Dr. Nargis Begum Javed:
Hepatitis B Virus Mother-to-Child-Transmission (MTCT): Can it be Prevented?
Hepatitis B virus (HBV) infection is a global public health issue, for which WHO has set the goal of removing this menace by 2030. MTCT is the main path of HBV transmission and is responsible for 40% to 50% chronic infection globally.1 Therefore, MTCT route obstruction can play a key role in reducing the prevalence of the disease and morbidity associated with it. The MTCT route can be blocked at different period of pregnancy through antiviral treatment or immunization.
The prevention of HBV MTCT begins with couple planning a child or soon after the women gets conceived.2 The prenatal or antenatal screening of the women for HBsAg is recommended and this approach is a part of routine antenatal care in several countries including India. If in the screening test results are negative, then the women should be provided standard antenatal care and counseled about the importance of immunizing their child for HBV. They should be made aware about the fact that chronic infection more likely develops in patients who get infected as infants (90%) and young children (30%).3 The women should be encouraged to follow hepatitis B immunization at birth for their infants which comprises of at least three doses of hepatitis B vaccine. The HBV immunization regime includes a birth dose which is administered within 24 hours of birth4, second dose at 1 month and third dose at 6 month. HBV immunization is included in National Immunization Program in many countries along with India. The mother should be encouraged to get infant undergo post-vaccination serologic testing (PVST) one month after completion of the regime. It should be explained to them during postpartum follow-up period that PVST which examines two markers (HBsAg and anti-HBs) is important for evaluating the effect of hepatitis B immunization and identification of HBV infection in infants. Anti-HBs level ≥100 IU/L ensures that the child is protected against HBV infection.5
However, if the test result is found to be positive for HBsAg, then the women should undergo a series of tests which include maternal HBV viral load (HBV DNA), HBeAg (serological marker), liver function test, and upper abdominal ultrasound to determine the level of liver injury. The known factors associated with the increased risk of MTCT are HBeAg positivity, high HBV viral load and instrumental delivery.6 Ninety percent HBeAg positive mother transmit HBV infection to their offspring as compared to only 10%-20% by HBeAg negative mothers.7
In the case of HBeAg positive women with high viral load and/or increased ALT level antiviral treatment with tenofovir disoproxil fumurate (TDF) or telbivudine (LdT) should be initiated from second trimester to prevent MTCT. However, the antiviral treatment during the late pregnancy (3rd trimester) has also shown to decrease the rate of MTCT in mothers with high viral loads.8 This approach has been recommended by major guidelines (AASLD 2018, EASL 2017, APASL 2015, CMA 2015 and NICE 2013). If the HBV DNA is positive with normal or slight increase in ALT levels in the pregnant women then antiviral therapy can be postponed but close monitoring should be done for symptoms and serology throughout the pregnancy. If the pregnant woman has chronic HBV infection, then antiviral therapy should be initiated as early as 24 week of gestation to delivery or 3 month post-delivery to prevent MTCT as per the major guidelines.
At the time of delivery, considering the safety of fetus, procedures that break the skin and mucosal barrier should be avoided as much as possible. The HBV MTCT mostly occur during labor and delivery in women especially who have risk factors like high maternal viral load, transfusion of mother’s blood during labor contractions, infection after rupture of membranes and direct contact of the fetus with infected secretions and blood from the maternal genital tract.5 Though HBV infection is known to be transmitted from mother to child through body fluids, and blood, still cesarean section is not recommended due to lack of strong evidence to support its benefit.
The standard precautions which should be followed in handling the newborn to prevent MTCT includes gentle wiping of visible blood, mucus and amniotic fluid present on the surface of neonate and the cord.
After delivery, it is recommended to provide active-passive immunoprophylaxis through use of hepatitis B immune globulin (HBIG) along with normal 3 dose regime of HBV vaccination to infants born to women with HBV infection.9
Infants born to HBsAg positive mothers should be followed up for completion of hepatitis B vaccination regime and post-vaccination serologic testing (PVST) as it is important for evaluating the effect of hepatitis B immunization and identification of HBV infection in infants. If HBsAg is found positive in the infant that means MTCT has occurred, the infant should be referred for appropriate clinical care. If HBsAg is negative and anti-HBs antibody (<10 IU/L) HBV DNA test should be done to rule out occult HBV infection. If HBV DNA in undetectable then, revaccination of 3 dose HBV regime should be performed and one month after the completion of regime PVST should be repeated.5
If PVST results show HBsAg negative and anti-HBs antibody level ≥10 IU/L but <100 IU/L that means there is a low response to the vaccination, and booster dose should be considered. If PVST result shows HBsAg negative and anti-HBs antibody level ≥100 IU/L that means the infant is protected against HBV infection and do not need further medical management.5 PVST should be performed at least one month after completion of all doses and it is recommended by WHO and Centers for Disease Control and Prevention (CDC).
MTCT has not been reported to occur through breast milk. Therefore mothers whether treated or not with anti-virals during pregnancy should be encouraged to breastfeed if their newborns have received combined immunoprophylaxis.5 In case mother received treatment with antivirals during pregnancy for preventing MTCT, treatment should be discontinued after delivery and if mother had received treatment for chronic hepatitis then treatment should be continued after delivery.
Author
Dr. Nargis Begum Javed, Ph.D (Molecular Virology), Maulana Azad Medical College, New Delhi, India.
Assistant Professor, Department of Public Health, College of Health Sciences, Saudi Electronic University, Dammam, KSA.
July 28, 2020
References:
1. Lamberth JR, Reddy SC, Pan JJ, et al. Chronic hepatitis B infection in pregnancy. World J Hepatol 2015;7:1233-1237.
2. National Health and Family Planning Commission of the People’s Republic of China. Action plan to prevent mother-to-child transmission of AIDS, syphilis, and hepatitis B 2015. Available from: http://www.nhfpc.gov.cn/ewebeditor/uploadfile/2015/06/docx.
3. McMahon BJ, Alward WL, Hall DB, et al. Acute hepatitis B virus infection: relation of age to the clinical expression of disease and subsequent development of the carrier state. J Infect Dis 1985;151:599–603.
4. World Health Organization. Hepatitis B vaccines: WHO position paper. Vaccine 2017;28:589–590.
5. Hou J, Cui F, Ding Y, et al. Management algorithm for interrupting mother-to-child transmission of hepatitis B virus. Clin Gastroenterol Hepatol 2019;17:1929-1936.
6. Yin Y, Wu L, Zhang J et al. Identification of risk factors associated with immunoprophylaxis failure to prevent the vertical transmission of hepatitis B virus. J Infect 2013;66:447-452.
7. Stevens CE, Beasley RP, Tsui J, Lee WC. Vertical transmission of hepatitis B antigen in Taiwan. N Engl J Med 1975;292:771–774.
8. Pan CQ, Duan Z, Dai E, et al. Tenofovir to prevent hepatitis B transmission in mother with high viral load. N Engl J Med 2016;374:2324-2334.
9. National Health Commission of the People’s Republic of China. Immunization programs and instructions of national immunization program for Children. 2016. Available from: http://www.nhfpc.gov.cn/jkj/s3581/201701/a91fa2f3f9264cc186e1dee4b1f24084.shtml.