Passive-active immunization in infants of hepatitis Be antigen-positive mothers. Comparison of the efficacy of early and delayed active immunization. A controlled clinical trial of the efficacy of the hepatitis B vaccine (Heptavax B): a final report. Evaluation of a low dose of hepatitis B vaccine given within a childhood immunisation programme in Singapore. Efficacy and safety of recombinant hepatitis B vaccine in infants born to HBsAg-positive mothers. An efficacy trial of a mammalian cell-derived recombinant DNA hepatitis B vaccine in infants born to mothers positive for HBsAg, in Shanghai, China. Prevention of perinatal acquisition of hepatitis B virus carriage using vaccine: preliminary report of a randomized, double-blind placebo-controlled and comparative trial. PREVENTION OF PERINATALLY TRANSMITTED HEPATITIS B VIRUS INFECTIONS WITH HEPATITIS B IMMUNE GLOBULIN AND HEPATITIS B VACCINE PREVENTION OF HEPATITIS B VIRUS CARRIER STATE IN INFANTS ACCORDING TO MATERNAL SERUM LEVELS OF HBV DNA Hepatitis B vaccine alone or in combination with anti-HBs immunoglobulin in the perinatal prophylaxis of babies born to HBsAg carrier mothers. A combination of hepatitis B vaccine and immunoglobulin does not protect all infants born to hepatitis B e antigen positive mothers. Comparison of the immune response of four different dosages of a yeast-recombinant hepatitis B vaccine in Singapore children: a four-year follow-up study. Simultaneous administration of Hepatitis B vaccine with other E.P.I. vaccines Completeness of safety reporting in randomized trials: an evaluation of 7 medical areas. Long term hepatitis B vaccine in infants born to hepatitis B e antigen positive mothers Protective efficacy of hepatitis B vaccine without HBIG in infants of HBeAg-positive carrier mothers in Thailand. A randomized control trial on interruption of HBV transmission in uterus. Hepatitis B infection in infants after neonatal immunization. Japanese and American reports of randomized trials: differences in the reporting of adverse effects. 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. Methods for combining randomized clinical trials: strengths and limitations. Passive-active immunisation of neonates of HBsAg positive carrier mothers: preliminary observations. Results of vaccinated infants born to HBsAg-positive mothers with different hepatitis B vaccines and doses. A preliminary study on interruption of HBV transmission in uterus. Long-term efficacy of recombinant hepatitis B vaccine and risk of natural infection in infants born to mothers with hepatitis B e antigen. Use of hepatitis B vaccine alone or in combination with hepatitis B immunoglobulin for immunoprophylaxis of perinatal hepatitis B infection. [Study on the efficacy of genetically engineered vaccines against hepatitis B for interruption of perinatal transmission]. Hepatitis B immunization in high risk neonates born from HBsAg and HBeAg positive mothers: comparison of standard and low dose regimens. Hepatitis B immunization in high risk neonates born from HBsAg positive mothers: comparison between plasma derived and recombinant DNA vaccine. A Reappraisal of Hepatitis B Virus Vaccination Strategies Using Cost-Effectiveness Analysis Controlled trial of immune response of preterm infants to recombinant hepatitis B and inactivated poliovirus vaccines administered simultaneously shortly after birth HEPATITIS B IMMUNISATION WITH A REDUCED NUMBER OF DOSES IN NEWBORN BABIES AND CHILDREN Twelve-year follow-up of a prospective randomized trial of hepatitis B recombinant DNA yeast vaccine versus plasma-derived vaccine without booster doses in children. Safety of neonatal hepatitis B vaccine administration. 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 Long-term immunogenicity and efficacy of hepatitis B vaccine in homosexual men. Long-term immunogenicity and efficacy of recombinant yeast derived hepatitis B vaccine for interruption of mother-infant transmission of hepatitis B virus. Prevalence of hepatitis B in children in a high risk New Zealand community, and control using recombinant DNA vaccine. Interruption of HBV intrauterine transmission: a clinical study. Multicenter trial on the efficacy of HBIG and vaccine in preventing perinatal hepatitis B. Final report. Five-year follow-up of a prospective randomized trial of hepatitis B recombinant DNA yeast vaccine vs. plasma-derived vaccine in children: immunogenicity and anamnestic responses. Hepatitis B vaccination: universal vaccination of newborn babies and children at 12 years of age versus high risk groups. A comparison in the field. Immunoprophylaxis of perinatal transmission of the hepatitis B virus: efficacy of hepatitis B immune globulin and hepatitis B vaccine in a low-prevalence area. Hepatitis B immunization of newborns according to a two dose protocol. The protective efficacy of recombinant hepatitis B vaccine in newborn infants of hepatitis B e antigen‐positive‐hepatitis B surface antigen carrier mothers A 5-year immunization field trial against hepatitis B using a Chinese hamster ovary cell recombinant vaccine in French Polynesian newborns: results at 3 years. Comparative efficacy, safety and immunogenicity of Hepavax-Gene and Engerix-B, recombinant hepatitis B vaccines, in infants born to HBsAg and HBeAg positive mothers in Vietnam: an assessment at 2 years.
OBJECTIVE To assess the efficacy of late active immunization against hepatitis B concomitant with diphtheria , pertussis , tetanus , and polio vaccine in high-risk infants receiving hepatitis B immune globulin at birth . DESIGN R and omized study of infants born to mothers positive for hepatitis B surface antigen ( HBsAg ) and hepatitis Be antigen ( HBeAg ) . SETTING Three large city hospitals and one rural area providing prenatal care and obstetric services . SUBJECTS Eighty neonates of HBsAg- and HBeAg-positive carrier mothers  received 0.5 mL/kg of body weight hepatitis B immune globulin within 2 hours of birth and hepatitis B vaccine ( 10 micrograms ) at 0 , 1 , 2 , and 11 months of age ( group A ) or at 3 , 4 , 5 , and 11 months of age concomitant with diphtheria , pertussis , tetanus , and polio immunization ( group B ) . A second dose of hepatitis B immune globulin was given to infants on schedule B at 3 months . MAIN OUTCOME MEASURES Blood sample s were collected at 0 , 3 , 6 , 11 , and 12 months of age and tested for antibodies against hepatitis B core antigen and HBsAg . Follow-up visits were scheduled annually up to 5 years of age . RESULTS Eight infants were excluded from analysis . During the study period , six children became HBsAg carriers , three in each group , which corresponds to a 5-year incidence of infection of 9 % and 8 % for groups A ( three of 35 ) and B ( three of 37 ) , respectively . Sub clinical infections ( persistent anti-HBc positivity beyond month 12 or appearance of anti-HBc ) were encountered in another eight infants ( four in each group ) . CONCLUSION Late active immunization starting at 3 months of age appears to provide similar protective efficacy as active immunization starting at birth when combined with hepatitis B immune globulin at 0 and 3 months of age A controlled , r and omized , double-blind trial in 1,083 homosexual men from New York confirmed that a highly purified , formalin-inactivated vaccine against hepatitis B prepared from HBsAg positive plasma , is safe immunogenic , and highly efficacious . Over 95 % of vaccinated subjects developed antibody against the surface antigen . Vaccine-induced antibody persisted for the entire 24-month follow-up period . The attack rate of all hepatitis B virus infections ( excluding conversions of anti-HBc alone ) was 3.2 % in vaccine recipients compared with 25.6 % in placebo recipients ( p less than 0.0001 ) . In those who received all three doses of vaccine , of 40 micrograms each , the protective efficacy rate was close to 100 % . The vaccine protects against acute hepatitis B , asymptomatic infection , and chronic antigenemia . There is reason to assume that the vaccine is also partially effective when given postexposure The feasibility of introducing low dose ( 5 micrograms ) hepatitis B ( HB ) virus vaccination at birth and again 1 and 2 months later as part of an existing primary immunisation programme of childhood , was assessed in 662 healthy newborn Singapore children . The vaccine ( B-Hepavac , Menck , Sharp and Dohme ) was given to three neonatal groups : those born to HB surface antigen (sAg)-negative mothers , HBsAg-positive/HBeAg-positive mothers and HBsAg-positive/HBeAg-negative mothers . A dose of 5 micrograms was compared in a r and omised study with the more usual 10 micrograms dose given at the same intervals . Neonates born to HBsAg-positive/HBeAg-positive mothers were also given hepatitis B immunoglobulin ( HBIg ) at birth . The 5 microgram dose of vaccine was as immunogenic as the 10 microgram dose in all three groups of children studied . At 1 year , anti-HBsAg seroconversion among infants of antigen-negative mothers was 95.8 % for