Hepatitis B Surface Antigen Carrier Mothers Research Articles

The Impact of Maternal HbsAg Carrier Status on Pregnancy Outcomes: An Institutional Experience

Background: To examine the impact of maternal HBsAg carrier status on pregnancy outcomes. Methods: Forty-seven carriers of Hepatitis B surface antigen (HBsAg) admitted in the antenatal ward were retrospectively studied and their obstetric outcome was assessed. Results: The prevalence of HBsAg carrier status amongst indoor antenatal hospital population was found to be around 0.5%with average age of patients being 26 years. Amongst the study population 89% (40) patients delivered at term whereas only 4.4% (2) and 6.6% (3) patients had preterm delivery and abortions respectively. In our study 71.1% (32) delivered vaginally and the LSCS rate was found to be 22.2% (10) Only 2.2% (1) patient had hyperbilirubinemia and all patients had normal serum alamine transferase levels. Associated obstetric problem was found in 40%(18) of study population out of which meconium stained amniotic fluid and premature rupture of membranes were present in approximately 10% of cases each. Average birth weight in our study population was 2.8 kg. Neonatal intensive care unit admission was 7.1% (3) while stillbirth rate was around 2.3% (1) of total deliveries. All neonatal intensive care admission were for respiratory distress and they were later shifted to mother and discharged healthy making the live birth rate around 98%amongst total deliveries. Conclusions: HBsAg carrier mothers are mostly asymptomatic and had excellent obstetric outcome. Meconium stained amniotic fluid and premature rupture of membranes are commonly associated obstetric problems. LSCS rate is comparable with general population. Active and passive immunization of neonate is the mainstay of management.

Cost-effectiveness of Augmenting Universal Hepatitis B Vaccination With Immunoglobin Treatment

To compare the cost-effectiveness of hepatitis B virus (HBV) control strategies combining universal vaccination with hepatitis B immunoglobulin (HBIG) treatment for neonates of carrier mothers. Drawing on Taiwan's experience, we developed a decision-analytic model to estimate the clinical and economic outcomes for 4 strategies: (1) strategy V-universal vaccination; (2) strategy S-V plus screening for hepatitis B surface antigen (HBsAg) and HBIG treatment for HBsAg-positive mothers' neonates; (3) strategy E-V plus screening for hepatitis B e-antigen (HBeAg), HBIG for HBeAg-positive mothers' neonates; (4) strategy S&E-V plus screening for HBsAg then HBeAg, HBIG for all HBeAg-positive, and some HBeAg-negative/HBsAg-positive mothers' neonates. Strategy S averted the most infections, followed by S&E, E, and V. In most cases, the more effective strategies were also more costly. The willingness-to-pay (WTP) above which strategy S was cost-effective rose as carrier rate declined and was <$4000 per infection averted for carrier rates >5%. The WTP below which strategy V was optimal also increased as carrier rate declined, from $1400 at 30% carrier rate to $3100 at 5% carrier rate. Strategies involving E were optimal for an intermediate range of WTP that narrowed as carrier rate declined. HBIG treatment for neonates of HBsAg carrier mothers is likely to be a cost-effective addition to universal vaccination, particularly in settings with adequate health care infrastructure. Targeting HBIG to neonates of higher risk HBeAg-positive mothers may be preferred where WTP is moderate. However, in very resource-limited settings, universal vaccination alone is optimal.

Transmission of “&lt;i&gt;a&lt;/i&gt;” Determinant Variants of Hepatitis B Virus in Immunized Babies Born to HBsAg Carrier Mothers

Hepatitis B virus (HBV) surface antigen mutations may lead to immune escape and eventually cause failure of immunization. In this report, we identified immune escape variants in immunized babies born to hepatitis B surface antigen (HBsAg) carrier mothers. A total of 68 babies were followed up for 2 years after the full course of vaccination; 2.9% (2/68) of babies were found to be infected with the variant HBV in spite of preexisting antibody to surface antigen (anti-HBs) at 24 months post immunization. Both infants were positive for HBV-DNA; sequencing results of the “a” determinant region of the surface gene revealed that both babies had point mutations at a different nucleotide position resulting in various amino acid substitutions. In addition, an intriguing variant having an addition-deletion mutation was observed in one of the babies. This is the first report to show the addition-deletion variant of HBV in India. However, the immunological significance of the above HBV variants needs to be further elucidated.

