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研究生:蘇楓喬
研究生(外文):Feng-Chiao Su
論文名稱:一、出生前後二手菸暴露對兒童健康之影響;二、錳、MnSOD與嬰兒生長及神經行為發展
論文名稱(外文):I. The Effect of Prenatal and Postnatal Environmental Tobacco Smoke Exposure on Child Health;II. Manganese, MnSOD, and Infant Growth and Neurobehavioral Development
指導教授:陳保中陳保中引用關係
指導教授(外文):Pau-Chung Chen
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
論文出版年:2006
畢業學年度:94
語文別:英文
論文頁數:97
中文關鍵詞:環境菸害出生結果兒童健康MnSOD基因多型性胎兒成長神經行為發展
外文關鍵詞:environmental tobacco smokebirth outcomeschild healthmanganeseMnSODgenetic polymorphismfetal growthneurobehavioral development
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一、
環境菸害(environmental tobacco smoke, ETS)為常見的室內空氣污染,而胎兒及嬰幼兒更是暴露於環境菸害的高危險群。環境菸害不只是會導致呼吸道疾病,也會帶來出生結果的不良影響。然而,關於出生結果,目前被研究證實與暴露於環境菸害相關的只有減少出生體重、低出生體重以及減少頭圍,其他的則為可能或沒有相關。故本研究是藉由在「台灣出生世代研究(TBCS)」中的自答式問卷來評估出生前後暴露於環境菸害對出生結果,如早產、低出生體重、small gestational age (SGA)以及兒童健康,如急診次數、住院、疾病的影響。我們訪問了2,048位生產後的母親,最後取得1,725對的母親及小孩作為我們研究的對象,並且利用複迴歸及趨勢測驗來分析暴露與出生結果及兒童健康的關係。分析後,我們發現母親於懷孕時暴露於環境菸害與小孩的早產、SGA、急診次數及住院有顯著的趨勢相關。此外,母親為主動抽菸者也與小孩的低出生體重、SGA、急診次數及住院有相關,然而,在校正共變項後,除了低出生體重與SGA外,其他的相關皆未達顯著。再者,我們也發現父親在母親懷孕時或懷孕後抽菸,與小孩的住院率有趨勢上的相關。最後,我們觀察到於懷孕期間暴露到ETS的母親,其嬰兒的出生體重會減低30.4克,而母親為主動抽菸者的嬰兒,其出生體重則會降低224.0克。總結來說,即使在台灣女性抽菸率如此低的國家(懷孕時2.3%、生產後5.9%),仍看得到出生前後環境菸害對胎兒及嬰幼兒的影響,這的確是需要公共衛生的關注的問題。

二、
錳是人體的必須元素,但也同時是潛在的神經毒性物質。在人體中,錳可以輕易地藉由主動運輸作用穿過胎盤。然而至今,並沒有足夠的研究證實懷孕婦女若暴露到錳,會對其本身以及胎兒造成何種影響。此外,錳是體內抗氧化酵素,如MnSOD的成分之一,MnSOD作用於粒線體中,可以保護人體免於過多的氧化壓力。而調控此酵素的基因被發現存在著某些突變,包括在exon2上T > C -9的突變(從valine 變成alanine)、在exon3上T > C 245的突變(從isoleucine變成threonine)、以及在promoter上C > T -102 的突變。這些基因多型性會影響酵素的表現、活性及數量,而它們更可能與某些人類的疾病,如癌症及神經退化性疾病相關。但卻很少有研究評估MnSOD的基因多型性與兒童健康的關係。因此,我們的研究目的,就是要探討嬰兒體內的錳濃度與個別的基因多型性,其出生結果以及神經行為發展的相關性。本研究的個案來自於「Taipei Birth Panel Study」,在2004年四月到2005年一月間,納入486對的父母及其活產胎兒。我們利用臍帶血分析胎兒體內的錳濃度及其基因多型性,以問卷訪視獲得個案的人口學相關資訊,並藉由「Neonatal Neurobehavioral Estimation in Chinese version (NNE-C)」及「Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT)」來評估胎兒的神經行為發展,且從病歷取得胎兒的出生結果資料,最後,使用PCR-DHPLC來偵測個案的基因多型性。結果顯示,本研究胎兒體內錳濃度的幾何平均值為48.9 ppb (GSD = 1.4),而Val16Ala、Ile58Thr及-102 C>T的wild type頻率則各為71.0%、100.0%與47.5%。再者,我們發現,當臍血中錳濃度較高時,嬰兒在CDIIT中精細動作(fine-motor)的表現分數會較差。若嬰兒的Val16Ala為突變型,則其在CDIIT的語言(language)分數會較低。此外,- 102 C>T突變型的嬰兒則會有較少的出生週數與出生體重,並且在CDIIT中的社會(social)分數會較差。不過,在NNE-C的部分,無論是錳濃度的高低或是基因多型性,則都沒有發現統計上的相關性。另外所探討的錳濃度與基因多型性的交互作用,也同樣沒有發現合理的相關。最後,在本研究中,仍有一些未知的干擾因子沒有加以控制,故仍需要更進一步的研究來證實。然而,為了避免暴露錳及MnSOD基因多型性所可能造成的風險,我們仍建議懷孕婦女可以適當地攝取具抗氧化作用的食物,如蔬菜、水果。
I.
