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研究生:沈芳瑩
研究生(外文):Fang-Ying Shen
論文名稱:一、環境中鉛與錳的產前暴露對兒童早期氣質表現的可能影響;二、台灣年輕人高血壓世代研究族群雙酚A與頸動脈內膜中層厚度之相關性
論文名稱(外文):Part I. Prenatal exposure to lead and manganese on temperament performance in early childhood. ; Part II. Association between bisphenol A and carotid intima-media thickness in a young hypertension cohort of Taiwan
指導教授:陳保中陳保中引用關係
指導教授(外文):Pau-Chung Chen
口試委員:謝武勳蘇大成黃耀輝李永凌
口試委員(外文):Wu-Shiun HsiehTa-Chen SuYawHuei HwangYungling Leo Lee
口試日期:2014-07-16
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:職業醫學與工業衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2014
畢業學年度:102
語文別:英文
論文頁數:78
中文關鍵詞:氣質幼兒期雙酚A頸動脈內膜中層厚度青少年
外文關鍵詞:temperamentleadmanganeseearly childhoodbisphenol Acarotid intima-media thicknessadolescents
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一、
研究背景與目的:鉛與錳金屬是環境中普遍知道的神經毒物,目前已知共同暴露這兩種金屬時,可能會造成兒童行為問題與神經發展上的負面影響。另外,嬰兒時期的氣質表現可以用來預測未來兒童的行為問題,視為未來行為問題的早期表現,然而,現在仍然不清楚當媽媽懷孕期間暴露鉛與錳金屬是否會對於兒童早期的氣質有影響。因此本篇的研究目的在於釐清母親懷孕期的鉛錳共同暴露與兒童早期氣質表現的相關性。
方法:本篇研究的族群來自於台灣出生世代追蹤研究(Taiwan Birth Panel Study,TBPS),共275 對母親與孩童參與,在母親生產時立即收集孩童的臍帶血,利用Agilent 7500C ICP-MS 進行鉛與錳的濃度量測,在兒童氣質表現的量測選用中文版幼兒氣質量表進行評估,由主要照顧者進行填答評估。我們利用linear regression與mixed-effect model 來分析母親鉛錳暴露與兒童氣質的相關性。
結果:我們發現在高錳暴露組,隨著鉛濃度上升,兒童氣質適應度分數會有下降的趨勢[B: -0.385; p-value: 0.058],且我們也發現反應閾分數趨勢亦同[B: -0. 404;p-value: 0.015]。
結論:媽媽懷孕期間鉛錳共同暴露對於兒童早期氣質表現可能具有交互作用的趨勢,但機制仍需要後續研究進一步釐清。

二、
研究背景與目的:雙酚A 普遍存在於聚碳酸酯塑膠、環氧樹脂製品及金屬罐頭襯裡…等食品包裝中,經接觸食品後釋出而造成暴露。雙酚A 是一種內分泌干擾物,影響體內荷爾蒙與代謝機制,造成肥胖、動脈硬化、心血管疾病…等疾病,現已知頸動脈內膜中層厚度為上述疾病的危險因子與早期的表現,然而目前探討雙酚A與頸動脈內膜中層厚度的研究有限,因此本篇研究目的在於探討在青少年與年輕成人族群中,雙酚A 的暴露與頸動脈內膜中層厚度的相關性。
方法:本研究使用極致液相層析串聯質譜儀(UPLC/MS/MS)分析887 位青少年與年輕成人血中雙酚A 濃度,並使用超因波儀量測頸動脈內膜中層厚度,代謝相關生化值則經由血液及健康檢查取得。我們利用線性迴歸探討雙酚A 暴露與頸動脈內膜中層厚度的相關性。
結果:我們發現相較於最低暴露組,在較高雙酚A 暴露組中,雙酚A 與頸動脈內膜中層增厚有關(p-value <0.0001, p for trends < 0.0001),亦發現與低密度膽固醇(p-value =0.001, p for trends = 0.001)及總膽固醇(p-value = 0.001, p for trends = 0.003)
增加有關。
結論:在青少年和年輕成年人族群中,我們發現雙酚A 暴露可能與頸動脈內膜中層厚度增加有關,亦可能直接傷害血管,加劇對頸動脈內膜中層厚度的影響,且對於女性或健康族群影響更為顯著,但機制仍需要後續研究進一步釐清。

Part I.
Background: The lead and manganese are the common neurotoxic metals in the environment. Co-exposure to lead and manganese could injure child neurodevelopment and cause behavior problems. Additionally, temperament performance in infant period may be a predictor of behavior problems in childhood. However, it is not clear that association between prenatal lead and manganese co-exposure and temperament performance in early childhood.
Aims: The purpose of this study is to understand the effect of prenatal exposure to lead and manganese on child temperament.
Methods: A total of 275 newborns from the Taiwan Birth Panel Study (TBPS) were followed up in northern Taiwan. We collected their cord blood for measuring lead and manganese levels by an Agilent 7500C ICP-MS. We used the Chinese Toddler Temperament Scale which was collected from parental reports for measuring temperament at infants and toddlers. We examined the association between lead and manganese co-exposure and child temperament by linear regression and mixed-effect models.
Results: We found that under the higher manganese level, lead level in cord blood was associated with the adaptability (B=-0.385, p-value =0.058). We also found that the co-exposure of lead and manganese was associated with threshold of responsiveness (B=-0.404, p-value=0.015).
Conclusions: Lead and manganese prenatal exposure may have an effect on early child temperament performance. Mechanistic studies are needed to elucidate the causal relationship.