Transformation of hepatitis B serologic markers in babies born to hepatitis B surface antigen positive mothers

To better understand the clinical significance of hepatitis B serologic markers in babies born to hepatitis B surface antigen (HBsAg) positive mothers, the incidence of maternal serologic markers of hepatitis B via placenta and its transformation in these babies were investigated. Mothers with positive HBsAg were selected in the third trimester of pregnancy. Their babies received immunoprophylaxis with hepatitis B immunoglobulin and hepatitis B vaccine after birth, and were consecutively followed up for hepatitis B serologic markers and HBV DNA at birth, mo 1, 4, 7, 12, and 24. Forty-two babies entered the study, including 16 born to hepatitis B e antigen (HBeAg)-positive HBsAg carrier mothers and 26 to HBeAg-negative HBsAg carrier mothers. Apart from four babies born to HBeAg-positive carrier mothers and demonstrated persistent positive HBeAg eventually became HBV carriers, all other babies developed anti-HBs before 12 mo of age. Among the other 12 babies born to HBeAg-positive carrier mothers, HBeAg was detected in 7 at birth, in 4 at mo 1, and in none of them thereafter. No antibody response to the transplacental HBeAg was detected. Among the babies born to HBeAg-negative carrier mothers, anti-HBe was detected 100% at birth and mo 1, in 88.5% at mo 4, in 46.2% at mo 7, in 4.2% at mo 12 and none in mo 24. Among all the immunoprophylaxis-protected babies born to either HBeAg-positive or HBeAg-negative carrier mothers, anti-HBc was detected in 100% at birth, mo 1 and mo 4, in 78.9% at mo 7, in 36.1% at mo 12 and in none at mo 24. HBeAg can pass through human placenta from mother to fetus and become undetectable before 4 mo of age, but no antibodies response to the transplacental HBeAg can be detected till mo 24 in the immunoprophylaxis-protected babies. The sole existence of anti-HBe before 1 year of age or anti-HBc before 2 years of age in babies born to HBsAg carrier mothers may simply represent the transplacental maternal antibodies, instead of indicators of HBV infection status.

Waning immunity to plasma-derived hepatitis B vaccine and the need for boosters 15 years after neonatal vaccination

Neonatal immunization with hepatitis B (HB) vaccine is highly effective; however, more needs to be learned about the duration of protection and indications for boosters. We measured antibody to HB core antigen (anti-HBc), HB surface antigen (HBsAg), and pre- and postbooster titers of HBsAg antibody (anti-HBs) 15 years after primary neonatal immunization with plasma-derived HB vaccines in 2 cohorts of 15-year-old children. Group A consisted of 78 children who were born to HB e antigen-positive HBsAg carrier mothers and had developed protective levels of anti-HBs antibodies (> or =10 mIU/mL) following HB immunization. Group B consisted of 113 apparently healthy children whose anti-HBs titers after vaccination were unknown. Anti-HBs was undetectable (antibody titer <10 mIU/mL) in 29.9% in group A and 62.4% in group B (P < .001). Anti-HBc was detected in 33.3 % in group A and 4.4 % in group B (P < .001). After a single booster dose of HB vaccine, 2.7% in group A and 3.3% in group B remained anti-HBs-negative. A blunted serological response was noted in approximately 20% in both groups. One HBsAg carrier was detected in group A (1.3%) and 4 in group B (3.5%). Fifteen years after neonatal immunization with plasma-derived HB vaccine, a large proportion of children exhibited waning immunity. This poses the risk of breakthrough infection. A single booster augmented the serological response to the vaccine in most but not all subjects. In conclusion, our findings suggest that one or more booster immunizations are needed in seronegative subjects by at least 15 years following neonatal immunization with plasma-derived HB vaccine.

