del Canho R, Grosheide P M, Mazel J A, Heijtink R A, Hop W C, Gerards L J, de Gast G C, Fetter W P, Zwijneberg J, Schalm S W
Department of Internal Medicine II, University Hospital Dijkzigt, Rotterdam, Netherlands.
Vaccine. 1997 Oct;15(15):1624-30. doi: 10.1016/s0264-410x(97)00080-7.
From 1982 to 1989, 705 infants born to HBsAg-positive mothers entered the Dutch neonatal hepatitis B vaccination program and received passive-active hepatitis B immunization in three randomized controlled trials testing variations in time of starting active vaccination, dose and type of vaccine, and number of hepatitis B immunoglobulin (HBIg) injections. A meta-analysis of individual patient data of the three randomized trials was performed to determine which independent host and vaccination related factors influence protective efficacy and long-term immunogenicity, and to assess whether hepatitis B vaccination concomitant with standard DKTP vaccination provides optimal protection. Statistical methodology included multivariate logistic regression analysis. Eight infants (1.1%), all born to HBeAg-positive mothers, became HBsAg carriers within the first year of life. The protective efficacy rate (PER) of passive-active immunization at 12 months follow-up was 92% for the total group of children from 114 HBeAg-positive mothers with no significant differences between children starting active immunization at birth or at 3 months of age, between infants starting at 3 months of age receiving one or two doses of HBIg or between those receiving plasma derived or recombinant vaccine. The only factor that affected the PER significantly was the level of maternal HBV DNA; PER was 100% if maternal HBV DNA was < 150 pg ml-1 and 68% for HBV DNA levels > 150 pg ml-1. After 5 years of follow-up, the group that started active immunization at birth had significantly more infants with loss of seroprotection (anti-HBs levels < 10 IU l-1, 15%) than the corresponding group starting at 3 months of age (anti-HBs < 10 IU l-2, 2%). One of 35 children with loss of seroprotection at 2 years became a HBsAg carrier in the fifth year of follow-up. This meta-analysis shows that the protective efficacy of passive-active hepatitis B vaccination is mainly influenced by material HBV DNA levels, and independent of the time of starting active vaccination at birth or at 3 months of age; long-term immunity was enhanced by starting active vaccination concomitant with DKTP vaccination. These findings allow incorporation of hepatitis B vaccine into the standard infant immunization programs for countries with a passive-active immunization strategy for the control of hepatitis B. Additional measures are needed to protect neonates of highly viremic women.
1982年至1989年期间，705名母亲为乙肝表面抗原（HBsAg）阳性的婴儿加入了荷兰新生儿乙肝疫苗接种计划，并在三项随机对照试验中接受了被动-主动联合乙肝免疫，这些试验测试了开始主动接种疫苗的时间、疫苗剂量和类型以及乙肝免疫球蛋白（HBIg）注射次数的变化。对这三项随机试验的个体患者数据进行了荟萃分析，以确定哪些独立的宿主和疫苗接种相关因素会影响保护效果和长期免疫原性，并评估与标准白喉、破伤风、百日咳疫苗（DKTP）接种同时进行的乙肝疫苗接种是否能提供最佳保护。统计方法包括多变量逻辑回归分析。8名婴儿（1.1%），其母亲均为乙肝e抗原（HBeAg）阳性，在出生后第一年内成为HBsAg携带者。在114名HBeAg阳性母亲的儿童总组中，12个月随访时被动-主动免疫的保护有效率（PER）为92%，在出生时或3个月大时开始主动免疫的儿童之间、3个月大开始接种的婴儿接受一剂或两剂HBIg之间，或接受血浆源性或重组疫苗的婴儿之间，无显著差异。唯一显著影响PER的因素是母亲的乙肝病毒（HBV）DNA水平；如果母亲的HBV DNA<150 pg/ml，PER为100%，而对于HBV DNA水平>150 pg/ml的情况，PER为68%。随访5年后，出生时开始主动免疫的组中血清保护丧失（抗-HBs水平<10 IU/l）的婴儿显著多于3个月大时开始接种的相应组（抗-HBs<10 IU/l，2%）。在随访的第五年，35名在2岁时血清保护丧失的儿童中有1名成为HBsAg携带者。这项荟萃分析表明，被动-主动联合乙肝疫苗接种的保护效果主要受母亲HBV DNA水平的影响，与出生时或3个月大时开始主动接种疫苗的时间无关；与DKTP疫苗接种同时开始主动接种疫苗可增强长期免疫力。这些研究结果使得在采用被动-主动免疫策略控制乙肝的国家，可将乙肝疫苗纳入标准婴儿免疫计划。需要采取额外措施来保护高病毒血症女性的新生儿。
