I. Introduction Mother-to-child transmission is the main route of HBV infection, and in China, 30% to 50% of patients with chronic hepatitis B are infected through the mother-to-child transmission route, therefore, interruption of mother-to-child transmission is a key means to control the hepatitis B epidemic in China. This paper discusses the non-specific prophylaxis, specific treatment, mother-to-child transmission options and evaluation of the efficacy of interruption, with the aim of reaching a consensus on the interruption of mother-to-child transmission of HBV. For women with chronic HBV infection who wish to become pregnant, if they meet the indications for anti-HBV treatment before pregnancy, they can be given antiviral treatment and pregnancy can be considered only after 6 months of antiviral response and drug withdrawal. For patients who do not meet the anti-HBV indication, if their HBV DNA load is low (HBV DNA less than 10^5 copies/ml in HBsAg-positive patients or less than 10^4 copies/ml in HBeAg-negative patients) and there is no significant liver fibrosis, such patients can delay antiviral therapy until after delivery. Such patients should be monitored for HBV DNA during pregnancy, and if the patient’s HBV DNA rises to greater than 10^7 copies/ml, pregnancy B drugs should be applied in the middle and late stages of pregnancy to reduce HBV DNA load and reduce the risk of mother-to-child transmission. 2, promote a healthy lifestyle: improve maternal health prevention and control knowledge: increase nutrition during pregnancy, avoid overwork, balanced nutrition, strengthen physical exercise, limit strenuous exercise, avoid abdominal collision and extrusion and shock, protect the placental barrier, avoid high-risk behavior, and quit smoking and alcohol. 3. Formal obstetric and liver examination: The general requirement for prenatal examination for the whole pregnancy is 9 to 13 times. The initial check-up should be performed at the beginning of pregnancy, within 28 weeks of menopause, every 4 weeks, between 28 and 35 weeks of pregnancy, every 2 weeks, and once a week after 35 weeks. pregnant women with HBV infection are high-risk pregnant women and should shorten their maternity check-up time appropriately, and in case of abnormalities, they must be checked regularly according to the follow-up date recommended by the specialist. During prenatal checkups, physicians should ask pregnant women in detail about their past menstrual cycles and overall health, whether they have a history of bad deliveries, and carefully ask about any recent history of fever, infection and any history of abnormal liver function to comprehensively evaluate the health status of the liver and predict whether they can safely survive pregnancy. 4. Measures during labor and delivery: Pay attention to energy supplementation during labor and delivery to reduce maternal physical exertion. Choose the mode of delivery for patients with mild hepatitis according to obstetric indications. For severe hepatitis, after 24-48 hours of active conservative treatment, perform cesarean section for delivery. Prevent obstetric injury during delivery, avoid or reduce neonatal birth injury, asphyxia and amniotic fluid aspiration, and reduce mother-to-child transmission. 5. Rapidly remove from the contaminated environment after delivery: Factors leading to mother-to-child transmission include exposure of the infant to cervical secretions and maternal blood, therefore, the newborn should be washed with warm water immediately after delivery to remove it from the contaminated environment as soon as possible to reduce the chance of infection. Specific treatment methods (a) Immunotherapy The probability of HBV infection in infants due to mother-to-child transmission in HBeAg-positive and negative pregnant women is about 90% and 40%, respectively. Trans-placental transmission constitutes ≤ 5% of mother-to-child transmission. Risk factors for transplacental transmission include maternal HBeAg positivity, high HBsAg titers, and high HBV DNA load. In HBsAg-positive pregnant women, the chance of perinatal transmission is not altered by mode of delivery, regardless of HBeAg positivity or high viral replication levels. Vaccination of newborns against HBV within 24 hours of delivery can reduce the risk of mother-to-child transmission by approximately 80%, and hepatitis B immune globulin (HBIG) should be administered within 24 hours of delivery (preferably within 6 hours) to help reduce the risk of mother-to-child transmission. 