Division of Research, Kaiser Permanente, Oakland, California.
Department of Medical Microbiology and Immunology, University of California, Davis, California.
Autism Res. 2019 Oct;12(10):1551-1561. doi: 10.1002/aur.2175. Epub 2019 Jul 17.
Maternal infection and fever during pregnancy have been implicated in the etiology of autism spectrum disorder (ASD); however, studies have not been able to separate the effects of fever itself from the impact of a specific infectious organism on the developing brain. We utilized data from the Study to Explore Early Development (SEED), a case-control study among 2- to 5-year-old children born between 2003 and 2006 in the United States, to explore a possible association between maternal infection and fever during pregnancy and risk of ASD and other developmental disorders (DDs). Three groups of children were included: children with ASD (N = 606) and children with DDs (N = 856), ascertained from clinical and educational sources, and children from the general population (N = 796), randomly sampled from state birth records. Information about infection and fever during pregnancy was obtained from a telephone interview with the mother shortly after study enrollment and maternal prenatal and labor/delivery medical records. ASD and DD status was determined by an in-person standardized developmental assessment of the child at 3-5 years of age. After adjustment for covariates, maternal infection anytime during pregnancy was not associated with ASD or DDs. However, second trimester infection accompanied by fever elevated risk for ASD approximately twofold (aOR = 2.19, 95% confidence interval 1.14-4.23). These findings of an association between maternal infection with fever in the second trimester and increased risk of ASD in the offspring suggest that the inflammatory response to the infectious agent may be etiologically relevant. Autism Res 2019, 12: 1551-1561. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Using data from a large multisite study in the United States-the Study to Explore Early Development-we found that women who had an infection during the second trimester of pregnancy accompanied by a fever are more likely to have children with ASD. These findings suggest the possibility that only more severe infections accompanied by a robust inflammatory response increase the risk of ASD.
母体感染和孕期发热与自闭症谱系障碍（ASD）的病因有关；然而，这些研究尚未能够将发热本身的影响与特定感染病原体对发育中大脑的影响区分开来。我们利用了美国一项名为“探索早期发育研究（SEED）”的病例对照研究的数据，该研究纳入了 2003 年至 2006 年间出生的 2 至 5 岁儿童，旨在探讨母体感染和孕期发热与 ASD 和其他发育障碍（DDs）风险之间可能存在的关联。纳入了三组儿童：来自临床和教育来源确定的 ASD 儿童（N=606）和 DD 儿童（N=856），以及从州出生记录中随机抽样的普通人群儿童（N=796）。孕期感染和发热的信息是通过在研究入组后不久对母亲进行电话访谈以及母亲的产前和分娩/分娩医疗记录获得的。ASD 和 DD 状态是通过对 3 至 5 岁儿童进行面对面的标准化发育评估来确定的。在调整了协变量后，孕期任何时候的母体感染均与 ASD 或 DDs 无关。然而，妊娠中期伴有发热的感染会使 ASD 的风险增加约两倍（aOR=2.19，95%置信区间 1.14-4.23）。这些关于妊娠中期母体感染伴发热与后代 ASD 风险增加之间关联的发现表明，感染因子引起的炎症反应可能与病因有关。自闭症研究 2019，12：1551-1561。©2019 国际自闭症研究协会，威利期刊，公司。
使用来自美国一项大型多地点研究的数据——探索早期发育研究，我们发现，妊娠中期感染伴有发热的女性更有可能生育患有 ASD 的儿童。这些发现表明，只有更严重的感染伴有强烈的炎症反应才会增加 ASD 的风险。
