Clinical Guidelines for the Prevention of Mother-to-child Transmission of Hepatitis B Virus (1st edition)
Obstetrics and Gynecology Section of the Chinese Medical Association
The main diagnosis of 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 of infants and children is emphasized. All pregnant women are required to have prenatal screening for hepatitis B serological markers (commonly known as hepatitis B two-and-a-half). If a pregnant woman is HBsAg positive, her newborn is at high risk of HBV infection and must be given hepatitis B immunoglobulin (HBIG) within 12 hours of birth in addition to hepatitis B vaccination. In order to standardize the preventive measures for mother-to-child transmission of HBV in China and to reasonably prevent HBV infection in newborns, experts in infectious diseases and obstetrics have jointly developed this guideline based on recognized research findings at home and abroad and with reference to relevant information from other countries.
I. Clinical diagnosis of HBV infection
Chronic HBV infection is defined as HBsAg positivity lasting for more than 6 months. If liver function is normal, it is called chronic HBV carriage; if liver function is abnormal and other causes are excluded, the diagnosis is chronic hepatitis B. Chronic HBV carriers need to have their liver function and other necessary tests reviewed every 6-12 months. mother-to-child transmission of HBV, i.e. HBV transmission from HBsAg-positive mothers to their offspring, occurs mainly during and after delivery, and Vertical transmission (intrauterine infection before delivery) has an infection rate of <3%... and is mostly seen in HBeAg-positive pregnant women.
The detection of hepatitis B serologic markers, namely HBsAg, hepatitis B surface antibody (anti-.HBs), HBeAg, hepatitis B e antibody (anti-HBe), and hepatitis B core antibody (anti-.HBc), can determine the presence or absence of infection or immunity, and the significance of their clinical diagnosis is shown in Table 1.
Clinical guidelines
A sign of active viral replication, high viral load, and high infectivity. Anti-HBs is a neutralizing antibody, and serum anti-one HBs level ≥ 10 mIU/ml is protective. Fluorescence real-time quantitative PCR technique 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 minor triplets), or even a few HBeAg positive (commonly known as major triplets), have HBV DNA below the lower limit of detection, which is called “HBV DNA negative”, but still have HBV in their blood and are infectious. Therefore, when a pregnant woman is HBsAg positive, regardless of her HBV DNA level, or even “negative”, her newborn will have the possibility of infection if she does not take immunoprophylaxis.
Second, the management of chronic HBV-infected patients during pregnancy
1. timing of pregnancy: before a woman with chronic HBV infection plans to become pregnant, it is best to have her liver function assessed by a specialist in infection or hepatology. Infected patients whose liver function is always normal can have a normal pregnancy; those with abnormal liver function can have a pregnancy if they return to normal after treatment and are rechecked normal for more than 6 months after stopping medication. Pregnancy during antiviral therapy must be done with caution. Interferon can inhibit the growth of the popular child, and contraception must be used during its use. Among the nucleoside (acid) analogues, adefovir and entecavir have adverse effects on fetal development or teratogenic effects orally1 and are contraindicated in the first 6 months of pregnancy and during pregnancy. Tenofovir and telbivudine belong to class B drugs for pregnancy pupil] and have no significant effect on the fetus when used in mid- and late pregnancy b Lamivudine belongs to class C drugs, but does not increase neonatal birth defects when used in early, mid- and late pregnancy to prevent HIV I mother-to-child transmission mouth]. Nevertheless, if pregnancy occurs during the use of any antiviral drug, the patient must be informed of the various risks of the drug used, and a consultation with the relevant physician must be sought to decide whether to interrupt the pregnancy or whether to continue antiviral therapy.
2. Pregnancy follow-up: After pregnancy, liver function must be reviewed regularly in chronic HBV-infected patients, especially in the early and late stages of pregnancy. If the liver function is normal in the first test, if there are no clinical symptoms of hepatitis, it should be rechecked once every 1 to 2 months; if the alanine transferase (ALT) is elevated but does not exceed 2 times the normal value (<80 U/L) and there is no elevated bilirubin level, there is no need for medication, but rest is still needed and rechecked at intervals of 1 to 2 weeks; if the ALT level is elevated more than 2 times the normal value (>80 U/L) or the bilirubin level is elevated. If the ALT level is more than 2 times the normal value (>80 U/L), or if the bilirubin level is elevated, it is necessary to consult the relevant professional physician, and if necessary, hospitalization, and in serious cases, termination of pregnancy.
