Risk of Febrile Seizures and Epilepsy After Vaccination With Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliovirus, and Haemophilus Influenzae Type b
Risk of Febrile Seizures and Epilepsy After Vaccination With Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliovirus, and Haemophilus Influenzae Type b
复制标题
DOI：
10.1001/jama.2012.165
复制
发表时间：
2012-02-22
影响因子：
120.7
通讯作者：
Vestergaard, Mogens
中科院分区：
文献类型：
--
作者：
Sun, Yuelian;Christensen, Jakob;Vestergaard, Mogens
背景接种全细胞百日咳疫苗会增加热性惊厥的风险，但这种风险是否适用于无细胞百日咳疫苗尚不清楚。在丹麦，无细胞百日咳疫苗已被纳入白喉类毒素-无细胞百日咳-灭活脊髓灰质炎病毒-B型流感嗜血杆菌联合疫苗目的评估DTaP-IPV-Hib疫苗接种后3、5和12个月发生热性惊厥和癫痫的风险。一项基于人群的队列研究，研究对象为2003年1月1日至2008年12月31日出生于丹麦的378834名儿童，随访至2009年12月31日;和一项基于队列随访期间热性惊厥儿童的自身对照病例系列研究（SCCS）。主要结果测量0至7天内热性惊厥的风险比（HR）（0、1-3和4-7天）和队列研究中首次接种后癫痫的HR。0 - 7天内热性惊厥的相对发生率结果7811例儿童在18个月前被诊断为热性惊厥，其中17例在第一次接种后0 ~ 7天内被诊断为热性惊厥。（发病率，0.8/100 000人日），第二次接种后32名儿童（1.3/100 000人日），第三次接种后201名儿童（8.5/100 000人日）。总体而言，与未在疫苗接种后0 - 7天内接种疫苗的儿童参考队列相比，儿童在3次疫苗接种后0 - 7天内发生热性惊厥的风险并不高。然而，与参考队列相比，在第一次接种当天（HR，6.02; 95% CI，2.86-12.65）和第二次接种当天（HR，3.94; 95% CI，2.18-7.10）发现热性惊厥风险较高，但在第三次接种当天（HR，1.07; 95% CI，0.73-1.57）未发现。在接种当天，9名儿童在第一次（每100 000人日5.5人）接种后被诊断为热性惊厥，12名儿童在第二次（每100 000人日5.7人）接种后被诊断为热性惊厥，27名儿童在第三次（每100 000人日13.1人）接种后被诊断为热性惊厥。SCCS研究设计的相对发生率与队列研究设计相似。在7年的随访中，131名未接种疫苗的儿童和2117名接种疫苗的儿童被诊断患有癫痫，813名在3至15个月之间被诊断（每1000人年2.4人），1304名在以后的生活中被诊断（每1000人年1.3人）。接种疫苗后，儿童在3至15个月之间患癫痫的风险较低（HR，0.63; 95% CI，0.50-0.79），并且在以后的生活中患癫痫的风险相似（HR，1.01; 95%可信区间，0.66-1.56）与未接种儿童相比。Hib疫苗接种与3个月和5个月时接种前2次疫苗当天的热性惊厥风险增加相关，尽管绝对风险很小。DTaP-IPV-Hib疫苗接种与癫痫风险增加无关。美国医学会杂志2012;307（8）：823-831 www.jama.com
Context Vaccination with whole-cell pertussis vaccine carries an increased risk of febrile seizures, but whether this risk applies to the acellular pertussis vaccine is not known. In Denmark, acellular pertussis vaccine has been included in the combined diphtheriatetanus toxoids-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine since September 2002.Objective To estimate the risk of febrile seizures and epilepsy after DTaP-IPV-Hib vaccination given at 3, 5, and 12 months.Design, Setting, and Participants A population-based cohort study of 378 834 children who were born in Denmark between January 1, 2003, and December 31, 2008, and followed up through December 31, 2009; and a self-controlled case series (SCCS) study based on children with febrile seizures during follow-up of the cohort.Main Outcome Measures Hazard ratio (HR) of febrile seizures within 0 to 7 days (0, 1-3, and 4-7 days) after each vaccination and HR of epilepsy after first vaccination in the cohort study. Relative incidence of febrile seizures within 0 to 7 days (0, 1-3, and 4-7 days) after each vaccination in the SCCS study.Results A total of 7811 children were diagnosed with febrile seizures before 18 months, of whom 17 were diagnosed within 0 to 7 days after the first (incidence rate, 0.8 per 100 000 person-days), 32 children after the second (1.3 per 100 000 person-days), and 201 children after the third (8.5 per 100 000 person-days) vaccinations. Overall, children did not have higher risks of febrile seizures during the 0 to 7 days after the 3 vaccinations vs a reference cohort of children who were not within 0 to 7 days of vaccination. However, a higher risk of febrile seizures was found on the day of the first (HR, 6.02; 95% CI, 2.86-12.65) and on the day of the second (HR, 3.94; 95% CI, 2.18-7.10), but not on the day of the third vaccination (HR, 1.07; 95% CI, 0.73-1.57) vs the reference cohort. On the day of vaccination, 9 children were diagnosed with febrile seizures after the first (5.5 per 100 000 person-days), 12 children after the second (5.7 per 100 000 person-days), and 27 children after the third (13.1 per 100 000 person-days) vaccinations. The relative incidences from the SCCS study design were similar to the cohort study design. Within 7 years of follow-up, 131 unvaccinated children and 2117 vaccinated children were diagnosed with epilepsy, 813 diagnosed between 3 and 15 months (2.4 per 1000 person-years) and 1304 diagnosed later in life (1.3 per 1000 person-years). After vaccination, children had a lower risk of epilepsy between 3 and 15 months (HR, 0.63; 95% CI, 0.50-0.79) and a similar risk for epilepsy later in life (HR, 1.01; 95% CI, 0.66-1.56) vs unvaccinated children.Conclusions DTaP-IPV-Hib vaccination was associated with an increased risk of febrile seizures on the day of the first 2 vaccinations given at 3 and 5 months, although the absolute risk was small. Vaccination with DTaP-IPV-Hib was not associated with an increased risk of epilepsy. JAMA. 2012;307(8):823-831 www.jama.com