Studies On The Risk Factors Of Intrauterine Infection Of Hepatitis B Virus

Objective: To investigate the risk factors of HBV(hepatitis B virus)intrauterine infection in neonates with HBsAg positive pregnant women,and provide the scientific rationale for prevention of mother to child transmission of HBV.Methods:1.Risk factors of HBV intrauterine infection:a case-control studyOur study design is case-control study.After screening,312 pregnant women positive with HBs Ag were enrolled from April,2013 to May,2015.Their infants were followed up to 6 months of age after birth.During the follow-up,questionnaire survey was performed to collect clinical epidemiological data,and the blood samples were collected from the pregnant women and their infants.Serum markers of HBV infection(including HBs Ag and HBe Ag,etc)were detected by using time-resolved immunofluorometric assay.The level of HBV DNA was determined using Polymerase chain reaction(PCR),and hepatic function parameters including ALT,AST,triglyceride and cholesterol,etc were detected using automatic biochemistry analyzer.At the end of follow-up,312 pregnant women were divided into intrauterine infection group and control group according to whether occurrence of HBV intrauterine infection.A logistic regression analysis was performed to identify the risk factors of HBV intrauterine infection.2.A systematic review and Meta-analysis of the risk factors of HBV intrauterine infectionWe collected papers about risk factors of HBV intrauterine infection published from the time of these database created to December,2016.The collected papers were screened according to inclusion and exclusion criteria.The quality of papers were evaluated according to Newcastle-Ottawa Scale(NOS)standard.The works of literatures screening,quality evaluation and data extraction were carried out by two individual reviewers.The association of risk factors with HBV intrauterine infection was determined by pooled odds ratio(OR)value with 95% confidence interval(CI).Heterogeneity between the studies was examined using Q test,and I2 values(25%,50% and 75% indicate low,middle,and high heterogeneity,respectively).ORs were pooled using a random effects model to manage heterogeneity on the condition that heterogeneity was significant(I2 ?50%);otherwise,a fixed effects model was applied.We evaluated potential publication bias using funnel plots.Sensitivity analysis was performed using the impact of fixed effects and random effect model.The data were analyzed by RevMan software(version 5.3).Results:1.1.Risk factors of HBV intrauterine infection: a case-control studyThirty-eight infants were detected as HBV intrauterine infection among the tested objectives.The infection rate was 12.18%.Of the 38 babies with positive HBsAg,there were 26 babies with both positive HBsAg and HBV DNA.The results of univariate analysis indicated that positive HBV DNA,positive HBe Ag and sexual activity during gestation of the pregnant women were significantly associated with HBV intrauterine infection(P < 0.05).However,positive HBs Ab,HBeAb,HBcAb,total cholesterol,triglyceride,abnormal ALT,or AST,threatened abortion,numbers of pregnancy and delivery were not found to be associated with HBV intrauterine infection(P > 0.05).Multivariate logistic regression analysis indicated that risk factors of HBV intrauterine infection were positive HBVDNA(OR = 2.76,95% CI =1.19~7.94),positive HBe Ag(OR=9.6,95% CI = 2.58~35.33)and sexual activity during gestation(OR = 1.53,95% CI = 1.07~6.40)of pregnant women.2.A systematic review and Meta-analysis of the risk factors of HBV intrauterine infectionAccording to the inclusion and exclusion criteria,29 qualified articles were finally included in the Meta-analysis.The 29 qualified studies were all carried out in China,17 studies on HBV DNA,26 studies on HBeAg,7 studies on HBIG,and 11 studies on cesarean sections among the included studies.Our mete-analysis showed that HBIG was associated with HBV intrauterine infection with pooled OR 1.21(95% CI: 0.95~1.55).The pooled OR values(95% CI)for the HBV DNA,HBeAg,and cesarean section were 3.51(95%CI: 2.59~4.76),4.88(95%CI: 3.81~6.24),and 0.44(95% CI: 0.30~0.63),respectively.The results indicated that HBV DNA,HBeAg and cesarean section of pregnant women were the potential risk factors of HBV intrauterine infection,but HBIG was not found to be associated with HBV intrauterine infection.Conclusions: We found that the risk factors for HBV intrauterine infection are positive HBV DNA,positive HBeAg,and sexual activity during gestation of pregnant women using a case-control study.We further confirmed that positive HBV DNA and positive HBeAg for pregnant women were risk factors of HBV intrauterine infection by using a systematic review and Meta-analysis.In addition,we found that cesarean section could protect neonates from HBV intrauterine infection,but HBIG injection during pregnancy had no protective effect on HBV intrauterine infection.