Prevention of mother-to-child transmission of hepatitis B virus

The main diagnosis of hepatitis B virus (hepatitis B virus, HBV) infection is based on HBsAg positivity. Mother-to-child transmission is the main cause of chronic HBV infection in China, so prevention in infants and children is emphasized. All pregnant women are required to undergo prenatal screening for hepatitis B serological markers (commonly known as hepatitis B two halves), and if a pregnant woman is HBsAg positive, her newborn is at high risk of contracting HBV, and in addition to hepatitis B vaccination, she must be injected with hepatitis B immunoglobulin (HBIG) within 12h after birth. In order to standardize the preventive measures for mother-to-child transmission of HBV in China and reasonably prevent HBV infection in newborns, experts in infectious diseases and obstetrics have worked together to formulate this guideline on the basis of recognized research results both at home and abroad, and with reference to the relevant information of other countries. I. Clinical diagnosis of HBV infection Chronic HBV infection is defined as HBsAg positivity lasting for more than 6 months. If the liver function is normal, it is called chronic HBV carrier; if the liver function is abnormal and other causes are excluded, chronic hepatitis B is diagnosed, and chronic HBV carriers need to review the liver function and other necessary tests every 6 to 12 months. Mother-to-child transmission of HBV, i.e., HBsAg-positive pregnant women pass HBV to their offspring, mainly occurs during and after delivery, while the infection rate of vertical transmission (intrauterine infection prior to delivery) is <3%, which is mostly seen in HBeAg-positive pregnant women. Detection of hepatitis B serological markers, i.e., HBsAg, hepatitis B surface antibody (anti-HBs), HBeAg, hepatitis B e antibody (anti-HBe), and hepatitis B core antibody (anti-HBc), determines the presence of infection or immunity, and the significance of their clinical diagnosis is shown in Table 1. HBsAg positivity indicates that the virus is replicating and is infectious; HBeAg positivity is A sign of active viral replication, high viral load and infectiousness. Anti-HB. is a neutralizing antibody, serum anti-HBs level ≥ lO mIU/ml is protective. Fluorescence real-time quantitative PCR technology detects HBV DNA level, which can reflect the level of viral load. However, about 30% of pregnant women who are HBsAg-positive and HBeAg-negative (commonly known as mini-positivity), or even a few HBeAg-positive (commonly known as maxi-positivity), have HBV DNA below the lower limit of detection, which is the so-called "HBV DNA-negativity", but there is still HBV in the blood, and it is infectious. Therefore, when pregnant women are HBsAg positive, regardless of their HBV DNA level, or even "negative", their newborns, if they do not take immunoprophylaxis, will have the possibility of infection. Second, the management of chronic HBV infection during pregnancy 1, timing of pregnancy: chronic HBV infection in women who plan to get pregnant, it is best to be infected by the Department of Hepatology or Hepatology specialist to assess liver function. Infected patients with normal liver function can have a normal pregnancy; those with abnormal liver function can have a normal pregnancy if they return to normal after treatment and have a normal recheck more than 6 months after stopping medication. Pregnancy during antiviral therapy must be cautious. Interferon can inhibit the growth of the fetus, and must be used during contraception. Among the nucleoside (acid) analogs, adefovir and entecavir have adverse or teratogenic effects on fetal development and are contraindicated in the first 6 months of pregnancy and during pregnancy. Tenofovir and telbivudine belong to class B drugs for pregnancy, and their use in the middle and late stages of pregnancy has no significant effect on the fetus. Lamivudine belongs to class C drugs, but does not increase neonatal birth defects when used in early, mid, and late pregnancy to prevent mother-to-child transmission of HIV [3]. Nevertheless, if pregnancy occurs during the use of any antiretroviral drug, the patient must be informed of the various risks of the drug used, and a consultation with a relevant physician must be requested to decide whether to terminate the pregnancy or continue antiretroviral therapy. Follow-up of pregnant women: After pregnancy, chronic HBV-infected patients must have their liver function checked regularly, especially in the early and late stages of pregnancy. For