ㄧ、台灣垃圾焚化廠周邊對新生兒不良出生結果之相關性探討 二、Cotinine、基因多型性與嬰兒成長及神經行為發展

1. Adverse Birth Outcomes near Municipal Waste Incinerators in Taiwan 2. Cotinine, Genetic Polymorphism, and Infant Growth and Neurobehavioral Development

尤詩妮(Shih-Ni Yu)

指導教授 ： 陳保中

國立臺灣大學/公共衛生學院/職業醫學與工業衛生研究所/碩士(2006年)

https://doi.org/10.6342/NTU.2006.01434

摘要

ㄧ、台灣垃圾焚化廠周邊對新生兒不良出生結果之相關性探討
由於國際間對於焚化廠煙道排放物質對於生殖健康效應的研究，至今尚未有一致的結論，故本研究的目的在探討廢棄物焚化廠周邊居民中，母親在懷孕過程暴露於焚化廠煙道排放物質（例如戴奧辛），對於其懷孕結果低出生體重、早產、胎兒生長遲滯（SGA，Small for gestational age）、嬰兒性別是否有關聯。研究地區的選取是根據90年「台灣地區焚化爐排放戴奧辛之健康風險評估研究」之結果，收集五座焚化廠完工運轉後歷次檢測之煙道戴奧辛濃度，以及焚化廠附近之氣象與地形資料，以工業污染源複合模式第三版（ISC3）進行大氣擴散與沉降之模擬。模擬的結果以地理資訊系統（GIS）界定出影響的行政區域範圍，接著將影響的行政區域範圍去連結內政部新生兒出生登記檔，收集每座焚化廠開始運作年份至2003年該期間新生兒出生的資料，進行統計分析。本研究結果並無法證明母親於懷孕期間暴露焚化廠煙道排放物質和新生兒不良出生結果有相關。

二、Cotinine、基因多型性與嬰兒成長及神經行為發展
近年來愈多的人們強調吸菸與暴露二手菸對於女性健康之危害，尤其是懷孕婦女所產生之危害可能影響其下一代，例如低出生體重。然而，在孕婦吸菸或暴露二手菸對於嬰兒與兒童神經行為發展的研究有限。此外，目前的研究都著重在吸菸與二手菸對出生結果的影響，但在環境暴露與基因的交互作用對兒童神經行為發展的影響仍然尚未清楚。
本研究藉由生物檢體及問卷所收集的資料，探討母親懷孕期間體內cotinine濃度及胎兒臍帶血中cotinine濃度之相關性，並且評估cotinine濃度對新生兒出生結果與胎兒的神經行為發展之影響，並於出生後二到五天、出生後六個月時對嬰兒進行神經行為和認知及動作發展的評估，以觀察cotinine濃度對於新生兒神經行為動作的相關性。另外，探討環境暴露與基因間對於嬰兒與兒童神經行為發展的貢獻程度。
本研究對象為2004年4月到2005年1月參與台北出生世代研究之孕婦及其嬰兒，總計328對。暴露的評估將透過收集孕婦生產時之血液及嬰兒之臍帶血，利用高效能液相層析儀連結串聯的質譜儀 (LC/MS/MS)進行cotinine濃度分析。吸菸、二手菸暴露資料及其他干擾因子則透過產後三天內進行問卷調查，嬰兒之出生結果將由病例得知，出生後二至五天以中文版神經行為評估量表由專業人員進行新生兒行為評估，內容包括肌力與動作型態、原始反射與意識反應。於嬰兒六個月大時，直接使用國際功能分類系統模式進行嬰幼兒綜合發展測驗，並請家長或主要照顧者填寫家庭環境觀察評估量表。干擾因子包括：母親年齡、種族、懷孕週數、胎次、喝酒與社經地位等。以ANOVA, MANOVA, 邏輯式迴歸模式進行cotinine濃度與新生兒成長發育及神經行為發展檢定。基因多型性方面以phaseⅡ的代謝基因為研究重點，探討GSTT1, GSTM1, GSTP1等基因。GSTT1, GSTM1基因利用polymerase chain reaction (PCR)方法，而GSTP1基因使用 PCR- restriction fragment length polymorphism (RFLP)方法，分析此三個基因的基因多型性。
結果發現懷孕時期母親吸菸或暴露二手菸，其體內cotinine濃度較高則會明顯增加不良的出生結果且具有劑量效應的關係，不良出生結果包括出生體重較低、懷孕週數較短、身長較短、頭圍較短。另外，在嬰兒神經行為發展方面，發現GSTT1, GSTM1, GSTP1等代謝基因與cotinine濃度之間的交互作用可能會與嬰兒神經行為發展有關係。

