Hepatitis B Immunisation For
Hepatitis B Immunisation For
Hepatitis B Immunisation For
-Based Child Health 2: 67155 (2007) Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/ebch.120
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review)
Lee C, Gong Y, Brok J, Boxall EH, Gluud C
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration, rst published in The Cochrane Library 2007, Issue 1 http://www.thecochranelibrary.com
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review)
Lee C, Gong Y, Brok J, Boxall EH, Gluud C
This version rst published online: 19 April 2006 in Issue 2, 2006 of The Cochrane Library. Lee C, Gong Y, Brok J, Boxall EH, Gluud C. Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers. Cochrane Database of Systematic Reviews 2007, Issue 2. Art. No.: CD004790. DOI: 10.1002/14651858.CD004790.pub2. Cochrane reviews are regularly updated as new evidence emerges and in response to feedback, and The Cochrane Library should be consulted for the most recent version of the review. Date of most recent substantive amendment: 22 February 2006
ABSTRACT 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 benecial and harmful effects of hepatitis B vaccines and hepatitis B immunoglobulin in newborn infants of HBsAgpositive mothers. Search strategy Trials were identied through The Cochrane Neonatal Group Controlled Trials Register, The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, and EMBASE (until February 2004), authors of trials, and pharmaceutical companies. Selection criteria Randomised clinical trials comparing: plasma-derived vaccine (PDV) or recombinant vaccine (RV) versus no intervention, placebo, or other active vaccines; hepatitis B immunoglobulin versus no intervention, placebo, or other control immunoglobulin; as well as PDV or RV plus hepatitis B immunoglobulin versus no intervention, placebo, or other control vaccines or immunoglobulin. Data collection and analysis Outcomes are assessed at maximal follow-up. The primary outcome measure was hepatitis B occurrence, based on a blood specimen positive for HBsAg, HBeAg, or antibody to hepatitis B core antigen (anti-HBc). Binary outcomes are reported as relative risks (RR) with 95% condence interval (CI). Subgroup analyses were performed with regard to methodological quality of the trial, mothers HBe-Ag status, and time of immunisation after birth. Main results We identied 29 randomised clinical trials, ve of which were considered high quality. Only three trials reported inclusion of hepatitis B e-antigen negative mothers. Compared with placebo/no intervention, vaccine reduced hepatitis B occurrence (RR 0.28, 95% condence interval (CI) 0.20 to 0.40, 4 trials). No signicant differences of hepatitis B occurrence were found comparing recombinant vaccine (RV) versus plasma-derived vaccine (PDV) (RR 1.00, 95% CI 0.71 to 1.42, 4 trials) and high-dose versus low-dose vaccine (PDV: RR 0.97, 95% CI 0.55 to 1.68, 3 trials; RV: RR 0.78, 95% CI 0.31 to 1.94, 1 trial). Compared with placebo/no intervention, hepatitis B immunoglobulin or the combination of vaccine plus hepatitis B immunoglobulin reduced hepatitis B occurrence (hepatitis B immunoglobulin: RR 0.50, 95% CI 0.41 to 0.60, 1 trial; PDV plus hepatitis B immunoglobulin: RR 0.08, 95% CI 0.03 to 0.17, 3 trials). Compared with vaccine, vaccine plus hepatitis B immunoglobulin reduced hepatitis B occurrence (RR 0.54, 95% CI 0.41 to 0.73, 10 trials). Hepatitis B vaccine and hepatitis B immunoglobulin seem safe, but few trials reported on adverse events. Authors conclusions Vaccine, hepatitis B immunoglobulin, and vaccine plus hepatitis B immunoglobulin prevent hepatitis B occurrence in newborn infants of HBsAg positive mothers.
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd 70
BACKGROUND Hepatitis B virus is a global acute and chronic communicable disease that causes major hepatic disease, with an estimated 350 million people infected (Beasley 1984). Mother to child transmission occurs frequently either in uterus (when the baby is still in the womb), through placental leakage, or through exposure to blood or blood contaminated uids at or around the time of birth. Such perinatal transmission is believed to account for 35% to 50% of hepatitis B carriers (Yao 1996). The risk of perinatal transmission is associated with the HBeAg status of the mother. If the mother is both HBsAg and HBeAg positive, 70% to 90% of the children become chronically infected (Stevens 1975; Akhter 1992). If the mother is HBsAg positive but HBeAg negative, the risk is signicantly reduced (Okada 1976; Beasley 1977; Beasley 1983b; Nayak 1987; Aggarwal 2004). Two types of vaccines have been licensed. One is derived from human plasma (plasma-derived vaccine (PDV)) and the other is derived from DNA recombinant technology (recombinant vaccine (RV)) from yeast or mammalian cells (Assad 1999). Repeated injections over months are required to mount an effective antibody response with vaccination. Hepatitis B immunoglobulin is an immune globulin, which contains a high level of antibody to hepatitis B surface antigen (anti-HBs). Hepatitis B immunoglobulin is considered immediately effective and seems protective for several months after which it wanes (Beasley 1983; Nair 1984). We have been unable to identify meta-analyses or systematic reviews on hepatitis B immunisation for newborn infants of HBsAg positive mothers. A narrative review regarding the efcacy of hepatitis B vaccine in neonates (Andre 1994) and several international guidelines (CDC 1999; WHO 2002) have been published. However, they do not represent systematic reviews containing an assessment of the methodological quality of the trials and presenting original data.
positive mothers.
CRITERIA FOR CONSIDERING STUDIES FOR THIS REVIEW Types of studies We included randomised clinical trials, irrespective of blinding, publication status, or language. Types of participants We included newborn infants of either gender born to HBsAgpositive mothers. The immunisation should start within the rst month of life. Types of intervention The following analyses were performed: PDV or RV versus placebo or no intervention. Hepatitis B immunoglobulin versus placebo or no intervention. PDV or RV plus hepatitis B immunoglobulin versus placebo, no intervention, PDV, or RV. Types of outcome measures All outcomes were assessed at maximal follow-up. Primary outcome (1) Hepatitis B occurrence: blood specimen positive for HBsAg, HBeAg, or antibody to hepatitis B core antigen (anti-HBc). Secondary outcomes (2) Number of newborn infants with anti-HBs less than 10 IU/L, which is considered insufcient to prevent hepatitis B virus infection (Szmuness 1981; Hadler 1986). (3) Anti-HBs, either expressed as geometric mean titre (GMT) or mean titre. (4) Systemic adverse events: adverse events such as malaise, nausea, fever, arthralgia, rash, after each injection of vaccine. (5) Local adverse events: adverse events such as pain, redness, swelling, and/or myalgia at the site after each injection of vaccine.
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OBJECTIVES To assess the benecial and harmful effects of hepatitis B vaccine and hepatitis B immunoglobulin in newborn infants of HBsAg-
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
SEARCH METHODS FOR IDENTIFICATION OF STUDIES See: Cochrane Hepato-Biliary Group methods used in reviews. We searched The Cochrane Neonatal Group Controlled Trials Register, The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials(CENTRAL) in The Cochrane Library, MEDLINE/PubMed, and EMBASE. The search strategies and time span of the searches are specied in Table 01. We consulted with The Cochrane Vaccines Field to identify further trials, but no reply was received. We read the bibliographies of retrieved articles to identify further trials. We checked the reference lists of relevant articles for any new trials. We wrote to the principal authors of the identied trials and the pharmaceutical companies (SmithKline Beecham and Merck, Sharp & Dohme; GreenCross Vaccine; GlaxoSmithKline; Pasteur; and Abbott) involved in the production of hepatitis B vaccines for missing information and additional published or unpublished trials.
METHODS OF THE REVIEW Selection of trials for inclusion CL made the decisions on which trials to be included, and the selection was validated by YG, JB, and CG. We were unblinded with regard to the names of the authors, investigators, institutions, and results. Excluded trials were identied and listed with the reasons for exclusion. Data extraction CL, YG, and JB independently extracted the data from the included randomised trials. We wrote to the authors of trials if data were missing in the report. We extracted: primary author; number of participants; inclusion and exclusion criteria; HBeAg status of the mother; methodological quality (see below); dosage and types of vaccines; site of injection; vaccination schedules; duration of follow-up; outcome measures; and number and type of adverse events in the intervention and the control groups. Methodological quality
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
METHODOLOGICAL QUALITY Generation of the allocation sequence was adequate in six trials (Piazza 1985; Oon 1986 AB/Oon 1986 CD; Farmer 1987; Halliday 1992 AB/Halliday 1992 CA/Halliday 1992 DC; Assateerawatt 1993; Hieu 2002). Treatment allocation was adequately concealed in six trials (Ip 1989 AD/Ip 1989 BD/Ip 1989 CD; Piazza 1985; Liu 1987 AB/Liu 1987 CA/Liu 1987 CB; Halliday 1992 AB/Halliday 1992 CA/ Halliday 1992 DC; Grosheide 1993; Hieu 2002). Adequate method of double blinding was reported in three trials (Ip 1989 AD/Ip 1989 BD/Ip 1989 CD; Liu 1987 AB/Liu 1987 CA/Liu 1987 CB; Halliday 1992 AB/Halliday 1992 CA/Halliday 1992 DC). According to our criteria, we classied ve trials as high quality trials (Ip 1989 AD/Ip 1989 BD/Ip 1989 CD; Piazza 1985; Liu 1987 AB/Liu 1987 CB; Halliday 1992 AB/Halliday 1992 CA/ Halliday 1992 DC; Hieu 2002). The numbers and reasons for dropouts and withdrawals were adequately reported in six trials (Beasley 1983a AB/Beasley 1983a CB/Beasley 1983b; Piazza 1985; Theppisai 1987; Halliday 1992 AB/Halliday 1992 CA/Halliday 1992 DC; Grosheide 1993).
RESULTS Hepatitis B vaccines versus placebo or no intervention (Comparison 01-01 to 01-05) Compared with placebo/no intervention, hepatitis B vaccination signicantly decreased the risk of hepatitis B occurrence (RR 0.28, 95% CI 0.20 to 0.40, 4 trials). The analysis showed heterogeneity (P = 0.07, I2 = 54.2%). The results of sensitivity analyses regarding dropouts were consistent. Analyses of PDV and RV individually
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Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
DISCUSSION Our systematic review demonstrates that hepatitis B vaccine, hepatitis B immunoglobulin, or the combination of vaccine plus hepatitis B immunoglobulin given to newborn infants of HBsAg-positive mothers prevent hepatitis B occurrence. Further, the combination of vaccine plus hepatitis B immunoglobulin was superior to vaccine alone. These benets were not signicantly associated with the methodological quality of the trials, the mothers HBeAg status, time of immunisation, or the number of infants dropping out. Our review has several potential limitations. First, some analyses include few trials and a small number of newborn infants. Second, most trials had low methodological quality. However, we did not nd strong association between the methodological quality and the trial results. This supports the robustness of our results, but does not exclude the possibility of bias affecting our results (Schultz 1995; Moher 1998; Kjaergard 2001; Als-Nielsen 2004). Third, although we did not nd funnel plot asymmetries, we cannot exclude publication bias. Fourth, only few investigators responded to our request for further information and often the information was that the details were lost. Fifth, most trials only reported surrogate outcomes (HBsAg status or anti-HBs level) and not longterm clinical outcomes. Of note is the fact that one trial with longterm follow-up found more patients with chronic hepatitis in the PDV plus hepatitis B immunoglobulin group compared with the PDV group (Ip 1989 AC). Such an increase of chronic hepatitis could be due to contamination of hepatitis B immunoglobulin with hepatitis C virus. Our results convincingly demonstrate that hepatitis B vaccination reduces hepatitis B infection in newborn infants of hepatitis B surface antigen-positive mothers. We found no signicant difference between RV and PDV on hepatitis B infections (RR 1.00, 95% CI 0.70 to 1.42). However, a greater number of newborn infants on PDV did not achieve anti-HBs level above 10 IU/L
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
NOTES 1. A protocol for a systematic review on this topic was rst published in Issue 2, 1998 of The Cochrane Library and continued to be published until Issue 1, 2004 with a title Vaccines for preventing hepatitis B in high risk newborn infants. The authors, Jefferson TO, Pratt M, Buttery J, and El-Shukri N, have abandoned the systematic review. This necessitated an update of the protocol and the conduct of the review be performed by a new team of reviewers who now consists of Lee C, Gong Y, Brok J, Boxall EH, and Gluud C. 2. We modied the denition of hepatitis B occurence as shown in the present review. 3. In our protocol we demanded that each trial had to assess serological outcome in two and more consecutive blood specimens. We realized that this requirement was not detainable in the majority of the trials. We therefore decided to delete this requirement.
AUTHORS CONCLUSIONS Implications for practice HBsAg positive mothers who are HBeAg positive Evidence suggests that hepatitis B vaccine, hepatitis B immunoglobulin, and the combination of hepatitis B vaccine and hepatitis B immunoglobulin reduce the risk of perinatal transmission of hepatitis B in newborn infants of HBsAg positive mothers who are also positive for HBeAg. However, the optimal treatment regimen remains unclear. HBsAg positive mothers who are HBeAg negative There is insufcient evidence to support or refute the use of hepatitis B vaccine, hepatitis B immunoglobulin, and the combination of hepatitis B vaccine and immunoglobulin in newborn infants of HBsAg postive mother who are HBeAg negative. The number
ACKNOWLEDGEMENTS We thank TO Jefferson, M Pratt, J Buttery, and N El-Shukri who participated in the formulation of the rst Cochrane protocol on this topic. D Nikolova, The Cochrane Hepato-Biliary Group, is
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Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
SOURCES OF SUPPORT External sources of support S.C. Van Foundation DENMARK Internal sources of support Public Health Laboratory Service UK Tri-Service General Hospital TAIWAN Copenhagen Trial Unit, Centre for Clinical Intervention Research, H:S Rigshospitalet DENMARK
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Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Ip HM, Wong VC, Lelie PN, Reesink HW, Schaasberg W, Yeung CY, et al. Hepatitis B infection in infants after neonatal immunization. Acta Paediatric Japanese 1989;31(6):6548.
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Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
versus vaccine alone in the interruption of the perinatal transmission of HBV carrier state]. Zhonghua Liu Xing Bing Xue Za Zhi 1987;8 (6):3258. Liu 1987 CB {published data only} Liu LH. [Comparative study of the efcacy of hepatitis B virus (HBV) vaccine combined with hepatitis B immunoglobulin(HBIG) versus vaccine alone in the interruption of the perinatal transmission of HBV carrier state]. Zhonghua Liu Xing Bing Xue Za Zhi 1987;8 (6):3258. Lo 1985 AB {published data only} Goudeau A, Lo KJ, Coursaget P, Tong MJ, Yeh CL, Tsai YT, et al. Prevention of hepatitis B virus infection in children born to HBsAg positive/HBeAg positive mothers. Preliminary results of active and passive-active immunization. Developmental Biology Standard 1983; 54:399404. Lo KJ, Tsai YT, Lee SD, Yeh CL, Wang JY, Chiang BN, et al. Combined passive and active immunization for interruption of perinatal transmission of hepatitis B virus in Taiwan. Hepatogastroenterology 1985;32(2):658.
