Prevention of perinatally transmitted hepatitis B virus infections with hepatitis B immune globulin and hepatitis B vaccine. Efficacy of hepatitis-B immunoglobulin and hepatitis-B vaccine in prevention of the HBsAg carrier state in newborn infants of mothers who are chronic carriers of HBsAg and HBeAg. A combination of hepatitis B vaccine and immunoglobulin does not protect all infants born to hepatitis B e antigen positive mothers. Use of hepatitis B vaccine alone or in combination with hepatitis B immunoglobulin for immunoprophylaxis of perinatal hepatitis B infection. Long-term hepatitis B vaccine in infants born to hepatitis B e antigen positive mothers. Prevention of the HBsAg carrier state in newborn infants of mothers who are chronic carriers of HBsAg and HBeAg by administration of hepatitis-B vaccine and hepatitis-B immunoglobulin. Double-blind randomised placebo-controlled study. Combined passive and active immunization for interruption of perinatal transmission of hepatitis B virus in Taiwan. Hepatitis B immunisation with a reduced number of doses in newborn babies and children. Efficacy of hepatitis B immune globulin for prevention of perinatal transmission of the hepatitis B virus carrier state: final report of a randomized double-blind, placebo-controlled trial.
A randomised blind controlled trial of hepatitis B immune globulin (HBIG) plus hepatitis B vaccine for the prevention of the perinatally transmitted HBsAg carrier state was conducted in Taipei. Infants of e-antigen-positive HBsAg carrier mothers were given HBIG immediately after birth, and then one of three schedules of vaccination. There was no difference in efficacy between the three schedules; the combined efficacy was 94%, compared with that of HBIG alone (71%) or of vaccination alone (75%). Persistent HBs antigenaemia developed in only 9 (6%) of the 159 infants receiving prophylaxis, but in 88% of the controls. Antibodies developed in all those who did not become antigenaemic and presumably will provide long-term protection from hepatitis B virus infection. HBIG should be given as soon as possible after birth and need not be given again if the infant is subsequently vaccinated. With HBIG coverage from birth, the timing of the start of vaccination does not seem to be of importance within the first month of life, but to maximise compliance and minimise costs hepatitis B vaccination should be initiated during the confinement. Combined prophylaxis of perinatal transmission of hepatitis B virus (HBV) with hepatitis-B immunoglobulin (HBIG) and hepatitis-B vaccine was investigated in 40 infants born to HBeAg positive carrier mothers. The efficacy of two combined prophylaxis schedules was compared to 78 similar infants in the control group receiving no treatment, by following the HBV markers at regular intervals up to one year of age. In both schedules, the HBIG and HBV vaccine were given at birth, followed by HBV vaccine given at 30 days and 60 days (group I) or 180 days (group II) of age. The incidence of persistent HBsAg carrier in infants born to HBeAg positive carrier mothers was significantly reduced from 92.6 percent at one year of age in the control group to zero percent (group I) and 11.5 percent (group II) in the treated groups. There was no statistical significant difference in the efficacy of these two combined prophylaxis schedules. HBIG given at birth did not interfere with infant immune response to the hepatitis B vaccine. At twelve months of age, anti-HBs could be detected in 77.8 percent of infants in group I and 89.5 percent in group II with mean titre of 621.4 and 1148.0 in group I and group II respectively. It was concluded that combined prophylaxis with HBIG and hepatitis-B vaccine immediately after birth is the best method for prevention of HBV perinatal transmission from HBeAg positive carrier mothers to their infants. In 42 infants of hepatitis B e antigen positive carrier mothers a randomised study of a low dose (5 micrograms) hepatitis B vaccine regimen starting within 24 hours of birth with or without hepatitis B immunoglobulin (0.25 ml/kg) showed that in the vaccine group 72% were antibody positive at the age of one year and in the vaccine plus immunoglobulin group 81%. In the vaccine group four of 18 infants were not protected and in those infants receiving vaccine plus immunoglobulin three of 21 were HBsAg carriers by 12 months of age. Hepatitis B vaccine either with or without concomitant HBIg did not protect all babies born of HBeAg positive mothers, from developing the HBsAg carrier status. Thus for full protection of all infants a more vigorous immunisation programme will be necessary. The efficacy of hepatitis B vaccine alone or in combination with immunoglobulin in neonates born to HBsAG positive mothers was investigated. Twenty-four infants were given three doses (at 0, 1, 2 months) of the vaccine alone, while 27 infants were given hepatitis B immunoglobulin (HBIG) and three doses of the vaccine. Fifty-eight infants born to HBsAg positive mothers who did not agree for vaccination or could not come for follow-up constituted the control group. The overall seroprotection rates (anti-HBS levels > or = 10 IU/l) were almost similar in both the groups at 6 months (81 and 76 per cent, respectively). However, the seroprotection rates in babies born to HBeAg positive mothers were better with combination of HBIG and vaccine (71 v. 57 per cent, respectively). It was also observed that seroprotection rates in babies born to anti-HBe positive mothers were even better (100 and 90 per cent in vaccine alone and combination group, respectively). No chronic carrier was detected in babies born to anti-HBe positive mothers. Neonates of hepatitis B surface antigen (HBsAg) positive and hepatitis B encoded antigen (HBeAg) positive mothers received 10 micrograms of recombinant hepatitis B vaccine at months 0, 1, 6, or 0, 1, 2, 12, with or without immunoglobulin at birth, and were followed up to the age of 8 years for HBsAg, anti-HBc, and anti-HBs. Some were boosted at month 60. The overall vaccine protection at month 12 was 96.2%. No child became a chronic carrier beyond the age of 3 years, showing