類風濕關節炎患者後代自閉症譜系障礙的風險

類風濕關節炎（RA）是一種常見的自身免疫性疾病，高發人群為15-45歲育齡期女性。因此近年來，評估類風濕關節炎患者孕育後代的風險也越來越受關注。

許多研究表明，自身免疫性疾病患者由於體內自身抗體及細胞因子水平較高，胎兒在母體接觸到相關因素可能與自閉症譜系障礙（ASD）的發生相關。ASD是學齡兒童最常見的神經發育障礙疾病之一，而母親的自身免疫性和炎症在ASD病理生理學中發揮重要的作用。

本次筆者與大家分享最近的一篇報道，該報道指出RA患者的後代與健康母親的後代相比，ASD發生的風險更大。這也從另一角度提醒醫患雙方在RA患者備孕時應注意的問題，而疾病活動度，細胞因子水平和自身抗體狀態，可能會對ASD風險起到一定的調節作用。

研究目的

最近的證據表明，胎兒在子宮內暴露於母體的抗體和細胞因子是自閉症譜系障礙（ASD）的重要危險因素。 我們的目的是系統地回顧與非風濕關節炎（RA）的母親所生的孩子比較，患有RA的母親所生的孩子患ASD的風險。

研究方法

我們對電子資料庫PubMed，EMBASE和Web of Science里的原創文章進行了系統回顧。

研究結果

我們共檢索到70篇文獻。 在檢索到的潛在的相關研究中，67個研究由於缺乏相關性和/或因為沒有報道原始數據被排除。最後分析了三項研究，一項病例對照研究無法檢測ASD患者與對照組其母親的RA患病率差異。另一項病例對照研究顯示與對照組相比，母親有自身免疫性疾病（包括RA）其後代患ASD幾率增加8倍，具有統計學意義。46%的ASD後代與RA一級相關，而對照組為26％。此外，在基於人群的隊列研究中，調查人員觀察到，與健康母親（不患RA）所生的孩子相比，有RA病史的母親的子女ASD風險增加。這些研究都具有方法上的局限性：沒有控制藥物暴露，只有1個研究控制了產科併發症，並考慮了RA診斷的時間與妊娠相關性；除1個研究外，所有研究均用病例對照研究設計。

研究結論

儘管該研究數據有限，但這個觀察性研究表明，與沒有RA的母親所生的孩子相比，患RA的母親所生的孩子ASD的風險可能會增加。

References:

Wojcik S, Bernatsky S, Platt RW, Pineau CA, Clarke AE, Fombonne E, et al. Risk of autism spectrum disorders in children born to mothers with rheumatoid arthritis: A systematic literature review. Arthritis Care Res (Hoboken). [Journal Article]. 2017 2017-03-20.

Risk of autism spectrum disorders in children born to mothers with rheumatoid arthritis: A systematic literature review(1).

OBJECTIVE

Recent evidence suggests in utero exposure to maternal antibodies and cytokines as important risk factors for autism spectrum disorders (ASD). We aimed to systematically review the risk of ASD in children born to mothers with rheumatoid arthritis (RA) compared to children born to mothers without RA.

METHODS

We conducted a systematic review of original articles using electronic databases: PubMed, EMBase, and Web of Science.

RESULTS

Our literature search identified a total of 70 articles. Of the potentially relevant studies retrieved, 67 were excluded for lack of relevance and/or because they did not report original data. Three studies were included in the final analysis. A case-control study was unable to detect a difference in the prevalence of RA in ASD mothers versus control mothers. Another case-control study showed a statistically significant 8-fold increase in autoimmune disorders, including RA, in mothers of ASD offspring compared to controls. Forty-six percent of ASD offspring had a first-degree relative with RA compared to 26% of controls. Moreover, in a population-based cohort study, investigators observed an increased risk of ASD in children with a maternal history of RA compared to children born to unaffected mothers. These studies had methodological limitations: none controlled for medication exposures, only 1 controlled for obstetrical complications and considered the timing of RA diagnosis in relation to pregnancy, and all but 1 used a case-control study design.

CONCLUSION

Observational studies suggest a potentially increased risk of ASD in children born to mothers with RA compared to children born to unaffected mothers, although data are limited.

摘自：類風濕關節炎在線

來源：廣東省第二人民醫院風濕免疫科

翻譯：黃學嬋

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