1. Active immunization – HBV vaccine A Meta-analysis showed that the relative risk of mother-to-child transmission was 0.28 (95% CI: 0.2C0.4) in those who had received HBV vaccine compared to those who had not. Active immunization with HBV vaccine alone (i.e., without HBIG) can be used in some remote areas where HBsAg testing of pregnant women is difficult. Results of a randomized, placebo-controlled clinical trial showed that neonates born to dual-positive mothers with HBsAg and HBeAg and given 3 to 4 doses of HBV vaccine without HBIG within 12 hours of birth prevented 70% to 95% of perinatal HBV infections according to the recommended regimen. research studies in areas with high prevalence of HBV infection showed that immediate postnatal administration of The first HBV vaccine, the second at 1 to 2 months of age, and the third at 6 to 8 months of age can produce a highly effective active immunization effect. In terms of maternal management, all pregnant women should be routinely screened for HBV markers early in pregnancy. Those who have had more than one or have HBsAg-positive sexual partners in the past 6 months should be retested at the time of delivery. 2. Passive immunization – hepatitis B immune globulin A Meta-analysis showed that the addition of passive immunization with HBIG further reduced the relative risk of HBV infection compared to neonates receiving the vaccine alone (0.54, 95% CI 0.41 to 0.73). Passive immunization with HBV vaccine and HBIG within 12 to 24 h after birth, followed by two to three consecutive vaccinations, is effective in preventing mother-to-child transmission in pregnant women with acute or chronic HBV infection who are both HBsAg and HBeAg positive, with an efficacy rate of 85% to 95%. Although clinical trials have confirmed that HBV vaccination and HBIG are effective only within 24 h of birth, studies have shown that HBIG given within 72 h of exposure may also provide protection, and newborns born to HBsAg-positive/HBeAg-negative mothers who receive HBV vaccine and HBIG are expected to have the same level of protection as newborns born to HBsAg and HBeAg-positive mothers. protection. (ii) Anti-HBV drugs and their reproductive safety studies Interferon and nucleoside (acid) drugs are the mainstream drugs for the treatment of hepatitis B at present. A large number of clinical studies have shown that interferon and nucleoside (acid) drugs can basically solve the problem of chronic tendency of acute hepatitis B in the natural state, and can stabilize and reverse the pathological process of about 80% of patients with chronic hepatitis B. Some clinical research data suggest that nucleoside (acid) drug therapy is also effective in hepatitis B-related decompensated cirrhosis and severe hepatitis. 1. telbivudine (LdT) In reproductive toxicity studies, no evidence of fertility impairment was observed in male and female rats exposed to 14 times the recommended therapeutic dose of LdT in humans. In preclinical studies, no teratogenic effects of LdT were observed, and no adverse effects of LdT on embryonic development were observed. Studies in pregnant rats and rabbits have shown that LdT can pass through the placenta. Developmental toxicology studies in rats and rabbits showed that no evidence of fetal damage from LdT was observed at exposure doses 6 and 37 times higher than the recommended human therapeutic dose, respectively. The literature on clinical studies of LdT for hepatitis B in pregnancy is sparse, and its reproductive and developmental toxicity in humans requires further observation. A domestic study observed the blocking effect of LdT on intrauterine infection in fetuses of patients with chronic hepatitis B in late pregnancy. 31 cases in the treatment group received LdT from 28 to 32 weeks of gestation until 30 days after delivery; 30 cases in the control group received concurrent observation from 28 to 32 weeks of gestation but did not receive LdT, and all infants were vaccinated within 6 hours and 30 days after birth All infants were vaccinated with HBV vaccine and hepatitis B immunoglobulin within 6 hours and 30 days after birth, and serum hepatitis B markers and HBV DNA were collected from femoral venous blood for examination before HBV vaccination and hepatitis B immunoglobulin and at 7 months of age, and the results showed that there was no significant difference between the serum HBV DNA levels of pregnant women in the two groups before treatment, but the serum HBV DNA of pregnant women in the treatment group was significantly lower than that in the control group before delivery. The serum HBsAg positivity rate at birth was 6.5% and 16.7% in the treated and control groups, respectively, with no significant difference between the two groups; however, the serum HBsAg positivity rate at 7 months of age was 0 and 13.3%, respectively, with significant difference between the two groups. There were 8 and 9 cases of elevated serum creatine kinase levels at birth in the treated and control groups, respectively, and no other adverse reactions were found in mothers and infants, suggesting that receiving LdT antiviral therapy in late pregnancy can safely and effectively interrupt mother-to-child transmission of HBV. 2, tenofovir ( tenofovir, TNV) animal experiments showed that no significant fetal developmental abnormalities were found in rhesus monkeys exposed to 25 times the recommended human therapeutic dose from 3 to 21 weeks of gestation, but slight osteoporosis was observed. Reversible impairment of bone mineralization, reduced bone mineral density, and bone softening occurred in infant and juvenile animals when high doses of tenofovir were applied in a variety of animals (monkeys, rats, and dogs, among others). Clinical studies on 606 pregnant women using TNV during the first 3 months of pregnancy and 336 pregnant women using TNV during 3-6 months of pregnancy showed not only effective suppression of HBV DNA in pregnant women, but also no significant side effects. The birth defect rate was 2.3% for pregnant women who used TNV in the first 3 months of pregnancy and 1.5% for users in 3-6 months, which is similar to the control group without nucleoside analogues. 