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Lee 1995 CB {published data only} Lee CY, Huang LM, Chang MH, Hsu CY, Wu SJ, Sung JL, et al. The protective efcacy of recombinant hepatitis B vaccine in newborn infants of hepatitis B e antigen-positive-hepatitis B surface antigen carrier mothers. The Pediatric infectious Disease Journal 1991;10(4): 299303. Lee PI, Lee CY, Huang LM, Chang MH. Long-term efcacy of recombinant hepatitis B vaccine and risk of natural infection in infants born to mothers with hepatitis B e antigen. The Journal of Pediatrics 1995;126(5 Pt 1):71621.
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Lo KJ, Tsai YT, Lee SD, Yeh CL, Wang JY, Chiang BN, et al. Combined passive and active immunization for interruption of perinatal transmission of hepatitis B virus in Taiwan. Hepatogastroenterology 1985;32(2):658.
Lee 1995 DE {published data only} Lee CY, Huang LM, Chang MH, Hsu CY, Wu SJ, Sung JL, et al. The protective efcacy of recombinant hepatitis B vaccine in newborn infants of hepatitis B e antigen-positive-hepatitis B surface antigen carrier mothers. The Pediatric infectious Disease Journal 1991;10(4): 299303. Lee PI, Lee CY, Huang LM, Chang MH. Long-term efcacy of recombinant hepatitis B vaccine and risk of natural infection in infants born to mothers with hepatitis B e antigen. The Journal of Pediatrics 1995;126(5 Pt 1):71621. Lee PI, Lee CY, Huang LM, Chen JM, Chang MH. A follow-up study of combined vaccination with plasma-derived and recombinant hepatitis B vaccines in infants. Vaccine 1995;13(17):16859.
Lo 1985 CB {published data only} Goudeau A, Lo KJ, Coursaget P, Tong MJ, Yeh CL, Tsai YT, et al. Prevention of hepatitis B virus infection in children born to HBsAg positive/HBeAg positive mothers. Preliminary results of active and passive-active immunization. Developmental Biology Standard 1983; 54:399404.
Lo KJ, Tsai YT, Lee SD, Yeh CL, Wang JY, Chiang BN, et al. Combined passive and active immunization for interruption of perinatal transmission of hepatitis B virus in Taiwan. Hepatogastroenterology 1985;32(2):658.
Lolekha 2002 {published data only} Lolekha S, Warachit B, Hirunyachote A, Bowonkiratikachorn P, West DJ, Poerschke G. Protective efcacy of hepatitis B vaccine without HBIG in infants of HBeAg-positive carrier mothers in Thailand. Vaccine 2002;20(31-32):373943. Oon 1986 AB {published data only} Oon CJ, Tan KL, Goh KT, Wong-Yong L, Viegas O, McCarthy T, et al. Evaluation of a low dose of hepatitis B vaccine given within a childhood immunisation programme in Singapore. The Journal of Infection 1986;13(3):25567. Oon 1986 CD {published data only} Oon CJ, Tan KL, Goh KT, Wong-Yong L, Viegas O, McCarthy T, et al. Evaluation of a low dose of hepatitis B vaccine given within a childhood immunisation programme in Singapore. The Journal of Infection 1986;13(3):25567.
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Liu 1987 AB {published data only} Liu LH. [Comparative study of the efcacy of hepatitis B virus (HBV) vaccine combined with hepatitis B immunoglobulin(HBIG) versus vaccine alone in the interruption of the perinatal transmission of HBV carrier state]. Zhonghua Liu Xing Bing Xue Za Zhi 1987;8 (6):3258. Liu 1987 CA {published data only} Liu LH. [Comparative study of the efcacy of hepatitis B virus (HBV) vaccine combined with hepatitis B immunoglobulin(HBIG)
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Xu ZY, Francis DP, Liu CB, Purcell RH, Duan SC, Chen RJ, et al. Prevention of hepatitis B virus carriage of infants using HBV vaccine in Shanghai. Preliminary report of a randomized doubleblind placebo-controlled trial. Chinese Medical Journal 1985;98(9): 6236. Xu ZY, Liu CB, Francis DP, Purcell RH, Gun ZL, Duan SC, et al. Prevention of perinatal acquisition of hepatitis B virus carriage using vaccine: preliminary report of a randomized, double-blind placebocontrolled and comparative trial. Pediatrics 1985;76(5):7138. Xu 1995 AD {published data only} Xu ZY, Duan SC, Margolis HS, Purcell RH, Ou-Yang PY, Coleman PJ, et al. Long-term efcacy of active postexposure immunization of infants for prevention of hepatitis B virus infection. United StatesPeoples Republic of China Study Group on Hepatitis B. The Journal of Infectious Diseases 1995;171(1):5460. Xu ZY, Francis DP, Liu CB, Purcell RH, Duan SC, Chen RJ, et al. Prevention of hepatitis B virus carriage of infants using HBV vaccine in Shanghai. Preliminary report of a randomized doubleblind placebo-controlled trial. Chinese Medical Journal 1985;98(9): 6236. Xu ZY, Liu CB, Francis DP, Purcell RH, Gun ZL, Duan SC, et al. Prevention of perinatal acquisition of hepatitis B virus carriage using vaccine: preliminary report of a randomized, double-blind placebocontrolled and comparative trial. Pediatrics 1985;76(5):7138. Xu 1995 BD {published data only} Xu ZY, Duan SC, Margolis HS, Purcell RH, Ou-Yang PY, Coleman PJ, et al. Long-term efcacy of active postexposure immunization of infants for prevention of hepatitis B virus infection. United StatesPeoples Republic of China Study Group on Hepatitis B. The Journal of Infectious Diseases 1995;171(1):5460. Xu ZY, Francis DP, Liu CB, Purcell RH, Duan SC, Chen RJ, et al. Prevention of hepatitis B virus carriage of infants using HBV vaccine in Shanghai. Preliminary report of a randomized doubleblind placebo-controlled trial. Chinese Medical Journal 1985;98(9): 6236. Xu ZY, Liu CB, Francis DP, Purcell RH, Gun ZL, Duan SC, et al. Prevention of perinatal acquisition of hepatitis B virus carriage using vaccine: preliminary report of a randomized, double-blind placebocontrolled and comparative trial. Pediatrics 1985;76(5):7138. Xu 1995 CB {published data only} Xu ZY, Duan SC, Margolis HS, Purcell RH, Ou-Yang PY, Coleman PJ, et al. Long-term efcacy of active postexposure immunization of infants for prevention of hepatitis B virus infection. United StatesPeoples Republic of China Study Group on Hepatitis B. The Journal of Infectious Diseases 1995;171(1):5460. Xu ZY, Francis DP, Liu CB, Purcell RH, Duan SC, Chen RJ, et al. Prevention of hepatitis B virus carriage of infants using HBV vaccine in Shanghai. Preliminary report of a randomized doubleblind placebo-controlled trial. Chinese Medical Journal 1985;98(9): 6236. Xu ZY, Liu CB, Francis DP, Purcell RH, Gun ZL, Duan SC, et al. Prevention of perinatal acquisition of hepatitis B virus carriage using vaccine: preliminary report of a randomized, double-blind placebocontrolled and comparative trial. Pediatrics 1985;76(5):7138.
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Theppisai 1987 {published data only} Theppisai U, Thanuntaseth C, Chiewsilp P, Siripoonya P. A comparison between the efcacy of passive-active and active immunization for prevention of perinatal transmission of hepatitis B virus. Journal of Medical Association, Thailand 1987;70(8):45962. Theppisai 1990 {published data only} Theppisai U, Thanuntaseth C, Chiewsilp P, Siripoonya P. Prevention of hepatitis B infection in infants born to hepatitis B carrier mothers: low dosage vaccination. International Journal of Gynaecology and Obstetrics 1990;32(4):3537. Xu 1995 AB {published data only} Xu ZY, Duan SC, Margolis HS, Purcell RH, Ou-Yang PY, Coleman PJ, et al. Long-term efcacy of active postexposure immunization of infants for prevention of hepatitis B virus infection. United StatesPeoples Republic of China Study Group on Hepatitis B. The Journal of Infectious Diseases 1995;171(1):5460.
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Linder 2000 Linder N, w-up-24.9p97 0-8iS5599j 6.95991 0 Td800T/R1it3R101 7.j 8.75986.75996 0 8. .5Tf en70.5Tf (Yi)Tj 9.47inh.11.87993 0 Td (F)Tjobser5998 0 Td (of)Tj T h9HBsthe 23.15979.47in Td Td f-14.7601 Td0.63989
Additional references
Aggarwal 2004 Aggarwal R, Ranjan P. Preventing and treating hepatitis B infection. BMJ (Clinical Research Ed.) 2004;329(7474):10806. Akhter 1992 Akhter S, Talukder MQ, Bhuiyan N, Chowdhury TA, Islam MN, Begum S. Hepatitis B virus infection in pregnant mothers and its transmission to infants. Indian Journal of Pediatrics 1992;59(4):411 5. Als-Nielsen 2004 Als-Nielsen B, Gluud LL, Gluud C. Methodological quality and treatment effects in randomised trials - a review of six empirical studies (abstract). Cochrane Colloquium 2004, Ottawa, Canada. 2004.
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Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
TABLES
Participants
Notes
Participants
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Beasley 1983a CB This trial is the same as Beasley 1983a BA, but has been entered with its own identier due to technical limits of RevMan in order to make data comparison.
Participants
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Participants
Outcomes Notes
Generation of allocation sequence: unclear - not described. Allocation concealment: unclear - not described. . ..5.7108 concM Td (dm98858ot)Tj 14.1on ethods Generation of allocation seq TdP113927 Tm a7egT3Tj 14.1538 tC 1 60.48 128.02 Tmiallocatiear)Tj 27(HBeAg)Tj 28.0737 027 T7(t4hwi81L4.3165 in)Tj6861 -11.4.68 1688.06 -11.4.68 f852.7844
Participants
Outcomes Notes
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Participants
Notes
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
A Adequate Halliday 1992 DC This trial is the same as Halliday 1992 BA, but has been entered with its own identier due to technical limits of RevMan in order to make data comparison.
ieu793r
Participants
B Unclear Ip 1989 AC This trial is the same as Ip 1989 AB, but has been entered with its own identier due to technical limits of RevMan in order to make data comparison.
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Participants
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
B Unclear Ip 1989 BD This trial is the same as Ip 1989 AD, but has been entered with its own identier due to technical limits of RevMan in order to make data comparison.
A Adequate Ip 1989 CD This trial is the same as Ip 1989 AD, but has been entered with its own identier due to technical limits of RevMan in order to make data comparison.
A Adequate Kang 1995 Generation of allocation sequence: unclear - not described. Allocation concealment: unclear - not described. Blinding: not performed. Follow-up: inadequate - not described. Country: China. Publication language: Chinese. Inclusion criteria: HBsAg+ HBeAg positive mothers. Participants: (1) Group A: (2) Group B: (3) Group C:
Participants
Interventions
Group A: received 20 microgram of RV at birth and at the age of 1 and 6 months, respectively. Group B: received 20 microgram of genetic engineering vaccine at birth and at the age of 1 and 6 months. Group C: received 10 microgram of genetic engineering vaccine and HBIG 200 IU at birth and 10 microgram doses of genetic engineering vaccine at the age of 1 and 6 months.
Outcomes
HBsAg, Anti-HBs
96
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Participants
Participants
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
B Unclear Kuru 1995 AC This trial is the same as Kuru 1995 AB, but has been entered with its own identier due to technical limits of RevMan in order to make data comparison.
B Unclear Kuru 1995 BC This trial is the same as Kuru 1995 AB, but has been entered with its own identier due to technical limits of RevMan in order to make data comparison.
Participants Interventions
B Unclear Lee 1995 CB This trial is the same as Lee 1995 A1C, but has been entered with its own identier due to technical limits of RevMan in order to make data comparison.
B Unclear Lee 1995 DE This trial is the same as Lee 1995 A1C, but has been entered with its own identier due to technical limits of RevMan in order to make data comparison.
B Unclear Liu 1987 AB Generation of allocation sequence: unclear - not described. Allocation concealment: adequate - sealed envelopes. Blinding: adequate - with placebo. Follow-up: inadequate - not described. Country: China. Publication language: Chinese. Inclusion criteria: HBsAg+ HBeAg positive mothers or HBsAg titre >= 1:512.
Participants
Interventions
Group A: received 20 microgram of vaccine at birth and at the age of 1, 2, and 6 months, respectively.
99
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
A Adequate Liu 1987 CB This trial is the same as Liu 1987 AC, but has been entered with its own identier due to technical limits of RevMan in order to make data comparison.
A Adequate Lo 1985 AB Generation of allocation sequence: unclear - not described. Allocation concealment: unclear - not described. Blinding: not performed. Follow-up: unclear. Country: Taiwan. Publication language: English. Inclusion criteria: HBsAg+ HBeAg positive mothers. Mother age: 20 to 36 years, mean 27 years old.
Participants
Interventions
Group A: received HBIG 50 IU at birth, then Hevac-B 5 microgram at 2 weeks, 6 weeks, and 10 weeks. Group B: received Hevac-B 5 microgram at 2 weeks, 6 weeks, and 10 weeks. Group C: received Hevac-B 5 microgram at 2 weeks, 6 weeks, and 10 weeks. Plus HBIG 50 IU at birth and one month of age.
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
100
Notes
B Unclear Lo 1985 CB This trial is the same as Lo 1985 BA, but has been entered with its own identier due to technical limits of RevMan in order to make data comparison.
B Unclear Lolekha 2002 Generation of allocation sequence: unclear - not described. Allocation concealment: unclear - not described. Blinding: not performed. Follow-up: inadequate - not described. Country: Thailand. Publication language: English. Inclusion criteria: HBsAg- and HBeAg-positive mothers. Infant birth weight >= 2000 gram, Apgar score >= 7 at 5 minutes Participants: (1) Group A
Participants
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Notes
Participants
Notes
B Unclear Oon 1986 CD This trial is the same as Oon 1986 EB, but has been entered with its own identier due to technical limits of RevMan in order to make data comparison.
Participants
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Participants
Participants
Notes
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Participants
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Participants
Notes
Participants
Notes
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Participants
Participants
B Unclear Xu 1995 BD This trial is the same as Xu 1995 AB, but has been entered with its own identier due to technical limits of RevMan in order to make data comparison.
B Unclear Xu 1995 CB This trial is the same as Xu 1995 AB, but has been entered with its own identier due to technical limits of RevMan in order to make data comparison.
B Unclear Xu 1995 CD This trial is the same as Xu 1995 AB, but has been entered with its own identier due to technical limits of RevMan in order to make data comparison.
B Unclear Yeoh 1986 Generation of allocation sequence: unclear - not described. Allocation concealment: unclear - not described. Blinding: not performed. Follow-up: inadequate. Country: China. Publication language: English.