that this vaccine provides immediate protection against HBsAg carriage, and long term protection against fetally acquired HBsAg. After month 60 hepatitis B serological markers without disease, indicating re-exposure to HBV, reappeared in comparable numbers among boosted and non-boosted children (5 for a total of 167 children). This vaccine provides long-term protection against hepatitis B chronic carriage and infection in high risk neonates with or without a month 60 booster. A booster at the age of 5-6 years or 11-12 years would reduce HBV infection, viral circulation and transmission, while ensuring long-term antibody persistence. Newborn infants of Chinese HBeAg-carrier mothers in Hong Kong were randomly assigned to one of four study groups. Group I was treated with 3 micrograms heat-inactivated hepatitis B (HB) vaccine at birth and at 1, 2, and 6 months thereafter, in conjunction with seven monthly HBIg injections; group II was treated according to the same vaccine schedule but received only one HBIg injection at birth; group III received only the vaccine, at months 0, 1, 2, and 6; and group IV received placebos for both vaccine and HBIg. The first set of injections was given within 1 h after birth. Comparisons were made in the 140 children who were at least six months old at the close of the trial (495 days). In all three treatment groups development of the persistent carrier state was significantly (p less than or equal to 0.0001) less frequent than in controls (2.9%, 6.8%, and 21.0% versus 73.2%). Although vaccination alone was significantly less protective than vaccination plus multiple HBIg injections (p = 0.03), the degree of protection was still remarkable. 12 months after the first set of injections 96-100% of the infants in the three treatment groups were anti-HBs positive; the geometric mean titres of anti-HBs in the three groups did not differ significantly. This indicates that even high doses of HBIg do not interfere with the anti-HBs response to the vaccine. Probable intra-uterine HB infections were observed in 3 infants. No serious side-effects were observed from the interventions, even in the babies with intra-uterine infections who had received HBIg and HB-vaccine at birth. To prevent development of the persistent HBsAg carrier state, and thereby the consequent chronic liver disease and/or primary carcinoma of the liver, HB vaccine and HBIg should be administered as soon as possible after birth to all newborn infants at risk of perinatal hepatitis B infection. We attempted a clinical trial to interrupt transmission of hepatitis B virus (HBV) infection from hepatitis B surface antigen (HBsAg) positive and hepatitis Be antigen (HBsAg) positive mothers to their infants in Taiwan. Screening of 5,595 pregnant women revealed that 856 (15.3%) were HBsAg positive. Three hundred and sixty-one (42.2%) of the HBsAg positive pregnant women were HBeAg positive. Infants born to HBsAg and HBeAg positive mothers were randomized into 3 groups to receive the HBV vaccine alone or combined with hepatitis B immune globulin (HBIG). HGV vaccine was given at 2, 6, and 10 weeks after birth. Group I received HBV vaccine alone while Group II received HBV vaccine in combination with HBIG at birth and group III received HBV vaccine plus HBIG at birth and again at one month old. Group IV constituted the control group when their parents refused vaccination. At 6 months of age, the HBV carrier rate was 23.7% (9/38) in Group I, 11.1% (4/36) in Group II, and 5.3% (2/38) in Group III infants. Compared with 90% of infants who became HBV carriers in the control group (Group IV), the efficacy of HBV vaccination in preventing HBV infection among these high risk infants at the 6th month was 73.7% in Group I, 87.7% in Group II, and 94.1% in Group III. The antibody to HBsAg (anti-HBs) positivity rate in sera of Group I, II, III infants at 6 months of age was 79.0%, 88.9% and 94.7%, respectively. These initial results indicate that combined passive and active immunization is efficacious in interrupting perinatal transmission of HBV infection. 74 healthy babies born to mothers positive for hepatitis B surface antigen (HBsAg) were randomly divided at birth to receive either HB immunoglobulin and 2 doses of HB vaccine 2 months apart, or HB immunoglobulin and 3 doses of HB vaccine 1 month apart. 80 healthy babies born to HBsAg, anti-HBs, and anti-HB core (c) negative mothers were randomly divided at birth to receive either 2 doses of vaccine 2 months apart or 3 doses 1 month apart. The seroconversion rates and the geometric means of anti-HBs titres were lower in both groups of babies given 2 doses of vaccine than in the groups given 3 doses. 60 pairs of children at risk, aged 1 to 12 years and HBsAg, anti-HBs, and anti-HBc negative, were randomly divided to receive either the 2-dose regimen or the 3-dose regimen. The seroconversion rates and the geometric means of anti-HBs titres were satisfactory in both groups. A randomized double-blind, placebo-controlled efficacy trial of hepatitis B immune globulin (HBIG) for prevention of the mother-to-infant transmitted HBsAg carrier state was conducted in Taiwan where the carrier rate in the general population is 15 to 20%. HBIG was given immediately after birth to infants of e antigen positive HBsAg carrier mothers, and all infants were followed for at least 15 months. Among 61 placebo recipients, the carrier rate was 92%; compared with 26% among 57 infants who received 0.5 ml HBIG at birth, 3 months, and 6 months, and 54% among 67 infants who received a single 1.0 ml dose of HBIG at birth only. Efficacy was 71 and 42%, respectively, for the two treatment schedules. The most common response of HBIG-treated infants was passive-active immunization which was 27% in the single-dose group and 61% in the three-dose group. Some of the infants who became carriers were probably infected as HBIG protection waned, and we expect that higher efficacy can be achieved by hepatitis B vaccine in conjunction with HBIG.
Vaccine, hepatitis B immunoglobulin, and vaccine plus hepatitis B immunoglobulin prevent hepatitis B occurrence in newborn infants of HBsAg positive mothers.