幼兒感染非小兒麻痺型腸病毒對於兒童過動症的關連

Abstract

背景：腸病毒屬一共可以分成五類，以往對兒童造成嚴重影響的是引發脊髓灰質炎(俗稱小兒痲痺)的脊髓灰質炎病毒，但隨著疫苗(沙賓及沙克疫苗)的研發及普遍施打後，目前在台灣已經鮮少有脊髓灰質炎的病例發生，而其他類型的腸病毒感染，一般以感染小孩為主，其中在台灣以克沙奇病毒(coxsackieviruses)A型與B型，以及腸病毒(Enteroviruses)較為常見，臨床症狀以手足口症、皰疹性咽峽炎及皮膚紅疹為特徵，成人感染則多半少有症狀；但近幾年在亞洲，腸病毒感染併發重症的案例時有所聞，包含肌抽躍（myoclonic jerks）之症狀或併發腦炎、急性肢體麻痺症候群、急性肝炎、心肌炎、急性心肌病變、心肺衰竭等，嚴重者甚至造成孩童死亡；而一些針對腸病毒重症病童的日後追蹤，發覺有些病例有神經行為發展的遲緩，如過動症、自閉症或智能發育不足。 方法：本次研究使用全民健保資料庫2000~2008的100萬歸人檔，以及全國過動症兒童就診紀錄，進行cohort study以及case-control study。 在cohort study中，選取2000-2003年新生兒族群，以ICD-9代碼：腸病毒感染(074,047,048,049)挑出曾經感染腸病毒住院就醫的族群，未曾感染的族群當作對照組；並以ICD-9代碼：過動症(314)作為兒童過動症族群；另外頭部創傷個案、新生兒缺氧個案、染色體異常個案等會影響兒童過動症的因素也予以去除。以性別、年齡、地區、時間、感染腸病毒與否為變相進行Cox Model分析。 在case-control study中，從全國有過過動兒診斷的族群中選取2000-2003年出生者為case組，以全國隨機抽樣100萬歸人檔中2000-2003出生族群，扣除有過動兒診斷的族群，做為對照組，並且與cohort study剔除標準一致，以性別、年齡、地區、時間、感染腸病毒與否為變相進行Logistic regression分析。 結果： 校正相關影響因子後，在cohort study中，小於兩歲兒童感染腸病毒有較高危害比(HR, 1.63 ; 95% CI, 1.20-2.23)，在case control study中，(1-2 years old; ORs, 1.32; 95% CI, 1.18-1.48; 3-4 years old; ORs, 1.28; 95% CI, 1.18-1.38) 結論：對於小於兩歲感染腸病毒後住院的兒童，相較於未得過腸病毒的兒童，有較高的風險在未來得到過動症。

Purpose: Some researches suggests that EV71 CNS involvement causes not only acute and severe complications with higher mortality but also long-term neurologic and psychiatric disorders. But these studies mainly focused on the patients of EV71 infection with severe complication. This study will estimate the association of attention-deficit/ hyperactivity disorder (ADHD) and infection of non-polio enteroviruses. Patients and Methods: In the study, we designed a case cohort study and a case control study. In cohort study, we conducted a population-based cohort study from the Taiwan National Health Insurance Research Database. A total of 43,810 newborns born during 2000 to 2003 were included as the study cohort. Each subject was individually tracked from 2000 to 2008 to identify incident cases of ADHD. Cox proportional hazard regressions were employed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between the infection of enteroviruses and the occurrence of ADHD in the cohort. In our case control study, data were abstracted from the NHIRD of all ADHD cases in Taiwan. We selected ADHD cases born during 2000 – 2003 as ADHD case group (N = 31,135). We selected control group from 1,000,000 individuals selected randomly from Taiwan’s NHIRD, who were born during 2000 – 2003 and had no diagnosis of ADHD (N= 42,489). Controls were individually matched to cases. Conditional logistic regressions were employed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between the infection of enteroviruses and the occurrence of ADHD in the cohort. Results: In cohort study, children whose infection age younger than 2 years old were more likely to have ADHD during the follow-up period than patients in the comparison cohort (HR, 1.63 ; 95% CI, 1.20-2.23). In case control study, there are significances in the group of infection age (1-2 years old; ORs, 1.32; 95% CI, 1.18-1.48; 3-4 years old; ORs, 1.28; 95% CI, 1.18-1.38) and the admission group (ORs, 1.29; 95% CI, 1.21-1.38). Conclusion: In conclusion, the infection of Enteroviruses might be associated with the occurrence of ADHD. The younger age of non-polio enterovirus infection has a higher hazard ratio of ADHD.