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Participants
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Notes
Participants
Participants
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
ADDITIONAL TABLES
20 February 2004
Not obtained
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
EMBASE
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Beasley 1983b
B: HBIG 0.5 ml (145 IU) and PDV 20 microgram at 1 month. Followed by boosters 1 and 6 months later. B: PDV 0.25 ml (5 microgram) at birth and at 6 weeks and 6 months. B: 10 microgram RV-2 at birth and at 1 and 2 months. B: HBIG 0.5 ml/kg body weight and PDV 10 microgram at 3, 4, 5, and 11 months (with diphtheria, pertussis, tetanus, poliomyelitis concomitantly). HBIG 0.5 ml/kg body weight at 3 months. B: PDV 20 microgram at birth and at 1 and 6 months. D: HBIG 260 IU at birth and RV 10 microgram at birth and at 1 and 6 months.
113
Farmer 1987
Halliday 1992
A: RV 20 microgram at birth and at 1 and 6 months. C: HBIG 260 IU at birth and RV 20 microgram at birth and at 1 and 6 months.
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
(Continued )
Control group B: HBIG 100 microgram + 10 microgram RV-2 at birth and Engerix-B at 30 and 180 days. B: PDV 3 microgram at birth and at 1, 2, and 6 months + HBIG 200 IU at birth. D: placebo.
Intervention group A: HBIG 100 microgram + 10 microgram RV-1 at birth and Hepavax at 30 and 180 days. A: PDV 3 microgram at birth and at 1, 2, and 6 months. Also, HBIG 200 IU at birth, and HBIG 100 IU at monthly intervals during the rst 6 months after birth. C: PDV 3 microgram at birth and at 1, 2, and 6 months. A: 20 microgram RV-1 at birth and at 1 and 6 months. A: RV 1 ml at birth and at 1, 2, and 14 months. A: PDV 0.5 ml (2.5 microgram) and HBIG 200 IU at birth and PDV at 1, 2, and 12 months. C: RV 0.5 ml (10 microgram) and HBIG 200 IU at birth and RV at 1, 2, and 12 months. A: HBIG 145 IU at birth + PDV 5 microgram at birth + 10 microgram RV-1 at 1, 2, and 12 months. C: HBIG 145 IU at birth + PDV 5 microgram at birth + 5 microgram RV-2 at 1, 2, and 12 months. E: HBIG 145 IU at birth + PDV 5 microgram at birth and 1 month + 10 microgram RV-1 at 2 and 12 months. G: HBIG 145 IU at birth + PDV 5 microgram at birth and RV-2 at 2 and 6 months. A: PDV 20 microgram at birth and at 1, 2, and 6 months. C: PDV 20 microgram at birth and at 1, 2, and 6 months and HBIG at birth. A: HBIG 50 IU at birth, then PDV 5 microgram at 2, 6, and 10 weeks. C: PDV 5 microgram at 2, 6, and 10 weeks + HBIG 50 IU at birth and 1 month. A: RV 5 microgram at birth and at 1 and 6 months. A: PDV 10 microgram at birth and at 1 and 2 months. C: HBIG 100 IU and PDV 10 microgram at birth and PDV 10 microgram at 1 and 2 months. A: PDV 5 microgram and HBIG 50 IU at birth and PDV at 1 and 2 months. A: 200 IU HBIG-1 at birth + 5 microgram PDV1 at birth and at 1 and 6 months. A: PDV 5 microgram and HBIG 100 IU at birth + PDV at 1, 2, and 12 months. A: RV 5 microgram and HBIG 100 IU at birth and RV at 1, 2, and 12 months. A: RV 10 microgram and HBIG 100 IU at birth and RV 10 microgram at 1 and 6 months. A booster was
B: 20 microgram RV-2 at birth and at 1 and 6 months. B: No vaccines. B: PDV 1 ml (5 microgram) and HBIG 200 IU at birth and PDV at 1, 2, and 12 months.
Lee 1995 *
B: HBIG 145 IU at birth + PDV 5 microgram at birth + PDV 5 microgram at 1, 2, and 12 months. D: HBIG 145 IU at birth + PDV 5 microgram at birth and 1 month + 5 microgram RV-2 at 2 and 12 months. F: HBIG 145 IU at birth + PDV 5 microgram at birth and RV-1 at 2 and 6 months.
Liu 1987
B: placebo (normal saline) at birth and at 1, 2, and 6 months. B: PDV 5 microgram at 2, 6, and 10 weeks.
Lo 1985
B: RV 5 microgram at birth and at 1, 2, and 12 months. B: PDV 5 microgram at birth and at 1 and 2 months. D: HBIG 100 IU and PDV 5 microgram at birth and PDV 5 microgram at 1 and 2 months. B:PDV 5 microgram and HBIG 50 IU at birth and PDV at 2 months. B: 100 IU HBIG-2 at birth + 10 microgram PDV2 at birth and at 1 and 6 months. B:PDV 2 microgram and HBIG 100 IU at birth + PDV at 1, 2, and 12 months. B: PDV 10 microgram and HBIG 100 IU at birth and PDV at 1, 2, and 12 months. B: RV 10 microgram at birth and at 1 and 6 months. A booster was administered at 60 months.
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Piazza 1985 Pongpipat 1986 Pongpipat 1988 Pongpipat 1989 Poovorawan 1997
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
(Continued )
Control group
Sehgal 1992
A: HBIG 0.5 ml and PDV 10 microgram at birth, and PDV at 4 and 8 weeks. A: HBIG 200 IU and PDV 10 microgram at birth and PDV 10 microgram at 1 and 6 months. A: HBIG 200 IU at birth and PDV 5 microgram at the age of 2 days, 1, 2, and 12 months. A: 16 microgram PDV-1 at birth and at 1 and 6 months. C: HBIG 250 IU at birth and 20 microgram PDV2 at birth and at 1 and 6 months. A: HBsAg(+)/ HBeAg(+) mothers (150 infants): HBIG 0.5 ml at birth and PDV 10 microgram at birth and at 1 and 6 months. C: HBsAg(+)/ HBeAg() mothers (150 infants). HBIG 0.5 ml at birth and PDV 10 microgram at birth and at 1 and 6 months. A: 16 microgram vaccine given at birth, 1 and 6 months. A: RV 20 microgram at birth and at 1 and 6 months.
Theppisai 1987
Theppisai 1990
B: HBIG 200 IU at birth and PDV 2 microgram at the age of 2 days, 1, 2, and 12 months. B: 20 microgram PDV-2 at birth and at 1 and 6 months. D: vaccine diluent plus adjuvant at birth and at 1 and 6 months. B: HBsAg(+)/ HBeAg(+) mothers (150 infants): HBIG 0.5 ml at birth and RV 5 microgram at birth and at 1 and 6 months. D: HBsAg(+)/ HBeAg(-) mothers (150 infants). HBIG 0.5 ml at birth and RV 5 microgram at birth and at 1 and 6 months. B: buffer of HBV given at birth, 1 and 6 months
Xu 1995
Yeoh 1986
Zhu 1987
Zhu 1994
ANALYSES
Outcome title 01 Hepatitis B events according to type of vaccine 02 Hepatitis B events according to methodological quality 03 Hepatitis B events - Sensitivity analyses 04 Hepatitis B events according to the mothers HBeAg status 05 Hepatitis B events according to rst time of vaccine administration
Statistical method Relative Risk (Fixed) 95% CI Relative Risk (Fixed) 95% CI Relative Risk (Fixed) 95% CI
Effect size 0.28 [0.20, 0.40] 0.28 [0.20, 0.40] Subtotals only 0.29 [0.20, 0.41] 0.28 [0.20, 0.40]
7 5
403 403
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Outcome title 01 Hepatitis B events 02 Hepatitis B events according to methodological quality 03 Hepatitis B events - sensitivity analyses 04 Hepatitis B events according to the mothers HBeAg status 05 Anti-HBs less than 10 IU/L
Statistical method Relative Risk (Fixed) 95% CI Relative Risk (Fixed) 95% CI Relative Risk (Fixed) 95% CI
Effect size 1.00 [0.70, 1.42] 1.00 [0.70, 1.42] Subtotals only 1.00 [0.70, 1.42] 0.51 [0.36, 0.72]
5 4
382 256
Outcome title 01 Hepatitis B events 02 Hepatitis B events according to methodological quality 03 Hepatitis B events - sensitivity analyses 04 Hepatitis B events according to the mothers HBeAg status 05 Anti-HBs less than 10 IU/L
Statistical method Relative Risk (Fixed) 95% CI Relative Risk (Fixed) 95% CI Relative Risk (Fixed) 95% CI
Effect size 0.91 [0.57, 1.46] 0.91 [0.57, 1.46] Subtotals only 0.91 [0.57, 1.46] 1.02 [0.82, 1.27]
5 2
582 166
Comparison 04. Three-dose PDV plus HBIG versus two-dose PDV plus HBIG
No. of studies 1 1 No. of participants 74 74
Statistical method Relative Risk (Fixed) 95% CI Relative Risk (Fixed) 95% CI
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Comparison 08. One type of RV versus another type of RV with the same vaccination schedule
Outcome title 01 Hepatitis B events 02 Anti-HBs less than 10 IU/L No. of studies No. of participants Statistical method Relative Risk (Fixed) 95% CI Relative Risk (Fixed) 95% CI Effect size Subtotals only Subtotals only
Relative Risk (Fixed) 95% CI 15 14 9 1086 1086 711 Relative Risk (Fixed) 95% CI Relative Risk (Fixed) 95% CI Relative Risk (Fixed) 95% CI
Subtotals only 0.52 [0.44, 0.63] 0.52 [0.44, 0.63] 0.53 [0.39, 0.74]
4 1
348 136
Relative Risk (Fixed) 95% CI Weighted Mean Difference (Fixed) 95% CI Relative Risk (Fixed) 95% CI
Comparison 10. Multiple HBIG plus PDV versus single HBIG plus PDV
Outcome title 01 Hepatitis B events No. of studies 2 No. of participants 198 Statistical method Relative Risk (Fixed) 95% CI Effect size 0.87 [0.30, 2.47]
Subtotals only
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Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
04 Hepatitis B events according to mothers HBeAg status 05 Hepatitis B events according to time of HBIG administration 06 Adverse events
5 4 2
Relative Risk (Fixed) 95% CI Relative Risk (Fixed) 95% CI Relative Risk (Fixed) 95% CI
INDEX TERMS Medical Subject Headings (MeSH) Hepatitis B [immunology; prevention & control]; Hepatitis B Antibodies [ therapeutic use]; Hepatitis B e Antigens [ blood]; Hepatitis B Vaccines [ therapeutic use]; Infant, Newborn; Randomized Controlled Trials MeSH check words Female; Humans
COVER SHEET Title Authors Contribution of author(s) Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers Lee C, Gong Y, Brok J, Boxall EH, Gluud C CL developed the search strategy, identied trials, extracted data, carried out the statistical analyses, and drafted parts of the review. YG extracted data, carried out the statistical analyses, drafted parts of the review, and revised the review. YG is the guarantor. JB validated the assessment of methodological quality of the included trials, validated data from six randomly selected trials, drafted parts of the review, and revised the review. EHB has research experience in this topic. She provided trials for this review, validated data extraction, and revised the review. CG coordinated the review, functioned as an adjudicator in cases of disagreement, drafted parts of the review, and revised the review. 2004/2 2006/2 22 February 2006 22 February 2006 Information not supplied by author Information not supplied by author Information not supplied by author 01 February 2004 Information not supplied by author Dr Yan Gong Copenhagen Trial Unit
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Issue protocol rst published Review rst published Date of most recent amendment Date of most recent SUBSTANTIVE amendment Whats New Date new studies sought but none found Date new studies found but not yet included/excluded Date new studies found and included/excluded Date authors conclusions section amended Contact address
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Centre for Clinical Intervention Research, Copenhagen University Hospital Dept. 7102, Blegdamsvej 9 H:S Rigshospitalet Copenhagen DK-2100 DENMARK E-mail: [email protected] Tel: +45 3545 7161 Fax: +45 3545 7101 DOI Cochrane Library number Editorial group Editorial group code 10.1002/14651858.CD004790.pub2 CD004790 Cochrane Hepato-Biliary Group HM-LIVER GRAPHS AND OTHER TABLES
Analysis 01.01.
Review:
Comparison 01 Vaccine versus placebo or no intervention, Outcome 01 Hepatitis B events according to type of vaccine
Comparison: 01 Vaccine versus placebo or no intervention Outcome: 01 Hepatitis B events according to type of vaccine Study Vaccine n/N 01 PDV versus placebo or no intervention Ip 1989 CD Liu 1987 AB Xu 1995 AD Xu 1995 BD Subtotal (95% CI) 7/35 3/27 7/60 14/60 182 23/34 21/26 12/30 12/30 120 26.2 24.0 17.9 17.9 86.0 0.30 [ 0.15, 0.60 ] 0.14 [ 0.05, 0.41 ] 0.29 [ 0.13, 0.66 ] 0.58 [ 0.31, 1.10 ] 0.31 [ 0.21, 0.45 ] Control n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
Total events: 31 (Vaccine), 68 (Control) Test for heterogeneity chi-square=6.00 df=3 p=0.11 I?? =50.0% Test for overall effect z=6.03 02 RV versus no intervention Khukhlovich 1996 Subtotal (95% CI) 2/70 70 9/31 31 14.0 14.0 0.10 [ 0.02, 0.43 ] 0.10 [ 0.02, 0.43 ] p<0.00001
Total events: 2 (Vaccine), 9 (Control) Test for heterogeneity: not applicable Test for overall effect z=3.09 Total (95% CI) p=0.002 252 151
0.01 0.1 1 10 100
100.0
Vaccine better
Control better
(Continued . . . )
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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(. . .
Study Vaccine n/N Total events: 33 (Vaccine), 77 (Control) Test for heterogeneity chi-square=8.74 df=4 p=0.07 I?? =54.2% Test for overall effect z=6.83 p<0.00001 Control n/N Relative Risk (Fixed) 95% CI Weight (%)
Continued )
0.01
0.1
10
100
Vaccine better
Control better
Analysis 01.02.
Review:
Comparison 01 Vaccine versus placebo or no intervention, Outcome 02 Hepatitis B events according to methodological quality
Comparison: 01 Vaccine versus placebo or no intervention Outcome: 02 Hepatitis B events according to methodological quality Study Vaccine n/N 01 High-quality trials Ip 1989 CD Liu 1987 AB Subtotal (95% CI) 7/35 3/27 62 23/34 21/26 60 26.2 24.0 50.1 0.30 [ 0.15, 0.60 ] 0.14 [ 0.05, 0.41 ] 0.22 [ 0.12, 0.40 ] Control n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
Total events: 10 (Vaccine), 44 (Control) Test for heterogeneity chi-square=1.40 df=1 p=0.24 I?? =28.7% Test for overall effect z=5.03 02 Low-quality trials Khukhlovich 1996 Xu 1995 AD Xu 1995 BD Subtotal (95% CI) 2/70 7/60 14/60 190 9/31 12/30 12/30 91 14.0 17.9 17.9 49.9 0.10 [ 0.02, 0.43 ] 0.29 [ 0.13, 0.66 ] 0.58 [ 0.31, 1.10 ] 0.34 [ 0.22, 0.54 ] p<0.00001
Total events: 23 (Vaccine), 33 (Control) Test for heterogeneity chi-square=5.61 df=2 p=0.06 I?? =64.3% Test for overall effect z=4.56 Total (95% CI) p<0.00001 252 151 100.0 0.28 [ 0.20, 0.40 ]
Total events: 33 (Vaccine), 77 (Control) Test for heterogeneity chi-square=8.74 df=4 p=0.07 I?? =54.2% Test for overall effect z=6.83 p<0.00001
0.01
0.1
10
100
Vaccine better
Control better
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Analysis 01.03.