3, the application of HBIG in late pregnancy has no role in preventing mother-to-child transmission: some scholars have proposed that HBIG applied to HBV-infected pregnant women in late pregnancy can prevent intrauterine infection in the fetus, but the following problems exist in the relevant studies: (1) the protection rate of neonates in the control group after immunoprophylaxis is only 55%-85%, which is significantly lower than the accepted protection rate, suggesting that there is no formal prevention in the control group; (2) the diagnostic criteria are incorrect and exaggerate the rate of intrauterine infection. exaggerated the rate of intrauterine infection; (3) some studies had contradictory results before and after themselves. In addition, there is no anti.HBsH o in the newborn after HBIG in pregnant women; gorilla experiments and studies on prevention of reinfection after liver transplantation in HBV-infected patients suggest that HBIG injections of 200-400 U every 4 weeks in late pregnancy are unlikely to reduce HBV viral load p1; it has also been reported in China that the regimen does not reduce mother-to-child transmission of M41. Therefore, it is important for HBV-infected pregnant women do not need to apply HBIG in late pregnancy.
4, the problem of antiviral treatment during pregnancy: high levels of HBV in pregnant women is the main risk factor for the occurrence of mother-to-child transmission, and reducing the amount of virus can reduce mother-to-child transmission. When pregnant women are HBsAg positive but HBeAg negative, their newborns have a protection rate of 98% to 100% after regular prevention. 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%-15% of newborns of HBeAg-positive pregnant women after regular prophylaxis. Although, it has been reported that treatment with lamivudine or tebivudine in the middle and late stages of pregnancy can reduce mother-to-child transmission, the number of cases in some studies is very small, and there are cases in which mother-to-child transmission still occurs after treatment in some control groups of newborns who may not have formal prophylaxis. Therefore, HBeAg-positive pregnant women cannot yet be treated with routine antiviral therapy as an indication for reducing mother-to-child transmission.
The following factors are also reasons for caution in anti-HBV therapy for pregnant women: (1) nucleoside (acid) analogs do not clear the virus, and the virus will return to its original level or even higher after discontinuation, even inducing serious liver function damage; (2) long-term medication will increase the financial burden and cause the virus to mutate and produce drug resistance and other side effects; (3) 85% to 95% of HBeAg-positive pregnant women are not treated with anti-HBV therapy even if their newborns are not treated. (3) 85% to 95% of HBeAg-positive pregnant women can be protected in their newborns after regular prophylaxis even without anti-HBV therapy; (4) anti-HBV therapy usually starts in mid- and late pregnancy and is not effective for intrauterine infection in early and mid-pregnancy. In conclusion, more rigorously designed, rigorously controlled, large sample, multicenter studies are needed to determine whether anti-HBV therapy is needed to reduce mother-to-child transmission in HBeAg-positive pregnant women. 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 cannot reduce mother-to-child transmission
It was believed that the contraction of the uterus during natural childbirth “squeezed” the placenta, prompting the virus in the mother to enter the fetus, causing intrauterine infection, so theoretically cesarean delivery can reduce the mother-to-child transmission of HBV. However, recent studies have demonstrated that the difference between the rate of HBV infection in neonates delivered by cesarean section and those delivered naturally after regular prophylaxis of chronically infected pregnant women is not statistically significant (P>0.05), indicating that cesarean section does not reduce the mother-to-child transmission of HBV. Therefore, cesarean delivery cannot be chosen for the purpose of interrupting mother-to-child transmission of HBV.
IV. Prevention of mother-to-child transmission of HBV
Hepatitis B vaccination is the most effective measure to prevent HBV infection. The active ingredient of the hepatitis B vaccine is HBsAg, which induces the body to actively produce anti-HBs and play a role. After the first dose of vaccine, most anti-HBs are still negative or below the lower limit of detection; about 1 week after the second dose, anti-HBs turns positive, i.e. 35-40 d after the start of vaccination, there is immunity to HBV; the third dose of vaccination can significantly increase the level of anti-HBs and prolong the years of protection. The anti-HBs positive conversion rate of newborns after full vaccination is as high as 95% to 100%, and the protection period can be more than 22 years. The human body has immune memory after actively producing anti-HBs, and even if the anti-HBs turns negative, the body can produce anti-HBs within a short time after being exposed to HBV again.
1. HBV prevention for full-term newborns: When a pregnant woman is HBsAg negative, regardless of HBV-related antibodies, newborns are vaccinated according to the “0, 1, 6 months” program, without the use of HBIG.