Evaluation of screening for hepatitis B surface antigen during pregnancy in a population with a high prevalence of hepatitis B surface antigen-positive/hepatitis B e antigen-negative carriers.

Universal hepatitis B vaccination in infancy was implemented in Israel in 1992. The program consists of active vaccination at birth and at 1 and 6 months of age, without hepatitis B surface antigen (HBsAg) screening during pregnancy. Infants of HBsAg carrier mothers do not receive specific hepatitis B immunoglobulin in addition to vaccine at birth. The recently arrived Jewish immigrants from Ethiopia are the group with the highest rate of HBsAg carriage (approximately 10%) in Israel. The objective of this study was to evaluate whether the present policy is effective against perinatal HBV transmission from mothers of Ethiopian origin to their infants. The study group included 411 Israeli born children, offspring of mothers of Ethiopian origin. All infants were fully vaccinated starting at birth. Sera were collected from the children at the age of 9 to 36 months and from their mothers. Tests for HBsAg, antibodies to HBsAg (anti-HBs) and antibodies to hepatitis B core antigen (anti-HBc) were performed. Eighty-nine percent of the children had detectable anti-HBs, including 82.2% with protective anti-HBs concentrations (> or =10 mIU/ ml). Although 24 mothers (6.2%) were HBsAg carriers, none of the children was HBsAg-positive. Seven of 394 infants (1.7%) tested positive for anti-HBc. This test became negative in 5 of 6 who were followed for 12 months. The percentage of infants with protective anti-HBs concentrations decreased significantly from 91.4% at 9 to 12 months to 70.1% at 31 to 36 months of age. The mother's infection status was not associated with the infant's response to vaccine. Calculation based on the above data suggests that screening for HBsAg in pregnancy in that group is not cost-effective. Our results suggest that the Israeli vaccination program against HBV infection is effective, even in a high risk population, and additional measures are not cost-effective.

Hepatitis B surface antigenemia at birth: a long-term follow-up study.

To investigate the prevalence and outcome of hepatitis B surface antigenemia in newborns of hepatitis B e antigen (HBeAg)-positive hepatitis B surface antigen (HBsAg) carrier mothers under the current immunoprophylaxis program. From 1984 to 1993, 665 high-risk newborns born to HBeAg-positive HBsAg carrier mothers were prospectively recruited. The newborns were tested for HBsAg soon after birth, before hepatitis B immune globulin administration. All newborns received hepatitis B immune globulin within 24 hours after birth plus subsequent hepatitis B vaccination. Those who were seropositive for HBsAg at birth were regularly followed up for their hepatitis B virus (HBV) markers, liver function profiles, and alpha-fetoprotein levels from 1984 to 1996. Sixteen (2.4%) of the 665 subjects were found to be seropositive for HBsAg at birth, and all remained HBsAg-positive at 6 months of age. Twelve of the 16 received long-term follow-up care, and all were confirmed to have chronic HBV infection. Of the 12, 2 had HBeAg seroconversion, and 1 had alanine aminotransferase flares without HBeAg seroconversion. Delayed appearance of hepatitis B core antibody (anti-HBc) occurred in 2 without alanine aminotransferase elevation. Current immunoprophylaxis strategy does not protect newborns with surface antigenemia, apparently acquired in utero, from becoming HBV carriers. Immunologic attempts to eliminate HBV may occur in carrier children infected in utero, despite their profound immune tolerance to HBV.

