The Efficacy And Safety Analysis Of TDF For Preventing Mother-to-child Transmission Of Hepatitis B Virus In Different Gestational Weeks

Background:At present,there is no agreement on the timing of the initiation of the treatment in using antiviral drugs to prevent the mother-to-child transmission（MTCT）of hepatitis B virus（HBV）during pregnancy.There has different advices between physicians of infectious disease and obstetricians,aslo in various regions at home and abroad.The guidelines of the Chinese Society of Infectious Diseases and the European Association for the Study of Liver Diseases recommend starting antiviral treatment during pregnancy 24-28 weeks.They were believed that early antiviral treatment may be beneficial to prevent early placental infection and intrauterine transmission on the premise of safety.However,the Chinese Society of Obstetrics and Gynecology,the American Gastroenterology Guide for Liver Diseases and Pregnancy,and the relevant guidelines of the Asia Pacific Association for the Study of Liver Diseases believe that when the purpose is to prevent mother-to-child transmission,it should start in the 28-32weeks of pregnancy,which not only can minimize the related risks,but also can be completely achieve the aim of preventing HBV MTCT.In addition,some patients have not undergone prenatal checkups on time during the first trimester,and some primiparas have not yet completed the hepatitis B serum marker test before pregnancy.As a result,antiviral treatment can only be started in the third trimester.Therefore,for the start of antiviral drugs for preventing MTCT at 24-28 weeks of gestation or 28-32 weeks of gestation,the effect between the two and the impact on mothers and babies still needs more data to provide clinical evidence.Objective:Analyzing the efficacy and safety of tenofovir dipivoxil fumarate（TDF）for preventing MTCT in pregnant women with high hepatitis B virus load at different gestational weeks in the middle and late stages of pregnancy.Methods:Retrospective data collection was performed on pregnant women who received TDF for preventing MCTC of HBV during the middle and late stages of pregnancy who were admitted to the Infection and Obstetrics department of the Affiliated Hospital of Yan’an University from February 2017 to May 2020.A total of 76 cases were included in this study according to the inclusion and exclusion criteria.All included subjects were hepatitis B virus deoxidation nucleic acid（HBV DNA）≥2×10⁵IU/ml before preventing,and have signed informed consent.They were divided into two groups according to the gestational weeks at which TDF was used.38 cases of group A(24-27⁺⁶weeks of gestation)and the same cases as group B（28-32 weeks of gestation）.Collecting the datas of all pregnants,including the gestational age,family history of hepatitis B,gestation history,baseline（before medication）and serum virological indicators during delivery,liver function（ALB,ALT,AST,TB,DB）,renal function（CRE,Urea,UA,β2-MG）,serum calcium and phosphorus test values,adverse childbirth events,general conditions at birth,delivery methods,etc.Follow-up the hepatitis B serological indicators and HBV DNA of infants after hepatitis B hepatitis vaccination.The software of SPSS25.0 was used to analyses data.Analyze the antiviral effects of TDF at different gestational weeks and the success rate of maternal and infant blockade;observe the maternal and infant outcomes and the safety at different gestational weeks.Results:1.The drug exposure time of pregnant women in group A and B during pregnancy was statistically significant（13.87±1.50 and 10.22±1.16 weeks,P<0.001）.There were no significant differences in HBV DNA level,age,family history,parity,HBe Ag positive rate,HBe Ag quantification,HBc Ab quantification,prothrombin time,liver function,renal function,serum calcium and phosphorus between the two groups of pregnant at baseline.2.The HBV DNA level of group A at baseline was 8.13（7.67,8.50）lg IU/ml,at delivery was 3.31±0.82 lg IU/ml,the difference was 4.65±0.76 lg IU/ml;the HBV DNA level of group B at baseline was 8.12（7.68,8.57）lg IU/ml,at delivery was 3.85±0.63 lg IU/ml,the difference was 4.09±0.69 lg IU/ml.HBV DNA levels in both groups decreased significantly at delivery than baseline（P<0.001）.Group A is lower than that of group B at delivery（P<0.05）,and the HBV DNA decline level is higher than that of group B（P<0.05）;.There were 81.58%（31cases）pregnants in group A and 55.26%（15cases）in group B with HBV DNA levels less than 4 lg IU/ml before delivery.There was a difference between the two groups（P<0.05）.3.There was no significant difference in the positive rate of HBe Ag during delivery between the two groups（P>0.05）,nor was there a significant difference in the positive rate of HBe Ag between the groups at time of delivery and baseline（P>0.05）.4.There was no significant difference in the levels of liver function,renal function,serum calcium and inorganic phosphorus between the two groups at baseline.Compared with the baseline,albumin in two groups decreased during delivery（P<0.001,P<0.05）,there was no statistical difference between the groups;Group A pregnants decreased in alanine aminotransferase during delivery（P<0.05）andbeta 2-microglobulin increased（P<0.05）.Creatinine and uric acid levels of the two groups increased significantly during delivery,and the serum phosphorus decreased significantly,with significant difference（P<0.001）.The levels of uric acid during delivery of the two groups increased,and the difference was statistically significant（P<0.05）.There was no statistical difference in the difference between two groups（P>0.05）.Furthermore,the aspartate aminotransferase,total bilirubin,direct bilirubin and serum calcium were not significantly changed between the two groups before and after TDF treatment with no statistically significant.5.There was no significant difference between the two groups of the gestational week,cesarean section rate of pregnant and the gender,birth body length,birth weight and Apagar score（at 1minute and 10 minutes）of newborns（P<0.05）.And the same result was observed in adverse birth events and neonatal adverse events between the two groups（P<0.05）.6.7 infants did not complete the follow-up on time.A total of 69 infants were followed up in the two groups.There was no one with HBs Ag or HBV DNA positive during the follow-up period.The difference of success rate was not statistically significant.Conclusion:1.The HBV DNA level of pregnant who started taking TDF at 24～27⁺⁶weeks of pregnancy was lower than that at 28～32 weeks of pregnancy.2.The success rate of preventing mother-to-child transmission of HBV by taking TDF from 28～32 weeks of gestation is equivalent to that of 24～27⁺⁶ weeks of gestation.3.During 24～27⁺⁶ weeks or 28～32 weeks of gestation taking TDF are all well tolerated and be generally safe for both mothers and infants.