Review:
Comparison 01 Vaccine versus placebo or no intervention, Outcome 03 Hepatitis B events Sensitivity analyses
Comparison: 01 Vaccine versus placebo or no intervention Outcome: 03 Hepatitis B events - Sensitivity analyses Study Vaccine n/N 01 Available patients course analysis Ip 1989 CD Khukhlovich 1996 Liu 1987 AB Xu 1995 AD Xu 1995 BD Subtotal (95% CI) 7/35 2/70 3/27 2/55 10/56 243 23/34 9/31 21/26 9/27 10/28 146 28.2 15.1 25.9 14.6 16.1 100.0 0.30 [ 0.15, 0.60 ] 0.10 [ 0.02, 0.43 ] 0.14 [ 0.05, 0.41 ] 0.11 [ 0.03, 0.47 ] 0.50 [ 0.24, 1.06 ] 0.23 [ 0.15, 0.35 ] Control n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
Total events: 24 (Vaccine), 72 (Control) Test for heterogeneity chi-square=7.74 df=4 p=0.10 I?? =48.3% Test for overall effect z=6.94 02 Assuming poor outcome Ip 1989 CD Khukhlovich 1996 Liu 1987 AB Xu 1995 AD Xu 1995 BD Subtotal (95% CI) 7/35 2/70 3/27 7/60 14/60 252 23/34 9/31 21/26 12/30 12/30 151 26.2 14.0 24.0 17.9 17.9 100.0 0.30 [ 0.15, 0.60 ] 0.10 [ 0.02, 0.43 ] 0.14 [ 0.05, 0.41 ] 0.29 [ 0.13, 0.66 ] 0.58 [ 0.31, 1.10 ] 0.28 [ 0.20, 0.40 ] p<0.00001
Total events: 33 (Vaccine), 77 (Control) Test for heterogeneity chi-square=8.74 df=4 p=0.07 I?? =54.2% Test for overall effect z=6.83 03 Assuming good outcome Ip 1989 CD Khukhlovich 1996 Liu 1987 AB Xu 1995 AD Xu 1995 BD Subtotal (95% CI) 7/35 2/70 3/27 2/60 10/60 252 23/34 9/31 21/26 9/30 10/30 151 28.3 15.1 25.9 14.5 16.2 100.0 0.30 [ 0.15, 0.60 ] 0.10 [ 0.02, 0.43 ] 0.14 [ 0.05, 0.41 ] 0.11 [ 0.03, 0.48 ] 0.50 [ 0.23, 1.07 ] 0.23 [ 0.15, 0.35 ] p<0.00001
Total events: 24 (Vaccine), 72 (Control) Test for heterogeneity chi-square=7.57 df=4 p=0.11 I?? =47.2% Test for overall effect z=6.91 p<0.00001
0.01
0.1
10
100
Vaccine better
Control better
(Continued . . . )
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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(. . .
Study Vaccine n/N 04 Extreme case favouring vaccine Ip 1989 CD Khukhlovich 1996 Liu 1987 AB Xu 1995 AD Xu 1995 BD Subtotal (95% CI) 7/35 2/70 3/27 2/60 10/60 252 23/34 9/31 21/26 12/30 12/30 151 26.2 14.0 24.0 17.9 17.9 100.0 Control n/N Relative Risk (Fixed) 95% CI Weight (%)
Continued )
0.30 [ 0.15, 0.60 ] 0.10 [ 0.02, 0.43 ] 0.14 [ 0.05, 0.41 ] 0.08 [ 0.02, 0.35 ] 0.42 [ 0.20, 0.85 ] 0.21 [ 0.14, 0.32 ]
Total events: 24 (Vaccine), 77 (Control) Test for heterogeneity chi-square=7.53 df=4 p=0.11 I?? =46.8% Test for overall effect z=7.39 p<0.00001
05 Extreme case favouring control Ip 1989 CD Khukhlovich 1996 Liu 1987 AB Xu 1995 AD Xu 1995 BD Subtotal (95% CI) 7/35 2/70 3/27 7/60 14/60 252 23/34 9/31 21/26 9/30 10/30 151 28.3 15.1 25.9 14.5 16.2 100.0 0.30 [ 0.15, 0.60 ] 0.10 [ 0.02, 0.43 ] 0.14 [ 0.05, 0.41 ] 0.39 [ 0.16, 0.94 ] 0.70 [ 0.35, 1.39 ] 0.30 [ 0.21, 0.44 ]
Total events: 33 (Vaccine), 72 (Control) Test for heterogeneity chi-square=10.35 df=4 p=0.03 I?? =61.4% Test for overall effect z=6.26 p<0.00001
0.01
0.1
10
100
Vaccine better
Control better
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Analysis 01.04.
Review:
Comparison 01 Vaccine versus placebo or no intervention, Outcome 04 Hepatitis B events according to the mothers HBeAg status
Comparison: 01 Vaccine versus placebo or no intervention Outcome: 04 Hepatitis B events according to the mothers HBeAg status Study Vaccine n/N 01 HBeAg positive Ip 1989 CD Liu 1987 AB Xu 1995 AD Xu 1995 BD Subtotal (95% CI) 7/35 3/27 5/30 9/29 121 23/34 21/26 10/15 11/16 91 26.3 24.1 15.0 16.0 81.4 0.30 [ 0.15, 0.60 ] 0.14 [ 0.05, 0.41 ] 0.25 [ 0.10, 0.60 ] 0.45 [ 0.24, 0.85 ] 0.27 [ 0.18, 0.40 ] Control n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
Total events: 24 (Vaccine), 65 (Control) Test for heterogeneity chi-square=4.08 df=3 p=0.25 I?? =26.4% Test for overall effect z=6.43 02 HBeAg unknown Khukhlovich 1996 Subtotal (95% CI) 2/70 70 9/31 31 14.1 14.1 0.10 [ 0.02, 0.43 ] 0.10 [ 0.02, 0.43 ] p<0.00001
Total events: 2 (Vaccine), 9 (Control) Test for heterogeneity: not applicable Test for overall effect z=3.09 03 HBeAg negative Xu 1995 AD Xu 1995 BD Subtotal (95% CI) 2/30 5/31 61 1/14 2/15 29 1.5 3.0 4.6 0.93 [ 0.09, 9.45 ] 1.21 [ 0.26, 5.53 ] 1.12 [ 0.31, 3.97 ] p=0.002
Total events: 7 (Vaccine), 3 (Control) Test for heterogeneity chi-square=0.03 df=1 p=0.85 I?? =0.0% Test for overall effect z=0.17 Total (95% CI) p=0.9 252 151 100.0 0.29 [ 0.20, 0.41 ]
Total events: 33 (Vaccine), 77 (Control) Test for heterogeneity chi-square=10.33 df=6 p=0.11 I?? =41.9% Test for overall effect z=6.88 p<0.00001
0.01
0.1
10
100
Vaccine better
Control better
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Analysis 01.05.
Review:
Comparison 01 Vaccine versus placebo or no intervention, Outcome 05 Hepatitis B events according to rst time of vaccine administration
Comparison: 01 Vaccine versus placebo or no intervention Outcome: 05 Hepatitis B events according to rst time of vaccine administration Study Vaccine n/N 01 Vaccine administered within 12 hours of birth Ip 1989 CD Khukhlovich 1996 Subtotal (95% CI) 7/35 2/70 105 23/34 9/31 65 26.2 14.0 40.1 0.30 [ 0.15, 0.60 ] 0.10 [ 0.02, 0.43 ] 0.23 [ 0.12, 0.42 ] Control n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
Total events: 9 (Vaccine), 32 (Control) Test for heterogeneity chi-square=1.78 df=1 p=0.18 I?? =43.9% Test for overall effect z=4.67 p<0.00001
02 Vaccine administered within 24 hours of birth Xu 1995 AD Xu 1995 BD Subtotal (95% CI) 7/60 14/60 120 12/30 12/30 60 17.9 17.9 35.9 0.29 [ 0.13, 0.66 ] 0.58 [ 0.31, 1.10 ] 0.44 [ 0.27, 0.72 ]
Total events: 21 (Vaccine), 24 (Control) Test for heterogeneity chi-square=1.72 df=1 p=0.19 I?? =42.0% Test for overall effect z=3.26 p=0.001
03 Vaccine administered within 48 hours of birth Liu 1987 AB Subtotal (95% CI) 3/27 27 21/26 26 24.0 24.0 0.14 [ 0.05, 0.41 ] 0.14 [ 0.05, 0.41 ]
Total events: 3 (Vaccine), 21 (Control) Test for heterogeneity: not applicable Test for overall effect z=3.59 Total (95% CI) p=0.0003 252 151 100.0 0.28 [ 0.20, 0.40 ]
Total events: 33 (Vaccine), 77 (Control) Test for heterogeneity chi-square=8.74 df=4 p=0.07 I?? =54.2% Test for overall effect z=6.83 p<0.00001
0.01
0.1
10
100
Vaccine better
Control better
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Analysis 02.01.
Review: Comparison: 02 RV versus PDV Outcome: 01 Hepatitis B events Study RV n/N 01 RV versus PDV Halliday 1992 AB Zhu 1994 Subtotal (95% CI) Total events: 30 (RV), 39 (PDV) 13/55 17/54 109
PDV n/N
Weight (%)
Test for heterogeneity chi-square=0.04 df=1 p=0.85 I?? =0.0% Test for overall effect z=1.41 p=0.2
02 RV plus HBIG versus PDV plus HBIG Lee 1995 AB Lee 1995 CB Pongpipat 1989 Subtotal (95% CI) Total events: 34 (RV), 5 (PDV) Test for heterogeneity chi-square=0.09 df=2 p=0.96 I?? =0.0% Test for overall effect z=1.90 Total (95% CI) Total events: 64 (RV), 44 (PDV) Test for heterogeneity chi-square=5.67 df=4 p=0.23 I?? =29.4% Test for overall effect z=0.02 p=1 p=0.06 227 155 100.0 1.00 [ 0.70, 1.42 ] 15/51 16/47 3/20 118 2/14 2/14 1/20 48 6.7 6.6 2.1 15.5 2.06 [ 0.53, 7.96 ] 2.38 [ 0.62, 9.13 ] 3.00 [ 0.34, 26.45 ] 2.33 [ 0.97, 5.56 ]
0.01
0.1 RV better
10
100
PDV better
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Analysis 02.02.
Review:
Comparison: 02 RV versus PDV Outcome: 02 Hepatitis B events according to methodological quality Study RV n/N 01 High-quality trials Halliday 1992 AB Subtotal (95% CI) Total events: 13 (RV), 18 (PDV) Test for heterogeneity: not applicable Test for overall effect z=1.05 02 Low-quality trials Lee 1995 AB Lee 1995 CB Pongpipat 1989 Zhu 1994 Subtotal (95% CI) Total events: 51 (RV), 26 (PDV) Test for heterogeneity chi-square=4.87 df=3 p=0.18 I?? =38.4% Test for overall effect z=0.70 Total (95% CI) Total events: 64 (RV), 44 (PDV) Test for heterogeneity chi-square=5.67 df=4 p=0.23 I?? =29.4% Test for overall effect z=0.02 p=1 p=0.5 227 155 100.0 1.00 [ 0.70, 1.42 ] 15/51 16/47 3/20 17/54 172 2/14 2/14 1/20 21/52 100 6.7 6.6 2.1 45.9 61.4 2.06 [ 0.53, 7.96 ] 2.38 [ 0.62, 9.13 ] 3.00 [ 0.34, 26.45 ] 0.78 [ 0.47, 1.30 ] 1.17 [ 0.75, 1.82 ] p=0.3 13/55 55 18/55 55 38.6 38.6 0.72 [ 0.39, 1.33 ] 0.72 [ 0.39, 1.33 ] PDV n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
0.01
0.1 RV better
10
100
PDV better
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Analysis 02.03.
Review:
Comparison: 02 RV versus PDV Outcome: 03 Hepatitis B events - sensitivity analyses Study RV n/N 01 Available patients course analysis Halliday 1992 AB Lee 1995 AB Lee 1995 CB Pongpipat 1989 Zhu 1994 Subtotal (95% CI) Total events: 17 (RV), 26 (PDV) Test for heterogeneity chi-square=2.20 df=4 p=0.70 I?? =0.0% Test for overall effect z=2.13 02 Assuming poor outcome Halliday 1992 AB Lee 1995 AB Lee 1995 CB Pongpipat 1989 Zhu 1994 Subtotal (95% CI) Total events: 64 (RV), 44 (PDV) Test for heterogeneity chi-square=5.67 df=4 p=0.23 I?? =29.4% Test for overall effect z=0.02 03 Assuming good outcome Halliday 1992 AB Lee 1995 AB Lee 1995 CB Pongpipat 1989 Zhu 1994 Subtotal (95% CI) Total events: 17 (RV), 26 (PDV) Test for heterogeneity chi-square=2.60 df=4 p=0.63 I?? =0.0% Test for overall effect z=2.34 p=0.02 4/55 2/51 3/47 2/20 6/54 227 12/55 2/14 2/14 1/20 9/52 155 42.3 11.1 10.9 3.5 32.3 100.0 0.33 [ 0.11, 0.97 ] 0.27 [ 0.04, 1.78 ] 0.45 [ 0.08, 2.41 ] 2.00 [ 0.20, 20.33 ] 0.64 [ 0.25, 1.68 ] 0.50 [ 0.28, 0.89 ] p=1 13/55 15/51 16/47 3/20 17/54 227 18/55 2/14 2/14 1/20 21/52 155 38.6 6.7 6.6 2.1 45.9 100.0 0.72 [ 0.39, 1.33 ] 2.06 [ 0.53, 7.96 ] 2.38 [ 0.62, 9.13 ] 3.00 [ 0.34, 26.45 ] 0.78 [ 0.47, 1.30 ] 1.00 [ 0.70, 1.42 ] p=0.03 4/46 2/38 3/34 2/19 6/43 180 12/49 2/14 2/14 1/20 9/40 137 42.0 10.6 10.2 3.5 33.7 100.0 0.36 [ 0.12, 1.02 ] 0.37 [ 0.06, 2.37 ] 0.62 [ 0.12, 3.31 ] 2.11 [ 0.21, 21.36 ] 0.62 [ 0.24, 1.59 ] 0.53 [ 0.30, 0.95 ] PDV n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
0.01
0.1 RV better
10
100
PDV better
(Continued . . . )
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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(. . .