the 5 microgram dose and 91.9 % for the 10 microgram dose . Suppression of anti-HBsAg formation was not seen even when maternal anti-HBsAg was present or HBIg given . Among infants born to HBsAg-positive/HBeAg-positive mothers , passive plus active immunisation was 100 % protective at doses of 5 micrograms and 10 micrograms vaccine in the newborns who were HBsAg-negative at 24 h. Seroconversion after both the 5 and 10 microgram doses of vaccine was reduced , however , to 88 % in each group of infants who were already HBsAg-positive at 24 h of age . Overall , passive plus active immunisation as well as HB vaccine alone ( 5 micrograms dose ) , given within the existing but exp and ed primary immunisation programme of childhood , was effective in preventing infection and the chronic carrier state in newborns exposed to risk of HB virus infection during infancy Infants born to HBsAg-positive women were r and omly assigned to receive either the plasma-derived hepatitis B vaccine or the yeast-derived recombinant hepatitis B vaccine within 12 h of birth , simultaneously with HBIg . The second and third doses of both vaccines were given at 1 and 6 months of age respectively . Two hundred and twenty-two infants received two doses , and 80 infants received three doses of either vaccine . Five infants were found to be HBsAg-positive at 6 months of age . Four of these infants had received the plasma vaccine and the remaining infant the recombinant vaccine .  Anti-HBs was present in all the HBsAg-negative infants at 6 months of age . The titres of anti-HBs were similar in both groups of infants who had received either the plasma or the recombinant hepatitis B vaccine . No major adverse reactions were reported with either vaccine . The preliminary results from this study suggest that the yeast-derived recombinant hepatitis B vaccine is safe , immunogenic and at least as effective as the plasma-derived hepatitis B vaccine in preventing the HBsAg carrier state in infants born to HBsAg-positive women We conducted a r and omized , double-blind clinical trial of an experimental mammalian cell-derived DNA hepatitis B vaccine ( Betagen , Connaught Laboratories Ltd , Toronto , Canada ) to determine its efficacy in infants born to mothers who were carriers of hepatitis B surface antigen ( HBsAg ) . Four groups of 55 infants received injections as follows : ( 1 ) a licensed plasma-derived vaccine ( Lanzhou , Lanzhou Institute for Biological Products , Lanzhou , People 's Republic of China ) , 20 micrograms ; ( 2 ) Betagen , 20 micrograms ; ( 3 ) Betagen , 20 micrograms+hepatitis B immune globulin ( HBIG ) ; and ( 4 ) Betagen , 10 micrograms+HBIG . Vaccine injections were given at birth and at 1 and 6 months and HBIG was given at birth . The vaccines were compared to a historical placebo control group . The efficacy of Betagen alone was 82.6 % compared to 51.0 % for the Lanzhou . Efficacy of Betagen increased with the concomitant use of HBIG . No infants who were HBsAg negative at birth and /or were born to hepatitis B e antigen ( HBeAg ) negative mothers became carriers . The rate of HBsAg in infants receiving Betagen alone , and born to mothers who were HBeAg positive , decreased from 60 % at birth to 20 % by the ninth month , compared to 62.5 % and 50 % ( respectively ) for Lanzhou . The percentage of infants with protective levels of antiHBs was significantly higher for Betagen alone than for Lanzhou , but the geometric mean titre of antiHBs for responders was not significantly different . We have shown that Betagen alone is highly efficacious in preventing the development of hepatitis B in infants born to mothers who are carriers of HBsAg and is also highly effective in reducing the carriage of HBsAg in infants who are HBsAg positive at birth and /or born to HBeAg positive mothers Hepatitis B is a serious disease of global significance . In developing countries , hepatitis B virus ( HBV ) infection and its sequelae rank among the public health problems of highest priority . Infants born to mothers who are chronic carriers of HBV are at particularly high risk of acquiring infection and becoming chronic HBV carriers . The efficacy of hepatitis B vaccine alone in preventing the transmission of HBV to infants born to HBV carrier mothers was determined in a double-blind placebo-controlled trial . Infants received plasma-derived vaccine at birth , 1 month , and 6 months of age . Of 180 infants born to hepatitis B surface antigen (HBsAg)-positive mothers , equal numbers received National Institute of Allergy and Infectious Disease ( NIAID ) vaccine , Beijing Institute of Vaccine and Serum ( BIVS ) vaccine , and placebo . The cumulative seroconversion to the vaccines at 1 year of age was 95 % and 75 % , respectively . Vaccine efficacy as measured by the prevention of HBsAg-positive events was 88 % for the NIAID vaccine and 51 % for the BIVS vaccine . Vaccine efficacy was similar among infants born to hepatitis Be antigen-positive mothers . Because of the low efficacy of the BIVS vaccine , an additional group of 28 infants was given vaccine and hepatitis B immune globulin at birth . The result ing efficacy was 83 % . The results of this trial indicate that hepatitis B vaccine alone can substantially reduce perinatally acquired HBV infection and the result ing chronic carrier state A r and omised 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 235 infants of HBeAg-carrier mothers in Hong Kong were assigned to four study groups . Groups I , II , and III received hepatitis-B ( HB ) vaccine at birth and at 1 , 2 , and 6 months . Group I also received seven monthly injections of HB immunoglobulin ( HBIg ) , and group II received one HBIg injection at birth . Group III received vaccine only and group IV received placebo for both vaccine and HBIg . At the age of 3 years , all infants of the three treatment groups were significantly protected against the HB virus ( HBV ) carrier state compared with the placebo group ( p less than 0.0001 ) ; the protective efficacy rates in groups I , II , and III were 87 % , 80 % , and 65 % , respectively . At all times , group I was significantly better protected than group III . In groups III and IV , infants of mothers with serum HBV DNA levels of 5 pg/ml or above were at a significantly higher risk of acquiring the HBV carrier state than those whose mothers had HBV DNA levels below 5 pg/ml . This difference was not significant in groups given HBIg . Of the 183 infants who initially escaped HBV infection  , 73 ( 40 % ) had transient and 8 ( 4 % ) chronic HBV infection between 6 and 36 months . Vaccinated infants who had actively formed anti-HBs remained well protected against the HBV carrier state . However , infants in groups I and II with no active anti-HBs response to vaccine became at risk for the HBV carrier state when the passively acquired anti-HBs antibodies had disappeared . HBIg should be included in HB vaccination schedules for all infants of HBeAg-positive mothers The efficacy of hepatitis B virus ( HBV ) vaccine alone ( group I ) or in combination with hepatitis B immunoglobulin ( HBIG ) ( group II ) for prevention of perinatal transmission of the virus was assessed in 21 and 24 neonates , respectively . 58 infants who could not be vaccinated constituted the control group . It was observed that in the unvaccinated group approximately 70 % of the infants became infected . In both the vaccinated groups , the seroconversion and seroprotection rates ( anti-HBs > or = 10 IU/1 ) were almost similar at 6 months of follow up , but , at 12 months , infants given HBIG and vaccine showed better seroprotection rate ( 85 % ) than those given vaccine alone ( 58.8 % ) . Immune response to the vaccine  was also better in both the groups if the mothers were anti-HBe positive . Despite immunization , 14.2 % and 25 % infants in group I and II , respectively , became chronic carriers if their mothers were HBeAG positive In 42 infants of hepatitis B e antigen positive carrier mothers a r and omised 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 immunogenicity of four different dosages of yeast-derived hepatitis B vaccine ( Merck , Sharp & Dohme : 0.6 micrograms , 1.25 micrograms , 2.5 micrograms and 5.0 micrograms ) , administered at 0 , 1 and 6 months ( 0 - 1 - 6 schedule ) intramuscularly , was evaluated in 122 seronegative healthy children 1 - 12 years of age . Three months after the first dose , 83.9 - 100 % of the vaccinees seroconverted . Peak geometric mean titres ( GMT ) of between 1088 mlU/ml and 1699 mlU/ml were attained 3 months after completion of the vaccination schedule . After 24 months , anti-HBs ( antibody to hepatitis B surface antigen ) was detected in 93.1 - 100 % of the vaccinees , but the GMT dropped to between 214.3 mlU/ml and 303.5 mlU/ml . After 48 months , 88.8 - 100 % of the vaccinees continued to possess anti-HBs and 70.3 - 87 % had titres above 10 mlU/ml . As expected , the GMT declined further to between 72.6 mlU/ml and 118.8 mlU/ml . There were no significant