those who have normal liver function in the first test, if there is no clinical symptom of hepatitis, review the test every l~2 months; if alanine transferase (ALT) is elevated but not more than 2 times of the normal value (<80U/L) and there is no elevation of bilirubin level, there is no need to use medication but still need to rest, and review the test in intervals of l~2 weeks; if ALT level is elevated more than 2 times of the normal value (>80U/L) or bilirubin level is elevated, it is necessary to ask the relevant professional physician for consultation. If the ALT level rises more than twice the normal value (>80U/L) or the bilirubin level rises, it is necessary to ask the relevant specialized physicians for consultation, hospitalization if necessary, and termination of pregnancy in serious cases. 3, late pregnancy application of HBIG does not prevent mother-to-child transmission: some scholars have proposed that HBV-infected pregnant women in late pregnancy application of HBIG can prevent intrauterine infection of the fetus, but the relevant research has the following problems: (1) the control group of newborns immunoprophylaxis after the rate of protection is only 55% to 85%, significantly lower than the recognized rate of protection, suggesting that the control group does not have a formal prophylaxis; (2) the diagnostic criteria is incorrect, exaggerated the rate of intrauterine infection, and the rate of infection in the control group is not correct. exaggerated the rate of intrauterine infection; (3) contradictory results before and after some of the studies themselves. In addition, after the use of HBIG in pregnant women, there is no anti-HB in the newborn. Gorilla experiments and studies on prevention of reinfection after liver transplantation in HBV-infected patients suggest that the injection of 200-400 U of HBIG every 4 weeks in late pregnancy is unlikely to reduce the virulence of HBV, and there are reports in our country indicating that this regimen does not reduce the mother-to-child transmission. Therefore, it is not necessary to apply HBIG to HBV-infected pregnant women in late pregnancy. 4. Problems of antiviral treatment during pregnancy: high level of HBV in pregnant women is the main risk factor for mother-to-child transmission, and lowering the viral load can reduce mother-to-child transmission. When pregnant women are HBsAg-positive but HBeAg-negative, the protection rate of their newborns has reached 98%~100% after formal prophylaxis [7-9]. Therefore, there is no need to use antiviral therapy to prevent mother-to-child transmission in HBeAg-negative infected pregnant women. Chronic HBV infection still occurs in 5% to 15% of newborns of HBeAg-positive pregnant women after formal prophylaxis. Although, treatment with lamivudine or tibivudine in mid- and late pregnancy has been reported to reduce mother-to-child transmission, some of these studies had small numbers of cases, and some control neonates may not have had formal prophylaxis, and there were cases in which mother-to-child transmission still occurred after treatment. Therefore, routine means of antiviral therapy for HBeAg positivity in pregnant women as an indication for reducing mother-to-child transmission is not yet available. The following factors are also reasons for caution in anti-HBV therapy for pregnant women: (1) nucleoside (acid) analogs cannot clear the virus, and after discontinuation, the virus will return to its original level, or even higher, and may even induce severe hepatic impairment; (2) long-term use of medication will increase the economic burden, and cause the virus to mutate and become resistant to the drug, as well as other side effects; (3) 85% to 95% of pregnant women who are HBeAg-positive will have their newborn babies treated even if they do not receive anti-HBV therapy, which is not recommended for pregnant women. HBV treatment, their newborns can be protected after regular prophylaxis; (4) anti-HBV treatment usually starts in the middle and late stages of pregnancy, and is not effective for intrauterine infections in the early and middle stages of pregnancy. In conclusion, more well-designed, rigorously controlled, large-sample, multicenter studies are needed to determine whether HBeAg-positive pregnant women need anti-HBV treatment to reduce mother-to-child transmission. In addition, abnormal liver function during pregnancy in HBV-infected patients does not increase the risk of mother-to-child transmission of HBV, and most pregnant women will return to normal liver function after