胎兒時期汞暴露與兒童成長及發展

Abstract

背景及目的：甲基汞已被確證實是一種具有神經毒性和致畸胎毒性的重金屬衍生物。在過去的動物實驗以及甲基汞汙染事件發現發育中的胎兒對於甲基汞毒性相較於成人更為易感。食用較大型的海水魚為人類暴露到甲基汞最主要的暴露途徑之一。不過，在一般吃魚族群的研究當中，胎兒時期甲基汞對於兒童神經發展與發育之影響的發現並不一致。而導致結果不一致的其中一個主要原因，被認為是因為海水魚類富含多種有益於胎兒和兒童成長發育的營養成分，例如：多元不飽脂肪酸、維生素A、B、D等，稀釋或抵銷了甲基汞的危害。然而，這並非唯一的解釋。易感基因在不同族群的分佈差異也可能是導致結果不一致的原因。本研究的目的為探討胎兒時期汞暴露與不同APOE基因多型性對兒童神經行為發展的影響。另外，探討胎兒時期汞暴露對嬰幼兒生長之長期影響以及討論其在不同性別之影響上有無差異。 方法：本研究之對象為在2004年5月至2005年1月間，參與台灣出生長期追蹤研究之486對母嬰配對。我們在產前以結構式問卷訪視母親，以了解母親懷孕期間之暴露和基本人口學資料。在生產時收集臍帶血，以感應藕合電漿質譜儀（Inductively Coupled Plasma Mass Spectrometry， ICP-MS）測量臍帶血中之總汞濃度，了解胎兒時期汞暴露的情況。同時，並於病歷上摘錄出生結果。在孩童兩歲時，由專業人員以嬰幼兒綜合發展測驗（Comprehensive Developmental Inventory for Infants and Toddlers，CDIIT）為工具進行兒童發展評估。且請家長填寫兒童行為檢核表 （Child Behavior Checklist，CBCL）作為兒童行為之評估。兒童生長資料則是摘錄自兒童健康手冊上紀錄之資料和兒童餐與０－９歲間追蹤活動時之所實際測量之資料。 結果：在探討不同的APOE基因多型性對於汞在兒童發展之影響的研究中，我們發現，在調整前和調整後，只在帶有APOE ε4基因的孩童中有發現臍帶血中的汞濃度對兒童的在CDIIT所有分項測驗皆有發現一致性不良的影響。在兒童行為的方面，將暴露為高低兩組後，我們發現，帶有APOE ε4基因型的孩童有較差（分數越高越不好）的整體的和分項的行為表現總分。進一步在帶有APOE ε4基因型且臍帶血汞濃度大於12

Background. Mercury (Hg) is recognized as a neurotoxin and teratogen. However, prenatal methyl mercury (MeHg) exposure on neurodevelopment among the fish-eating population remains controversial. The benefit of the nutritious elements in fish is insufficient for explaining the controversial finding regarding prenatal mercury (Hg) exposure, and neurodevelopment and child behavioral; the varying frequency of susceptible genes among these populations may shed light on these observations. Prenatal mercury exposure is associated with first two years postnatal growth. How long that this negative impact of prenatal Hg exposure on child growth will remain is and the gender different in susceptible to prenatal mercury exposure on child growth is limited. Objectives. First, we intend to examine and investigate the role of genetic polymorphism of apolipoprotein E (APOE) in different neurodevelopmental and neurobehavioral outcome. Second, we aim to investigate the relation of cord blood Hg concentration and child growth from birth to 9 years of ages and to examine the present of gender different in susceptible to prenatal Hg exposure. Methods. The study population was 486 mother-infant pairs who gave births in Taiwan between August 2004 and January 2005 from Taiwan Birth Panel Study. We interviewed them by a structured questionnaire before delivery, collected umbilical cord blood at birth. Mercury levels in umbilical cord blood were analyzed by using ICP-MS and the detection limited of this method was 0.18 ng /ml. Genetic polymorphisms of Apoe were analyzed by methods of Polymerase Chain Reaction–Restriction Fragment Length Polymorphism. We followed their neurodevelopment and behavior by using the Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT) and Child Behavior Checklist (CBCL) at subjects two years of age. Growth data form birth to 9 years old were extracted from Child Healthcare Handbooks and follow-up studies. Results. For the modification effect of Apoe to mercury on neurodevelopment, the results showed that adverse effects on neurodevelopment were consistently associated with prenatal Hg exposure in all subtests of CDIIT among