differences in seroconversion rates and GMT among the different dosage groups . All the vaccinees remained asymptomatic and free from hepatitis B virus infection . The study showed that reduced dosages of the vaccine ( 0.6 micrograms , 1.25 micrograms and 2.5 micrograms ) were as immunogenic as the st and ard dose ( 5 micrograms ) ; the 2.5-micrograms dose was recommended for the national childhood immunization programme in Singapore . No booster is necessary for at least four years after vaccination Development of recombinant DNA vaccine against hepatitis B grown on cultured yeast cell has made it possible to mount a world-wide effort to control and eradicate Hepatitis B infection . However , the currently recommended schedules ( 0 , 1 & 2 months , and 0–1 and 6 months ) do not coincide with the scheduled visits for other E.P.I. vaccines , and necessitate additional visits for Hepatitis B vaccination . This study was therefore carried out to find out if adequate seroconversion occurs to Hepatitis B vaccine when given with other EPI vaccines or not?Thirty nine infants born to Australia antigen positive mothers from among 850 screened pregnant mothers were recruited to receive Hepatitis B vaccine ( Engerix B-10 micro gram each ) at 0 , 6 and 14 wks ( group A ) or at 0 , 1 and 2 months ( group B ) . Thirty-one infants were recruited in group A and 8 in group B. The cord blood was collected and the first dose of vaccine was given within 48 hours of birth . Simultaneous B.C.G. was given at the left deltoid . Other E.P.I. vaccines were given qt 6 , 10 and 14 wks in group A and at 2 , 3 and 4 months in group B. Repeat blood sample s were collected prior to giving each dose of Hepatitis B vaccine , and 4 weeks after the last dose . All blood sample s were assayed for HBsAg and HBsAb at the National Institute Of Communicable Diseases , utilizing st and ard ELISA kits . The seroconversion rates following one , two and three doses of Hepatitis B vaccine were 3.33 % , 55.5 % , 96.15 % and 0 % , 62.5 % and 100 % in group A and B respectively . Only one infant in group A failed to develop HbsAb even after 3 doses of Hepatitis B vaccine , 5 infants in group A were available at 9 months of age and were still positive for HBsAb and negative for HBsAg . Recombinant DNA Hepatitis B vaccine ( Engerix-B ) is a highly effective vaccine which can safely and effectively be given together with other childhood vaccines CONTEXT R and omized trials with adequate sample size offer an opportunity to assess the safety of new medications in a controlled setting ; however , generalizable data on drug safety reporting are sparse . OBJECTIVE To scrutinize the completeness of safety reporting in r and omized trials .  DESIGN , SETTING , AND PATIENTS Survey of safety reporting in 192 r and omized drug trials 7 diverse topics with sample sizes of at least 100 patients and at least 50 patients in a study arm ( N = 130074 patients ) . Trial reports were identified from comprehensive meta-analyses in 7 medical areas . MAIN OUTCOME MEASURES Adequate reporting of specific adverse effects and frequency and reasons for withdrawals due to toxic effects ; article space allocated to safety reporting and predictors of such reporting . RESULTS Severity of clinical adverse effects and laboratory-determined toxicity was adequately defined in only 39 % and 29 % of trial reports , respectively . Only 46 % of trials stated the frequency of specific reasons for discontinuation of study treatment due to toxicity . For these 3 parameters , there was significant heterogeneity in rates of adequate reporting across topics ( P = .003 , P<.001 , and P = .02 , respectively ) . Overall , the median space allocated to safety results was 0.3 page . A similar amount of space was devoted to contributor names and affiliations ( P = .16 ) . On average , the percentage of space devoted to safety in the results section was 9.3 % larger in trials involving dose comparisons than in those that did not ( P<.001 ) and 3.8 % smaller in trials reporting statistically significant results for efficacy outcomes ( P = .047 ) . CONCLUSIONS The quality and quantity of safety reporting vary across medical areas , study design s , and setting s but they are largely inadequate . Current st and ards for safety reporting in r and omized trials should be revised to address this inadequacy Neonates of hepatitis B surface antigen ( HBsAg ) positive and hepatitis B encoded antigen ( HBeAg ) positive mothers received 10 μg 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 The primary objective of this study was to estimate the efficacy of a recombinant hepatitis B vaccine ( H-B-VAXII ) in preventing chronic hepatitis B infection when given alone without concomitant hepatitis B immune globulin ( HBIG ) to healthy Thai infants born of HBeAg-positive carrier mothers . The infants received a 0.5 ml ( 5 micro g HBsAg ) intramuscular injection of H-B-VAXII either at birth , 1 , and 6 months of age ( Schedule A ) or at birth , 1 , 2 , and 12 months of age ( Schedule B ) . Blood drawings for the determination of hepatitis B virus ( HBV ) serologic markers were scheduled 4 , 9 , and 13 months following the initial dose of vaccine . At 13 months , 5 ( 10 % ) of 50 infants vaccinated on Schedule A and 7 ( 14.9 % ) of 47 infants vaccinated on Schedule B had experienced chronic HBV infection . Based on an expected infection rate in unimmunized infants of either 70 or 90 % , the overall efficacy for both schedules combined was estimated to be 82.3 % ( 95 % CI : 70.6 , 90.6 ) or 86.2 % ( 95 % CI : 77.1 , 92.7 ) , respectively . Corresponding schedule-specific estimates were for Schedule A : 85.7 % ( 95 % CI : 68.8 , 95.3 ) or 88.9 % ( 95 % CI : 75.8 , 96.3 ) and for Schedule B : 78.7 % ( 95 % CI : 59.6 , 91.1 ) or 83.4 % ( 95 % CI : 68.6 , 93.1 ) . These results suggest that in areas of high endemicity , where mothers may not always be screened for HBV infection , routine vaccination of infants at birth with a course of hepatitis B vaccine alone should be highly protective , even for very high-risk infants of HBeAg-positive mothers OBJECTIVE To study the interruptive effect of hepatitis B virus ( HBV ) specific immunolobulin ( HBIG ) before delivery in attempt to prevent intrauterine transmission of HBV . METHODS Nine hundred and eighty HBsAg carrier pregnant women were r and omly divided into HBIG group and control group . Each subject in the HBIG group received 200 IU or 400 IU of HBIG intramuscularly at 3 , 2 and 1 month before delivery . The subjects in the control group did not receive any specific treatment . All newborn infants received 100 IU of HBIG intramascularly after venous blood sample s were taken at birth and 2 weeks after birth , followed by 30 micro g plasma-derived HB vaccine or 5 micro g recombinant yeast-derived hepatitis B vaccine at 1 , 2 and 7 months of age . Blood tests were performed for all the lying-in women and their neonates . Blood specimens were tested for HBsAg and HBeAg by enzyme immunoassay . All infants were followed up for 1 year . RESULTS In the HBIG  group , 491 neonates were born to 487 HBV carrier mothers ; and in the  control group , 496 neonates were born to 493 HBV carrier mothers . The rates of intrauterine transmission in the two groups were 14.3 % and 5.7 % respectively ( chi(2 ) = 20.280 , P < 0.001 ) , and the rates of chronic hepatitis B in the two groups were 2.2 % and 7.3 % respectively ( chi(2 ) = 13.696 , P < 0.001 ) . The high risk factors of intrauterine HBV infection included HBsAg HBeAg double positive and HBV DNA positive in the peripheral blood of pregnant women . CONCLUSION HBV infection in the uterus may be interrupted by injecting multiple intramuscular HBIG injections before delivery without causing any side-effects A double-blind r and omized placebo-controlled study to prevent hepatitis B infection in 235 babies born to chronic hepatitis B , HBeAg carriers was carried out . Babies in three treatment groups all received heat-inactivated hepatitis B vaccine . In addition multiple doses of HBIG and a single dose of HBIG were given in groups I and II respectively . After three years of follow-up , 4/60 ( Group I ) , 3/64 ( Group II ) , and 1/64 ( Group III ) developed chronic infection . For those who escaped chronic infection , other hepatitis events also occurred . They were transient HBs-antigenaemia , anti-HBc conversion and significant rise in anti-HBs titre without seroconversion for anti-HBc . It was deduced that 30 % of babies born to hepatitis carriers are naturally protected from chronic infection . Immunization , with vaccine only , protects another 46 % . The addition of single and multiple doses of HBIG protects another 10 % and 5 % , respectively . 