When a pregnant woman is positive for HBsAg, regardless of whether she is positive or negative for HBeAg, the newborn must receive HBIG and the full course of hepatitis B vaccination (3 doses at 0, 1 and 6 months) in a timely manner. If the results of HBsAg in pregnant women are unknown, it is better to give HBIG to newborns if possible. The protection rate for newborns of HBsAg and HBeAg-positive pregnant women is 85%-95%. If HBIG is not used, only the application of vaccine prevention, the overall protection rate is only 55% to 85%.
2. Immunoprophylaxis for preterm infants: preterm infants have immature immune systems and usually need 4 doses of hepatitis B. Preterm infants of HBsAg-negative pregnant women with stable vital signs and a birth mass of ≥2000 g can be vaccinated according to the 3-dose program at 0, 1 and 6 months of age, and it is best to reinforce 1 dose at I-2 years of age; if the vital signs of preterm infants are unstable, they should first be treated for related diseases and then vaccinated according to the above program after they are stable. If the vital signs of preterm infants are unstable, they should first be treated for relevant diseases and then be vaccinated according to the above protocol after stabilization. If the premature infant is <2000 g, the first injection should be given after the body mass reaches 2000 g (if the body mass does not reach 2000 g before discharge, the first injection should be given before discharge); after 1 to 2 months, the vaccination should be re-administered according to the 3-shot protocol at 0, 1 and 6 months. A second injection is required after an interval of 3 - 4 weeks. If the vital signs are stable, there is no need to consider the body mass, and the 1st vaccination will be given as soon as possible; if the vital signs are unstable, the 1st vaccination will be given as soon as possible after stabilization; after 1 to 2 months or after the body weight reaches 2000 g, the vaccination will be given again according to the 3-dose protocol for 0, 1 and 6 months.
3, HBV-infected pregnant women’s newborn breastfeeding: 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 nipples by infants may transmit the virus to infants, but these are theoretical analysis, the lack of evidence-based medical evidence. Even without immunoprophylaxis, the infection rate of breastfed and artificially fed newborns is almost the same. More evidence proves that breastfeeding does not increase the risk of infection even if the pregnant woman is HBeAg positive. Therefore, after formal prevention, regardless of whether a pregnant woman is HBeAg positive or negative, her newborn can be breastfed without detecting the presence of HBV DNA in the breast milk.
4, follow-up of newborns of HBsAg-positive pregnant women: the newborns of healthy pregnant women do not need to be checked regularly for hepatitis B serological markers. newborns of HBsAg-positive pregnant women need to be followed up for hepatitis B serological markers and the appropriate time is chosen for the purpose of clarifying whether immunoprophylaxis is successful, whether there is HBV infection, and whether booster immunization is needed. A negative test for HBsAg and HBeAg in cord blood or newborn Jhgl,week blood cannot exclude mother-to-child transmission because of the long latency period of HBV infection; a positive test also cannot confirm intrauterine infection or perinatal infection because HBsAg, HBeAg and related antibodies can enter the fetus through the placenta. In addition, serum HBsAg positive tan…can also occur within 2 to 3 weeks after vaccination of newborns. Therefore, testing for HBV serum markers before 6 months of age is not recommended for newborns without symptoms of hepatitis.
The appropriate time for follow-up is from 1 month (7 months of age) to 12 months of age after the third vaccination; if not, follow-up is still needed after 12 months of age. 7 months of age is when the body has the strongest response to hepatitis B vaccine and the highest titer of anti-HBs. (2) HBsAg negative, anti-HBs positive, but <100 mU/ml, indicating successful prevention, but weak response to the vaccine, can be booster vaccination at the age of 2-3 years to extend the years of protection; (3) HBsAg and anti-HBs are negative (or <10 mU/m1), indicating no HBV infection, but no response to the vaccine (3) HBsAg and anti-HBs are both negative (or <10 mU/m1), indicating no HBV infection but no response to the vaccine, requiring another full vaccination (3-dose regimen) followed by a review; (4) HBsAg is positive and anti-HBs is negative, highly suggestive of immunoprophylaxis failure; HBsAg is still positive after 6 months of review, which can determine prevention failure and chronic HBV infection. After successful prevention, annual follow-up is not required. For children of HBeAg-positive mothers, review every 2 to 3 years; if the anti-HBs drops below 10 mU/ml, it is best to receive a booster vaccination; follow-up is generally not necessary after 10 years of age.
