After a steady decline in rates of new hepatitis B virus (HBV) cases in the United States, an increase in new cases was reported in 2017.1 The estimated US prevalence of HBV is <2% in the general population and 0.7% to 0.9% among pregnant women.2 Approximately 25,000 infants in the United States are born to women with HBV each year, with mother-to-child transmission occurring in roughly 0.4% of these cases.1 Current data suggest that 90% of children infected at birth will develop chronic infection, and an estimated 25% of these individuals will die prematurely, underscoring the need for timely screening and prevention.1

“Attention to perinatal hepatitis B infection is essential for the prevention of mother to child transmission…and also provides an opportunity to link silently infected women with appropriate follow-up to reduce lifelong morbidity,” as well as the risk for mortality associated with HBV infection, as noted in a review published in March 2020 in Clinical Obstetrics and Gynecology.2 “Continued prevention of perinatal transmission is an essential component of the ongoing effort to decrease the worldwide impact of hepatitis B,” the authors added.

For an in-depth discussion regarding the topic, we interviewed Shane Reeves, MD, associate professor in the Department of Ob/Gyn-Maternal Fetal Medicine at the University of Colorado School of Medicine at Anschutz Medical Campus in Aurora, and Susanne L. Bathgate, MD, associate professor in the Department of Obstetrics and Gynecology at George Washington University School of Medicine and Health Sciences in Washington, DC.

What are some of the latest developments or new findings regarding HBV in pregnancy?

Dr Reeves: Approximately 50% of chronically infected individuals will acquire infection perinatally or in childhood.3 Between 15% and 40% of those patients will ultimately develop complications including cirrhosis or hepatocellular carcinoma, so prevention of perinatal transmission is important.2 New treatments are now available that can prevent transmission and further reduce morbidity.

Transmission of HBV infection is decreasing in the United States secondary to maternal vaccination, but the risk is still present. In fact, it is increasing in tandem with the US opioid crisis.1

Therefore, recommendations continue to be that all women should be screened in pregnancy for hepatitis B surface antigen (HBsAg) at her first prenatal clinic visit, and repeat screening at 28 weeks should be done for women who have a high risk of acquiring infection.4

For those women with chronic HBV, transmission to the fetus is dependent upon several factors. In women with HBsAg+ and HBeAg, the risk for transmission is 10% without immune prophylaxis. If the woman is HBsAg+ and HBeAg+ with high viral loads, the risk for transmission is 70% to 90% without prophylaxis.3,4 Immune prophylaxis within 12 hours of birth for infants born to women with high HBV infectivity reduces the rate of transmission to 5%.2 Of note, women who have had an infant who demonstrates nonresponse to immunoprophylaxis have a higher risk of transmitting HBV to their infants from subsequent pregnancies.3

Dr Bathgate: Universal screening of pregnant women for HBV using a blood test for HBsAg has been recommended for the last several decades and functions alongside the strategy of interrupting maternal-to-child transmission by administering hepatitis B vaccine and hepatitis B immune globulin (HBIG) within 12 hours of birth. This strategy prevents approximately 90% of perinatal infections.

However, perinatal infection occurs in about 10% of neonates, despite immunization and immunoprophylaxis.5 One significant new development is the ability to measure HBV viral load. Pregnant women with the highest HBV viral load have the highest risk (up to 30%) of transmitting HBV to their babies.5

Drawing on experience treating HIV in pregnancy, researchers have targeted decreasing transmission of HBV by using antenatal antiviral medications in women with HBV to reduce in utero infection and maximize neonatal prevention.

In 2016, the Society for Maternal Fetal Medicine recommended that women who test positive for HBsAg during pregnancy have further evaluation using HBV viral load, and further recommended that women with a high viral load be treated with antiviral therapy beginning in the third trimester.6 Tenofovir has been suggested as a first-line agent, although lamivudine and telbivudine have also been effectively used for this purpose. Using antiviral medications in this manner for women with high viral load in some trials has reduced the risk for perinatal transmission to 0% to 5%.5

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What is the optimal approach to treatment of pregnant women with HBV, and what are some of the challenges of treatment and prevention of mother-to-child transmission?

Dr Reeves: New treatment with antivirals in pregnancy has been shown to further reduce transmission above that of postnatal immunoprophylaxis. Tenofovir, telbivudine, lamivudine, adefovir, and entecavir are all medications currently being used or studied in the prevention of mother-to-child transmission of HBV.

For women who have HBV with a viral load >7 log10 viral copies/mL, the risk of transmitting the infection to their infant is increased.6 In these women, treatment with tenofovir, lamivudine, or telbivudine is recommended. One metanalysis demonstrated that the risk for mother-to-child transmission of HBV was 80% lower among women who received treatment with lamivudine. Further, lamivudine and tenofovir were both associated with a reduction in the risk for mother-to-child transmission of HBV (0% and 2%, respectively) compared with no antiviral therapy (20% transmission).7

During delivery, it is recommended to avoid practices that would possibly increase the risk for transmission. A provider should be cautious about using a fetal scalp electrode or vacuum device for delivery. In general, cesarean section is reserved for other obstetric indications, except in women who have a viral load >20 million IU/mL, in whom cesarean delivery may reduce risk.

After delivery, all neonates should receive hepatitis B vaccination and HBIG within 12 hours after birth.