2 % acquired intrauterine infection and 7 % failed to respond to the most intensive immunization schedule We sought to identify differences in the description of adverse drug experiences in reports of r and omized clinical trials ( RCTs ) from the United States and Japan , using diclofenac and simvastatin as test drugs . Reports were identified in Medline ( Index Medicus 1966 - 1990 ) , EMBASE ( Excerpta Medica 1974 - 1990 ) , JAPICDOC ( 1979 - 1990 ) , and JOIS-III ( JMEDICINE 1980 - 1990 ) . In each search keywords describing study design were paired with the drugs ' generic names , chemical names , and development numbers . Twenty-seven U.S. reports ( 18 for diclofenac and 9 for simvastatin ) and 22 Japanese reports ( 17 for diclofenac and 5 for simvastatin ) identified in these four data bases were selected for review . For each paper we identified the relation of the article to the data ( preliminary , primary , and secondary reports , review s ) , the means of identifying adverse reactions , the principal outcomes of the trials , and a variety of descriptive measures relating to study design , authors hip , and elements of presentation . With few exceptions , Japanese reports were not indexed in English- language data bases , and studies from the United States were not carried out in the Japanese data bases . The Japanese literature consisted exclusively of primary reports of clinical trials , whereas the U.S. literature was dominated by review articles and secondary reports of data from trials not fully published elsewhere . Japanese reports contained more detail on adverse experiences but reported principally those attributed to the drugs by attending clinicians . U.S. reports by contrast offered little detail but tended to include all adverse experiences , whether or not clinical ly attributed to drugs . A preponderance of U.S. articles reported significant differences between drugs in safety or treatment efficacy , whereas only one third of the Japanese articles did so for the same agents . Reports from both countries offered few details of the methods used to gather information on adverse drug experiences , and as a result the reported absolute frequencies of such events are difficult to compare between trials or to generalize to other setting s. In conclusion , the reporting of adverse reactions in clinical trials is inadequate in both the United States and Japanese literature . The shortcomings are complementary in that reports of U.S. trials contain insufficient detail and Japanese reports do not interpret or synthesize experience . Clinical research into drug safety in both countries could be improved through the adoption of simple st and ards of clarity and consistency in the monitoring and reporting of drug adverse effects A r and omized 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 Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . Screening of pregnant women for hepatitis B surface antigen ( HBsAg ) in three areas of Holl and led to the identification of HBsAg carriers , 20 of whom were subsequently delivered . Within two hours after birth all infants received hepatitis B immune globulin ( 0.5 ml/kg body weight ) and , after r and omisation , hepatitis B vaccine ( 10 micrograms ) was given either at 0 , 1 , and 2 months of age or at 3 , 4 , and 5 months of age , the latter concomitantly with DPTP vaccination .  Eighteen infants complying with the protocol were followed up for at least six months . No side effects were observed after either passive or active immunisation . All infants developed high concentrations of anti-HBs antibodies ; no interference of high dose passive immunisation with active immunisation was observed . Concentrations of anti-HBs at three months were significantly lower in infants given delayed active immunisation than in those given early active immunisation . These data suggest that passive-active immunisation against hepatitis B virus infection is well tolerated by neonates under 3 months of age and that both early and late active immunisation in combination with passive immunisation will result in excellent anti-HBs production Seventy-eight infants born to HBsAg-positive women were r and omly assigned to receive either the plasma-derived vaccine or 0.5 ml ( 10 micrograms HBsAg ) yeast-derived recombinant hepatitis B vaccine within 24 hours of birth , simultaneously with hepatitis B hyperimmunoglobulin . In 67 infants who received the plasma-derived vaccine  , one of the doses of 0.5 ml ( 25 micrograms HBsAg ) was used r and omly . In all of the infants , the second and third doses of both vaccines were given at one and two months of age , respectively . The booster doses were given at 12 month of age in all of the infants . These vaccinated infants were followed up until 13 months of age . There were differences in the seroconversion rates with different vaccines and doses . The recipients of the half-dose of plasma-derived vaccine showed lower seroconversion rates than the others , and the newborns in this group showed more seronegativity ( 13.2 % ) than the others ( p < 0.05 ) . The lowest anti-HBs geometric mean titers ( GMTs ) were obtained in newborns vaccinated with Hevac B 0.5 ml . Sixty percent of the anti-HBs GMTs in this group were under 100 mlU/ml . There were statistically significant differences between males and females in anti-HBs seronegativity rates , with males having lower anti-HBs GMTs than females . The difference was particularly significant among male newborns vaccinated with a half-dose of plasma-derived vaccine OBJECTIVE The infection of Hepatitis B virus ( HBV ) in the uterus may occur in neonates born to HBV carrier mothers . The rates of intrauterine transmission in these neonates were 10%-16 % , Recent studies on the methods of combined passive and active immunizations indicate an efficacy approaching 70%-90 % , but intrauterine infection of HBV is the major cause of failure of vaccination to combat hepatitis B in neonates born to HBV carrier mothers . We studied the interruptive effect of HBV specific immunoglobulin ( HBIG ) before delivery in the prevention of intrauterine transmission of HBV . METHODS Of 3632 pregnant women , two hundred and four were HBV carriers ; they were r and omly divided into an HBIG group and a control group . Each subject in the HBIG group received 200 IU of HBIG intramuscularly at 3 , 2 and 1 month before delivery . The subjects in the control group did not receive any specific treatment . Blood tests were conducted for all the subjects and their neonates after birth . Blood specimens were tested for HBsAg and HBeAg by enzyme immunoassay ( Abbott Kits ) . RESULTS The results showed that the rates of intrauterine transmission in the two groups were 5.7 % and 14.7 % respectively ( X2 = 4.58 P < 0.05 ) . No significant differences were observed for the positive rates of HBsAg and HBeAg between the two groups after delivery , but titer of HBsAg was reduced significantly in the HBIG group ( t = 4.82 , P < 0.01 ) . CONCLUSIONS Our study suggests that HBV infection in the uterus may be interrupted using multiple HBIG intramuscularly before delivery without any side effects To evaluate the long-term protection afforded by the vaccine , recombinant hepatitis B ( HB ) vaccine was given to 171 infants born to hepatitis B e antigen-positive carrier mothers . Group A ( 53 infants ) and group B ( 57 infants ) received four doses of HB vaccine at birth and at 1 , 2 , and 12 months of age , with a dose of 20 micrograms in group A and 10 micrograms in group B. Group C ( 61 infants ) received three 20 micrograms doses of HB vaccine at birth and at 1 and 6 months of age . These children were followed up annually up to 5 years of age . Six children ( 4 % ) became HB carriers before 1 year of age , and the carrier state persisted to the end of follow-up . The overall seropositive rate of HB surface antibody ( anti-HBs ) dropped from 99 % at 1 year of age to 83 % at 5 years of age . Among 548 serum pairs taken at 1-year intervals from children negative for HB surface antigen ( HBsAg ) , a fourfold rise of anti-HBs titer was noted in 58 ( 11 % ) and a 10-fold rise of anti-HBs was noted in 17 ( 3 % ) . Maternal HB core antibody disappeared in most children ( 151/152 , 99 % ) before 2 years of age . Natural infections , as judged by persistence or reappearance of HB core antibody , occurred in 19 of 163 ( 12 % ) HBsAg-negative children . None of these episodes was associated with HBsAg positivity . We conclude that the long-term protection afforded by recombinant HB vaccine is satisfactory and that a further booster dose before 5 years of age is not 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 The infectivity rate of newborn babies who had been borne from HBsAG(+ ) , HBeAg(+ ) and anti-HBc(+ ) mothers was very high ( 85 % ) . 