Study RV n/N 04 Extreme case favouring RV Halliday 1992 AB Lee 1995 AB Lee 1995 CB Pongpipat 1989 Zhu 1994 Subtotal (95% CI) Total events: 17 (RV), 44 (PDV) Test for heterogeneity chi-square=3.17 df=4 p=0.53 I?? =0.0% Test for overall effect z=4.33 p=0.00001 4/55 2/51 3/47 2/20 6/54 227 18/55 2/14 2/14 1/20 21/52 155 38.6 6.7 6.6 2.1 45.9 100.0 PDV n/N Relative Risk (Fixed) 95% CI Weight (%)
Continued )
0.22 [ 0.08, 0.61 ] 0.27 [ 0.04, 1.78 ] 0.45 [ 0.08, 2.41 ] 2.00 [ 0.20, 20.33 ] 0.28 [ 0.12, 0.63 ] 0.30 [ 0.18, 0.52 ]
05 Extreme case favouring PDV Halliday 1992 AB Lee 1995 AB Lee 1995 CB Pongpipat 1989 Zhu 1994 Subtotal (95% CI) Total events: 64 (RV), 26 (PDV) Test for heterogeneity chi-square=2.17 df=4 p=0.70 I?? =0.0% Test for overall effect z=2.25 p=0.02 13/55 15/51 16/47 3/20 17/54 227 12/55 2/14 2/14 1/20 9/52 155 42.3 11.1 10.9 3.5 32.3 100.0 1.08 [ 0.54, 2.16 ] 2.06 [ 0.53, 7.96 ] 2.38 [ 0.62, 9.13 ] 3.00 [ 0.34, 26.45 ] 1.82 [ 0.89, 3.71 ] 1.64 [ 1.07, 2.52 ]
0.01
0.1 RV better
10
100
PDV better
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
128
Analysis 02.04.
Review:
Comparison 02 RV versus PDV, Outcome 04 Hepatitis B events according to the mothers HBeAg status
Comparison: 02 RV versus PDV Outcome: 04 Hepatitis B events according to the mothers HBeAg status Study RV n/N 01 HBeAg positive Lee 1995 AB Lee 1995 CB Pongpipat 1989 Zhu 1994 Subtotal (95% CI) Total events: 51 (RV), 26 (PDV) Test for heterogeneity chi-square=4.87 df=3 p=0.18 I?? =38.4% Test for overall effect z=0.70 02 HBeAg unknown Halliday 1992 AB Subtotal (95% CI) Total events: 13 (RV), 18 (PDV) Test for heterogeneity: not applicable Test for overall effect z=1.05 03 HBeAg negative Subtotal (95% CI) Total events: 0 (RV), 0 (PDV) Test for heterogeneity: not applicable Test for overall effect: not applicable Total (95% CI) Total events: 64 (RV), 44 (PDV) Test for heterogeneity chi-square=5.67 df=4 p=0.23 I?? =29.4% Test for overall effect z=0.02 p=1 227 155 100.0 1.00 [ 0.70, 1.42 ] 0 0 0.0 Not estimable p=0.3 13/55 55 18/55 55 38.6 38.6 0.72 [ 0.39, 1.33 ] 0.72 [ 0.39, 1.33 ] p=0.5 15/51 16/47 3/20 17/54 172 2/14 2/14 1/20 21/52 100 6.7 6.6 2.1 45.9 61.4 2.06 [ 0.53, 7.96 ] 2.38 [ 0.62, 9.13 ] 3.00 [ 0.34, 26.45 ] 0.78 [ 0.47, 1.30 ] 1.17 [ 0.75, 1.82 ] PDV n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
0.01
0.1 RV better
10
100
PDV better
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
129
Analysis 02.05.
Review: Comparison: 02 RV versus PDV
Outcome: 05 Anti-HBs less than 10 IU/L Study RV n/N Halliday 1992 AB x Kuru 1995 AC Kuru 1995 BC Zhu 1994 Total (95% CI) Total events: 25 (RV), 50 (PDV) Test for heterogeneity chi-square=1.17 df=2 p=0.56 I?? =0.0% Test for overall effect z=3.81 p=0.0001 6/46 0/5 0/6 19/43 100 PDV n/N 16/49 0/25 1/42 33/40 156 Relative Risk (Fixed) 95% CI Weight (%) 30.9 0.0 0.8 68.2 100.0 Relative Risk (Fixed) 95% CI 0.40 [ 0.17, 0.93 ] Not estimable 2.05 [ 0.09, 45.42 ] 0.54 [ 0.37, 0.77 ] 0.51 [ 0.36, 0.72 ]
0.01
0.1 RV better
10
100
PDV better
Analysis 03.01.
Review:
Comparison: 03 High-dose versus low-dose vaccine Outcome: 01 Hepatitis B events Study High dose n/N 01 High-dose PDV versus low-dose PDV x Oon 1986 AB Subtotal (95% CI) 0/141 141 0/102 102 0.0 0.0 Not estimable Not estimable Low dose n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
Total events: 0 (High dose), 0 (Low dose) Test for heterogeneity: not applicable Test for overall effect: not applicable 02 High-dose PDV plus HBIG versus low-dose PDV plus HBIG Oon 1986 CD Pongpipat 1988 Theppisai 1990 Subtotal (95% CI) 10/70 3/20 8/30 120 10/59 6/20 4/30 109 36.4 20.1 13.4 69.9 0.84 [ 0.38, 1.89 ] 0.50 [ 0.14, 1.73 ] 2.00 [ 0.67, 5.94 ] 0.97 [ 0.55, 1.68 ]
Total events: 21 (High dose), 20 (Low dose) Test for heterogeneity chi-square=2.91 df=2 p=0.23 I?? =31.3% Test for overall effect z=0.12 p=0.9
0.01
0.1
10
100
(Continued . . . )
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
130
(. . .
Study High dose Low dose Relative
Continued )
(. . .
Study High-dose vaccine n/N Total events: 28 (High-dose vaccine), 29 (Low-dose vaccine) Test for heterogeneity chi-square=3.06 df=3 p=0.38 I?? =1.8% Test for overall effect z=0.39 p=0.7 Low-dose vaccine n/N Relative Risk (Fixed) 95% CI Weight (%)
Continued )
0.01
0.1
10
100
Analysis 03.03.
Review:
Comparison 03 High-dose versus low-dose vaccine, Outcome 03 Hepatitis B events sensitivity analyses
Comparison: 03 High-dose versus low-dose vaccine Outcome: 03 Hepatitis B events - sensitivity analyses Study High-dose vaccine n/N 01 Available patients course analysis Halliday 1992 DC x Oon 1986 AB Oon 1986 CD Pongpipat 1988 Theppisai 1990 Subtotal (95% CI) 2/50 0/141 10/70 1/18 2/24 303 3/49 0/102 10/59 1/15 2/28 253 18.0 0.0 64.5 6.5 11.0 100.0 0.65 [ 0.11, 3.74 ] Not estimable 0.84 [ 0.38, 1.89 ] 0.83 [ 0.06, 12.22 ] 1.17 [ 0.18, 7.67 ] 0.84 [ 0.44, 1.63 ] Low-dose vaccine n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
Total events: 15 (High-dose vaccine), 16 (Low-dose vaccine) Test for heterogeneity chi-square=0.20 df=3 p=0.98 I?? =0.0% Test for overall effect z=0.51 02 Assuming poor oucome Halliday 1992 DC x Oon 1986 AB Oon 1986 CD Pongpipat 1988 Theppisai 1990 Subtotal (95% CI) 7/55 0/141 10/70 3/20 8/30 316 9/55 0/102 10/59 6/20 4/30 266 30.1 0.0 36.4 20.1 13.4 100.0 0.78 [ 0.31, 1.94 ] Not estimable 0.84 [ 0.38, 1.89 ] 0.50 [ 0.14, 1.73 ] 2.00 [ 0.67, 5.94 ] 0.91 [ 0.57, 1.46 ] p=0.6
Total events: 28 (High-dose vaccine), 29 (Low-dose vaccine) Test for heterogeneity chi-square=3.06 df=3 p=0.38 I?? =1.8% Test for overall effect z=0.39 03 Assuming good outcome p=0.7
0.01
0.1
10
100
(Continued . . . )
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(. . .
Study High-dose vaccine n/N Halliday 1992 DC x Oon 1986 AB Oon 1986 CD Pongpipat 1988 Theppisai 1990 Subtotal (95% CI) 2/55 0/141 10/70 1/20 2/30 316 3/55 0/102 10/59 1/20 2/30 266 Low-dose vaccine n/N Relative Risk (Fixed) 95% CI Weight (%) 17.8 0.0 64.4 5.9 11.9 100.0
Continued )
Relative Risk (Fixed) 95% CI 0.67 [ 0.12, 3.84 ] Not estimable 0.84 [ 0.38, 1.89 ] 1.00 [ 0.07, 14.90 ] 1.00 [ 0.15, 6.64 ] 0.84 [ 0.43, 1.63 ]
Total events: 15 (High-dose vaccine), 16 (Low-dose vaccine) Test for heterogeneity chi-square=0.12 df=3 p=0.99 I?? =0.0% Test for overall effect z=0.52 p=0.6
04 Extreme case favouring high-dose vaccine Halliday 1992 DC x Oon 1986 AB Oon 1986 CD Pongpipat 1988 Theppisai 1990 Subtotal (95% CI) 2/55 0/141 10/70 1/20 8/30 316 9/55 0/102 10/59 6/20 2/30 266 32.3 0.0 39.0 21.5 7.2 100.0 0.22 [ 0.05, 0.98 ] Not estimable 0.84 [ 0.38, 1.89 ] 0.17 [ 0.02, 1.26 ] 4.00 [ 0.92, 17.30 ] 0.72 [ 0.42, 1.24 ]
Total events: 21 (High-dose vaccine), 27 (Low-dose vaccine) Test for heterogeneity chi-square=9.82 df=3 p=0.02 I?? =69.5% Test for overall effect z=1.18 p=0.2
05 Extreme case favouring low-dose vaccine Halliday 1992 DC x Oon 1986 AB Oon 1986 CD Pongpipat 1988 Theppisai 1990 Subtotal (95% CI) 7/55 0/141 10/70 3/20 8/30 316 3/55 0/102 10/59 1/20 4/30 266 15.9 0.0 57.6 5.3 21.2 100.0 2.33 [ 0.64, 8.56 ] Not estimable 0.84 [ 0.38, 1.89 ] 3.00 [ 0.34, 26.45 ] 2.00 [ 0.67, 5.94 ] 1.44 [ 0.84, 2.48 ]
Total events: 28 (High-dose vaccine), 18 (Low-dose vaccine) Test for heterogeneity chi-square=3.02 df=3 p=0.39 I?? =0.5% Test for overall effect z=1.31 p=0.2
0.01
0.1
10
100
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
133
Analysis 03.04.
Review:
Comparison 03 High-dose versus low-dose vaccine, Outcome 04 Hepatitis B events according to the mothers HBeAg status
Comparison: 03 High-dose versus low-dose vaccine Outcome: 04 Hepatitis B events according to the mothers HBeAg status Study High-dose vaccine n/N 01 HBeAg positive Oon 1986 CD Pongpipat 1988 Theppisai 1990 Subtotal (95% CI) 10/70 3/20 8/30 120 10/59 6/20 4/30 109 36.4 20.1 13.4 69.9 0.84 [ 0.38, 1.89 ] 0.50 [ 0.14, 1.73 ] 2.00 [ 0.67, 5.94 ] 0.97 [ 0.55, 1.68 ] Low-dose vaccine n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
Total events: 21 (High-dose vaccine), 20 (Low-dose vaccine) Test for heterogeneity chi-square=2.91 df=2 p=0.23 I?? =31.3% Test for overall effect z=0.12 02 HBeAg unknown Halliday 1992 DC Subtotal (95% CI) 7/55 55 9/55 55 30.1 30.1 0.78 [ 0.31, 1.94 ] 0.78 [ 0.31, 1.94 ] p=0.9
Total events: 7 (High-dose vaccine), 9 (Low-dose vaccine) Test for heterogeneity: not applicable Test for overall effect z=0.54 03 HBeAg negative x Oon 1986 AB Subtotal (95% CI) 0/102 102 0/141 141 0.0 0.0 Not estimable Not estimable p=0.6
Total events: 0 (High-dose vaccine), 0 (Low-dose vaccine) Test for heterogeneity: not applicable Test for overall effect: not applicable Total (95% CI) 277 305 100.0 0.91 [ 0.57, 1.46 ] Total events: 28 (High-dose vaccine), 29 (Low-dose vaccine) Test for heterogeneity chi-square=3.06 df=3 p=0.38 I?? =1.8% Test for overall effect z=0.39 p=0.7
0.01
0.1
10
100
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
134
Analysis 03.05.
Review:
Comparison 03 High-dose versus low-dose vaccine, Outcome 05 Anti-HBs less than 10 IU/L
Comparison: 03 High-dose versus low-dose vaccine Outcome: 05 Anti-HBs less than 10 IU/L Study High-dose vaccine n/N 01 High dose PDV versus low dose PDV Kuru 1995 AB Subtotal (95% CI) 1/42 42 0/25 25 1.6 1.6 1.81 [ 0.08, 42.90 ] 1.81 [ 0.08, 42.90 ] Low-dose vaccine n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
Total events: 1 (High-dose vaccine), 0 (Low-dose vaccine) Test for heterogeneity: not applicable Test for overall effect z=0.37 p=0.7
02 High dose RV versus low dose RV Halliday 1992 DC Subtotal (95% CI) 39/50 50 38/49 49 98.4 98.4 1.01 [ 0.81, 1.24 ] 1.01 [ 0.81, 1.24 ]
Total events: 39 (High-dose vaccine), 38 (Low-dose vaccine) Test for heterogeneity: not applicable Test for overall effect z=0.05 Total (95% CI) p=1 92 74 100.0 1.02 [ 0.82, 1.27 ]
Total events: 40 (High-dose vaccine), 38 (Low-dose vaccine) Test for heterogeneity chi-square=0.14 df=1 p=0.71 I?? =0.0% Test for overall effect z=0.17 p=0.9
Analysis 04.01.
Review:
Comparison 04 Three-dose PDV plus HBIG versus two-dose PDV plus HBIG, Outcome 01 Hepatitis B events
Comparison: 04 Three-dose PDV plus HBIG versus two-dose PDV plus HBIG Outcome: 01 Hepatitis B events Study Three doses n/N Piazza 1985 Total (95% CI) 1/37 37 Two doses n/N 2/37 37 Relative Risk (Fixed) 95% CI Weight (%) 100.0 100.0 Relative Risk (Fixed) 95% CI 0.50 [ 0.05, 5.28 ] 0.50 [ 0.05, 5.28 ]
Total events: 1 (Three doses), 2 (Two doses) Test for heterogeneity: not applicable Test for overall effect z=0.58 p=0.6
0.01
0.1
10
100
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Analysis 04.02.