The role of transplacental hepatitis B core antibody in the mother-to-infant transmission of hepatitis B virus

Aims/Methods: To investigate the influence of transplacental hepatitis B core antibody (anti-HBc) on perinatal hepatitis B virus (HBV) transmission, we studied the anti-HBc titers in 294 mother-neonate pairs. Results: The anti-HBc titer was highest (10 5.13±0.80 to 10 4.36±0.97 in mothers, 10 5.13±0.76 to 10 5.52±0.98 in infants) in the 200 hepatitis B e antigen (HBeAg) positive hepatitis B surface antigen (HBsAg) carrier mothers and their infants, second highest (10 4.51±0.76 and 10 4.68±0.76) in the 60 HBeAg-negative HBsAg carrier mothers and their infants, and lowest (10 3.11±0.76 and 10 3.24±0.83) in the 34 non-carrier mothers and their infants ( p<0.05). One hundred and ninety-two infants of HBeAg-positive carrier mothers received hepatitis B immunoglobulin as well as hepatitis B vaccines, and were followed prospectively from birth. Ten infants became HBsAg carriers, and their mothers had significantly lower anti-HBc titers than those of the mothers of 182 infants who did not become carriers ( p=0.003), while maternal serum hepatitis B virus DNA levels (29.9±23.6 versus 39.9±58.1 pg/10 ml) did not differ in those two gruops ( p>0.25). The same trend was observed in the infants' anti-HBc titers in those two groups ( p=0.0006). Conclusions: The association of lower anti-HBc titers in HBeAg-positive carrier mother-infant pairs and the development of carrier status in the infants suggests a positive role of anti-HBc in the modulation of mother-to-infant transmission of HBV. A high maternal anti-HBc level in serum may be a negative predictor of immunoprophylaxis failure in high-risk infants.

Hepatitis B vaccine trial in neonates

AbstractIn an attempt to interrupt perinatal and postnatal transmission of hepatitis B virus (HBV) infection, hepatitis B vaccine trials were initiated in October 1981 in Taiwan, starting in neonates of hepatitis B e antigen (HBeAg)‐positive hepatitis B surface antigen (HBsAg) carrier mothers and extending to neonates of non‐carrier mothers. All neonates had received a four‐dose schedule of Pasteur plasma‐derived hepatitis B vaccine. Among neonates of HBeAg‐positive HBsAg carrier mothers, the protective efficacy rate of vaccination was 75% in those who received vaccine alone and 90% in those who received vaccine plus hepatitis B immunoglobulin (HBIG) at birth. Among neonates of HBeAg‐negative HBsAg carrier mothers, the protective efficacy rate was 100% whether they had received vaccine alone or vaccine plus HBIG at birth. The protective efficacy rate was also 100% in neonates of non‐carrier mothers. During 6–9 years of long‐term follow‐up, 12 (6%) responsive vaccinees of HBeAg‐positive carrier mothers, one (2%) child of HBeAg‐negative carrier mothers and one child (0.4%) of non‐carrier mothers had seroconverted to antibody to hepatitis B core antigen (anti‐HBc) positivity. ‘Natural booster’ phenomenon, defined as a spontaneous sharp rise in serum antibody to HBsAg (anti‐HBs) titres in the absence of anti‐HBc and HBsAg, was observed in 7% of vaccinees whose mothers were HBeAg‐positive, 6% of vaccinees whose mothers were HBeAg‐negative HBV carriers, and 8% in vaccinees of non‐HBV carrier mothers. None of the responsive vaccinees had seroconverted to HBsAg. Thus, in the first decade of life, the protective efficacy in neonates who responded to plasma‐derived hepatitis B vaccine was 100%.

Absence or delayed appearance of hepatitis B core antibody in chronic hepatitis B surface antigen carrier children