5. Other matters for prevention of mother-to-child transmission of HBV: If women of childbearing age are negative for serological markers of hepatitis B in pre-pregnancy screening, it is best to receive hepatitis B vaccine (10 or 20 doug) before pregnancy. If pregnancy occurs during the vaccination period, no special treatment is required and the full course of vaccination can be completed, as the hepatitis B vaccine has no significant adverse effects on either the pregnant woman or the fetus. HBIG is best administered to newborns when there is no screening for HBsAg during pregnancy or when it is not possible to determine whether the pregnant woman is HBsAg positive or negative; HBIG is strongly recommended for newborns if there is a family history of hepatitis B. When a pregnant woman is HBsAg negative but the father of the newborn is HBsAg positive, he is usually in close contact with the newborn due to his care, increasing his risk of infection, so it is best for the newborn to HBIG injection; semen cannot cause HBV infection in the fetus. similarly, other family members who are HBsAg-positive are better off injecting HBIG in the newborn if they are in close contact with the newborn.
HBIG is a blood product, and it is best to complete informed consent and sign before delivery to avoid delays in its use. It is advisable to have HBIG available in obstetrics and gynecology wards so that high-risk newborns born at night, on weekends or during holidays13 can receive timely formal prophylaxis. HBV is likely to be present on the skin surface of newborns of HBV-infected mothers, and it is important to wash and adequately disinfect the skin before any treatment that damages the skin and to inject HBIG before other injectable treatments, etc. Amniocentesis of HBV-infected pregnant women who HBeAg negative, does not increase the risk of mother-to-child transmission of HBV in newborns ugly earth, if HBeAg positive, whether to increase the risk of fetal infection is less studied, and further research is needed.
V. Key points of neonatal hepatitis B immunoprophylaxis
1, pregnant women need to be tested for hepatitis B serological markers before delivery: HBsAg positive, indicating that HBV infection, infectious; HBeAg positive, highly infectious; anti-HBs positive, immune to hepatitis B.
2, HBsAg negative in pregnant women: newborns are vaccinated with hepatitis B vaccine according to the 3-dose program at 0, 1 and 6 months, i.e. 1 dose within 24 h of birth, 1 month and 6 months respectively; no need to inject HBIG again.
3.Pregnant women with positive HBsAg: 1 intramuscular injection of HBIG within 12 h of birth; at the same time, 3 doses of hepatitis B vaccine according to the 0, 1 and 6 months vaccination program.
4.Breastfeeding for HBsAg-positive pregnant women: after formal prevention of the newborn, breastfeeding is feasible regardless of whether the pregnant woman is HBeAg-negative or positive.
5, mode of delivery and mother-to-child transmission: cesarean delivery cannot reduce the rate of mother-to-child transmission of HBV.
6, preterm infants: when the birth mass ≥ 2000 g, no special treatment. If the body mass < 2000 g, the first vaccine should be injected after the body mass reaches 2000 g, and then after an interval of 1-2 months, the vaccine should be administered according to the 3-dose program at 0, 1 and 6 months. If the pregnant woman is HBsAg-negative and the premature baby is in good health, treat as above; if the health condition is not good, treat the related disease first and wait for recovery before vaccination. If the pregnant woman is HBsAg positive, regardless of the health condition of the premature baby, one injection of HBIG will be given intramuscularly within 12 hours, and another injection will be required after an interval of 3-4 weeks; vaccination will be given within 24 hours, 3-4 weeks, 2-3 months and 6-7 months after birth, and follow-up will be conducted.
7, other family members HBsAg positive: If the newborn is in close contact with HBsAg positive members, it must be injected with HBIG; without close contact, it is not necessary to inject.
8.Follow-up of newborns of HBsAg-positive pregnant women: at 7-12 months, test for serological markers of hepatitis B. If HBsAg negative and anti-one HBs positive, prevention is successful and resistant; if HBsAg negative and anti-one HBs negative, prevention is successful but requires another 3 doses of vaccination program; if HBsAg positive, prevention fails and becomes chronic infected.
9.Other precautions: Any operation that damages the skin mucosa must be fully cleaned and disinfected before proceeding.
10.Whether anti-HBV treatment should be performed in HBsAg-positive pregnant women to reduce the rate of mother-to-child transmission: when HBeAg-negative, no antiviral is needed; when HBeAg-positive, whether anti-HBV treatment should be performed is inconclusive and requires a rigorous multi-center controlled study.