12~15个月幼儿接种麻疹疫苗惊厥风险低

《美国医学会杂志•儿科学》10月14日在线发表的一项研究结果显示，与在16~23个月接种含有麻疹成分的疫苗的幼儿相比，按照推荐接种时间在12~15个月接种疫苗的幼儿较少发生与疫苗接种相关的惊厥(JAMA Pediatr. 2013 Oct. 14 [doi: 10.1001/jamapediatrics.2013.2745])。

在这项回顾性队列研究中，华盛顿大学流行病学系的Ali Rowhani-Rahbar博士及其同事考察了年龄因素对接种后惊厥风险的影响，研究队列为2001~2011年期间接种MMR或MMRV疫苗的840,348例美国儿童。结果发现，2岁幼儿接种含有麻疹成分疫苗后的惊厥风险大小与接种年龄相关。

研究者指出，虽然在12~15个月接种含有麻疹成分疫苗与接种后7~10天惊厥风险增加相关，但在16~23个月时延迟接种可导致这一不良事件风险更大。


Ali Rowhani-Rahbar博士

目前尚不清楚与年龄相关的惊厥风险差异的原因。研究者认为，这或许只是因为年龄较大儿童惊厥背景风险较大，也可能是年龄较大儿童免疫系统功能相对较好，对疫苗产生更为强烈的免疫应答，从而高热惊厥风险提高。另外，还可能是由于医学原因，对惊厥易感的儿童推迟接种，结果在年龄较大后接种疫苗更容易出现惊厥。但研究者强调，无论原因如何，所有年龄儿童的惊厥风险均非常低。

研究者指出，上述研究结果支持应按照现行推荐指南，应及时给予儿童接种首剂含有麻疹成分的疫苗。

研究者利用美国疾控中心(CDC)疫苗安全数据库资料，分析比较了儿童接种后7~10天“暴露期”与接种后42天“对照期”惊厥发病率，进而比较12~15个月和16~23个月幼儿接种疫苗后的发病率。

总体上，接种后42天共计发生1,810例惊厥事件，包括接种后7~10天期间发生的519例(28.7%)事件。对照期惊厥发病率与普通人群背景发病率一致，发病高峰年龄也均在15~16个月。不同接种年龄儿童暴露期惊厥总发病率均显著高于对照期。

最重要的结果是，16~23个月接种儿童惊厥相对风险(RR，6.5)显著高于12~15个月接种儿童(RR，3.4)。

归因风险分析结果显示，16~23个月儿童每接种10,000剂疫苗，则有9.5例额外病例，而12~15个月儿童为4.0例额外病例。敏感性分析结果仍然显著。

研究者称，上述结果一致表明，在对高热惊厥易感的年龄接种含有麻疹成分疫苗的疫苗或可导致接种后类似不良事件风险同样增加。

该研究由美国健康保险计划承担的CDC疫苗安全数据库项目资助。Rowhani-Rahbar博士报告无利益冲突，其同事报告与葛兰素史克、默克及其他公司存在利益关系。

随刊述评：现行接种程序是最佳选择

宾州大学儿科系、费城儿童医院传染病与疫苗教育中心的Feemster博士和 Offit博士在评论中指出，现行疫苗接种推荐程序是以多年的安全性和有效性数据为基础的，上述研究结果进一步证实了其安全性。

许多父母延迟儿童接种时间，认为这样可使惊厥等不良事件风险减小到最低程度。但这项研究明确显示，如果担心疫苗安全性，遵循现行推荐程序是预防疾病和减少不良事件的最佳选择(JAMA Pediatrics 2013 [doi: 10.1001/jamapediatrics.2013.3071])。

Feemster博士和 Offit博士均报告无经济利益冲突。

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By: MARY ANN MOON, Clinical Neurology News Digital Network

Measles-containing vaccines are less likely to be associated with seizures when given at 12-15 months of age as recommended than when delayed until 16-23 months of age, according to results from a study published online Oct. 14 in JAMA Pediatrics.