Dr Bathgate: The optimal approach to treating pregnant women with HBV involves ensuring that all pregnant women are screened for HBV, that women who test positive for HBsAg have follow-up testing for HBV viral load, and that those with high viral load are treated with antiviral medication to reduce in utero and peripartum transmission. In some cases, this would involve referral to a provider with experience with antiviral medications in pregnancy. Tenofovir has been suggested as a first-line antiviral agent for this purpose.

One of the challenges in providing the best neonatal care for infants born to women infected with HBV involves identifying those women at the time of delivery. For women admitted in labor, records of HBsAg testing in that pregnancy should be immediately available or obtained. If no documentation of HBsAg testing is available by the time of delivery, the neonate should be treated with HBV vaccine and HBIG within 12 hours of delivery.

As per Society for Maternal Fetal Medicine recommendations, cesarean delivery is not recommended for the sole indication for reduction of vertical HBV transmission.6

Breastfeeding may be encouraged as long as the infant has received HBV vaccination and HBIG at birth. For women with HBV who have an indication for genetic testing, invasive testing such as amniocentesis or chorionic villus sampling may be offered. However, counseling should include the fact that the risk for maternal-fetal transmission may increase with high HBV viral load.

What are other key recommendations for clinicians regarding this topic?

Dr Reeves: Women who have cirrhosis as a result of chronic HBV have increased risks in pregnancy including miscarriage, bleeding disorders, thrombocytopenia, rupture of esophageal varices, fetal growth restriction, and fetal prematurity. If hepatocellular carcinoma develops during pregnancy, the course is more aggressive. 

Also, in pregnant women with HBV, postnatal coordination with the pediatric team and public health department is important. Equally important is for the family to complete screening as well as the immunization schedule for the baby. 

Further, amniocentesis does not seem to increase the risk for transmission to the fetus if the HBV DNA is low.

Approximately 25% of women will develop alanine aminotransferase flares postpartum.7 These are usually mild and resolve with no sequelae. However, preeclampsia with severe features should be ruled out in these cases.

Finally, breastfeeding is safe for infants who have received postexposure prophylaxis for HBV.

Dr Bathgate: All women should be screened each pregnancy for HBV infection. Those pregnant women who are positive for HBsAg should receive HBV viral load testing and should be treated with antiviral medications in the third trimester if their HBV viral load is high. Their newborns should receive HBV vaccine and HBIG within 12 hours of birth to optimally prevent maternal-child HBV transmission.

All women should be immunized against HBV as part of recommended immunizations. As part of preventative care, HBV vaccination should be recommended for women who have not received it as part of childhood immunizations. HBV vaccine should also be offered to women without evidence of HBV immunity before or during pregnancy; this is to prevent new maternal HBV infection.

What are remaining needs in this area in terms of research or education?

Dr Reeves: Combination therapy is being studied to evaluate potential further benefit. Long-term data regarding infants exposed to HBV in utero are currently lacking. The safety data of antiviral therapy come from HIV-treated mothers, and existing studies show no increase in birth defects, miscarriage, or fetal growth restriction. Long-term effects have not been well-investigated.

Education of patients regarding vaccination, safe sex practices, and avoidance of intravenous drug use is important. With the antivaccination movement, the risk for vertical transmission and infection with HBV will increase.

Dr Bathgate: In terms of education, a recent survey of obstetrics/gynecology residency directors showed that almost all surveyed screened for chronic HBV in pregnancy, but “significant gaps still exist in practitioner comfort and training regarding the management of HBV during pregnancy.”8 Because of the success of neonatal treatment in the past, some providers may not be aware of the need to treat the women at highest risk for HBV transmission by testing HBV viral load and treating with antiviral medications in the third trimester.

Ensuring that every pregnant woman has access to adequate prenatal care needs to be a priority. Without access to screening for HBV, the opportunity to intervene and reduce transmission in women at high risk is lost.

For babies born to women with HBV chronic infection, it is especially important that they receive follow-up care and completion of their HBV vaccine series. Education should be provided to the parents regarding this follow-up before the baby leaves the hospital.

References

1. US Department of Health and Human Services. Hepatitis B basic information. https://www.hhs.gov/hepatitis/learn-about-viral-hepatitis/hepatitis-b-basics/index.html. Accessed online February 25, 2020.

2. Hamburg-Shields E, Prasad M. Infectious hepatitis in pregnancy. Clin Obstet Gynecol. 2020;63(1):175-192.

3. Piratvisuth T. Optimal management of HBV infection during pregnancy. Liver Int. 2013;33(Suppl 1):188-194.

4. Lam NC, Gotsch PB, Langan RC. Caring for pregnant women and newborns with hepatitis B or C. Am Fam Physician. 2010;82(10):1225-1229.

5. Aslam A, Campoverde Reyes KJ, Malladi VR, Ishtiaq R, Lau DTY. Management of chronic hepatitis B during pregnancy. Gastroenterol Rep (Oxf). 2018;6(4):257-262.

6. Society for Maternal-Fetal Medicine (SMFM), Dionne-Odom J, Tita AT, Silverman NS. #38: Hepatitis B in pregnancy screening, treatment, and prevention of vertical transmission. Am J Obstet Gynecol. 2016;214(1):6-14.

7. Giles M, Visvanathan K, Lewin S, et al. Clinical and virological predictors of hepatic flares in pregnant women with chronic hepatitis B. Gut 2015;64(11):1810-1815.

8. Niu B, Marzio DH, Fenkel JM, Herrine SK. Obstetricians’ and gynecologists’ knowledge, education, and practices regarding chronic hepatitis B in pregnancy. Ann Gastroenterol. 2017;30(6):670-674.