delivery. Therefore, routine anti-HBV treatment cannot be given to those with abnormal liver function, and the indications for anti-HBV treatment should be strictly controlled. Third, cesarean delivery can not reduce mother-to-child transmission It was previously believed that natural delivery due to uterine contraction “squeeze” the placenta, prompting the mother’s virus into the fetus, resulting in intra-organic infections, so theoretically, cesarean delivery can reduce the mother-poppy transmission of HBV. However, recent studies have proved that, after the neonates of chronically infected pregnant women were formally prophylactic, there was no statistically significant difference in the rate of HBV infection between cesarean section and neonates delivered naturally (P>0.05) [15], indicating that cesarean section could not reduce the mother-to-child transmission of HBV. Therefore, cesarean delivery cannot be chosen for the purpose of blocking HBV mother-to-child transmission. Fourth, the prevention of mother-to-child transmission of HBV Hepatitis B vaccination is the most effective measure to prevent HBV infection. The active ingredient of hepatitis B vaccine is HBsAg, which induces the body to actively produce anti-HBs and play a role. After the 1st vaccination, most of the anti-HBs is still negative or below the lower limit of the detection value; about l week after the 2nd vaccination, the anti-HBs turns positive, that is, 35~40d after the start of the vaccination has immunity to HBV; according to the 3rd vaccination can make the level of anti-HBs rise significantly, prolonging the years of protection. The positive conversion rate of anti-HBs in neonates after full vaccination is as high as 95%~100% [8,18], and the protection period can reach more than 22 years. After the body actively produces anti-HBs, it has an immune memory, even if anti-HBs turns negative and is exposed to HBV again, the body can produce anti-HBs in a short period of time [19], therefore, non-high-risk groups do not need to be boosted with hepatitis B vaccine. 1, when pregnant women are HBsAg positive, regardless of whether HBeAg is positive or negative, newborns must be promptly injected with HBIG and the full course of hepatitis B vaccine (3-dose regimen at 0, 1, and 6 months).HBIG needs to be used within 12 h after birth (theoretically, the earlier, the better), and its active ingredient is anti-HBs, which begins to work 15~30 min after intramuscular injection, and protective anti- HBs can be maintained for at least 42~63d, at this time the body has actively produce anti-HBs, so there is no need for a second injection of HBIG. If the pregnant woman’s HBsAg result is not known, it is best to give the newborn injection of HBIG if possible. After taking the above formal precautions, the neonatal protection rate of the HBsAg-positive and HBeAg-negative pregnant women is 98%-100%, and the protection rate of the HBsAg-negative pregnant women is 98%-100%. After taking the above formal prophylaxis, the protection rate for HBsAg-positive but HBeAg-negative pregnant women is 98%-100%, and for HBsAg and HBeAg-positive pregnant women, the protection rate for newborns is 850/0-95% [7-9]. If only vaccine prophylaxis is applied without the use of HBIG, the overall protection rate is only 55%-85%. 2, immunoprophylaxis of preterm infants: preterm infants with immature immune system usually need 4 shots of hepatitis B vaccine. preterm infants of HBsAg-negative pregnant women can be vaccinated according to the program of 3 shots at the age of O, 1, and 6 months, preferably at the age of 1-2 years and then strengthened with a shot; if preterm infants with unstable signs of vital signs, they should be treated with related diseases first, and then be vaccinated according to the above program after stabilization. If the vital signs of preterm infants are unstable, the relevant diseases should be treated first, and then vaccination should be given according to the above program after stabilization. If the preterm infant is <2000 g, the 1st injection should be given after the body mass reaches 2000 g (if the body mass does not reach 2000 g before discharge, the 1st injection should be given before discharge); l-2 months later, the 3-injection regimen of O, 1, and 6 months should be repeated [16]. Preterm infants of HBsAg-positive pregnant women must be injected intramuscularly with HBIG within 12 h after birth, regardless of their physical condition, and another injection is required after an interval of 3-4 weeks. If the vital signs are stable, no need to consider