDR)<0.01.TNF and IL-6 were significantly differentially expressed genes.4.The concentration of IL-6 and phosphorylated STAT3 detected in premature delivery was higher than that in premature rupture of membranes and full-term delivery (P<0.05).Nine serotypes were identified in 79 strains of GBS.Genotypes of pregnant women with full-term delivery and premature rupture of membranes were I a,Ⅰ b,Ⅱ,Ⅲ,Ⅳ,Ⅴ,Ⅵ,Ⅶand Ⅷ.Serotype Ⅲ(58.3%)was found in premature delivery cases,followed by type la(16.6%)and type Ⅴ(8.3%)and two untyped cases(16.6%).Conclusion1.There was no significant change in vaginal flora between early and late pregnancy.The vaginal microflora imbalance of GBS positive pregnant women was higher than that of negative pregnant women,with statistical difference.Among the cases of adverse pregnancy events such as abortion,premature delivery,premature rupture of membranes and neonatal infection,GBS positive patients with abnormal vaginal microecology were higher than those with negative GBS and normal microecology.The positive rate of GBS is low,but the rate of abortion,premature delivery and premature rupture of membranes is higher than that of the latter.Patients with GBS positive cervical secretions and abnormal vaginal microecology are more likely to have adverse pregnancy events caused by ascending infection.Only those with GBS positive vaginal secretion and normal vaginal microenvironment were colonized,and the incidence of adverse pregnancy events was low.2.The positive rates of amniotic fluid,placenta and umbilical cord blood in GBS pusitive mothers during pregnancy were than those in GBS negative mothers.Infected newborns with positive amniotic fluid,placenta and umbilical cord blood have a certain carrier rate and infection rate.Infected newborns are premature infants with serious condition,which should be paid attention by obstetricians.3.The expression of TNF and IL-6 in GBS-activated inflammation pathways related to preterm delivery has changed significantly.According to the transcriptome data,the responses of these two factors related to birth initiation support the theory that GBS may cause premature delivery.4.The expression of IL-6 and phosphorylated STAT3 in vaginal secretion of GBS-positive preterm delivery was significantly higher than that of premature rupture of membranes and full-term delivery.Premature GBS strains were mainly virulent type III,and two strains were non-typable.The unknown strain may have strong pathogenicity to pregnant women and newborns.The high expression of IL-6 and STAT3 changes of vaginal microenvironment can induce premature delivery synergistically.