關鍵字

出生結果 ； 早產 ； 低出生體重 ； 性別比 ； 戴奧辛 ； 焚化爐 ； 抽菸 ； 環境二手菸 ； cotinine ； 神經行為發展 ； 出生體重 ； 頭圍 ； 胸圍 ； 身長 ； 懷孕週數 ； 中文版神經行為評估量表 ； 嬰幼兒綜合發展測驗

並列摘要

Thesis 1. Adverse Birth Outcomes near Municipal Waste Incinerators in Taiwan
Nowadays, the adverse influence of municipal waste incinerators on human health is both suspected and feared. Relevant studies are ongoing, especially in Taiwan, with its high densities of population and waste incinerators. Because there have been inconsistent conclusions on the reproductive health effects of waste incinerator emissions, we tried to investigate that the relationship between the exposure to waste incinerators and pregnancy outcomes such as preterm delivery, low birth weight, small for gestational age, and infant gender. Study areas were based on the research results of “ Health Risk Assessment on Incinerator-Emitted Dioxins in Taiwan”. The industrial source complex short-term model was used to determine the dioxins impact areas. A geographic information system was then used to plot the simulated results. All birth data would be linked from the birth registration database to do statistical analysis. We did not find any relationships between exposure to waste incinerators and adverse birth outcomes.

Thesis 2. Cotinine, Genetic Polymorphism, and Infant Growth and Neurobehavioral Development
More and more people emphasize that the women health effects of smoking and environmental tobacco smoke (ETS) exposure in recent years, especially the harm on pregnant women may affect their fetal, such as low birth weight (LBW). However, there are few studies about the association between smoking or ETS exposure among pregnant women and neurobehavioral development of their fetal. At present, associations between birth outcomes and smoking or ETS exposure have been investigated in many studies, however exposures to environmental and genetic factors in the etiology of adverse neurobehavioral development for infants are still not clear.
We analyzed cotinine concentrations from maternal blood and umbilical cord blood, and evaluated the association among cotinine level, fetal growth, and neonate neurobehavioral development. In addition, we tried to understand the contribution from environmental exposure and genetic modification for the neurobehavioral development of neonate and children.
Our study subjects were pregnant women and their neonates from the pilot of Taipei Birth Panel Study (TBPS) between April 2004 and January 2005, and a total of 328 maternal-newborn pairs. The cotinine concentrations of maternal bloods and umbilical cord bloods were analyzed with high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC/MS/MS). For all neonates, neonatal neurobehavioral performance at two to five days after delivery is measured by Neonatal Neurobehavioral Examination in Chinese version (NNE-C). During six months of age, Infant/Toddler HOME of Home Observation for Measurement of the Environment Inventory (IT-HOME) and Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT) were used to measure the performance of cognition and movement of infants. GSTT1, GSTM1and GSTP1 genetic polymorphisms were analyzed by polymerase chain reaction (PCR) method.
Maternal smoking or ETS exposure during pregnancy negatively affects birth outcomes obviously, including birth weight, gestational age, birth length, and head circumference, and negatively affects neurobehavioral development, especially in motor performance. In addition, adverse effects of maternal smoking or ETS exposure on neurobehavioral development could be modified by metabolic genotypes, possibly by GSTT1, GSTM1, and GSTP1. There was a suggestive increase in risk for the newborn or maternal carrying more variant genotypes of GST1, GSTM1, and GSTP1.

並列關鍵字

very preterm ； preterm delivery ； very low birth weight ； low birth weight ； small for gestational age ； sex ratio ； dioxins ； incinerator ； smoking ； environmental tobacco smoke (ETS) ； cotinine ； birth outcomes ； neurobehavioral development ； birth weight ； head circumference ； chest circumference ； length ； gestational age ； neonatal neurobehavioral examination in Chinese version (NNE-C) ； infant/toddler home observation for measurement of the environment inventory (IT-HOME) ； comprehensive developmental inventory for infants and toddlers (CDIIT) ； polymerase chain reaction (PCR)

參考文獻

13. Hsieh W, Wu H, Jeng S, Liao H, Su Y, Lin S, et al. Nationwide Singleton Birth Weight Percentiles by Gestational Age in Taiwan, 1998-2002. Acta Paediatr Tw 2006;47:25-33.

24. Lin CM, Li CY, Mao IF. Ambient dioxin exposure to incinerators inassociation with adverse birth outcomes. Taiwan J Public Health 2002;21:197-206.

34. Chen PC, Doyle PE, Pain L, Wang JD. Parental socioeconomic status and low birthweight, preterm delivery, and small for gestational age in Taiwan. Chin J Public Health 1999;18:105-115.

58. Liao HF, Wang TM, Yao G, Lee WT. Concurrent validity of the Comprehensive Developmental Inventory for Infants and Toddlers with the Bayley Scales of Infant Development-II in preterm infants. J Formos Med Assoc 2005;104:731-7.

Thesis 1. Adverse Birth Outcomes near Municipal Waste Incinerators in Taiwan