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研究生：	王叔源 Wang, Shu-Yuan
論文名稱：	環境空氣汙染暴露與自閉症障礙之風險 Ambient air pollution exposure and risk of Autism Spectrum Disorder
指導教授：	郭浩然 Guo, How-Ran
學位類別：	碩士 Master
系所名稱：	醫學院 - 環境醫學研究所 Department of Environmental and Occupational Health
論文出版年：	2016
畢業學年度：	104
語文別：	英文
論文頁數：	55
中文關鍵詞：	自閉症障礙、空氣污染物、台灣健保資料庫、空氣監測站資料
外文關鍵詞：	Autism Spectrum Disorders, air pollution, National Insurance Research Database, air quality monitors database
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研究背景：自閉症障礙為一系列孩童神經發展疾病，然其致病原因至今仍不明。環境空氣汙染物，已知對於人體有許多健康危害，但在環境空氣汙染物與自閉症障礙風險相關研究仍相當稀少。本研究目的為探討環境空氣污染暴露與自閉症障礙之風險相關性。
材料與方法：本研究為一回溯型世代研究，使用台灣健保資料庫2000年百萬歸人檔(LHID2000)，篩選1996-2000年活產之新生兒進入研究世代。以投保地回推兒童母親懷孕時期之居住地，結合環境保護署空氣監測站資料。評估不同懷孕時期暴露空氣污染物所造成的影響，並將孕期分成五時間段，包含第一孕期、第二孕期、第三孕期、姙娠期及出生當月。評估的空氣汙染物包含臭氧、一氧化碳、二氧化氮、二氧化硫及氣動力徑小於10微米之懸浮微粒。追蹤研究世代內兒童是否有發病至2013年研究結束。存活分析以Cox比例風險模式評估環境空氣污染暴露與自閉症障礙之風險相關。
結果：本研究納入共62,919位新生兒進入研究，共有466位自閉症患者。在校正性別、出生年、共病症等危險因子後，全孕期暴露每ppm之一氧化碳，增加1.88倍的自閉症障礙罹病風險(95 % 信賴區間[CI]: 1.49-2.36)；第一孕期暴露為1.93倍風險(95 % CI: 1.55-2.39)；第二孕期暴露為1.77倍風險(95 % CI: 1.41-2.22)；第三孕期暴露為1.75倍風險(95 % CI: 1.39-2.21)。校正後暴露每10ppb之二氧化氮，於全孕期為1.42倍之罹病風險(95 % CI: 1.22-1.66)；於第一孕期為1.39倍之罹病風險(95 % CI: 1.22-1.58)；於第二孕期為1.25倍之罹病風險(95 % CI: 1.10-1.42)；於第三孕期為1.18倍之罹病風險(95 % CI: 1.03-1.34)。校正後暴露每10 μg/m3之氣動力徑小於10微米之懸浮微粒，於全孕期為0.90倍之罹病風險(95 % CI: 0.98-0.99)；於第二孕期為0.94倍之罹病風險(95 % CI: 0.90-0.99)；於第三孕期為0.91倍之罹病風險(95 % CI: 0.87-0.96)。校正後暴露每10ppb之臭氧於全孕期罹病風險為0.74倍(95 % CI: 0.56-0.97)。
結論：本研究發現懷孕時期暴露一氧化碳及二氧化氮，將增加日後孩童於早年發展自閉症障礙的風險，然而在暴露氣動力徑小於10微米之懸浮微粒及臭氧，並未發現同樣增加的風險。

