Hepatitis B infection during pregnancy presents a unique set of management issues. Aspects of care that must be considered include maternal and fetal effects of hepatitis B, effects of pregnancy itself on the course of hepatitis B infection and its complications, treatment of hepatitis B during pregnancy, and prevention of perinatal infection.

In addition to the usual issues of drug efficacy and safety in the affected individuals, effects on the developing fetus must be considered.

Susceptible women who develop acute hepatitis B during pregnancy may have an illness indistinguishable from that in the general population. Acute HBV infection must be differentiated from other acute liver diseases that occur during pregnancy. It does not appear that acute HBV infection increases mortality during pregnancy, or that it causes birth defects or cancer. However, a higher incidence of low birth weight and prematurity has been reported.

In addition, acute HBV early in pregnancy is associated with a 10% perinatal transmission rate, and the rate increases substantially with HBV infection in the third trimester.

Effects of Chronic HBV Infection on Pregnancy
The effects of chronic HBV infection on pregnancy outcomes have not been clearly defined. One large study demonstrated no differences in gestational age at delivery, birth weight, incidence of prematurity, neonatal jaundice, congenital anomalies or perinatal mortality comparing HBsAg positive women to non-infected women.

It has been known for some time that a proportion of women have hepatitis flares with or without HBeAg seroconversion within the first months after delivery. Seroconversion rates of 12.5% to 17% have been described. Although usually this is well tolerated, cases of exacerbation of hepatitis and even fulminant hepatic failure have been described in the peripartum period. It appears prudent to monitor HBV infected women closely for several months after delivery for hepatitis flares and seroconversion.

HBV Treatment for Pregnant Women
There are two principal indications for administration of antiviral agents to HBV-infected pregnant women: (1) Treatment of chronic hepatitis in the mothers, and (2) Prevention of perinatal HBV transmission to the newborns.

Most women with chronic HBV infection have mild liver disease during pregnancy, although hepatitis may flare after delivery, as described above.

Interferon, lamivudine, adefovir and entecavir are classified by the FDA as Class C, and telbivudine and tenofovir as Class B. In most cases, this is because there’s insufficient data in humans to show teratogenic or embryotoxic effects.

For these reasons, in most instances, it is reasonable to defer therapy until after delivery, to avoid fetal exposure to the therapeutic agents. After delivery, standard therapy indications, as expressed in the several available HBV guidelines, will apply. However, if maternal liver disease requires treatment, or if a pregnancy occurs in a woman already receiving a medication for HBV, decisions must be made about treatment course.

Currently, there are no standards regarding managing HBV in women who become pregnant while receiving antiviral therapy. One option is discontinuation of treatment as soon as pregnancy is recognized. This is an option only for those with mild hepatitis, with low risk of serious flare or disease progression. Other possibilities include continued careful monitoring or change of therapy to lamivudine, either temporarily or permanently, acknowledging the risk of development of resistance.

Protecting Newborns Against HBV
Immunoprophylaxis provided to newborns clearly reduces the incidence of perinatal HBV transmission. However, there are clearly a substantial number of newborn infections, even with prompt administration of active and passive vaccination.

The estimates vary, and depend on maternal HBeAg status, but most studies demonstrate anywhere from 1% to 10% chronic HBV infection in infants who were appropriately immunized. Clearly, with millions of at-risk pregnancies each year throughout the world, significant numbers of perinatally acquired chronic HBV infection are still occurring.

Strategies studied to further decrease the likelihood of perinatal HBV transmission have included provision of hepatitis B immune globulin (HBIG), or, more recently, antiviral agents, during the third trimester in high-risk pregnancies. As of yet, there are no official recommendations or guidelines for this type of therapy.

Breastfeeding and HBV
Several studies have documented no difference in rates of perinatal infection between breastfed and formula-fed vaccinated infants, which was between 0 and 5% in both groups, although many of the women in these studies were HBeAg negative. In addition, it appears that breastfeeding does not interfere with the immune response to HBV vaccine. These data support the recommendation of the American Academy of Pediatrics, that HBV infection not be considered a contraindication to breastfeeding of infants who receive HBIG and HBV vaccine as advised.

Critical Medical Challenges
Management of HBV during pregnancy includes recognition of maternal virologic status, assessment of liver disease, and minimization of risk for perinatal transmission of infection. This may include simple monitoring, changes in obstetrical care, or administration of antiviral therapy in late pregnancy or throughout pregnancy.

Passive and active immunoprophylaxis and monitoring for infection or immunity in newborns is an integral part of this management. Opportunities exist for case detection and prevention in household and sexual partners as well. The unique aspects of this management, with consequences for both mothers and newborns, and the relative lack of data, make this a critical medical challenge.

HBF appreciates the contribution of this article from Dr. Maureen Jonas, Clinical Director of the GI Division, Children’s Hospital Boston and Associate Professor, Harvard Medical School.