Abstract and Introduction
Abstract
Abstract In the United Kingdom, the National Screening Programme for identification of hepatitits B virus (HBV) infection in pregnant women uses HBV e antigen (HBeAg) and antibody to HBeAg (anti-HBe) as markers of infectivity to determine use of immunoglobulin for hepatitis B. Serum samples from 114 HBV-infected women were analyzed. Viral loads correlated with HBeAg/anti-HBe status and viral genotypes. Among 95 mothers whose serum contained anti-HBe, viral loads ranged between undetectable and 8.6 × 10 IU/mL (median 228 IU/mL). Ten (10.5%) of these mothers had plasma viral loads >10 IU/mL; 6 were infected with genotype E and one each with genotypes A, B, C, and D. All viruses had precore stop codon or basal core promoter mutations. Preponderance of genotypes other than A among antenatal mothers in the United Kingdom reflects increasing globalization and trends in immigration. HBeAg serostatus is no longer sufficiently accurate for inferring potential infectivity of pregnant HBV carriers.
Introduction
Hepatitis B virus (HBV) infection remains a major health problem worldwide and mother-to-infant transmission represents one of the most efficient ways of maintaining hepatitis B carriage in any population. Intervention to prevent this route of infection is a key part of the global program of hepatitis B control. Although there are 3 routes of transmission of HBV from infected mothers to their infants, including transplacental and postnatal, most transmission is likely to occur perinatally at the time of labor and delivery. HBV e antigen (HBeAg) in maternal serum is associated with high infectivity; in the absence of intervention after delivery, including both passive and active immunization, 90% of babies born to carrier mothers whose serum contains HBeAg will become chronically infected with HBV. Babies born to mothers whose serum contains antibody to HBeAg (anti-HBe) become infected far less frequently. However, babies who are infected may be at risk of developing fulminant hepatitis B.
The prevalence of HBV infection in the United Kingdom is low (0.4%). In the late 1990s, the World Health Organization (WHO) recommended introduction of global universal hepatitis B immunization programs; by March 2002, a total of 151 countries, including 34 in Europe, had introduced HBV vaccine within their national immunization programs. However, current control of mother-to-infant HBV transmission in the United Kingdom is based on selective hepatitis B immunization of infants at risk. A recent WHO survey in Europe indicated that 8 other countries also used this approach. This requires routine antenatal screening for HBV infection, offered by 34 countries in Europe, with infants born to all hepatitis B-infected mothers being offered immediate postnatal active immunization with hepatitis B vaccine. In the United Kingdom, babies at highest risk for infection, those born to mothers whose serum does not contain anti-HBe, are offered additional passive immunization prophylaxis with 200 IU of hepatitis B immunoglobulin (HBIg) within 24 hours of delivery. In this protocol, detection of anti-HBe is used to infer low infectivity.
Despite full prophylaxis for neonates, a small proportion of infants still become persistently infected and are at risk of developing sequelae of chronic HBV infection and increasing the HBV reservoir. Although the causes for these failures could be many, we noted that in management of HBV-infected healthcare workers, inference of infectivity is now based upon plasma viral load for HBV rather than HBe markers. Until 2001 in the United Kingdom, fitness of an HBV-infected healthcare worker to undertake invasive procedures was predicated upon absence of HBeAg, a protocol that was found to enable transmission to patients. All transmission involved infections by viruses with the pre-core premature stop codons, which reflected changes in viral genotypes caused by increased migration in UK healthcare workers. To investigate potential inappropriate categorization of infection risk through continued use of HBe markers in the antenatal setting, we undertook a study to relate HBe markers to HBV DNA levels and genotypes as predictors of potential infectivity.