142 babies born in the hospital were divided into three groups , in this study . In the group 1 , 57 babies were inoculated with 20 micrograms recombinant DNA vaccinia vaccines against hepatitis B. The injections were given at newborn , 1 month , and 6 months , respectively . In group 2 , 41 babies were inoculated with 20 micrograms genetic engineering vaccines against hepatitis B at same time were intervals as group 1 . In group 3 , 44 newborn babies were inoculated with 10 micrograms as same vaccines as group 2 HBIG plus 1ml ( 200 U/ml ) , at same time intervals as group 1 . The immune pretection rates of newborn babies in three groups were 88.2 % , 85.9 % and 100 % , respectively . The anti-HBs pasitive conversion rates were 82 % , 86 % and 98 % , respectively . The group 3 was compared with group 1 and 2 . Statistical analysis showed the significant differences ( P < 0.05 ) . The result showed the immune program of group 3 was superior to that of group 1 and 2 , and none of the 44 babies in group 3 were infected . The efficacy of immunization by genetic engineering vaccines were superior to that of blood-derived vaccine . The genetic engineering vaccines against hepatitis B would be more useful for interruption of perinatal transmission of HBV A reduced dose of plasma derived hepatitis B vaccine ( Hevac B ) was tested for efficacy in the prevention of perinatal hepatitis B virus ( HBV ) transmission in high risk neonates born from e-antigen positive HBsAg carrier mothers . Forty newborn infants born of these mothers were given hepatitis B immune globulin ( HBIG ) 100 IU intramuscularly immediately after birth , combined with either st and ard or reduced doses of HBV vaccine . The infants were divided into two groups of 20 infants each . The st and ard dose of HBV vaccine ( 5 micrograms ) was given to group I , while infants in group II received reduced dose ( 2 micrograms ) at birth and at 1 , 2 and 12 months of age . There was no statistically significant difference in the efficacy and antibody responses of these two combined prophylaxis regimens . The protective efficacy rate of HBV vaccine  was found to be 94.0 and 93.2 percent in group I and group II , respectively . At twelve months of age , the anti-HBs seroconversion rates were 80.0 percent in group I and 86.7 percent in group II , with geometric mean titres of 84.57 mlU/ml and 78.56 mlU/ml , in group I and group II , respectively . One month after a booster at one year of age , anti-HBs could be detected in 86.7 percent of the infants in both groups . The geometric mean titres were 429.04 and 664.81 mlU/ml , in group I and group II , respectively . Anti-PreS2 antibody was detected in high titre as early as 4 months after the first dose of HBV vaccine , with a geometric mean titre of 116.30 mlU/ml and 107.97 mlU/ml , in group I and group II , respectively . ( ABSTRACT TRUNCATED AT 250 WORDS A half dose recombinant hepatitis B vaccine ( HBVax II , MSD , 5 micrograms ) was investigated for efficacy in the prevention of perinatal hepatitis B virus ( HBV ) transmission in high risk neonates born from e-antigen positive HBsAg carrier mothers as compared to the half-st and ard dose regimen of plasma derived hepatitis B vaccine ( HBVax , MSD , 10 micrograms ) . Forty infants born to carrier mothers were given hepatitis B immune globulin ( HBIG ) 100 IU intramuscularly immediately after birth , combined with either the recombinant or plasma derived hepatitis B vaccine . The infants were r and omly divided into two groups of 20 infants each . The plasma derived vaccine ( 10 micrograms ) was given to group I , while infants in group II received the recombinant vaccine ( 5 micrograms ) at birth , 1 and 6 months of age . There were no statistically significant differences in the efficacy and the seroconversion rate of these two combined prophylaxis regimens . The protective efficacy rate of both kinds of HBV vaccine was found to be 94.6 and 89.2 percent in group I and group II respectively . At twelve months of age , the anti-HBs seroconversion rates were 95.0 percent in group I and 84.2 percent in group II . However , the geometric mean titres in group I ( 179.55 mIU/ml ) was significantly higher than those in group II ( 42.2 mIU/ml ) but the anti-HBs titre was still above protective level ( 10 mIU/ml ) in most of the infants . ( ABSTRACT TRUNCATED AT 250 WORDS Hepatitis B virus ( HBV ) is the world 's most common blood-borne viral infection , chronically infecting more than 200 million people worldwide [ 1 ] . It is responsible for substantial morbidity and mortality and is a leading cause of hepatocellular carcinoma . Approximately 300 000 Americans are infected with HBV each year , an annual incidence rate of 11.5/10 000 population [ 2 , 3 ] . Serologic evidence of previous infection is found in 4.8 % of the U.S. population [ 4 ] . Each year approximately 4000 persons in the United States die of HBV-related cirrhosis and about 800 people die of HBV-related hepatocellular carcinoma [ 3 , 5 , 6 ] . The goal of our study was to determine the clinical and economic impact of alternative HBV vaccination strategies for selected U.S. population s. This analysis up date s the earlier work of Mulley and colleagues [ 7 ] by incorporating more recent data on incidence of HBV infection , cost of acute disease and chronic sequelae , and safety and effectiveness of HBV vaccine  , by focusing on a broader range of population s , and by modeling a longer period . A safe and effective vaccine to prevent HBV infection was introduced in the United States in 1981 . Nonetheless , the overall incidence of HBV infection increased 14.5 % between 1981 and 1987 [ 2 , 3 ] , especially in selected high-risk groups [ 8 ] ( 77 % increase between 1981 and 1988 among injection drug abusers ) . The clear relationship between HBV infection and primary hepatocellular carcinoma indicates that HBV vaccine is the first effective anti-cancer vaccine [ 6 ] . However , the vaccine is not administered to most high-risk people ( fewer than 50 % of high-risk health care workers have received a complete HBV vaccination series ) [ 3 , 9 , 10 ] . Acute HBV infection manifests itself clinical ly along a spectrum from asymptomatic , sub clinical infection through fatal fulminant hepatitis [ 1 , 5 , 11 ] . More than 50 % of HBV infections in adolescents and adults in the United States are asymptomatic [ 2 , 9 , 12 , 13 ] . Others exhibit a variety of nonspecific viral symptoms ; one quarter become ill with jaundice [ 3 ] . More than 10 000 people with acute HBV infection are hospitalized annually [ 3 ] . About 250 die each year of fulminant infection [ 3 ] . Both asymptomatic and nonfulminant symptomatic HBV infection are similarly associated with chronic forms of infection , which , in turn , may lead to cirrhosis and hepatocellular carcinoma [ 1 , 5 , 6 , 11 , 14 - 16 ] . The epidemiology of HBV infection varies greatly by geography and sociodemographic factors [ 1 - 4 , 17 ] . Population s at greatest risk include those with multiple sex partners , sexually active male homosexuals , injection drug abusers , family members of HBV carriers , newborn children of actively infected mothers , medical personnel who are exposed to blood and blood products , immigrants from HBV endemic areas , and sexual partners of members of high-risk groups [ 3 ] . Epidemiologic studies have documented serologic evidence of HBV infection in as many as 50 % of members of high-risk groups [ 2 , 3 , 18 ] . This combination of increasing incidence , exp and ing high-risk population s , and failure to deliver the vaccine to those at highest risk warrants a re-evaluation of current HBV vaccine policy . The Centers for Disease Control ( CDC ) has recommended universal vaccination of newborns and of high-risk adolescents [ 19 ] . The Occupational Safety and Health Administration ( OSHA ) has issued guidelines requiring HBV vaccination for all at-risk health care workers [ 20 ] . Others have proposed more limited vaccination strategies [ 21 ] . Methods Structure of the Model : Basic Decision Tree We used decision analysis to model clinical and economic consequences of alternative approaches to prevention and management of HBV infection . We focused on number and costs of cases prevented , deaths prevented , and years of life saved [ 22 ] . The decision model examined three different HBV management strategies ( no vaccination , universal vaccination , and screen and vaccinate ) in four different U.S. cohorts : 1 ) newborns ; 2 ) adolescents at age 10 ; 3 ) a high-risk adult population with HBV infection incidence of 5 % per annum ; and , 4 ) the general adult population ( 12 to 50 years old ) . In addition , we examined a mixed population strategy of screening all pregnant women before or during labor for evidence of active HBV infection ( HBsAg ) , administering HBV vaccine and hepatitis B immune globulin ( HBIG ) to the newborns of mothers who test positive , and then vaccinating all children at age 10 and again 10 years later . Each analysis followed a cohort of 10 000 individuals for three consecutive 10-year periods , because probabilities of infection or sequelae change over time . Cyclical Markov modeling could have been used , but its complexity makes presentation more difficult to underst and , and accuracy is not importantly improved . The decision model used in this analysis was developed after a critical review of the literature , with input from