In the retrospective cohort study examining the effect of age at immunization on 840,348 U.S. children given the MMR or MMRV vaccines during the second year of life in 2001-2011, "we found that the magnitude of increased risk of seizures following immunization with measles-containing vaccines during the second year of life depends on age.

"While measles-containing vaccines administered at 12-15 months of age are associated with an increased risk of seizures 7-10 days following immunization, their delayed administration at 16-23 months of age may result in an even greater increased risk of that adverse event following immunization," said Dr. Ali Rowhani-Rahbar of the department of epidemiology at the University of Washington, Seattle, and his associates.

The reason for this age-related difference in seizure risk is not yet known. It may simply be attributable to the fact that the background risk of seizures is higher in the older age group. Or a better-functioning immune system at the older age may allow children to mount a more rigorous immunologic response to the vaccine, raising the risk of febrile seizures.

It also is possible that vaccination is delayed among children thought to be susceptible to seizures for medical reasons, and that these children are more likely to develop seizures when they finally are vaccinated at the later age.

Regardless of the reasons for this age association, the increase in risk of seizures was very small for all age groups.

"Our findings are of direct relevance to the recommended childhood immunization schedule; they support the timely immunization of children with the first dose of measles-containing vaccine in accordance with current recommendations," the researchers noted.

Dr. Rowhani-Rahbar and his colleagues used data from the Centers for Disease Control and Prevention’s Vaccine Safety Datalink to examine this issue. The incidence of seizures was analyzed for each child during the 7- to 10-day "exposure period" following immunization and compared with the "control period" of the 42 days after that interval.

Then the rates of seizures were compared between children who were vaccinated at 12-15 months of age and those who were vaccinated at 16-23 months of age.

Overall, there were 1,810 seizure events during the 42 days following immunization, including 519 events (28.7%) that occurred during the 7- to 10-day exposure period.

The incidence of seizures during the control intervals was consistent with background rates reported in the general population. It also peaked at age 16-18 months, which is consistent with the peak that occurs in the general population.

The overall incidence of seizures was significantly higher during the exposure periods than the control intervals at all ages.

The most important finding was that the relative risk of seizures during the exposure interval was significantly greater among children vaccinated at 16-23 months of age (RR, 6.5) than among those vaccinated at 12-15 months of age (RR, 3.4) , the investigators reported (JAMA Pediatr. 2013 Oct. 14 [doi: 10.1001/jamapediatrics.2013.2745]).

The attributable risk was 9.5 excess cases of seizure per 10,000 doses given at 16-23 months of age, compared with 4.0 excess cases of seizure per 10,000 doses given at 12-15 months of age. These results remained robust in a sensitivity analysis of the data.

"These findings collectively suggest that the administration of measles-containing vaccines at the age of highest vulnerability to febrile seizures may result in an even greater increased risk of those adverse events following immunization," Dr. Rowhani-Rahbar and his associates said.

This study was supported by the CDC-sponsored Vaccine Safety Database through a subcontract with America’s Health Insurance Plans. Dr. Rowhani-Rahbar reported no financial conflicts of interest; his associates reported ties to GlaxoSmithKline, Merck, and other companies.

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Current schedule is best choice

The findings of this study confirm the well-established safety of the current recommended vaccination schedule, "which is based on many years of ... safety and effectiveness data."

Many parents delay immunization, thinking that this will minimize the risk of an adverse event such as seizures. But this study clearly shows that "if vaccine safety is a concern, the currently recommended schedule is the best choice for preventing disease and minimizing adverse events," they said.

Dr. Feemster and Dr. Offit are both in the department of pediatrics at the University of Pennsylvania, Philadelphia, and in the division of infectious diseases and the Vaccine Education Center at Children’s Hospital of Philadelphia. They reported no financial conflicts of interest. These remarks were taken from their editorial accompanying Dr. Rowhani-Rahbar’s report (JAMA Pediatrics 2013 [doi: 10.1001/jamapediatrics.2013.3071]).