Part II.
Background: The lead and manganese are the common neurotoxic metals in the environment. Co-exposure to lead and manganese could injure child neurodevelopment and cause behavior problems. Additionally, temperament performance in infant period may be a predictor of behavior problems in childhood. However, it is not clear that association between prenatal lead and manganese co-exposure and temperament performance in early childhood.
Aims: The purpose of this study is to understand the effect of prenatal exposure to lead and manganese on child temperament.
Methods: A total of 275 newborns from the Taiwan Birth Panel Study (TBPS) were followed up in northern Taiwan. We collected their cord blood for measuring lead and manganese levels by an Agilent 7500C ICP-MS. We used the Chinese Toddler Temperament Scale which was collected from parental reports for measuring temperament at infants and toddlers. We examined the association between lead and manganese co-exposure and child temperament by linear regression and mixed-effect models.
Results: We found that under the higher manganese level, lead level in cord blood was associated with the adaptability (B=-0.385, p-value=0.058). We also found that the co-exposure of lead and manganese was associated with threshold of responsiveness (B=-0.404, p-value=0.015).
Conclusions: Lead and manganese prenatal exposure may have an effect on early child temperament performance. Mechanistic studies are needed to elucidate the causal relationship.


Contents
Part I …………………………………………………….………………………....5
中文摘要 ………………………………………………………….….………………....6
Abstract ………………………………………………………..….….……………...….7
Introduction ……………………………………………………..….……………...…...8
Material and Methods ……………………………………………..…………………10
Study design and population ……………………………………..……………...…..10
Measurement of metals ……………………………………..……………….…...….11
Measurement of temperament ……………………………………………..…..……11
Other co-variables……………………………………..………………………...…...12
Statistical analysis ……………………………………..……………………….……12
Results ………………………………………………………..……………………..…14
Discussion ………………………………………………………..………………….....19
Conclusions ………………………………………………………..…………….…….22
Reference ………………………………………………………..……………….…….23
Appendix 1 …………………………………………………………..…………….…..27
Appendix 2 …………………………………………………………..…………….…..28
Appendix 3 …………………………………………………………..…………….…..29
Appendix 4 …………………………………………………………..…………….…..35



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Part II …………………………………………………..................……..………...……40
中文摘要 …………………………………………………………………...………….41
Abstract …………………………………………………………..…………...……….42
Introduction ……………………………………………………………......………….44
Materials and methods …………………………………………………….……….....45
Study design and population ………………………………………………………...45
Anthropometric and biochemical data ……………………………………………....46
Measurement of carotid intima-media thickness …………………………………....47
Measurement of BPA concentration ………………….……………………..……….48
Chemicals and reagents …………………………………….…………………….48
Sample preparation and calibration experiments ………….…..………………...49
Instrumental analysis …………………………………….……………………….49
Method validation and quantification ……………….……………...…………….51
Statistical analysis …………………………………….……………………………..53
Results …………………………………………………………………………………54
BPA level in human serum …………………………………………..……………....54
BPA exposure and carotid intima-media thickness …………………………….…....56
Discussion …………………………………………………………………...…….…...62
Conclusions ………………………………………………………………...…….……68
Reference ……………………………………………………………………………....69
Appendix 1 ………………………………………………………………….…………73
Appendix 2 ………………………………………………………………….…………74
Appendix 3 ………………………………………………………………….…………75
Appendix 4 ………………………………………………………………….…………76
Appendix 5 ………………………………………………………………….…………76
Appendix 6 ………………………………………………………………….…………77
Appendix 7 ………………………………………………………………….…………78
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Figure of contents
Part I
Figure 1. Scatterplots and regression lines of cord blood lead and adaptability temperament among children with cord blood manganese in percentile less than 75th (Mn1, interaction p-value=0.76) and more than 75th (Mn2, interaction p-value=0.07) ..................................................................................................................18
Figure 2. Scatterplots and regression lines of cord blood lead and threshold of responsiveness temperament among children with cord blood manganese in percentile less than 75th (Mn1, interaction p-value=0.13) and more than 75th (Mn2, interaction p-value=0.08) ..................................................................................................................18


Part II
Figure 1. The flow chart of study population ….............................................................46
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Table of contents
Part I
Table 1. Manganese and lead concentration in each characteristics of the study population .......................................................................................................................15
Table 2. Linear regression models and linear mixed-effect model of lead concentration (

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