3. lamivudine (LAM) No significant reproductive toxicity of LAM was found in animal studies. When LAM was given to rats and rabbits at 60 times the clinically recommended dose in humans, no significant teratogenic effects were observed. The early embryonic mortality rate was increased in rabbits when blood concentrations were similar to the recommended human dose, but no increase in early embryonic mortality was observed in rats when blood concentrations reached 60 times the recommended human dose. Studies in pregnant rats and rabbits have shown that LAM can enter the fetus through the placenta, but neither showed significant teratogenic effects. LAM has a long history of use in the treatment of chronic HBV infection in pregnant women, but no clinical reports of lamivudine-related reproductive or embryotoxic effects have been reported to date. A controlled clinical study of 38 HBV-infected women who were pregnant and took LAM continuously throughout pregnancy showed no pregnancy complications or fetal defects and no perinatal HBV transmission events, and the rate of HBV infection was not significantly different compared to the same population using conventional active and passive immunization. And 35 of the 38 pregnant women on antiviral therapy were free of HBV viremia and 10 (26.3%) achieved HBeAg seroconversion. 2 pregnant women who chose to discontinue lamivudine therapy during pregnancy resulted in progression to active hepatitis (abnormal ALT) in the sixth month. In a multicenter controlled clinical trial, 89 and 61 patients with chronic hepatitis B received LAM treatment and simultaneous follow-up from 32 ± 2 weeks of gestation to 4 weeks before and after delivery, respectively. all infants were vaccinated against HBV after birth, and some were given hepatitis B immunoglobulin 200 U within 24 hours of birth. hepatitis B virological markers were measured 52 weeks after birth, and the results showed that the LAM group The rate of undetectable serum HBVDNA in mothers (98%) was significantly higher than that in the control group (31%); the rate of serum anti-HBs positivity in infants in the lamivudine group (84%) was significantly higher than that in the control group (61%); the incidence of maternal and infant adverse events was similar in both groups, and no serious adverse events occurred in either group. It is suggested that the use of LAM antiviral in late pregnancy can safely and effectively reduce the mother’s serum HBV DNA load and reduce the risk of mother-to-child transmission of HBV. 4, other antiviral drugs (1) entecavir (entecavir, ETV): at 35 times the recommended human dose, ETV causes degenerative changes in the vas deferens in rodents and dogs. At 3100 times the recommended human dose, ETV caused reduced body weight, abnormal tail and spine morphology, and reduced ossification (vertebrae, toes, and phalanges) in rat fetuses, and excess lumbar vertebrae and ribs were observed in fetuses, as well as reduced ossification and excess rib formation in fetal rabbits at higher doses. (2) Adefovir (ADV): Intravenous administration of ADV to rats during pregnancy at a dose 38 times the recommended human therapeutic dose produced not only significant maternal toxicity, but also observed embryotoxicity and fetal malformations, as evidenced by an increased incidence of generalized edema, sunken eye blisters, umbilical hernia, and tail kinking. (3) Interferon drugs: Animal studies have shown that interferon-α and -β have significant reproductive toxicity, manifested by dose-related ovulation arrest and abortion. There are also clinical reports of congenital malformations and pre-term abortions in humans. Therefore, the use of ETV, ADV or interferon-based drugs for the treatment of HBV-infected pregnant women during the first 6 months of pregnancy and any period of pregnancy is not advocated, nor is the use of these three drugs for the prevention of mother-to-child transmission of HBV. (iii) Pregnancy classification of anti-HBV drugs There is a significant correlation between HBV carriage status and perinatal mortality, congenital malformations, and low birth weight, and maternal HBV load status is an independent risk factor for adverse perinatal outcomes. Although hepatitis may flare up after delivery, most pregnant women with chronic HBV infection have less severe liver lesions during pregnancy.