the body mass, as soon as possible to vaccinate the first injection; if the vital signs are unstable, to be stabilized, as early as possible to vaccinate the first injection; 1-2 months later or after the weight reaches 2000 g, and then re-vaccination according to the 0, 1, 6 months 3 shots program (ix). Breastfeeding of newborns of HBV-infected pregnant women: Although HBsAg and HBV DNA feet can be detected in the milk of HBV-infected pregnant women, and some scholars believe that cracked nipples, excessive sucking or even biting of the nipple by infants may transmit the virus to infants, these are theoretical analyses and lack of evidence-based medical evidence. Even without immunoprophylaxis, the infection rate of breastfed and artificially fed newborns is almost the same". There is more evidence that breastfeeding does not increase the risk of infection in pregnant women, even if they are HBeAg-positive". Therefore, after formal prophylaxis, whether pregnant women are HBeAg positive or negative, their newborns can be breastfed without the need to test for HBV DNA in breast milk. 4. Follow-up of newborns of HBsAg-positive pregnant women: Newborns of healthy pregnant women do not need to be tested for hepatitis B serologic markers on a regular basis, while those of HBsAg-positive pregnant women need to be followed up with hepatitis B serologic markers, at an appropriate time, in order to clarify the immunoprophylaxis. time, with the aim of clarifying the success of immunoprophylaxis, the presence or absence of HBV infection, and the need for booster immunization. Detection of HBsAg and HBeAg in umbilical cord blood or newborn Jhgl,peripheral blood, negative can not rule out mother-to-child transmission, because the incubation period of HBV infection is long; positive can not confirm the diagnosis of intrauterine infection or perinatal infection, because HBsAg, HBeAg, and the related antibodies can pass through the placenta into the fetus. In addition, serum HBsAg positivity can also occur within 2 to 3 weeks after neonatal vaccination tam.... Therefore, testing for HBV serum markers before 6 months of age is not recommended for neonates without symptoms of hepatitis. The appropriate time for follow-up is 1 month after the third vaccine dose (7 months of age) to 12 months of age; if not, follow-up is still needed after 12 months of age. 7 months of age is the time when the body has the strongest response to the hepatitis B vaccine, with the highest titer of anti-HBs, and the following results are available: (1) HBsAg-negative, anti-HBs-positive, and >100 mU/ml, which indicates that the prevention is successful and the response is good, and does not require any special treatment; (2) HBsAg-negative, anti-HBs-positive, and >100 mU/ml, which indicates that the prevention is successful and the response is good, and does not require special treatment; (2) HBsAg negative, anti-HBs positive, but <100 mU/ml, indicating successful prevention, but weak response to the vaccine, can be reinforced with 1 shot at 2-3 years of age to prolong the years of protection; (3) HBsAg and anti-HBs are negative (or <10 mU/m1), indicating that there is no infection of HBV, but no response to the vaccine, need to be re-vaccinated (or <10 mU/m1), need to be re-vaccinated throughout the whole course of the vaccine (or <100 mU/m1), need to be re-vaccinated; (4) HBsAg and anti-HBs negative, indicating that no infection of HBV, but no response to the vaccine. (4) HBsAg positive, anti-HBs negative, highly suggestive of immunoprophylaxis failure; HBsAg is still positive after 6 months, which can be determined that the prevention has failed, and has been chronic HBV infection. After successful prophylaxis, annual follow-up is not required. HBeAg positive mother's children, every 2 to 3 years to review; if anti-HBs down to less than 10 mU / ml, it is best to strengthen the vaccine l; 10 years old generally do not need to follow up. 5, the prevention of HBV mother-to-child transmission of other matters: if women of childbearing age pre-pregnancy screening of hepatitis B serological markers are negative, it is best to vaccinate against hepatitis B before pregnancy (10 doug or 20 doug). If pregnancy occurs during vaccination, no special treatment is needed and the full course of vaccination can be completed because hepatitis B vaccine has no significant adverse effects on either the mother or the fetus. In the absence of screening for HBsAg during pregnancy, or when it is not possible to determine whether a pregnant woman is HBsAg positive or negative, it