Environmental tobacco smoke (ETS) is a common indoor pollution. Fetus, neonates, and young children are the highest risk groups from ETS exposure. The harmful health effects of exposure to ETS may be not only respiratory illnesses, but also adverse reproductive outcomes. However, in birth outcomes, only decreased birthweight or low birthweight (LBW), and reduced head circumference have proven associations of exposure to ETS, while other outcomes have possible or no associations. In this study, we used the self-reported questionnaire from the pilot study of the population-based Taiwan Birth Cohort Study (TBCS) to evaluate the effects of exposure to prenatal and postnatal ETS on birth outcomes, including preterm delivery (PTD), low birthweight (LBW), and small for gestational age (SGA) as well as child health including emergency cases, hospitalization, and diseases. We recruited 2,048 mothers at six months after their deliveries and finally recruited 1,725 pairs of mothers and their children. We analyzed the association of adverse birth outcome and child health with exposures to prenatal and postnatal ETS by multiple linear and logistic regression (P-value
I.
摘要-2
Abstract-4
Contents-6
Introduction-7
Materials and Methods-9
Study population and sample strategy-9
Data collection-9
Statistical analysis-10
Results-12
Discussion-14
Conclusion-18
Acknowledgments-19
Reference-20
Table 1. The demographic data of subjects (N=1725)-25
Table 2. The exposure to prenatal and postnatal ETS (N=1725)-27
Table 3. The risks of adverse birth outcomes by factors of prenatal and postnatal ETS-28
Table 4. The risks for child health by factors of prenatal and postnatal ETS -29
Table 5. Associations between prenatal and postnatal ETS and birth outcomes-30
Figure 1. Random sampling 29 towns (in black) out of 369 in Taiwan-31

II.
摘要-33
Abstract-35
Contents-38
Introduction-40
Materials and Methods-44
Study population-44
Data collection-45
Questionnaires -45
Growth and neurobehavioral development measurements-45
Laboratory analysis -47
Manganese levels analysis-47
DNA preparation and PCR amplification-47
DHPLC analysis-48
Sequence analysis-50
Covariates-50
Statistical analysis-51
Results-52
Discussion-55
Conclusion-61
Reference-62
Table 1. Primer sequences, PCR conditions, and DHPLC conditions of three SNPs in MnSOD gene-72
Table 3. Fetal growth and neurobehavioral development outcomes of subjects-75
Table 4. Genetic polymorphisms of MnSOD in infants -76
Table 5. Simple linear regression models of birth outcomes, the level of manganese, and genetic polymorphisms (n= 440)-77
Table 6. Multiple linear regression models of birth outcomes, the level of manganese, and genetic polymorphisms (n= 440)-78
Table 7. Simple logistic regression models of birth outcomes, the level of manganese, and genetic polymorphisms (n= 440)-79
Table 8. Multiple logistic regression models of birth outcomes, the level of manganese, and genetic polymorphisms (n= 440)-81
Table 9. Simple linear regression models of NNE-C, the level of manganese, and genetic polymorphisms (n= 249)-83
Table 10. Multiple linear regression models of NNE-C, the level of manganese, and genetic polymorphisms (n= 249)-84
Table 11. Simple logistic regression models of NNE-C, the level of manganese, and genetic polymorphisms (n= 249)-85
Table 12. Multiple logistic regression models of NNE-C, the level of manganese, and genetic polymorphisms (n= 249)-87
Table 13. Simple linear regression models of CDIIT, the level of manganese, and genetic polymorphisms (n= 141)-89
Table 14. Multiple linear regression models of CDIIT, the level of manganese, and genetic polymorphisms (n= 141)-90
Table 15. Simple logistic regression models of CDIIT, the level of manganese, and genetic polymorphisms (n= 141)-91
Table 17. Simple logistic regression models of CDIIT, the level of manganese, and genetic polymorphisms (n= 141)-95
Table 18. Multiple logistic regression models of CDIIT, the level of manganese, and genetic polymorphisms (n= 141)-96
Figure 1. The DHPLC chromatography and sequence analysis of exon 2 (Val16Ala) of the MnSOD gene-97
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