The prevalence of HBsAg positivity in pregnant mothers mirrors the general population (Table 9.2) [26] and varies by race: 6 % Asian, 1 % Black, 0.6 % Caucasian, and 0.14 % Hispanic.

In American-born patients, the most likely source of infection is drug use or sexual transmission, whereas patients born in endemic areas have most likely acquired the infection at birth. Foreign-born individuals represent the majority of HBsAg-positive mothers. In the United States, there is universal screening for HBV infection in all pregnant women with an estimated 96 % of all pregnant women tested. Mothers who have not had antenatal testing are tested at delivery by the birthing hospital [27].

It is thought that hepatitis B virus infection does not adversely affect the course of pregnancy, nor does pregnancy adversely affect the natural history of the disease. Indeed large retrospective cohorts have shown no difference in maternal or fetal outcomes compared to healthy non-HBV-infected controls. However, acute HBV infection is associated with high vertical transmission rates when occurring in the third trimester and increased incidence of low birth weight and prematurity [28]. Moreover recent studies suggested an increased risk of preterm birth, antepartum hemorrhage, and gestational diabetes in mothers chronically infected with hepatitis B [29, 30]. However, it is possible that the underlying advanced liver disease itself contributed to the high complication rate rather than the HBV infection itself.

HBV-related liver disease typically does not worsen during pregnancy. However, a small percentage of patients may develop cholestasis, chronic hepatitis B flare, or liver failure [28, 31]. During normal pregnancy, increased HBV viral load has been observed, leading to minor fluctuations in liver function tests and thought to be secondary to high levels of adrenal corticosteroids and estrogen hormones [32].

In one study, HBV virus levels remained stable, but ALT levels increased particularly in late pregnancy and postpartum periods. Further evidence supports the postpartum period as the most vulnerable time for HBV exacerbations. In a Japanese study, of 269 pregnant patients with chronic HBV infection, alteration of liver function was found in 43 % during the first month postpartum with some exacerbations leading to HBV seroconversion. Given the uncertainty of the natural history of HBV infection during and after pregnancy, patients should be monitored closely during pregnancy and postpartum.

Overall, the virus infects 75 % of all babies born from HBsAg-positive mothers in the absence of immunoprophylaxis. If the mother has a high viral load, as is the case in hepatitis B eAg-positive patients, this number is more than 90 %. However, newborns from mothers who are healthy carriers with minimal viral replication and hepatitis BeAb positivity are infected in less than 10 % of cases [34]. In the United States, the vertical transmission of hepatitis B has been reduced dramatically by the implementation of a nationally funded Perinatal Hepatitis Prevention Programs. Table 9.6 summarizes the steps.

Currently, available vaccines are safe in pregnancy, and mothers who are at risk for acquiring infection during pregnancy (injection drug users, patients with multiple sexual partners or who are infected with other sexually transmitted diseases] should be vaccinated and retested for HBsAg again in the third trimester close to the time of delivery [35]. Passive immunoprophylaxis with HBIG is also safe in pregnancy and should be given to women with documented exposure. Management of babies born from HBsAg + mothers (including preterm infants) is outlined above. This schedule has achieved nearly a 97 % success rate in preventing overall vertical transmission [36].

Despite HBIG administration and vaccination, the rate of HBV infection in the newborn may still reach 8.5 % in mothers with high viral load [37]. CDC estimated that 1,000 newborns are infected vertically each year in the United States. In a recent study, all cases of immunoprophylaxis failure occurred in mothers with high viral load (defined as >10⁶ copies/mL) [38]. The reason for immunoprophylaxis failure is that multifactorial prophylaxis regimens have been implemented in only 62 % [39] of cases. Vertical transmission of HBV occurs during delivery from blood-to-blood contact and occasionally in uteri by transplacental translocation of the virus [40]. Amniocentesis risk is controversial and not well established, but the test should be performed only if absolutely necessary [41].

Elective cesarean session has been found in some studies to be protective from immunization failure, and it is advocated for mothers with high viral load and risk of vertical transmission [42]. However, this recommendation is not generally accepted, and conflicting data still exist in the literature. Specific guidelines do not exist regarding the mode of delivery [43, 44].

Breastfeeding has been a major concern for source of transmission; however, several studies have refuted this and shown that breastfeeding carries no additional risk to transmission of the virus in the setting of prompt newborn immunoprophylaxis and vaccination [45].

Antiviral agents are used in pregnancy both to treat the expectant mother and to reduce vertical transmission.

Decisions regarding therapy initiation, continuation, and termination should be the same for pregnant patients and general population. Antiviral therapy in pregnancy, however, is in general postponed until after birth unless necessary for treatment of acute flares or advanced liver disease. Successful treatment of liver failure in pregnancy has been described with antiviral therapy.

The discontinuation of treatment will result in rebound increasing viremia and subsequent disease flares. Continuation of the therapy in pregnancy is prudent especially in view of their relatively safe profile and the risk of fulminant hepatic failure associated with disease flares in pregnancy and postpartum [24] (Table 9.7).

Immunization failure has been prevented by short courses of antiviral therapy during the second and third trimester of gestation in a few studies [46, 47]. In this patient population of high viral load mothers with otherwise limited underlying liver damage, therapy was initiated solely to prevent immunization failure.

Current use of antiviral to decrease vertical transmission is endorsed by many experts and was incorporated in the 2012 EASL Guidelines. This strategy is not uniformly accepted. Substantial debate still exists regarding the patient population to treat, choice of drug, length of treatment, and appropriate follow-up [48].

Two meta-analyses concluded that lamivudine treatment from 24 to 32 weeks of gestation until 1 month postpartum in those mothers who had high viral loads (>10⁶) was not only safe but more effective than HBIG and vaccination of the newborn alone [43, 49]. Most recently, a meta-analysis included four randomized controlled trials with a total of 306 mothers showing that telbivudine given late in pregnancy was safe as well as effective in reducing vertical transmission [50].

The safety data for antiviral therapy is derived from the antiretroviral pregnancy registry (APR) and the Development of Antiretroviral Therapy Study (DART). No significant differences in rates of adverse outcomes have been reported for HB antiviral drugs initiated throughout the three trimesters of pregnancy [51]. These rates were comparable to the defect rates in the general population (reported by the CDC).

Lamivudine and tenofovir have the largest data set because they have been used in HIV-infected patients. Tenofovir and entecavir are the most potent drugs with less likelihood of developing resistance and the ones recommended to treat nonpregnant patients. Tenofovir has been associated with skeletal abnormalities [52], and further studies assessing newborn bone density are planned. Limited data are available for entecavir and adefovir use in pregnancy Table 9.8.