An absence of the hepatitis B core antibody (anti-HBc) in hepatitis B surface antigen (HBsAg) carrier children has been reported before, but whether anti-HBc will ultimately appear is unknown. In a group of 420 HBsAg carrier children who were followed longitudinally, 10 (2.4%) had an absence or delayed appearance of serum anti-HBc. These 10 children were persistently seropositive for HBsAg, hepatitis B e-antigen, and hepatitis B virus DNA (HBV-DNA). Anti-HBc never appeared in 4, one of whom was a case of hepatitis B vaccine failure and became an HBsAg carrier. Three of the 4 were born to HBsAg carrier mothers. Liver biopsy in one revealed non-specific reactive hepatitis (NSRH). All 4 were asymptomatic during follow-up. Mothers of the other 6 children who had delayed appearance of anti-HBc were also HBsAg carriers. The children seroconverted to anti-HBc positivity between 2 and 8 years of age, and the titer of serum anti-HBc at the first appearance varied. There were no significant changes in liver function tests, HBV-DNA levels, or associated symptoms and signs before and after seroconversion. Liver biopsies were performed before anti-HBc seroconversion in 2 children and showed NSRH. All 10 children had a moderate to high replication of HBV as shown by the high titer of HBsAg and HBV-DNA. The absence of anti-HBc occurred almost exclusively in children who were infected perinatally.(ABSTRACT TRUNCATED AT 250 WORDS)

Membranous nephropathy in 52 hepatitis B surface antigen (HBsAg) carrier children in Taiwan

To elucidate the prognosis and the causative viral antigens of hepatitis B virus (HBV)-associated childhood membranous nephropathy (MN), the clinical course and glomerular HBV antigens were studied in 52 HBsAg carrier children with MN (40 boys, 12 girls). With Fab fragments of monoclonal antibodies, hepatitis Be antigen (HBeAg) was detected in the glomerular deposits in 41 (95%) of 43 cases but HBsAg and hepatitis B core antigen (HBcAg) in none. HBeAg was detected in sera from 43 (93%) of 46 children examined. These results suggest that HBeAg plays an important role in the development of MN in HBsAg carrier children. During the follow-up period (mean, 4 years), complete remission was found in 64% and 92% of the patients followed for one and seven years, respectively; only one child had mild renal function impairment. These findings suggest a favorable outcome of HBsAg-associated childhood MN. The patient's age, disease duration, amount of glomerular deposit, focal sclerosis and disease stage appeared to affect the clinical course. HBsAg seroconversion to HBsAg-negative occurred in seven cases, and all (100%) had quick remission in two years. In patients with persistent HBsAg carriage, serum HBeAg status alone did not correlate with remission rate and remission occurred usually before the HBeAg seroconversion to anti-HBe. These findings, together with the predominant horizontal infection in these children in contrast to the frequent vertical (perinatal) transmission from HBsAg carrier mothers in HBsAg carriers in Taiwan, suggest that factors other than HBeAg per se may also play important roles.

Inadequacy of immunoglobulin M hepatitis B core antibody in detecting acute hepatitis B virus infection in infants of HBsAg carrier mothers.

To study the usefulness of IgM hepatitis B core antibody (anti-HBc IgM) for detecting hepatitis B virus infections in infants of hepatitis B surface antigen (HBsAg) carrier mothers, serial serum samples from 86 infants of carrier mothers were tested for anti-HBc IgM with a highly specific enzyme immunoassay. Asymptomatic hepatitis B infection occurred frequently in infants under 12 mo of age. Anti-HBc IgM never became positive in 25 infants infected under 9 mo old. It was positive in only 1 of 6 infected at 9 mo and 4 of 13 infected at 12 mo of age. The IgM antibody lasted for less than 6 mo. Although the infection was delayed in 28 infants receiving hepatitis B immune globulin, the poor anti-HBc IgM response did not seem to be due to the immune prophylaxis. Our study clearly indicates the limitation of anti-HBc IgM for detecting acute hepatitis B infection in infants born to HBsAg carrier mothers.

Perinatal transmission of the hepatitis B virus and of the HBV-associated delta agent from mothers to offspring in northern Italy.