is preferable to inject the newborn with HBIG; if there is a family history of hepatitis B, injection of HBIG into the newborn is strongly recommended. pregnant women who are HBsAg negative, but whose fathers are HBsAg positive, are often in close contact with their newborns due to care of the newborns, which increases the risk of infection, and it is preferable to inject the newborn with HBIG; spermatozoa are also used as the mainstay of the vaccination program. Injection of HBIG; semen cannot cause HBV infection in the fetus. Similarly, other family members who are HBsAg positive are preferable to be injected with HBIG in the newborn if they are in close contact with the neonate. HBIG is a blood product and informed consent should preferably be completed and signed by the mother prior to delivery to avoid delay in its use. HBIG should ideally be available in maternity wards to enable timely access to formal prophylaxis for high-risk newborns born at night, on weekends, or during holidays13. HBV is likely to be present on the skin surface of newborns of HBV-infected pregnant women, and it is important to wash and adequately disinfect the skin before performing any skin-damaging treatments, and to administer HBIG before any other injectable treatments, etc. Amniocentesis in HBV-infected pregnant women does not increase the risk of mother-to-child transmission of HBV to the newborn ugly earths if it is HBeAg-negative, and if it is HBeAg-positive, whether or not the risk of fetal infection is increased is less well-studied. If HBeAg positive, whether it increases the risk of fetal infection is less studied and needs to be further researched. Fifth, neonatal hepatitis B immunoprophylaxis points 1, pregnant women need to be tested prenatally hepatitis B serological markers: HBsAg positive, indicating that has been HBV infection, infectious; HBeAg positive, highly contagious; anti-HBs positive, hepatitis B immunity. 2, pregnant women HBsAg negative: newborns according to 0, 1, 6 months 3 shots program vaccination against hepatitis B, that is, within 24 h of birth, 1 month and 6 months were vaccinated with 1 injection; do not have to be injected with HBIG. 3, pregnant women HBsAg positive: newborns are born within 12 h of the birth of an intramuscular injection of 1 injection of HBIG; at the same time, according to the 0, 1, 6 months 3 shots program vaccination against hepatitis B. 4.Breastfeeding of HBsAg positive pregnant women: after the newborn is formally prevented, breastfeeding is feasible regardless of whether the pregnant woman is HBeAg negative or positive. 5, the mode of delivery and mother-to-child transmission: cesarean delivery can not reduce the rate of mother-to-child transmission of HBV. 6. Preterm infants: no special treatment is needed when the birth weight is ≥2000 g. If the birth weight is <2000 g, the infants should be treated before delivery. When the body mass is <2000 g, the first vaccine injection should be given after the body mass reaches 2000 g, and then the 3-shot regimen of 0, 1 and 6 months should be carried out after an interval of 1-2 months. When the pregnant woman is HBsAg negative and the preterm infant is in good health, treat as above; when the health condition is good, treat the related diseases first, and then administer the vaccine after recovery. HBsAg-positive pregnant women, regardless of the health status of preterm infants, intramuscular injection of HBIG within 12 h, and need to be injected again after an interval of 3-4 weeks; within 24 h of birth, 3-4 weeks, 2-3 months, 6-7 months, respectively, vaccination, and follow-up. 7, other family members HBsAg-positive: if the newborn and HBsAg-positive members of close contact, must be injected with HBIG; not close contact, do not have to be injected. 8.Follow-up of newborns of HBsAg-positive pregnant women: at 7-12 months, test for hepatitis B serologic markers. If HBsAg negative, anti-a HBs positive, prevention success, resistance; if HBsAg negative, anti-.HBs negative, prevention success, but need to be re-vaccinated with 3 shots of vaccine program; if HBsAg positive, prevention failure, become chronically infected. 9, other precautions: any damage to the skin and mucous membranes before the operation, must be fully cleaned and disinfected before proceeding. 10, HBsAg-positive pregnant women whether anti-HBV treatment to reduce the rate of mother-to-child transmission: HBeAg-negative, no need for antiviral; HBeAg-positive, whether anti-HBV treatment is inconclusive, the need for rigorous multi-center controlled studies.