Review:
Comparison 04 Three-dose PDV plus HBIG versus two-dose PDV plus HBIG, Outcome 02 Anti-HBs less than 10 IU/L
Comparison: 04 Three-dose PDV plus HBIG versus two-dose PDV plus HBIG Outcome: 02 Anti-HBs less than 10 IU/L Study Three doses n/N Piazza 1985 Total (95% CI) 0/37 37 Two doses n/N 10/37 37 Relative Risk (Fixed) 95% CI Weight (%) 100.0 100.0 Relative Risk (Fixed) 95% CI 0.05 [ 0.00, 0.78 ] 0.05 [ 0.00, 0.78 ]
Total events: 0 (Three doses), 10 (Two doses) Test for heterogeneity: not applicable Test for overall effect z=2.13 p=0.03
Analysis 05.01.
Review:
Comparison 05 PDV at birth versus PDV at one month, Outcome 01 Hepatitis B events
Comparison: 05 PDV at birth versus PDV at one month Outcome: 01 Hepatitis B events Study At birth n/N Beasley 1983b Total (95% CI) 3/50 50 5/58 58 At one month n/N Relative Risk (Fixed) 95% CI Weight (%) 100.0 100.0 Relative Risk (Fixed) 95% CI 0.70 [ 0.18, 2.77 ] 0.70 [ 0.18, 2.77 ]
Total events: 3 (At birth), 5 (At one month) Test for heterogeneity: not applicable Test for overall effect z=0.51 p=0.6
0.01
0.1
10
100
At birth better
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
136
Analysis 06.01.
Review:
Comparison 06 One type of PDV versus another type of PDV, Outcome 01 Hepatitis B events
Comparison: 06 One type of PDV versus another type of PDV Outcome: 01 Hepatitis B events Study NIAID n/N 01 NIAID versus BIVS Xu 1995 AB Total (95% CI) 7/60 60 14/60 60 100.0 100.0 0.50 [ 0.22, 1.15 ] 0.50 [ 0.22, 1.15 ] BIVS n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
Total events: 7 (NIAID), 14 (BIVS) Test for heterogeneity: not applicable Test for overall effect z=1.63 p=0.1
0.01
0.1
10
100
NIAID better
BIVS better
Analysis 07.01.
Review:
Comparison: 07 Four RV vaccinations versus three RV vaccinations Outcome: 01 Hepatitis B events Study 0-1-2-12 schedule n/N Lolekha 2002 Total (95% CI) 7/47 47 5/50 50 0-1-6 schedule n/N Relative Risk (Fixed) 95% CI Weight (%) 100.0 100.0 Relative Risk (Fixed) 95% CI 1.49 [ 0.51, 4.37 ] 1.49 [ 0.51, 4.37 ]
Total events: 7 (0-1-2-12 schedule), 5 (0-1-6 schedule) Test for heterogeneity: not applicable Test for overall effect z=0.73 p=0.5
0.01
0.1
10
100
0-1-2-12 better
0-1-6 better
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Analysis 07.02.
Review:
Comparison 07 Four RV vaccinations versus three RV vaccinations, Outcome 02 Anti-HBs level less than 10 IU/L
Comparison: 07 Four RV vaccinations versus three RV vaccinations Outcome: 02 Anti-HBs level less than 10 IU/L Study 0-1-2-12 schedule n/N Lolekha 2002 Total (95% CI) 2/47 47 4/50 50 0-1-6 schedule n/N Relative Risk (Fixed) 95% CI Weight (%) 100.0 100.0 Relative Risk (Fixed) 95% CI 0.53 [ 0.10, 2.77 ] 0.53 [ 0.10, 2.77 ]
Total events: 2 (0-1-2-12 schedule), 4 (0-1-6 schedule) Test for heterogeneity: not applicable Test for overall effect z=0.75 p=0.5
0.01
0.1
10
100
0-1-2-12 better
0-1-6 better
Analysis 08.01.
Review:
Comparison 08 One type of RV versus another type of RV with the same vaccination schedule, Outcome 01 Hepatitis B events
Comparison: 08 One type of RV versus another type of RV with the same vaccination schedule Outcome: 01 Hepatitis B events Study RV1 n/N RV2 n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
01 Hepavax-Gene plus HBIG versus Engerix-B plus HBIG Hieu 2002 Subtotal (95% CI) Total events: 1 (RV1), 2 (RV2) Test for heterogeneity: not applicable Test for overall effect z=0.59 p=0.6 1/53 53 2/52 52 100.0 100.0 0.49 [ 0.05, 5.25 ] 0.49 [ 0.05, 5.25 ]
02 HB VAX II plus HBIG versus Engerix-B plus HBIG Lee 1995 CA Lee 1995 DE Subtotal (95% CI) Total events: 6 (RV1), 6 (RV2) Test for heterogeneity chi-square=0.53 df=1 p=0.47 I?? =0.0% Test for overall effect z=0.05 p=1 3/34 3/36 70 2/38 4/35 73 31.8 68.2 100.0 1.68 [ 0.30, 9.44 ] 0.73 [ 0.18, 3.03 ] 1.03 [ 0.35, 3.02 ]
03 RV1 (Beijing, China) versus RV2 (Institute of Preventive Medicine, China ) Kang 1995 Subtotal (95% CI) Total events: 9 (RV1), 5 (RV2) Test for heterogeneity: not applicable Test for overall effect z=0.50 p=0.6 9/57 57 5/41 41 100.0 100.0 1.29 [ 0.47, 3.58 ] 1.29 [ 0.47, 3.58 ]
0.01
0.1
10 RV2 better
100
RV1 better
Analysis 08.02.
Review:
Comparison 08 One type of RV versus another type of RV with the same vaccination schedule, Outcome 02 Anti-HBs less than 10 IU/L
Comparison: 08 One type of RV versus another type of RV with the same vaccination schedule Outcome: 02 Anti-HBs less than 10 IU/L Study RV n/N 01 Hepavax-Gene versus Engerix-B Hieu 2002 Subtotal (95% CI) 4/53 53 5/52 52 100.0 100.0 0.78 [ 0.22, 2.76 ] 0.78 [ 0.22, 2.76 ] Engerix-B n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
Total events: 4 (RV), 5 (Engerix-B) Test for heterogeneity: not applicable Test for overall effect z=0.38 02 Cuban versus Engerix-B Garcia 1992 Subtotal (95% CI) 0/54 54 1/24 24 100.0 100.0 0.15 [ 0.01, 3.59 ] 0.15 [ 0.01, 3.59 ] p=0.7
Total events: 0 (RV), 1 (Engerix-B) Test for heterogeneity: not applicable Test for overall effect z=1.17 p=0.2
Analysis 09.01.
Review:
Comparison: 09 HBIG versus placebo or no intervention Outcome: 01 Hepatitis B events Study HBIG n/N 01 HBIG versus placebo or no intervention Beasley 1983a AB Beasley 1983a CB Subtotal (95% CI) Total events: 66 (HBIG), 68 (Control) Test for heterogeneity chi-square=7.81 df=1 p=0.005 I?? =87.2% Test for overall effect z=7.17 02 HBIG plus PDV versus PDV Farmer 1987 Ip 1989 AC 3/21 5/60 4/18 7/32
0.001 0.01 0.1 HBIG better 1 10 100 1000 Control better
Control n/N
Weight (%)
34/36 34/37 73
p<0.00001
2.3 4.8
(Continued . . . )
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(. . .
Study HBIG n/N Ip 1989 BC Liu 1987 CA Lo 1985 AB Lo 1985 CB Sehgal 1992 Theppisai 1987 Xu 1995 CB Subtotal (95% CI) Total events: 33 (HBIG), 51 (Control) Test for heterogeneity chi-square=5.97 df=8 p=0.65 I?? =0.0% Test for overall effect z=3.38 03 HBIG plus RV versus RV Assateerawatt 1993 Halliday 1992 CA Poovorawan 1997 Subtotal (95% CI) Total events: 28 (HBIG), 46 (Control) Test for heterogeneity chi-square=0.35 df=2 p=0.84 I?? =0.0% Test for overall effect z=2.35 Total (95% CI) p=0.02 615 471 100.0 6/30 7/55 15/63 148 11/30 13/55 22/64 149 5.8 6.8 11.5 24.1 p=0.0007 9/64 0/27 4/36 2/38 6/27 2/27 2/28 328 Control n/N 8/32 3/27 4/19 5/19 4/24 2/18 14/60 249 Relative Risk (Fixed) 95% CI Weight (%) 5.6 1.8 2.8 3.5 2.2 1.3 4.7 29.0
Continued )
Relative Risk (Fixed) 95% CI 0.56 [ 0.24, 1.32 ] 0.14 [ 0.01, 2.64 ] 0.53 [ 0.15, 1.88 ] 0.20 [ 0.04, 0.94 ] 1.33 [ 0.43, 4.17 ] 0.67 [ 0.10, 4.31 ] 0.31 [ 0.07, 1.26 ] 0.49 [ 0.32, 0.74 ]
0.55 [ 0.23, 1.28 ] 0.54 [ 0.23, 1.25 ] 0.69 [ 0.40, 1.21 ] 0.61 [ 0.41, 0.92 ]
Total events: 127 (HBIG), 165 (Control) Test for heterogeneity chi-square=13.88 df=13 p=0.38 I?? =6.3% Test for overall effect z=7.03 p<0.00001
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Analysis 09.02.
Review:
Comparison 09 HBIG versus placebo or no intervention, Outcome 02 Hepatitis B events according to methodological quality of the trials
Comparison: 09 HBIG versus placebo or no intervention Outcome: 02 Hepatitis B events according to methodological quality of the trials Study HBIG n/N 01 High-quality trials Halliday 1992 CA Liu 1987 CA Subtotal (95% CI) Total events: 7 (HBIG), 16 (Control) Test for heterogeneity chi-square=0.76 df=1 p=0.38 I?? =0.0% Test for overall effect z=1.93 02 Low-quality trials Assateerawatt 1993 Beasley 1983a AB Beasley 1983a CB Farmer 1987 Ip 1989 AC Ip 1989 BC Lo 1985 AB Lo 1985 CB Poovorawan 1997 Sehgal 1992 Theppisai 1987 Xu 1995 CB Subtotal (95% CI) 6/30 45/76 21/63 3/21 5/60 9/64 4/36 2/38 15/63 6/27 2/27 2/28 533 11/30 34/36 34/37 4/18 7/32 8/32 4/19 5/19 22/64 4/24 2/18 14/60 389 5.8 24.3 22.6 2.3 4.8 5.6 2.8 3.5 11.5 2.2 1.3 4.7 91.3 0.55 [ 0.23, 1.28 ] 0.63 [ 0.51, 0.77 ] 0.36 [ 0.25, 0.52 ] 0.64 [ 0.17, 2.50 ] 0.38 [ 0.13, 1.10 ] 0.56 [ 0.24, 1.32 ] 0.53 [ 0.15, 1.88 ] 0.20 [ 0.04, 0.94 ] 0.69 [ 0.40, 1.21 ] 1.33 [ 0.43, 4.17 ] 0.67 [ 0.10, 4.31 ] 0.31 [ 0.07, 1.26 ] 0.53 [ 0.44, 0.64 ] p=0.05 7/55 0/27 82 13/55 3/27 82 6.8 1.8 8.7 0.54 [ 0.23, 1.25 ] 0.14 [ 0.01, 2.64 ] 0.45 [ 0.20, 1.01 ] Control n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
Total events: 120 (HBIG), 149 (Control) Test for heterogeneity chi-square=12.89 df=11 p=0.30 I?? =14.7% Test for overall effect z=6.79 Total (95% CI) p<0.00001 615 471 100.0 0.52 [ 0.44, 0.63 ]
Total events: 127 (HBIG), 165 (Control) Test for heterogeneity chi-square=13.88 df=13 p=0.38 I?? =6.3% Test for overall effect z=7.03 p<0.00001
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Analysis 09.03.
Review:
Comparison 09 HBIG versus placebo or no intervention, Outcome 03 Hepatitis B events sensitivity analyses
Comparison: 09 HBIG versus placebo or no intervention Outcome: 03 Hepatitis B events - sensitivity analyses Study HBIG n/N 01 Available patients course analysis Assateerawatt 1993 Beasley 1983a AB Beasley 1983a CB Farmer 1987 Halliday 1992 CA Ip 1989 AC Ip 1989 BC Liu 1987 CA Lo 1985 AB Poovorawan 1997 Sehgal 1992 Theppisai 1987 Xu 1995 CB Subtotal (95% CI) 1/25 36/67 15/57 3/21 2/50 5/60 9/64 0/27 4/36 0/48 3/24 0/25 1/27 531 3/22 28/30 28/31 4/18 4/46 7/32 8/32 3/27 4/19 3/45 1/21 2/18 10/56 397 2.5 29.9 28.1 3.3 3.2 7.1 8.3 2.7 4.1 2.8 0.8 2.2 5.0 100.0 0.29 [ 0.03, 2.62 ] 0.58 [ 0.45, 0.73 ] 0.29 [ 0.19, 0.46 ] 0.64 [ 0.17, 2.50 ] 0.46 [ 0.09, 2.39 ] 0.38 [ 0.13, 1.10 ] 0.56 [ 0.24, 1.32 ] 0.14 [ 0.01, 2.64 ] 0.53 [ 0.15, 1.88 ] 0.13 [ 0.01, 2.53 ] 2.63 [ 0.29, 23.36 ] 0.15 [ 0.01, 2.87 ] 0.21 [ 0.03, 1.54 ] 0.44 [ 0.35, 0.55 ] Control n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
Total events: 79 (HBIG), 105 (Control) Test for heterogeneity chi-square=13.95 df=12 p=0.30 I?? =14.0% Test for overall effect z=7.11 02 Assuming poor outcome Assateerawatt 1993 Beasley 1983a AB Beasley 1983a CB Farmer 1987 Halliday 1992 CA Ip 1989 AC Ip 1989 BC Liu 1987 CA Lo 1985 AB 6/30 45/76 21/63 3/21 7/55 5/60 9/64 0/27 4/36 11/30 34/36 34/37 4/18 13/55 7/32 8/32 3/27 4/19
0.001 0.01 0.1 HBIG better 1 10 100 1000 Control better
p<0.00001
0.55 [ 0.23, 1.28 ] 0.63 [ 0.51, 0.77 ] 0.36 [ 0.25, 0.52 ] 0.64 [ 0.17, 2.50 ] 0.54 [ 0.23, 1.25 ] 0.38 [ 0.13, 1.10 ] 0.56 [ 0.24, 1.32 ] 0.14 [ 0.01, 2.64 ] 0.53 [ 0.15, 1.88 ]
(Continued . . . )
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(. . .