five HBV experts to ensure accuracy and validity . The basic decision tree ( Figure 1 ) incorporated the sensitivity and specificity of screening tests for previous or current HBV infection , estimates of compliance with vaccine administration , the probability of protection if vaccine is administered , the probability of exposure to HBV , and the probability of acute infection after exposure to HBV . All strategies assume that some individuals will be protected from HBV by virtue of previous infection . The terminal branches that end with no hepatitis B infection identify persons who remain uninfected with HBV at the end of the period . They enter the model again at the same starting point as everyone else ( no previous HBV infection ) for up to two additional consecutive 10-year periods . The terminal branches of the basic tree that end with hepatitis B infection lead to a subtree Figure 2 that reflects the distribution of types of acute disease and the probability of long-term sequelae of HBV infection . Figure 1 . Structure of basic adult decision tree for first 10-year period . Figure 2 . Structure of the decision tree for persons who contract hepatitis B virus . Data Sources We obtained the data used in the model from three sources . First , we critically review ed the medical literature and found probability estimates of incidence and prevalence , clinical course and patient management of HBV infection and its sequelae in the community ; safety and efficacy of HBV vaccine ; and compliance with the administration of HBV vaccines  . Second , using a modified Delphi technique , an expert panel review ed these estimates , reconciled conflicting data , and provided consensus estimates for probabilities , events , patient management in the community , and outcomes for which reliable data were unavailable in the medical literature . Third , we obtained data on costs from actual private insurer payments , adjusted for expected patient out-of-pocket expenditures . Screening Strategies We used two screening strategies . First , the antibody to hepatitis B surface antigen ( anti-HBsAg ) was used in the adult population s to screen for previous infection to identify those individuals who were protected from recurrent infection and who , therefore , did not require vaccination . Second , HBV surface antigen ( HBsAg ) was used to screen mothers for active infection to identify newborns at high risk for HBV infection who would benefit from HBV vaccine and HBIG [ 22 , 23 ] . Compliance and Vaccine Effectiveness Table 1 shows the input values for screening tests , vaccine compliance , and vaccine effectiveness used for the base case analysis . We assumed 100 % compliance with maternal screening for HBV before or at the time of delivery . For other groups , we assumed compliance with screening to be 20 % greater than the probability that they would comply with at least the first dose of vaccine . The literature and expert panel suggested a 50 % compliance rate with the full series of three vaccinations ( 0 , 1 , and 6 months ) among adults and adolescents , with lower compliance rates among high-risk population s and higher compliance rates among newborns because of accessibility in the hospital for the first dose of vaccine . People who did not comply with any of the initial series of vaccinations were assumed not to comply with any subsequent vaccine booster doses . Table 1 . Base Case Input Values ( Per Person ) * Efficacy for full and partial vaccination series were estimated from r and omized and historical clinical trials ( Table 1 ) [ 7 , 17 , 23 - 34 ] . Antibody titers decrease over time after vaccination [ 26 , 35 - 38 ] . Although epidemiologic studies do not indicate that such decreases in titers result in reduced protection against HBV infection , such studies have been limited to 7 or fewer years after vaccination [ 38 ] . The CDC currently does not recommend administration of vaccine boosters but is following population s of immunized patients to determine if such boosters will be required . The base case model we report here assumed that vaccine efficacy persisted for 10 years , after which a single booster dose was required to provide continuing protection against HBV infection for an additional 10 years , a conservative assumption that biases the model against the cost-effectiveness of all vaccination strategies . Among those who responded to the vaccine by developing protective antibodies , we made counterbalancing assumptions : no decrease in protection from HBV vaccine before 10 years but no protection after 10 years unless a booster is administered . We assumed that HBV vaccine did not incur any side effects that required medical care [ 26 , 27 ] and that persons infected with HBV despite vaccination followed the same clinical course as those never vaccinated . Newborns of mothers who tested positive for active hepatitis B infection ( HBsAg+ ) were assumed to be treated with HBIG plus HBV vaccine . These infants also underwent serologic testing at 1 year of age and those with low antibody titers ( 10 % of neonates receiving a full primary series of HBV AIM The study was conducted to evaluate the immunogenicity of an early , extra dose of enhanced inactivated poliovirus vaccine ( IPV ) administered simultaneously with recombinant hepatitis B vaccine ( HBV ) to preterm infants shortly after birth . METHODS Three groups were studied . Fifty preterm infants received IPV  intramuscularly within 24 hours of birth , in addition to routine recommended childhood immunisations . Fifty two preterm infants and 35 full term infants received routine immunisations only  ( routine vaccination timing : HBV at birth , 1 and 6 months of age ; IPV at 2 and 4 months ; oral polio vaccine ( OPV ) at 4 and 6 months ; diphtheria-tetanus-pertussis ( DTP ) at 2 , 4 , and 6 months ; and Haemophilus influenzae B vaccine at 2 and 4 months )  . Blood sample s were taken at birth , 3 and 7 months of age from all infants , and at 1 month of age from preterm infants only . RESULTS At birth , a lower percentage of both study and control preterm infants had antipoliovirus type 3 titres ⩾ 1:8 than full term infants . At 1 and 3 months of age significantly more early IPV infants had antipoliovirus type 3 titres ⩾ 1:8 than routinely vaccinated preterm infants ( p < 0.05 ) . At 7 months of age there were no significant differences in percentage of antipoliovirus titres ⩾ 1:8 or geometric mean times ( GMTs ) between the early IPV group and the routinely vaccinated preterm group . At 3 and 7 months of age , the percentage of positive antihepatitis B titres ( ⩾ 1:10 ) and the GMT of the early IPV preterm group did not differ significantly from those of preterm controls . There was no significant difference in percentage of positive antihepatitis B titres between the early IPV group and full term controls at any time . GMTs for hepatitis B antibodies were significantly lower in the early IPV preterm group than in full term controls at 3 and 7 months of age . CONCLUSIONS Administration of an additional dose of IPV simultaneously with routine HBV to preterm infants shortly after birth provides early protection from poliovirus and hepatitis B infection , and does not interfere with poliovirus antibody production at the age of 7 months 74 healthy babies born to mothers positive for hepatitis B surface antigen ( HBsAg ) were r and omly 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 r and omly 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 r and omly 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 total of 318 children were prospect ively r and omized in group 1 with two 5-microg doses of recombinant vaccine given at 0 and 1 month ; in group 2 with three 5-microg doses of recombinant vaccine given at 0 , 1 , and 6 months ; or in group 3 with three doses of plasma-derived vaccine given at 0 , 1 , and 6 months . Eleven subjects with a hepatitis B surface antigen antibody ( anti-HBs ) titer of less than 10 mIU/mL at 12 months were given an extra dose of  vaccine and were excluded from analysis . No booster doses were given to any other subjects . All children were followed up yearly for the level of anti-HBs titers and for the detection of hepatitis B infection . At the 12th year of follow-up , there were significantly fewer subjects with anti-HBs of 10 mIU/mL or above in group 1 ( 60.4 % ) when compared with group 2 ( 81.4 % ; P = .0287 ) and group 3 ( 79.0 % ; P = . 