一、妊娠時期環境鉛錳暴露與其孩童兩歲行為發展之相關性 二、青少年與青年尿中丙烯醯胺代謝物分布與生化值變化之關係

Abstract

中文摘要一 研究背景與目的：錳、鉛、砷與汞為常見具有神經毒之金屬。然而，於妊娠時期暴露低劑量神經毒性金屬與其孩童往後神經行為發展之相關性目前仍不清楚。因此，本研究目的為探討妊娠時期神經毒性金屬暴露與其孩童兩歲神經行為發展之相關性。 材料與方法：本研究之230位足月單胞胎個案選自台北出生世代追蹤研究（Taiwan Birth Panel Study），於孩童兩歲大時進行嬰幼兒綜合發展測驗（Comprehensive Developmental Inventory for Infants and Toddlers, CDIIT），以評估其認知、語言、動作（含粗大動作及精細動作）、社會與自理能力之發展。以Agilent 7500C型感應耦合電漿質譜儀（ICP-MS）測量臍帶血中金屬濃度，並使用複迴歸來探討神經毒性金屬暴露與神經行為發展之關係。 結果：臍帶血之錳、鉛、砷與汞中位數濃度分別為47.90 μg/L、11.41 μg/L、4.05 μg/L與12.17 μg/L。在調整母親年齡、孩童性別、環境二手菸暴露與家庭物理環境評估後，錳濃度較高的組別其認知與語言發展商數（developmental quotients）較低（β = -4.72, SE = 2.16, P = 0.029; β = -3.91, SE = 1.87, P = 0.038），鉛濃度較高的組別其認知與社會發展商數較低（β = -5.21, SE = 2.18, P = 0.018; β = -6.36, SE = 2.50, P = 0.012）。在多金屬分析下，錳濃度與鉛濃度都較高的組別，其認知、語言與社會的發展商數則更低（β = -7.48, SE = 2.67, P = 0.006; β = -7.62, SE = 3.18, P = 0.018; β = -7.29, SE = 2.76, P = 0.009; β = -7.57, SE = 3.65, P = 0.039）。 結論：妊娠時期暴露較高濃度的金屬鉛或錳，其孩童兩歲神經行為發展較差；若共同暴露到較高濃度的鉛與錳，對其神經行為發展則會有加乘之交互作用。 中文摘要二 研究背景與目的：丙烯醯胺具神經毒性且被國際癌症研究署（IARC）歸類為人類可能致癌物質。近年來，於香菸的主流菸與高溫長時間烹煮碳水化合物含量較高的食品中皆發現含有較高濃度之丙烯醯胺。研究指出比起成年人，兒童與年輕族群可能會因飲食習慣不同而攝取較多的丙烯醯胺。由於目前針對兒童與年輕族群暴露丙烯醯胺的內在劑量評估較缺乏，而丙烯醯胺與人體內生化值改變之關係，尤其是在醣類與酯質恆定方面目前也仍不清楚。因此，本研究目的為分析青少年與青年尿中丙烯醯胺代謝物（N-acetyl-S-(propionamide)-cysteine, AAMA）濃度，並探討其分布與生化值變化之關係。 材料與方法：本研究選自1992至2000年台灣省中小學生尿液篩檢陽性者，且於2006至2008年接受追蹤檢查與問卷訪談的台北地區個案，並於追蹤時收集個案尿液與血液檢體進行分析，使用極致液相層析－串聯質譜儀（UHPLC-MS/MS）分析尿液中丙烯醯胺主要代謝物濃度。 結果：本研究共納入800位年齡介於12至30歲之個案，其尿中AAMA之中位數濃度為56.51 μg/L，經由尿中肌酸酐校正後之中位數濃度為39.37μg/g creatinine。女性、體重過輕者、高家庭收入者與抽菸者有較高之AAMA濃度。速食、咖啡與甜食的攝取頻率沒有顯著改變AAMA的濃度。在調整性別、年齡、家庭收入、身體質量指數、抽菸、喝酒、肥肉攝取頻率、高血糖和高血壓後，AAMA與血清中三酸甘油脂的濃度（per log10 unit: β = -0.05, SE = 0.02, P = 0.009）和球蛋白的濃度（per log10 unit: β = -0.09, SE = 0.03, P = 0.003）呈現負相關。 結論：於青少年與青年族群中，抽菸為丙烯醯胺暴露的主要貢獻因子，且尿中丙烯醯胺代謝物濃度與血清中三酸甘油脂和球蛋白呈負相關，但仍需要更多長期或動物研究來釐清其相關之生理代謝機制。

