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Evaluation Of Risk Factors Related To Mother-to-child Transmission Of Hepatitis B Virus And Preliminary Study On Relationship Between The Gene Polymorphism Of CD209, CD209l In The Pregnant Women With HBV Positive And Intrauterine Infection

Posted on:2013-02-27Degree:DoctorType:Dissertation
Country:ChinaCandidate:L LiFull Text:PDF
GTID:1114330374478667Subject:Obstetrics and gynecology
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Chronic hepatitis B (CHB) threatens the public health in the world and is also the majorinfectious diseases in our country. With the exception of a small number of acute hepatitisself-limited, the chronicity is a prominent problem. A large number of people died of livercirrhosis, hepatocellular carcinoma caused by hepatitis B each year. The pregnant womenwith HBV were1,500,000to2,000,000each year and there will be many fetuses becomechronic carriers if not effectively prevented and treatment. About30%~50%HBV carrierswere infected by the way of mother-to-child HBV transmission in the perinatal period. Atpresent, the HBV infection rate is greatly declined when the newborns were vaccinated withroutine hepatitis B vaccine and hepatitis B immunoglobulin, but there is still5%-15%of thenewborns were infected by HBV vertical or horizontal transmission in the late follow-up. Sothe study on perinatal risk factors of HBV mother-to-child transmission is still meaningful forhow to block mother-to-child HBV transmission.The infection rate of mother-to-child HBV transmission in neonates of pregnant womenwith hepatitis B was largely blocked both at birth and at postpartum with the application ofhepatitis B vaccine and HBIG, but there is still a certain failure rate if HBV intrauterineinfection had happened. This may be related to the risk factors of maternal venous blood viralload, mode of delivery, maternal serum status of HBeAg and postpartum feeding patterns andso on. Therefore the purpose of this study is a statistical analysis with high risk factors andlow risk factor of HBV mother-to-child transmission and the outcome of pregnancy, whichcould be used to provide powerful guidance to prevent mother-to-child HBV transmission.The pathway of intrauterine infection of mother-to-child HBV transmission is mainly transmitted by HBV through damaged placental chorionic vascular in the third trimester, butthe mechanism of HBV intrauterine transmission was still not clear. Some neonates werechronic infection, while others were to generate protective antibodies when exposed in thesame risk factors. It may be related to pathogenic characteristics, environmental factors andbackground of host genetics. The gene CD209is a molecular weight of44KD, type IItransmembrane protein, which belongs to C type exogenous lectin superfamily. It is1.3kblength and located on chromosome19p13.3. The polymorphisms of CD209and CD209Lgenes are associated with HIV, HCV, SARS virus infection, and expressed both in placentaltrophoblast cells and microvascular endothelial cells, which may also correlated with HBVintrauterine infection.For the above issues, we collected161cases of pregnant women and their newborns(including a pair of twins), a retrospective study of the161cases of pregnant women withhepatitis B surface antigen (HBsAg) positive and the relationship between the mother-to-childHBV transmission and maternal age at delivery, gestational age, mode of delivery, maternalvenous blood HBV DNA level and feeding patterns.Compared the the pregnant outcomes ofthe pregnant women with HBV and the normal pregnant women. In order to study thepossible mechanism of HBV intrauterine infection, we collected16samples of the pregnantwomen and their newborns and6of whom, as the experimental group, were mother-to-childHBV transmission, the others were as the control group. We used PCR amplification, gelelectrophoresis and DNA sequencing methods for preliminary screening the SNP sitedistribution of the genes of CD209and CD209L, which may be related to HBV intrauterineinfection. The aim of the study was to provide a new train of thought for further blockingtargets of mother-to-child HBV transmission.Main Results:1,The rate of mother-to-child transmission of HBV was4.29%after routine preventiveinoculation in this study. The peripheral blood HBV DNA levels and HBeAg-positive wereobservably related to cord blood HBV DNA levels(P<0.05). Cord blood HBV DNA levelswas distinctly correlated to the HBV DNA levels in infant venous blood after6months(P<0.05). The age, gestational weeks, delivery modes and feeding patterns had nothing to do withmother-to-child transmission of HBV (P>0.05).2. In the study, the rate of high glycocholic acid and premature rupture of fetal membranes in the group of pregnant women with HBV were significantly higher than that ofthe group of nomal preanant women (P <0.05) and the rate of postpartum hemorrhage andpreterm birth in two groups were no different (P>0.05). The rate of low birth weight andmacrosomia were lower compared to standard weight and the difference was statisticallysignificant (P=0.011), which suggested that HBV had nothing to do with birth weight, butthe rate of fetal distress in the group of pregnant women with HBV is higher than the group ofnormal pregnant women and the difference was statistically significant (P=0.009).3. according to the promoter region SNP loci (rs2287887) of CD209L gene, the alleles ofexperimental group were mainly the C (5/6), and the genotype were mainly the CC (4/6),while the alleles of control group were mainly the A (8/10), and the genotype were the AA(3/10) and AC (5/10). For the promoter region SNP loci (rs11260029) of CD209L gene, thegenotype of experimental group were mainly the TT (5/5), and the genotype of control groupwere the CT (3/9) and TT (6/9), and the allele variation were the T both in the experimentalgroup and the control group. The other SNP locis of CD209and CD209L genes had nodifference. According to the tfsearch site, the transcription factor of SNP loci (rs11260029)should be GATA-1.From these results, we draw conclusions as follows:1. Spontaneous labor, breast feeding is low risk factors of HBV mother-to-childtransmission, and high HBV DNA level of perinatal maternal venous blood is the highrisk factors. Cesarean section can not reduce mother-to-child HBV transmission risk.Breast feeding and mixed feeding does not increase the risk of HBV transmission.2. Pregnant women with HBV were prone to be complicated with high cholylglycineand premature rupture of membranes, and their newborns were prone to complicated withfetal distress. For this reason, the newborns of the pregnant women with HBV requiremore close monitoring in perinatal period in order to guarantee the safety of mothers andinfants.3. It may have relationship with HBV mother-to-child transmission if the site(rs2287887) of the single nucleotide polymorphism (SNP) of CD209L gene promoter wasallele C and genotypes CC and HBV mother-to-child transmission may not happen if thesite changes from C allele to A allele which was a heterozygous mutation; and HBVmother-to-child transmission could not happen if the mutation of the site (rs11260029) ofthe SNP of CD209L gene promoter changes from T allele to C allele. Above all, it stillneeds to further expand the sample size and function research to confirm.
Keywords/Search Tags:Hepatitis B virus, Mother-to-child transmission, Risk factors, Single-nucleotide polymorphism, Pregnancy outcome, Feedingpatterns, Delivery mode
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