0381 ) . The geometric mean titers ( GMTs ) of subjects of group 1 were significantly lower than those of group 2 and group 3 throughout the 12 years of follow-up . A total of 65 subjects had one or more episodes of anamnestic response . No subject became positive for hepatitis B surface antigen ( HBsAg ) ; 2 became positive for hepatitis B core antigen antibody ( anti-HBc ) . In conclusion , the long-term protective immunity was better with three doses of hepatitis B vaccine ( either the recombinant or plasma-derived ) than with two doses . However , protection from hepatitis B infection could be equally achieved by either two doses or three doses of the vaccine . Booster doses were not necessary , probably because of effective anamnestic response OBJECTIVE To determine whether hepatitis B vaccination of newborns increases the incidence of fever and /or suspected sepsis . METHODS A prospect i ve clinical study was undertaken at the Kaiser Permanente San Francisco Medical Center involving normal full term newborns born between November 1 , 1991 , and April 30 , 1994 . During this time 3302 infants were vaccinated within 21 days of birth with hepatitis B vaccine , and 2353 were not .  Clinical and demographic data were collected from Kaiser Permanente 's existing clinical information systems , and laboratory data for blood and cerebrospinal fluid ( CSF ) cultures were obtained from the comprehensive automated regional laboratory reporting system . RESULTS There were no significant differences between vaccinated and unvaccinated newborns in the proportion of infants who received care for fever ( 0.8 % vaccinated and 1.1 % unvaccinated , P = 0.28 ) , allergic reactions , seizures or other neurologic events in the first 21 days of life . Vaccinated newborns were significantly less likely to undergo microbiologic evaluation for possible sepsis . Among vaccinated newborns 4.0 % had blood cultures and 1.6 % had CSF cultures . Among infants who were not vaccinated 8.3 % had blood cultures and 1.6 % had CSF cultures ( P < 0.001 for both tests ) . CONCLUSION This study found no evidence that newborn hepatitis B vaccination is associated with an increase in the number of febrile episodes , sepsis evaluations or allergic or neurologic events . In addition our data did not support any increase in medical procedures attributed to receipt of hepatitis B vaccine Newborn infants of Chinese HBeAg-carrier mothers in Hong Kong were r and omly 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 To study the duration of antibody persistence and protection provided by the hepatitis B vaccine , we followed 773 homosexual men for five years after completion of vaccination . Among the 635 participants in whom antibody levels above 9.9 sample ratio units ( SRU ) developed after  vaccination  , 15 percent lost antibody altogether , and in another 27 percent , antibody levels declined below 10 SRU within five years . The extent of the maximal antibody response strongly predicted the persistence of protective antibody .  Hepatitis B infection occurred in 55 men ; 8 of these infections were clinical ly important ( characterized by the presence of the hepatitis B surface antigen and elevation of liver-enzyme levels ) , and two of the patients became hepatitis B virus carriers . The long-term risk of hepatitis B infection was inversely related to the maximal antibody response to vaccine . Most severe infections occurred among those who responded poorly or had no response to the vaccination . The risk of late infection with hepatitis B in those with an initially adequate vaccine response increased markedly when antibody levels decreased below 10 SRU , but only 1 of 34 late infections result ed in viremia and liver inflammation . A second series of vaccinations induced a moderate antibody response in 50 percent of the subjects who initially had no response or a poor response ; however , the persistence of antibody was poor . Both antibody loss and the risk of severe disease should be considered when booster-dose strategies for the hepatitis B vaccine are being design ed Recombinant DNA Yeast-Derived Hepatitis B Vaccine ( RYHB vaccine ) is comparable to and can replace Plasma-Derived Hepatitis B Vaccine ( PHB vaccine ) for the prevention of mother-infant transmission of hepatitis B virus ( HBV ) , but the duration of immune efficacy of RYHB vaccine is not clear . This study indicates the long-term efficacy for the prevention of mother-infant transmission of HBV . One hundred and six neonates born to HBsAg-carrier mothers with HBeAg positive were r and omly divided into two groups , one receiving 20 micrograms per dose of RYHB vaccine and the another receiving 20 micrograms per dose of PHB vaccine on the day of birth , at 1 month and at 6 months ( three times ) . Physical examination and blood tests were performed for all infants at 6 , 12 , 24 , 36 , 48 and 60 months of age . The results showed that the protective efficacies at 6 , 12 , 24 , 36 , 48 and 60 months were 67 % , 75 % , 63 % , 62 % , 57 % and 56 % , respectively for the RYHB vaccine group and 58 % , 76 % , 51 % , 41 % , 24 % and 18 % , respectively for the PHB vaccine group . The protective efficacy was notably significant in the last two years . The study indicates that the duration of protective efficacy is over 5 years with RYHB vaccine , being longer than that of PHB vaccine . These recipients of RYHB vaccine showed no side effects , and the vaccine is regarded as safe and effective Two hundred and sixty-six children aged 3 - 10 years were tested for hepatitis B virus ( HBV ) serologic markers . Thirty-eight were positive , including seven who were positive for hepatitis B surface antigen ( HBsAg ) . Two hundred and fifteen healthy children were r and omised to receive either 3 x 5 micrograms doses or 3 x 10 micrograms doses of Smith Kline Biologicals Engerix B recombinant DNA ( rDNA ) hepatitis B vaccine into the deltoid muscle at 0 , 1 and 6 months . They were tested for seroconversion and levels of antibody to hepatitis B surface antigen ( anti-HBs ) one month after dose 3 . Ninety-nine percent of children in each group seroconverted for anti-HBs . Geometric mean titres ( GMT ) or anti-HBs in IU/L were higher with 10 micrograms doses . Nevertheless , 3 x 5 micrograms is the appropriate regimen for protecting children in this age group , as long as cost of vaccine remains a major factor in immunisation programmes AIM To investigate the effect of hepatitis B virus ( HBV ) specific immunoglobin ( HBIG ) and lamivudine on HBV intrauterine transmission in HBsAg positive pregnant women . METHODS Each subject in the HBIG group ( 56 cases ) was given 200 IU HBIG intramuscularly ( i m . ) every 4 weeks from 28-week ( wk ) of gestation , while each subject in the  lamivudine group ( 43 cases ) received 100 mg lamivudine orally ( po . ) every day from 28-wk of gestation until the 30(th ) day after labor . Subjects in the control group ( 52 cases ) received no specific treatment .  Blood specimens were tested for HBsAg , HBeAg , and HBV-DNA in all maternities at 28-wk of gestation , before delivery , and in their newborns 24 hours before the administration of immune prophylaxis . RESULTS Reductions of HBV DNA in both treatments were significant ( P<0.05 ) . The rate of neonatal intrauterine HBV infection was significantly lower in HBIG group ( 16.1 % ) and lamivudine group ( 16.3 % ) compared with control group ( 32.7 % ) ( P<0.05 ) , but there was no significant difference between HBIG group and lamivudine group ( P>0.05 ) . No side effects were found in all the pregnant women or their newborns . CONCLUSION The risk of HBV intrauterine infection can be effectively reduced by administration of HBIG or Lamivudine in the 3(rd ) trimester of HBsAg positive pregnant women In an attempt to interrupt perinatal transmission of hepatitis B , 92 infants born to HBsAg carrier mothers ( 49 to HBeAg-positive mothers , 30 to anti-HBe-positive with abnormally elevated ALT levels , and 13 to HBeAg/anti-HBe-negative mothers ) received 0.5 ml/kg BW of HBIG at birth and at 1 month of age . Three IM injections of hepatitis B vaccine were given at 3 , 4 , and 9 months of life . All babies who were given the three doses of vaccine developed an active anti-HBs response : of these , 53 ( 62.3 % ) had antibody titers higher than 1,000 mIU/ml , 29 ( 34.2 % ) had levels between 100 and 1,000 mIU/ml , and the other three ( 3.5 % ) were below 100 mIU/ml . At the end of the 2-year follow-up , these three poor responders became anti-HBs negative , whereas the others still had antibody . All but three babies were protected by HBIG plus vaccine treatment . Two chronic HBV infections occurred within 6 months of life presumably because the babies were already infected when prophylaxis started . The third baby became an HBsAg carrier at 9 months of age in spite of a previous response to the vaccine . Simultaneous presence of HBsAg of y specificity and anti-HBs ( anti-a ) was still detectable at 24 months of age . The vaccine was well tolerated . Passive plus active immunization is an effective procedure for preventing perinatally transmitted HBV infection In a prospect i ve r and omized trial , 318 children aged between 3 mo and 11 yr who were negative for all hepatitis B markers were r and omized to receive two 5-micrograms doses of hepatitis B recombinant DNA yeast vaccine at 0 and 1 mo ( group 1 ) , three 5-micrograms doses of hepatitis B recombinant DNA yeast vaccine at 0 , 1 and 6 mo ( group 2 ) or three 10-micrograms doses of plasma-derived