Study HBIG n/N Lo 1985 CB Poovorawan 1997 Sehgal 1992 Theppisai 1987 Xu 1995 CB Subtotal (95% CI) 2/38 15/63 6/27 2/27 2/28 615 Control n/N 5/19 22/64 4/24 2/18 14/60 471 Relative Risk (Fixed) 95% CI Weight (%) 3.5 11.5 2.2 1.3 4.7 100.0
Continued )
Relative Risk (Fixed) 95% CI 0.20 [ 0.04, 0.94 ] 0.69 [ 0.40, 1.21 ] 1.33 [ 0.43, 4.17 ] 0.67 [ 0.10, 4.31 ] 0.31 [ 0.07, 1.26 ] 0.52 [ 0.44, 0.63 ]
Total events: 127 (HBIG), 165 (Control) Test for heterogeneity chi-square=13.88 df=13 p=0.38 I?? =6.3% Test for overall effect z=7.03 03 Assuming good outcome Assateerawatt 1993 Beasley 1983a AB Beasley 1983a CB Farmer 1987 Halliday 1992 CA Ip 1989 AC Ip 1989 BC Liu 1987 CA Lo 1985 AB Lo 1985 CB Poovorawan 1997 Sehgal 1992 Theppisai 1987 Xu 1995 CB Subtotal (95% CI) 1/30 36/76 15/63 3/21 2/55 5/60 9/64 0/27 4/36 2/38 0/63 3/27 0/27 1/28 615 3/30 28/36 28/37 4/18 4/55 7/32 8/32 3/27 4/19 5/19 3/64 1/24 2/18 10/60 471 2.2 28.4 26.4 3.2 3.0 6.8 8.0 2.6 3.9 5.0 2.6 0.8 2.2 4.8 100.0 0.33 [ 0.04, 3.03 ] 0.61 [ 0.45, 0.82 ] 0.31 [ 0.20, 0.51 ] 0.64 [ 0.17, 2.50 ] 0.50 [ 0.10, 2.62 ] 0.38 [ 0.13, 1.10 ] 0.56 [ 0.24, 1.32 ] 0.14 [ 0.01, 2.64 ] 0.53 [ 0.15, 1.88 ] 0.20 [ 0.04, 0.94 ] 0.15 [ 0.01, 2.75 ] 2.67 [ 0.30, 23.96 ] 0.14 [ 0.01, 2.67 ] 0.21 [ 0.03, 1.59 ] 0.44 [ 0.35, 0.56 ] p<0.00001
Total events: 81 (HBIG), 110 (Control) Test for heterogeneity chi-square=13.12 df=13 p=0.44 I?? =0.9% Test for overall effect z=6.76 p<0.00001
04 Extreme case favouring HBIG Assateerawatt 1993 Beasley 1983a AB Beasley 1983a CB Farmer 1987 Halliday 1992 CA 1/30 36/76 15/63 3/21 2/55 11/30 34/36 34/37 4/18 13/55
0.001 0.01 0.1 HBIG better 1 10 100 1000 Control better
0.09 [ 0.01, 0.66 ] 0.50 [ 0.39, 0.64 ] 0.26 [ 0.16, 0.41 ] 0.64 [ 0.17, 2.50 ] 0.15 [ 0.04, 0.65 ]
(Continued . . . )
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Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
(. . .
Study HBIG n/N Ip 1989 AC Ip 1989 BC Liu 1987 CA Lo 1985 AB Lo 1985 CB Poovorawan 1997 Sehgal 1992 Theppisai 1987 Xu 1995 CB Subtotal (95% CI) 5/60 9/64 0/27 4/36 2/38 0/63 3/27 0/27 2/28 615 Control n/N 7/32 8/32 3/27 4/19 5/19 22/64 4/24 2/18 10/60 471 Relative Risk (Fixed) 95% CI Weight (%) 4.8 5.7 1.9 2.8 3.5 11.9 2.2 1.6 3.4 100.0
Continued )
Relative Risk (Fixed) 95% CI 0.38 [ 0.13, 1.10 ] 0.56 [ 0.24, 1.32 ] 0.14 [ 0.01, 2.64 ] 0.53 [ 0.15, 1.88 ] 0.20 [ 0.04, 0.94 ] 0.02 [ 0.00, 0.36 ] 0.67 [ 0.17, 2.68 ] 0.14 [ 0.01, 2.67 ] 0.43 [ 0.10, 1.83 ] 0.32 [ 0.26, 0.40 ]
Total events: 82 (HBIG), 161 (Control) Test for heterogeneity chi-square=24.65 df=13 p=0.03 I?? =47.3% Test for overall effect z=9.85 p<0.00001
05 Extreme case favouring control Assateerawatt 1993 Beasley 1983a AB Beasley 1983a CB Farmer 1987 Halliday 1992 CA Ip 1989 AC Ip 1989 BC Liu 1987 CA Lo 1985 AB Lo 1985 CB Poovorawan 1997 Sehgal 1992 Theppisai 1987 Xu 1995 CB Subtotal (95% CI) 6/30 45/76 21/63 3/21 7/55 5/60 9/64 0/27 4/36 2/38 15/63 6/27 2/27 1/28 615 3/30 28/36 28/37 4/18 4/55 7/32 8/32 3/27 4/19 5/19 3/64 1/24 2/18 14/60 471 2.2 28.1 26.1 3.2 3.0 6.8 7.9 2.6 3.9 4.9 2.2 0.8 1.8 6.6 100.0 2.00 [ 0.55, 7.27 ] 0.76 [ 0.59, 0.98 ] 0.44 [ 0.30, 0.65 ] 0.64 [ 0.17, 2.50 ] 1.75 [ 0.54, 5.64 ] 0.38 [ 0.13, 1.10 ] 0.56 [ 0.24, 1.32 ] 0.14 [ 0.01, 2.64 ] 0.53 [ 0.15, 1.88 ] 0.20 [ 0.04, 0.94 ] 5.08 [ 1.55, 16.69 ] 5.33 [ 0.69, 41.20 ] 0.67 [ 0.10, 4.31 ] 0.15 [ 0.02, 1.11 ] 0.73 [ 0.59, 0.89 ]
Total events: 126 (HBIG), 114 (Control) Test for heterogeneity chi-square=33.05 df=13 p=0.002 I?? =60.7% Test for overall effect z=3.12 p=0.002
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Analysis 09.04.
Review:
Comparison 09 HBIG versus placebo or no intervention, Outcome 04 Hepatitis B events according to the mothers HBeAg status
Comparison: 09 HBIG versus placebo or no intervention Outcome: 04 Hepatitis B events according to the mothers HBeAg status Study HBIG n/N 01 HBeAg positive Assateerawatt 1993 Beasley 1983a AB Beasley 1983a CB Farmer 1987 Ip 1989 AC Ip 1989 BC Liu 1987 CA Lo 1985 AB Lo 1985 CB Poovorawan 1997 Theppisai 1987 Xu 1995 CB Subtotal (95% CI) 6/30 45/76 21/63 3/21 5/60 9/64 0/27 4/36 2/38 15/63 2/27 2/17 522 11/30 34/36 34/37 4/18 7/32 8/32 3/27 4/19 5/19 22/64 2/18 9/29 361 5.8 24.2 22.5 2.3 4.8 5.6 1.8 2.7 3.5 11.5 1.3 3.5 89.4 0.55 [ 0.23, 1.28 ] 0.63 [ 0.51, 0.77 ] 0.36 [ 0.25, 0.52 ] 0.64 [ 0.17, 2.50 ] 0.38 [ 0.13, 1.10 ] 0.56 [ 0.24, 1.32 ] 0.14 [ 0.01, 2.64 ] 0.53 [ 0.15, 1.88 ] 0.20 [ 0.04, 0.94 ] 0.69 [ 0.40, 1.21 ] 0.67 [ 0.10, 4.31 ] 0.38 [ 0.09, 1.55 ] 0.51 [ 0.42, 0.61 ] Control n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
Total events: 114 (HBIG), 143 (Control) Test for heterogeneity chi-square=11.50 df=11 p=0.40 I?? =4.4% Test for overall effect z=7.18 02 HBeAg unknown Halliday 1992 CA Sehgal 1992 Subtotal (95% CI) Total events: 13 (HBIG), 17 (Control) Test for heterogeneity chi-square=1.58 df=1 p=0.21 I?? =36.6% Test for overall effect z=0.92 03 HBeAg negative Xu 1995 CB Subtotal (95% CI) Total events: 0 (HBIG), 5 (Control) Test for heterogeneity: not applicable Test for overall effect z=0.99 p=0.3 0/11 11 5/31 31 1.6 1.6 0.24 [ 0.01, 4.06 ] 0.24 [ 0.01, 4.06 ] p=0.4 7/55 6/27 82 13/55 4/24 79 6.8 2.2 9.0 0.54 [ 0.23, 1.25 ] 1.33 [ 0.43, 4.17 ] 0.73 [ 0.38, 1.42 ] p<0.00001
(Continued . . . )
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(. . .
Study HBIG n/N Total (95% CI) 615 Control n/N 471 Relative Risk (Fixed) 95% CI Weight (%) 100.0
Continued )
Total events: 127 (HBIG), 165 (Control) Test for heterogeneity chi-square=13.79 df=14 p=0.47 I?? =0.0% Test for overall effect z=7.04 p<0.00001
Analysis 09.05.
Review:
Comparison 09 HBIG versus placebo or no intervention, Outcome 05 Hepatitis B events according to time of HBIG administration
Comparison: 09 HBIG versus placebo or no intervention Outcome: 05 Hepatitis B events according to time of HBIG administration Study HBIG n/N 01 HBIG administered within 12 hours of birth Beasley 1983a AB Beasley 1983a CB Halliday 1992 CA Ip 1989 AC Ip 1989 BC Lo 1985 AB Lo 1985 CB Poovorawan 1997 Theppisai 1987 Subtotal (95% CI) 45/76 21/63 7/55 5/60 9/64 4/36 2/38 15/63 2/27 482 34/36 34/37 13/55 7/32 8/32 4/19 5/19 22/64 2/18 312 24.3 22.6 6.8 4.8 5.6 2.8 3.5 11.5 1.3 83.2 0.63 [ 0.51, 0.77 ] 0.36 [ 0.25, 0.52 ] 0.54 [ 0.23, 1.25 ] 0.38 [ 0.13, 1.10 ] 0.56 [ 0.24, 1.32 ] 0.53 [ 0.15, 1.88 ] 0.20 [ 0.04, 0.94 ] 0.69 [ 0.40, 1.21 ] 0.67 [ 0.10, 4.31 ] 0.52 [ 0.43, 0.62 ] Control n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
Total events: 110 (HBIG), 129 (Control) Test for heterogeneity chi-square=10.07 df=8 p=0.26 I?? =20.6% Test for overall effect z=6.92 p<0.00001
02 HBIG administered within 24 hours of birth Assateerawatt 1993 Farmer 1987 Sehgal 1992 Xu 1995 CB 6/30 3/21 6/27 2/28 11/30 4/18 4/24 14/60
0.001 0.01 0.1 HBIG better 1 10 100 1000 Control better
0.55 [ 0.23, 1.28 ] 0.64 [ 0.17, 2.50 ] 1.33 [ 0.43, 4.17 ] 0.31 [ 0.07, 1.26 ]
(Continued . . . )
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(. . .
Study HBIG n/N Subtotal (95% CI) Total events: 17 (HBIG), 33 (Control) Test for heterogeneity chi-square=2.81 df=3 p=0.42 I?? =0.0% Test for overall effect z=1.79 p=0.07 106 Control n/N 132 Relative Risk (Fixed) 95% CI Weight (%) 15.0
Continued )
03 HBIG administered within 48 hours of birth Liu 1987 CA Subtotal (95% CI) Total events: 0 (HBIG), 3 (Control) Test for heterogeneity: not applicable Test for overall effect z=1.31 Total (95% CI) p=0.2 615 471 100.0 0.52 [ 0.44, 0.63 ] 0/27 27 3/27 27 1.8 1.8 0.14 [ 0.01, 2.64 ] 0.14 [ 0.01, 2.64 ]
Total events: 127 (HBIG), 165 (Control) Test for heterogeneity chi-square=13.88 df=13 p=0.38 I?? =6.3% Test for overall effect z=7.03 p<0.00001
Analysis 09.06.
Review:
Comparison 09 HBIG versus placebo or no intervention, Outcome 06 Hepatitis B events according to standard and rapid schedule of vaccines
Comparison: 09 HBIG versus placebo or no intervention Outcome: 06 Hepatitis B events according to standard and rapid schedule of vaccines Study HBIG+vaccine n/N 01 Standard schedule (0-1-6 months) Farmer 1987 Halliday 1992 CA Theppisai 1987 Xu 1995 CB Subtotal (95% CI) 3/21 7/55 2/27 2/28 131 4/18 13/55 2/18 14/60 151 5.1 15.3 2.8 10.5 33.8 0.64 [ 0.17, 2.50 ] 0.54 [ 0.23, 1.25 ] 0.67 [ 0.10, 4.31 ] 0.31 [ 0.07, 1.26 ] 0.49 [ 0.27, 0.90 ] Vaccine n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
Total events: 14 (HBIG+vaccine), 33 (Vaccine) Test for heterogeneity chi-square=0.73 df=3 p=0.87 I?? =0.0% Test for overall effect z=2.29 p=0.02
13.0
(Continued . . . )
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(. . .
Study HBIG+vaccine n/N Ip 1989 AC Ip 1989 BC Liu 1987 CA Poovorawan 1997 Subtotal (95% CI) 5/60 9/64 0/27 15/63 244 Vaccine n/N 7/32 8/32 3/27 22/64 185 Relative Risk (Fixed) 95% CI Weight (%) 10.8 12.6 4.1 25.8 66.2
Continued )
Relative Risk (Fixed) 95% CI 0.38 [ 0.13, 1.10 ] 0.56 [ 0.24, 1.32 ] 0.14 [ 0.01, 2.64 ] 0.69 [ 0.40, 1.21 ] 0.55 [ 0.38, 0.81 ]
Total events: 35 (HBIG+vaccine), 51 (Vaccine) Test for heterogeneity chi-square=1.93 df=4 p=0.75 I?? =0.0% Test for overall effect z=3.07 Total (95% CI) p=0.002 375 336 100.0 0.53 [ 0.39, 0.74 ]
Total events: 49 (HBIG+vaccine), 84 (Vaccine) Test for heterogeneity chi-square=2.75 df=8 p=0.95 I?? =0.0% Test for overall effect z=3.83 p=0.0001
Analysis 09.07.
Review:
Comparison 09 HBIG versus placebo or no intervention, Outcome 07 Anti-HBs less than 10 IU/L
Comparison: 09 HBIG versus placebo or no intervention Outcome: 07 Anti-HBs less than 10 IU/L Study HBIG n/N 01 HBIG plus PDV versus PDV Sehgal 1992 Subtotal (95% CI) Total events: 6 (HBIG), 4 (Control) Test for heterogeneity: not applicable Test for overall effect z=0.49 02 HBIG plus RV versus RV Assateerawatt 1993 Halliday 1992 CA Poovorawan 1997 Subtotal (95% CI) Total events: 21 (HBIG), 13 (Control) Test for heterogeneity chi-square=0.20 df=2 p=0.90 I?? =0.0% 1/30 11/55 9/63 148 1/30 6/55 6/64 149 5.8 34.9 34.6 75.4 1.00 [ 0.07, 15.26 ] 1.83 [ 0.73, 4.61 ] 1.52 [ 0.58, 4.03 ] 1.63 [ 0.85, 3.11 ] p=0.6 6/27 27 4/24 24 24.6 24.6 1.33 [ 0.43, 4.17 ] 1.33 [ 0.43, 4.17 ] Control n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
0.01
0.1
10
100
HBIG better
Control better
(Continued . . . )
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(. . .