We report a prospective study on infants born to hepatitis B surface antigen (HBsAg) carrier mothers to estimate the incidence of perinatal transmission of HBV and HBV-associated delta agent in Northern Italy. The risk of infection to the infant was related to the presence of the HBe antigen-antibody system, HBV-specific DNA polymerase activity and antibody to delta in maternal sera, and to the titer of anti-HBe in babies at birth. The data of this study indicate: 1. Babies born to HBsAg carrier mothers with HBeAg in serum are at extremely high risk of acquiring HBV infection and of developing a chronic carrier state, whereas those born to anti-HBe-positive mothers are at a lower (P less than .01) yet consistent risk of infection. 2. HBs antigenemia is usually prolonged and symptomatic in babies born to HBeAg-positive mothers while being self-limited and asymptomatic in babies born to anti-HBe-positive mothers. 3. DNA polymerase activity in maternal serum appears to be the most sensitive marker predicting HBV transmission to the infant since it was detected in all the HBeAg-positive mothers and also in two anti-HBe-positive mothers and in one HBeAg/anti-HBe-negative mother who transmitted infection to their babies. 4. High titers of anti-HBe (up to 1:103) do not prevent HBV infection. 5. Vertical transmission of delta infection seems to occur only in circumstances that permit perinatal transmission of HBV infection.

Epidemiology of hepatitis B infection in Liberian infants

To provide background for a hepatitis B vaccine efficacy trial, sera were collected from 0- to 4-year-old Liberian infants and their mothers, on two occasions an average of 14.75 months apart, and tested for serological markers of hepatitis B virus infection. The prevalence of the hepatitis B surface antigen (HBsAg) was 2.9% in the 0- to 6-month age group and 23% in infants 3 to 4 years of age. HBsAg persisted for the 14.75-month average follow-up period in 80.8% of the infants tested. The annual incidence of development of HBsAg was 18.9% for infants less than 1 year of age and 13.6% in infants 3 to 4 years of age. Infants born to HBsAg carrier mothers had significantly higher age-specific prevalence and incidence of hepatitis B virus infection. However, it was estimated that only a minor proportion of hepatitis B infections in Liberia are derived by vertical transmission from carrier mothers.

Transmission of Hepatitis B Virus Infection by Asymptomatic Chronic HBsAg Carrier Mothers

The courses of 18 children born to 13 chronic hepatitis B surface antigen (HBsAg) carrier mothers were followed prospectively for serological and biochemical evidence of type B hepatitis. Three children developed transient HBsAg positivity accompanied by the appearance of antibody to the hepatitis B core antigen. Two others had no detectable HBsAg but developed antibody to HBsAg. These serological manifestations of hepatitis B virus infection occurred late--6 to 24 months after birth. None of the children had clinical evidence of hepatitis and none became chronic HBsAg carriers. The infrequency of transmission of infection, the mild course of disease, and the lack of persistence of HBsAg in these children probably reflected the low level of infectivity of the chronic carrier mothers and perhaps the healthy immunologic status of the children.

Failure of Immune Serum Globulin to Prevent Hepatitis B Virus Infection in Infants Born to HBsAg-Positive Mothers

Twelve infants, born to mothers with hepatitis B virus infection, were inoculated within 7 days of birth with immune serum globulin containing antibody to hepatitis B surface antigen (HBsAg) titers of 1:32 to 1:64 as measured by passive hemagglutination. Six of nine infants (66.7%) born to HBsAg-positive carrier mothers became HBsAg-positive within 3 mo of age. In addition, two of three treated infants born to mothers with acute hepatitis B during the delivery period also developed HBsAg. The hepatitis e antigen was detected in four of five carrier mothers and in two mothers with acute hepatitis, whose infants subsequently became HBsAg positive. In addition, hepatitis B-specific DNA polymerase activity was detected in the seven HBsAg-positive mothers who transmitted the virus to their infants. All eight infants have remained persistently HBsAg positive. Thus, the immune serum globulin containing low-titer antibody to HBsAg is not protective when given to infants born to HBsAg carrier mothers or to mothers with acute hepatitis B during the delivery period.

HEPATITIS B SURFACE ANTIGEN AND CHRONIC HEPATITIS IN INFANTS BORN TO ASYMPTOMATIC CARRIER MOTHERS

Shiraki, Kazuo; Yoshihara, Namiko; Kawana, Takashi; Yasui, Hiroshi; Sakurai, Michiro Author Information