Department of Public Health, Aarhus University, Bartholins Allé 2, DK-8000 Aarhus C, Denmark.
JAMA. 2012 Feb 22;307(8):823-31. doi: 10.1001/jama.2012.165.
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 diphtheria-tetanus toxoids-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine since September 2002.
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.
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.
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.
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.
全细胞百日咳疫苗接种会增加发热性惊厥的风险，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，自 2002 年 9 月以来，无细胞百日咳疫苗已被纳入白喉-破伤风类毒素-无细胞百日咳-灭活脊髓灰质炎病毒-流感嗜血杆菌 b 型（DTaP-IPV-Hib）联合疫苗中。
评估 3、5 和 12 个月龄时接种 DTaP-IPV-Hib 疫苗后发热性惊厥和癫痫的风险。
设计、地点和参与者：这是一项基于人群的队列研究，纳入了 2003 年 1 月 1 日至 2008 年 12 月 31 日期间在丹麦出生的 378834 名儿童，并随访至 2009 年 12 月 31 日；以及一项基于队列研究中随访期间发生热性惊厥的儿童的自我对照病例系列（SCCS）研究。
队列研究中每次接种后 0 至 7 天（0、1-3 天和 4-7 天）发热性惊厥的危险比（HR）和首次接种后癫痫的 HR。SCCS 研究中每次接种后 0 至 7 天（0、1-3 天和 4-7 天）发热性惊厥的相对发病率。
共有 7811 名儿童在 18 个月前被诊断为热性惊厥，其中 17 名在首次接种后 0 至 7 天内被诊断（发病率为每 100000 人日 0.8 例），32 名在第二次接种后被诊断（每 100000 人日 1.3 例），201 名在第三次接种后被诊断（每 100000 人日 8.5 例）。总体而言，与未在 0 至 7 天内接种疫苗的儿童参考队列相比，儿童在 3 次接种后 0 至 7 天内发热性惊厥的风险并未增加。然而，首次接种当天（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）发热性惊厥的风险较高，但第三次接种当天（HR，1.07；95%CI，0.73-1.57）风险与参考队列相似。在接种当天，9 名儿童在首次接种后（每 100000 人日 5.5 例）、12 名儿童在第二次接种后（每 100000 人日 5.7 例）和 27 名儿童在第三次接种后（每 100000 人日 13.1 例）被诊断为热性惊厥。来自 SCCS 研究设计的相对发病率与队列研究设计相似。在 7 年的随访期间，131 名未接种疫苗的儿童和 2117 名接种疫苗的儿童被诊断为癫痫，813 名在 3 至 15 个月（每 1000 人年 2.4 例）和 1304 名在生命后期（每 1000 人年 1.3 例）被诊断为癫痫。接种疫苗后，3 至 15 个月（HR，0.63；95%CI，0.50-0.79）和生命后期（HR，1.01；95%CI，0.66-1.56）儿童癫痫的风险较低，与未接种疫苗的儿童相比。
在 3 个月和 5 个月龄时接种 DTaP-IPV-Hib 疫苗会增加首次 2 次接种后的发热性惊厥风险，但绝对风险较小。接种 DTaP-IPV-Hib 疫苗与癫痫风险增加无关。
