麻疹、腮腺炎、风疹疫苗接种与自闭症：全国队列研究。

Measles, Mumps, Rubella Vaccination and Autism: A Nationwide Cohort Study.

机构信息

Statens Serum Institut, Copenhagen, Denmark (A.H., J.V.H., M.F.).

Statens Serum Institut and University of Copenhagen, Copenhagen, Denmark, Stanford University School of Medicine, Stanford, California (M.M.).

出版信息

Ann Intern Med. 2019 Apr 16;170(8):513-520. doi: 10.7326/M18-2101. Epub 2019 Mar 5.

DOI:10.7326/M18-2101

PMID:30831578

Abstract

BACKGROUND

The hypothesized link between the measles, mumps, rubella (MMR) vaccine and autism continues to cause concern and challenge vaccine uptake.

OBJECTIVE

To evaluate whether the MMR vaccine increases the risk for autism in children, subgroups of children, or time periods after vaccination.

DESIGN

Nationwide cohort study.

SETTING

Denmark.

PARTICIPANTS

657 461 children born in Denmark from 1999 through 31 December 2010, with follow-up from 1 year of age and through 31 August 2013.

MEASUREMENTS

Danish population registries were used to link information on MMR vaccination, autism diagnoses, other childhood vaccines, sibling history of autism, and autism risk factors to children in the cohort. Survival analysis of the time to autism diagnosis with Cox proportional hazards regression was used to estimate hazard ratios of autism according to MMR vaccination status, with adjustment for age, birth year, sex, other childhood vaccines, sibling history of autism, and autism risk factors (based on a disease risk score).

RESULTS

During 5 025 754 person-years of follow-up, 6517 children were diagnosed with autism (incidence rate, 129.7 per 100 000 person-years). Comparing MMR-vaccinated with MMR-unvaccinated children yielded a fully adjusted autism hazard ratio of 0.93 (95% CI, 0.85 to 1.02). Similarly, no increased risk for autism after MMR vaccination was consistently observed in subgroups of children defined according to sibling history of autism, autism risk factors (based on a disease risk score) or other childhood vaccinations, or during specified time periods after vaccination.

LIMITATION

No individual medical charts were reviewed.

CONCLUSION

The study strongly supports that MMR vaccination does not increase the risk for autism, does not trigger autism in susceptible children, and is not associated with clustering of autism cases after vaccination. It adds to previous studies through significant additional statistical power and by addressing hypotheses of susceptible subgroups and clustering of cases.

PRIMARY FUNDING SOURCE

Novo Nordisk Foundation and Danish Ministry of Health.

摘要

背景

麻疹、腮腺炎、风疹（MMR）疫苗与自闭症之间的假设关联持续引起关注，并对疫苗接种率构成挑战。

目的

评估麻疹、腮腺炎、风疹疫苗是否会增加儿童、儿童亚组或疫苗接种后特定时间段发生自闭症的风险。

设计

全国性队列研究。

设置

丹麦。

参与者

1999 年 1 月 1 日至 2010 年 12 月 31 日期间在丹麦出生的 657461 名儿童，随访至 2013 年 8 月 31 日。

测量方法

丹麦人口登记处用于将 MMR 疫苗接种、自闭症诊断、其他儿童疫苗接种、自闭症谱系障碍兄弟姐妹史和自闭症风险因素与队列中的儿童相关联。采用 Cox 比例风险回归法对自闭症诊断时间进行生存分析，根据 MMR 疫苗接种状态估计自闭症的危险比，同时调整年龄、出生年份、性别、其他儿童疫苗接种、自闭症谱系障碍兄弟姐妹史和自闭症风险因素（基于疾病风险评分）。

结果

在 5025754 人年的随访期间，有 6517 名儿童被诊断为自闭症（发病率为 129.7/100000 人年）。与 MMR 未接种疫苗的儿童相比，MMR 接种疫苗的儿童自闭症发病危险比为 0.93（95%CI，0.85 至 1.02）。同样，在根据自闭症谱系障碍兄弟姐妹史、自闭症风险因素（基于疾病风险评分）或其他儿童疫苗接种或疫苗接种后特定时间段定义的儿童亚组中，也没有观察到 MMR 接种后自闭症风险增加。