Background:Autism Spectrum Disorders (ASD) is a group of neurodevelopmental disorders of which the mechanism is still unknown. Ambient air pollution has adverse health effects, but studies on the associations between air pollutants and ASD are limited. Therefore, we conducted a study in Taiwan to evaluate the possible associations.
Methods:We conducted a retrospective cohort study of all the infants born between 1996 and 2000 who were included in the Taiwan National Insurance Research Database, which is a random sample of one million people. We traced back the mother's residence at pregnancy and assess the exposure to air pollutants using the data obtained from the air quality monitoring database maintained by the government. The effects of the exposures in five different periods were evaluated, including the first trimester, the second trimester, the third trimester, the gestation, and the month of birth. The air pollutants evaluated including ozone (O3), carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), and particles with diameter less than 10 mm (PM10). All the participants were followed until the end of 2013 for the occurrence of ASD. Cox proportional hazard models were constructed to evaluate the risks associated with the pollutants.
Results:We identified 62,919 newborns were in the database, and 466 children developed to ASD. After adjusting for other risk factors, such as gender, birth year and comorbidities, the hazard ratio (HR) of developing ASD associated with an increase of each ppm of CO was 1.88 (95 % confidence interval [CI]: 1.49-2.36) in gestation, 1.93 (95 % CI: 1.55-2.39) in the first trimester, 1.77 (95 % CI: 1.41-2.22) in the second trimester, and 1.75 (95 % CI: 1.39-2.21) in the third trimester. The adjusted HR associated with 10 ppb of NO2 was 1.42 (95 % CI: 1.22-1.66) in the gestation, 1.39 (95 % CI: 1.22-1.58) in the first trimester, 1.25 (95 % CI: 1.10-1.42) in the second trimester, and 1.18 (95 % CI: 1.03-1.34) in the third trimester. The adjusted HR associated with 10 μg/m3 of PM10 was 0.90 (95 % CI: 0.98-0.99) in gestation, 0.94 (95 % CI: 0.90-0.99) in the second trimester, and 0.91 (95 % CI: 0.87-0.96) in the third trimester. The adjusted HR associated with 10 ppb of O3 was 0.74 (95 % CI: 0.56-0.97) in gestation.
Conclusion:Our study found that prenatal exposure to CO and NO2 increased the risk of developing ASD in the early childhood, while exposure to PM10 and O3 were not.

目錄
中文摘要	I
英文摘要	III
誌謝	V
目錄	VI
圖目錄	VIII
表目錄	IX
Chapter 1 Introduction	1
1.1	Background and Motivation	1
1.2	Research question	2
Chapter 2 Literature review	3
2.1	The epidemiology of Autism Spectrum Disorders	3
2.2	The mechanism of Autism Spectrum Disorders	4
2.3	The ambient air pollution and ASD	5
Chapter 3 Significance	6
3.1	Objective	6
3.2	Significance	6
Chapter 4 Materials and Methods	7
4.1	Study structure and study design	7
4.2	Study cohort	7
4.3	Outcome of interest	7
4.4	Exposure assessment	7
4.5	Covariates	8
4.6	Statistical analysis	9
Chapter 5 Results	10
5.1	Description of sample	10
5.2	Air pollution	10
5.3	The risk of Autism Spectrum Disorders	11
Chapter 6 Discussion	13
6.1   Past Literatures	13
6.2   The increased risk for exposing CO and NO2	14
6.3   The decreased risk for exposing PM10	15
6.4   The risk of trimester-specific exposure	15
6.5   Strength and Limitation	16
Chapter 7 Conclusion	18
Reference	19
Appendix	24

圖目錄
FIGURE 1. Study flow chart	24
FIGURE 2. Taiwanese counties’ cumulative incidence rate of ASD in 2013. The incidence rate represented as cases per 10,000 children.	27
FIGURE 3. Taiwanese towns’ cumulative incidence rate of ASD in 2013. The incidence rate represented as cases per 10,000 children.	28
FIGURE 4. The monthly variation of air pollutants level over the study years.	30
FIGURE 5. The yearly variation of air pollutants level over the study years. The dot represented the average air pollution level and the error bars represent ±1 S.D.	32
FIGURE 6. The seasonal variation of air pollutants level over the study years. The dot represented the average air pollution level and the error bars represent ±1 S.D.	35
FIGURE 7. The Taiwanese town scale concentration of carbon monoxide in main Taiwan Island.	38
FIGURE 8. The Taiwanese town scale concentration of nitrogen dioxide in main Taiwan Island.	40
FIGURE 9. The Taiwanese town scale concentration of ozone in main Taiwan Island.	42
FIGURE 10. The Taiwanese town scale concentration of sulfur dioxide in main Taiwan Island.	44
FIGURE 11. The Taiwanese town scale concentration of particulate matter less than 10 mm in diameter in main taiwan island.	46
FIGURE 12. The hazard ratios variation for exposing air pollutants in each trimester. The dots were the adjusted hazard ratio, and the error bars were the 95% of confidence interval.	54
表目錄
TABLE 1. The demographic data of the study cohort.	25
TABLE 2. The median of seasonal air pollutants level.	33
TABLE 3. Spearman correlation coefficient of monthly average air pollution level.	36
TABLE 4. Crude hazard ratios (95 % confidence interval [CI]) for Autism Spectrum Disorders from univariate model.	47
TABLE 5. Crude and adjusted hazard ratios (95 % confidence interval [CI]) for Autism Spectrum Disorders from single air pollutant model.	48
TABLE 6. Stratification of adjusted hazard ratios (95% confidence interval [CI]) of Autism Spectrum Disorders for exposing per 10 mg/m3 of particulate matter less than 10 mm in diameter.	55


                                    

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