hepatitis B vaccine ( group 3 ) . The HBs antibody response rate at 8 mo was between 93 % and 99 % ; it was still 75 % to 87 % at 5 yr in all three groups . Geometric mean titers at 1 yr were 83 , 1,085 and 858 mIU/ml in groups 1 , 2 and 3 , respectively . These values had decreased after 5 yr to 47 , 131 and 250 mIU/ml . Subjects in group 1 showed a significantly less proportional drop in geometric mean titer at the fifth year than did subjects in group 2 ( p = 0.05 ) or group 3 ( p = 0.015 ) . None of the children developed HBc antibody , even after 5 yr of follow-up . We noted 42 episodes of significantly increased HBs antibody titers , probably due to anamnestic response , even when the titers had dropped to low levels . The mean age at which anamnestic response occurred was 8.7 yr . ( ABSTRACT TRUNCATED AT 250 WORDS From 1983 to 1993 two anti-hepatitis B vaccinal strategies were adopted in two small towns of Southern Italy at high incidence for HBV infections : Afragola ( prevalence of HBsAg carriers of 13.4 % ) and Frattamaggiore ( prevalence of HBsAg carriers of 12.9 % ) . In Afragola , the universal vaccination of infants in their first year of life and adolescents at 12 years of age was carried out , while in Frattamaggiore the selective vaccination of high risk groups of population was introduced . During this study , the changes in the HBV infection endemicity in both towns has been tested by monitoring the incidence of new cases of viral hepatitis B and by the prevalence study of HBsAg carriers prior to and 10 years after the beginning of the immunization programme ( 1978 - 1993 ) . The results suggest that universal vaccination of infants in the first year of life and adolescents at 12 years of age has a greater efficiency on the improvement on the endemic status of the infection in the general population in comparison with selective vaccination , when the incidence of new cases of disease and the prevalence of number of HBsAg and anti-HBc carriers in the two population s are considered One hundred eleven newborn infants born of Spanish hepatitis B surface antigen ( HBsAg ) carrier mothers were consecutively assigned to one of three treatment groups . Group A was treated with three or four doses of hepatitis B immune globulin ( HBIG ) in one of three different schedules . Group B received one dose of hepatitis B vaccine ( Hevac-B , Pasteur ) at birth and at 1 , 2 and 12 months . Group C was treated with the same vaccination schedule as group B and in addition received a single dose of HBIG at birth . Comparisons were made in the 85 babies who had strictly completed the immunization schedule and had been followed for at least 12 months . The three immunization protocol s were equally effective , since none of the children became a chronic HBsAg carrier or developed acute symptomatic infection . There were five transient and sub clinical infections among children who received only HBIG ( group A ) , one transient infection in group B , and one in group C. There seems to be some correlation between anti-HBs levels and degree of protection , since all transient infections in group A occurred in the subgroups who did not maintain protective antibodies during the first 6 months . Although the percentage of responders in the two vaccinated groups did not differ significantly , children who received only vaccine reached higher antibody levels than those who also received HBIG . Our results suggest that any immunization schedule able to maintain anti-HBs levels during the first 6 months of life would be useful to prevent mother-to-infant transmission of the hepatitis B virus in areas where most of the carrier women are expected to be anti-HBe positive and hence relatively less infectious Experimental  hepatitis B immunization trial in newborns was carried out in Burundi . Newborns were r and omly divided into vaccine and control groups . Vaccinated newborns were given two injections of hepatitis B vaccine : one at birth and another 2 months later . A booster dose was given at 12 months of age . Results obtained show that two months after the second dose of HB vaccine , 96.8 % of the vaccinated babies had anti-HBs ; at the age of one year this figure had fallen to 83.8 % . Six months after the booster dose , 95.6 % were anti-HBs positive , with a geometric mean titre of 214 mIU ml-1 . The anti-HBs responses in these infants was compared to those observed in previous studies performed in Senegal in infants ( same protocol ) or in newborns ( 3 dose protocol ) . The anti-HBs responses were lower in terms of mean titre values in neonates who received the two dose protocol than in older children and in neonates who received three doses at one month intervals . Vaccine efficacy was monitored during a two year period in neonates both immunized and nonimmunized . Protective efficacy was found to be 100 % if considering HBsAg positive events and 75 % if considering all HBV events ( HBsAg and /or anti-HBc positive ) Recombinant hepatitis B vaccine has been shown to be as safe and effective as plasmaderived vaccines . However , its efficacy in the prevention of perinatal infection has not been fully evaluated in an endemie area . We recruited 110 high risk infants born to hepatitis B e antigen-positive-hepatitis B surface antigen ( HBsAg ) carrier mothers in a study of recombinant vaccine efficacy . They were r and omized into 2 groups , A ( 54 infants ) and B ( 56 infants ) , to receive 4 doses of vaccine , containing 20 or 10 μg of surface antigen , respectively , at 0 , 1,2 and 12 months of age . An additional 60 high risk infants were recruited later ( Group C ) and received three 20-μg doses of vaccine at 0 , 1 and 6 months of age . AH infants also received a dose ( 145 IU ) of hepatitis B immunoglobulin soon after birth . Sera were collected at 0 , 1 , 2 , 3 , 6 , 12 and 14 months of age to assay HBsAg and anti-HBs . At 12 months of age the HBsAg carrier rates were 7.4 and 1.8 % , in Groups A and B , respectively . In Group C the HBsAg-positive rate was 3.3 % . HBsAg was invariably first observed be-tween 0 and 2 months of age . Virtually ail noncarrier infants developed substantial titers of anti-HBs at 12 months of age . No serious adverse effect was observed after vaccination A hepatitis immunization field trial , using a Chinese hamster ovary ( CHO ) cell recombinant vaccine , was implemented for newborns in the Austral archipelago of French Polynesia in 1988 . Three different schedules were used : ( 1 ) four vaccine doses at months ( M ) M0 , M1 , M2 and M12 ; ( 2 ) three vaccine doses at M0 , M1 and M6 ; and ( 3 ) three vaccine doses at M0 , M1 and M12 . The programme evaluation was performed yearly at fixed date s , i.e. October-November 1989 , 1990 and 1991 . After the third year , of the 582 children who received one or more doses of vaccine , four were HBsAg carriers . After one or two doses , 88 and 98 % , respectively , had seroconverted for at least one of the two measured antibodies , anti-HBs or anti pre-S2 . After three doses , seroconversion rates and geometric mean anti-HBs titres were , respectively , 94 % and 187 mIU ml-1 using schedule M0 , M1 , M2 ; 95 % and 507 mIU ml-1 using schedule M0 , M1 , M6 and 96 % and 476 mIU ml-1 using schedule M0 , M1 , M12 . After four doses ( M0 , M1 , M2 , M12 ) the corresponding results were 99 % and 1518 mIU ml-1 . One of the 16 vaccinated neonates born to HBsAg/HBeAg-positive mothers was an HBsAg carrier , implying a protective rate for the prevention of perinatal transmission of 93 % . Overall , these results indicate that , in field conditions , indiscriminate vaccination of newborns with a CHO-recombinant vaccine without hepatitis B immunoglobulin ( HiBG ) result ed in high immunogenicity . Final evaluation in 1993 - 1994 will permit confirmation of the effectiveness of the two three-dose vaccine schedules In a r and omized , controlled trial , 105 healthy full-term infants born to HBsAg and HBeAg positive mothers received three doses ( at 0 , 1 and 6 months ) of either a new recombinant hepatitis B vaccine ( Hepavax-Gene ) or Engerix-B. Both groups were also given hepatitis B specific Hepa-big immunoglobulin ( HBIG ) within 24h of birth . Levels of antibodies to hepatitis B surface antigen ( anti-HBs ) were assessed on days 30 , 60 , 210 , 360 , and 2 years post-vaccination . Efficacy and immunogenicity and safety of the two vaccines were not significantly different ; both vaccines achieved > 94 % seroprotection within 360 days . At 2 years , only one subject ( 1.9 % ) in the Hepavax-Gene group and two subjects ( 3.9 % ) in the Engerix-B group were HBsAg positive . No serious adverse events ( AEs ) were observed in either group
BACKGROUND Hepatitis B vaccine and hepatitis B immunoglobulin are considered for newborn infants of HBsAg-positive mothers to prevent hepatitis B infection .
OBJECTIVES To assess the beneficial and harmful effects of hepatitis B vaccines and hepatitis B immunoglobulin in newborn infants of HBsAg-positive mothers .