Study HBIG n/N Test for overall effect z=1.47 Total (95% CI) Total events: 27 (HBIG), 17 (Control) Test for heterogeneity chi-square=0.30 df=3 p=0.96 I?? =0.0% Test for overall effect z=1.54 p=0.1 p=0.1 175 173 100.0 Control n/N Relative Risk (Fixed) 95% CI Weight (%)
Continued )
0.01
0.1
10
100
HBIG better
Control better
Analysis 09.08.
Review:
Comparison: 09 HBIG versus placebo or no intervention Outcome: 08 Anti-HBs level Study N Poovorawan 1997 Subtotal (95% CI) 45 45 p=0.7 HBIG Mean(SD) 3.64 (1.44) N 48 48 Control Mean(SD) 3.74 (1.43) Weighted Mean Difference (Fixed) 95% CI Weight (%) 100.0 100.0 Weighted Mean Difference (Fixed) 95% CI -0.10 [ -0.68, 0.48 ] -0.10 [ -0.68, 0.48 ]
Test for heterogeneity: not applicable Test for overall effect z=0.34
-10.0
-5.0
5.0
10.0
HBIG better
Control better
Analysis 09.09.
Review:
Comparison: 09 HBIG versus placebo or no intervention Outcome: 09 Adverse events Study HBIG n/N Beasley 1983a CB Total (95% CI) Total events: 1 (HBIG), 0 (Control) Test for heterogeneity: not applicable Test for overall effect z=0.77 p=0.4 1/63 63 Control n/N 0/73 73 Relative Risk (Fixed) 95% CI Weight (%) 100.0 100.0 Relative Risk (Fixed) 95% CI 3.47 [ 0.14, 83.67 ] 3.47 [ 0.14, 83.67 ]
0.01
0.1
10
100
HBIG better
Control better
Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers (Review) Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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Analysis 10.01.
Review:
Comparison 10 Multiple HBIG plus PDV versus single HBIG plus PDV, Outcome 01 Hepatitis B events
Comparison: 10 Multiple HBIG plus PDV versus single HBIG plus PDV Outcome: 01 Hepatitis B events Study Multiple HBIG n/N Ip 1989 AB Lo 1985 CA Total (95% CI) 4/60 2/38 98 Single HBIG n/N 3/64 4/36 100 Relative Risk (Fixed) 95% CI Weight (%) 41.4 58.6 100.0 Relative Risk (Fixed) 95% CI 1.42 [ 0.33, 6.09 ] 0.47 [ 0.09, 2.43 ] 0.87 [ 0.30, 2.47 ]
Total events: 6 (Multiple HBIG), 7 (Single HBIG) Test for heterogeneity chi-square=0.97 df=1 p=0.32 I?? =0.0% Test for overall effect z=0.27 p=0.8
0.1 0.2
0.5
10
Analysis 11.01.
Review:
Comparison 11 PDV plus HBIG versus placebo or no intervention, Outcome 01 Hepatitis B events
Comparison: 11 PDV plus HBIG versus placebo or no intervention Outcome: 01 Hepatitis B events Study PDV + HBIG n/N Ip 1989 AD Ip 1989 BD Liu 1987 CB Xu 1995 CD Total (95% CI) 1/36 2/35 0/27 2/28 126 Control n/N 12/17 11/17 21/26 24/60 120 Relative Risk (Fixed) 95% CI Weight (%) 23.9 21.7 32.1 22.4 100.0 Relative Risk (Fixed) 95% CI 0.04 [ 0.01, 0.28 ] 0.09 [ 0.02, 0.35 ] 0.02 [ 0.00, 0.35 ] 0.18 [ 0.05, 0.70 ] 0.08 [ 0.03, 0.17 ]
Total events: 5 (PDV + HBIG), 68 (Control) Test for heterogeneity chi-square=2.73 df=3 p=0.43 I?? =0.0% Test for overall effect z=6.17 p<0.00001
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Analysis 11.02.
Review:
Comparison 11 PDV plus HBIG versus placebo or no intervention, Outcome 02 Hepatitis B events according to methodological quality of the trials
Comparison: 11 PDV plus HBIG versus placebo or no intervention Outcome: 02 Hepatitis B events according to methodological quality of the trials Study PDV + HBIG n/N 01 High-quality trials Ip 1989 AD Ip 1989 BD Liu 1987 CB Subtotal (95% CI) 1/36 2/35 0/27 98 12/17 11/17 21/26 60 23.9 21.7 32.1 77.6 0.04 [ 0.01, 0.28 ] 0.09 [ 0.02, 0.35 ] 0.02 [ 0.00, 0.35 ] 0.05 [ 0.02, 0.14 ] Control n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
Total events: 3 (PDV + HBIG), 44 (Control) Test for heterogeneity chi-square=1.13 df=2 p=0.57 I?? =0.0% Test for overall effect z=5.44 02 Low-quality trials Xu 1995 CD Subtotal (95% CI) 2/28 28 24/60 60 22.4 22.4 0.18 [ 0.05, 0.70 ] 0.18 [ 0.05, 0.70 ] p<0.00001
Total events: 2 (PDV + HBIG), 24 (Control) Test for heterogeneity: not applicable Test for overall effect z=2.46 Total (95% CI) p=0.01 126 120 100.0 0.08 [ 0.03, 0.17 ]
Total events: 5 (PDV + HBIG), 68 (Control) Test for heterogeneity chi-square=2.73 df=3 p=0.43 I?? =0.0% Test for overall effect z=6.17 p<0.00001
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Analysis 11.03.
Review:
Comparison 11 PDV plus HBIG versus placebo or no intervention, Outcome 03 Hepatitis B events - sensitivity analyses
Comparison: 11 PDV plus HBIG versus placebo or no intervention Outcome: 03 Hepatitis B events - sensitivity analyses Study PDV + HBIG n/N 01 Available patients course analysis Ip 1989 AD Ip 1989 BD Liu 1987 CB Xu 1995 CD Subtotal (95% CI) 1/36 2/35 0/27 1/27 125 12/17 11/17 21/26 19/55 115 24.9 22.6 33.4 19.1 100.0 0.04 [ 0.01, 0.28 ] 0.09 [ 0.02, 0.35 ] 0.02 [ 0.00, 0.35 ] 0.11 [ 0.02, 0.76 ] 0.06 [ 0.02, 0.15 ] Control n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
Total events: 4 (PDV + HBIG), 63 (Control) Test for heterogeneity chi-square=1.34 df=3 p=0.72 I?? =0.0% Test for overall effect z=5.89 02 Assuming poor outcome Ip 1989 AD Ip 1989 BD Liu 1987 CB Xu 1995 CD Subtotal (95% CI) 1/36 2/35 0/27 2/28 126 12/17 11/17 21/26 24/60 120 23.9 21.7 32.1 22.4 100.0 0.04 [ 0.01, 0.28 ] 0.09 [ 0.02, 0.35 ] 0.02 [ 0.00, 0.35 ] 0.18 [ 0.05, 0.70 ] 0.08 [ 0.03, 0.17 ] p<0.00001
Total events: 5 (PDV + HBIG), 68 (Control) Test for heterogeneity chi-square=2.73 df=3 p=0.43 I?? =0.0% Test for overall effect z=6.17 03 Assuming good outcome Ip 1989 AD Ip 1989 BD Liu 1987 CB Xu 1995 CD Subtotal (95% CI) 1/36 2/35 0/27 1/28 126 12/17 11/17 21/26 19/60 120 25.0 22.7 33.6 18.6 100.0 0.04 [ 0.01, 0.28 ] 0.09 [ 0.02, 0.35 ] 0.02 [ 0.00, 0.35 ] 0.11 [ 0.02, 0.80 ] 0.06 [ 0.02, 0.15 ] p<0.00001
Total events: 4 (PDV + HBIG), 63 (Control) Test for heterogeneity chi-square=1.39 df=3 p=0.71 I?? =0.0% Test for overall effect z=5.87 p<0.00001
04 Extreme case favouring PDV plus HBIG Ip 1989 AD Ip 1989 BD 1/36 2/35 12/17 11/17
0.001 0.01 0.1 PDV + HBIG better 1 10 100 1000 Control better
23.9 21.7
(Continued . . . )
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(. . .
Study PDV + HBIG n/N Liu 1987 CB Xu 1995 CD Subtotal (95% CI) 0/27 1/28 126 Control n/N 21/26 24/60 120 Relative Risk (Fixed) 95% CI Weight (%) 32.1 22.4 100.0
Continued )
Relative Risk (Fixed) 95% CI 0.02 [ 0.00, 0.35 ] 0.09 [ 0.01, 0.63 ] 0.06 [ 0.02, 0.15 ]
Total events: 4 (PDV + HBIG), 68 (Control) Test for heterogeneity chi-square=1.19 df=3 p=0.76 I?? =0.0% Test for overall effect z=5.91 p<0.00001
05 Extreme case favouring control Ip 1989 AD Ip 1989 BD Liu 1987 CB Xu 1995 CD Subtotal (95% CI) 1/36 2/35 0/27 2/28 126 12/17 11/17 21/26 19/60 120 25.0 22.7 33.6 18.6 100.0 0.04 [ 0.01, 0.28 ] 0.09 [ 0.02, 0.35 ] 0.02 [ 0.00, 0.35 ] 0.23 [ 0.06, 0.90 ] 0.08 [ 0.04, 0.18 ]
Total events: 5 (PDV + HBIG), 63 (Control) Test for heterogeneity chi-square=3.51 df=3 p=0.32 I?? =14.4% Test for overall effect z=6.11 p<0.00001
Analysis 11.04.
Review:
Comparison 11 PDV plus HBIG versus placebo or no intervention, Outcome 04 Hepatitis B events according to mothers HBeAg status
Comparison: 11 PDV plus HBIG versus placebo or no intervention Outcome: 04 Hepatitis B events according to mothers HBeAg status Study PDV + HBIG n/N 01 HBeAg positive Ip 1989 AD Ip 1989 BD Liu 1987 CB Xu 1995 CD Subtotal (95% CI) 1/36 2/35 0/27 2/17 115 12/17 11/17 21/26 21/31 91 23.3 21.2 31.3 21.3 97.1 0.04 [ 0.01, 0.28 ] 0.09 [ 0.02, 0.35 ] 0.02 [ 0.00, 0.35 ] 0.17 [ 0.05, 0.65 ] 0.07 [ 0.03, 0.17 ] Control n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
Total events: 5 (PDV + HBIG), 65 (Control) Test for heterogeneity chi-square=2.78 df=3 p=0.43 I?? =0.0% Test for overall effect z=6.26 p<0.00001
(Continued . . . )
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(. . .
Study PDV + HBIG n/N 02 HBeAg unknown Subtotal (95% CI) 0 0 0.0 Control n/N Relative Risk (Fixed) 95% CI Weight (%)
Continued )
Not estimable
Total events: 0 (PDV + HBIG), 0 (Control) Test for heterogeneity: not applicable Test for overall effect: not applicable 03 HBeAg negative Xu 1995 CD Subtotal (95% CI) 0/11 11 3/29 29 2.9 2.9 0.36 [ 0.02, 6.40 ] 0.36 [ 0.02, 6.40 ]
Total events: 0 (PDV + HBIG), 3 (Control) Test for heterogeneity: not applicable Test for overall effect z=0.70 Total (95% CI) p=0.5 126 120 100.0 0.08 [ 0.04, 0.18 ]
Total events: 5 (PDV + HBIG), 68 (Control) Test for heterogeneity chi-square=3.63 df=4 p=0.46 I?? =0.0% Test for overall effect z=6.36 p<0.00001
Analysis 11.05.
Review:
Comparison 11 PDV plus HBIG versus placebo or no intervention, Outcome 05 Hepatitis B events according to time of HBIG administration
Comparison: 11 PDV plus HBIG versus placebo or no intervention Outcome: 05 Hepatitis B events according to time of HBIG administration Study PDV + HBIG n/N 01 HBIG administered within 12 hours of birth Ip 1989 AD Ip 1989 BD Subtotal (95% CI) 1/36 2/35 71 12/17 11/17 34 23.9 21.7 45.6 0.04 [ 0.01, 0.28 ] 0.09 [ 0.02, 0.35 ] 0.06 [ 0.02, 0.19 ] Control n/N Relative Risk (Fixed) 95% CI Weight (%) Relative Risk (Fixed) 95% CI
Total events: 3 (PDV + HBIG), 23 (Control) Test for heterogeneity chi-square=0.45 df=1 p=0.50 I?? =0.0% Test for overall effect z=4.80 p<0.00001
02 HBIG administered within 24 hours of birth Xu 1995 CD Subtotal (95% CI) 2/28 28 24/60 60 22.4 22.4 0.18 [ 0.05, 0.70 ] 0.18 [ 0.05, 0.70 ]
(Continued . . . )
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(. . .
Study PDV + HBIG n/N Test for heterogeneity: not applicable Test for overall effect z=2.46 p=0.01 Control n/N Relative Risk (Fixed) 95% CI Weight (%)
Continued )
03 HBIG administered within 48 hours of birth Liu 1987 CB Subtotal (95% CI) 0/27 27 21/26 26 32.1 32.1 0.02 [ 0.00, 0.35 ] 0.02 [ 0.00, 0.35 ]
Total events: 0 (PDV + HBIG), 21 (Control) Test for heterogeneity: not applicable Test for overall effect z=2.70 Total (95% CI) p=0.007 126 120 100.0 0.08 [ 0.03, 0.17 ]
Total events: 5 (PDV + HBIG), 68 (Control) Test for heterogeneity chi-square=2.73 df=3 p=0.43 I?? =0.0% Test for overall effect z=6.17 p<0.00001
Analysis 11.06.
Review:
Comparison 11 PDV plus HBIG versus placebo or no intervention, Outcome 06 Adverse events
Comparison: 11 PDV plus HBIG versus placebo or no intervention Outcome: 06 Adverse events Study PDV+HBIG n/N Ip 1989 AD Ip 1989 BD Total (95% CI) 1/36 2/35 71 Control n/N 2/17 3/17 34 Relative Risk (Fixed) 95% CI Weight (%) 40.2 59.8 100.0 Relative Risk (Fixed) 95% CI 0.24 [ 0.02, 2.43 ] 0.32 [ 0.06, 1.76 ] 0.29 [ 0.07, 1.13 ]
Total events: 3 (PDV+HBIG), 5 (Control) Test for heterogeneity chi-square=0.05 df=1 p=0.83 I?? =0.0% Test for overall effect z=1.78 p=0.07
0.01
0.1
10
100
PDV+HBIG better
Control better
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