Abstract 1 Background and objective: Manganese, lead, arsenic and mercury are common neurotoxic metals in the environment. Nonetheless, the association between prenatal exposure to low-dose neurotoxic metals and neurodevelopment in children were not clear. The objective of this study is to explore the association between in utero exposure to environmental neurotoxic metals and neurodevelopment at 2 years of age. Methods: The population of this study was from the Taiwan Birth Panel Study. To prevent confounding factors, we finally included 230 pairs of non-smoking mothers without any occupational exposure and their singleton full-term children. The information during pregnancy was obtained by a structured questionnaire and manganese, lead, arsenic and mercury levels in umbilical cord blood was analyzed by using inductive couple plasma - mass spectrometry. We used Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT) to evaluate child developmental status at 2 years of age and examined the association between in utero exposure to environmental metals in umbilical cord blood and neurodevelopment by linear regression models. Results: The median concentrations of manganese, lead, arsenic and mercury in cord blood were 47.90 μg/L (17.88 - 106.85), 11.41 μg/L (0.16 - 43.22), 4.05 μg/L (1.50 - 12.88) and 12.17 μg/L (1.53 - 64.87) in this study, respectively. After adjusting for maternal age, infant gender, environmental tobacco smoke during pregnancy and after delivery, Home Observation for Measurement of the Environment, arsenic and mercury levels in cord blood and the group of manganese levels ≥ 75th percentile and lead levels ≥ 75th percentile in umbilical cord blood had a significantly adverse association with the whole, cognitive, language and social developmental quotients of CDIIT (β = -7.48, SE = 2.67, P = 0.006; β = -7.62, SE = 3.18, P = 0.018; β = -7.29, SE = 2.76, P = 0.009; β = -7.57, SE = 3.65, P = 0.039, respectively). Conclusions: In utero exposure to environmental manganese and lead may have an adverse association with neurodevelopment at 2 years of age. And there is an interaction effect between manganese and lead in cord blood. Abstract 2 Background and objective: Acrylamide, a neurotoxicant and probable human carcinogen, has been found in certain foods by high-temperature processing and in the mainstream of cigarette smoke. The dietary intakes of acrylamide in children and young populations were relatively higher than in adults, but few studies focused on the assessment of internal dose in this population. The effect of acrylamide exposure related to biochemistry changes, especially in glucose and lipid homeostasis, in human is still not clear. The objective of this study was to explore the acrylamide exposure and biochemistry changes among adolescents and young adults. Methods: The population of this study was recruited from the urine screening project conducted by Chinese Foundation of Health for school-age students from 1992 to 2000 in Taiwan. From 2006 to 2008, we invited these subjects who had been studied in Taipei to conduct a urine screening and complete questionnaires about lifestyles. We used ultra performance liquid chromatography – tandem mass spectrometry to analyze the N-acetyl-S-(propionamide)-cysteine (AAMA) which was the major and noninvasive biomarker in urine to assess the exposure of acrylamide levels. Subjects with urine creatinine levels below 0.3 g/L or over 3 g/L were excluded. Half of detection limit would be regarded as the AAMA levels in urine if the AAMA levels were lower than the limits of detection. Results: The mean (range) age of 800 subjects was 21.3 (12-30) years old and the median (range) levels of AAMA were 56.51 (< LOD-1012.78) μg/L and 39.37 (0.14-718.80) μg/g creatinine. Females, current smokers and subjects with low BMI and higher household income had higher AAMA levels. There were no significant AAMA level differences in different intake frequency of fast-food, coffee and sweet food. After adjusting for confounders (sex, age, BMI, current number of cigarettes, alcohol intake status, household income, fatty meat consumption, hyperglycemia and hypertension), each 1-unit increase in log AAMA was associated with a decrease in serum triglyceride (β = -0.05, SE = 0.02, P = 0.009) and globulin (β = -0.09, SE = 0.03, P = 0.003). Conclusion: Cigarette smoking is the major contributor to the overall acrylamide exposure among adolescents and young adults. Acrylamide exposure may have an inverse association with serum triglycerides and globulin, and this effect is still needed to be clarified by further longitudinal and animal studies.