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  • 學位論文

極低出生體重早產兒體內砷濃度、砷甲基化代謝能力對神經發展的影響

The relationship between arsenic concentration and arsenic methylation profiles on early neurodevelopment effects in very low birth weights preterm infants

指導教授 : 簡伶朱

摘要


砷為一級致癌物質,具神經毒性會對神經系統造成影響,過去研究指出兒童暴露於砷對其生長發育、神經發展情形有害,極低出生體重早產兒 (very low birth weight, VLBW) (出生體重小於或等於1500公克)出生後前兩年神經發展預後會影響未來學齡期及青春期的發展,故其幼兒時期環境污染物的累積暴露量為一急需被重視的議題。過去的研究發現兒童早期砷暴露、砷甲基化能力與神經發展間未有明確一致的結果。因此本研究目的是探討極低出生體重早產兒尿液砷濃度、砷甲基化能力以及腳趾甲累積總砷濃度對其認知、語言、動作發展之影響。本研究以預產期2010年10月起至2012年4月止出生之早產兒,收集兒童矯正年齡2歲時的尿液與腳趾甲作為評估砷暴露與累積之生物檢體,兒童在追蹤期間6個月、1歲、2歲時於醫院以貝萊嬰幼兒發展評估量表第三版進行評估,項目包括認知、語言、動作發展。生物檢體分析,尿液使用HPLC-HG-AAS (高效液相層析儀氫化器原子吸收光譜儀)分析尿液砷物種,腳趾甲水浴消化後使用ICP-MS (感應耦合電漿質譜儀)分析總砷濃度。 本研究共納入60名個案,尿液總砷濃度平均值為28.6 μg/g creatinine (肌酸酐校正後)、無機砷濃度平均值為1.01 μg/L,無機砷百分比、單甲基砷酸百分比、雙甲基砷酸百分比平均值分別為3%、2%、95%,一級甲基化指標、二級甲基化指標分別為1.29與136,腳趾甲累積總砷濃度平均值225 ng/g。尿液砷濃度、砷甲基化能力指標、腳趾甲累積總砷濃度與6個月、1歲、2歲時的生理指標、貝萊嬰幼兒發展量表評估結果沒有顯著相關性,而出生時的生理指標,如:體重、頭圍、懷孕週數等,與6個月、1歲、2歲時的貝萊嬰幼兒發展量表評估結果整體呈現顯著相關性。結果顯示本研究中的極低出生體重早產兒有較低的砷暴露情形,即砷甲基化指標DMA5+%為95%。建議未來的研究可同時分析可能對神經發展有影響的有害物質,例如鉛、鎘、汞、多氯聯苯等,可進一步釐清體內砷濃度對兒童神經發展的影響。

並列摘要


Arsenic has been classified as a “group 1 carcinogen” by the International Agency for Research on Cancer and it could affect the nervous system. Few researches have shown that children exposed to arsenic could affect to their growth and neurodevelopment. The neurological prognosis of the very low birth weight (VLBW) preterm infants at first two years will influence their neurodevelopment during school-age and adolescent. Thus, children exposure to environmental contaminants should be paying more attention in the postnatal period. The purpose of this study was to investigate the relationship between urine arsenic concentrations, arsenic methylation capability and toenail accummulated arsenic concentration on cognitive, language and motor developments. The participants in our study were recruited from October 2010 to April 2012. The urine and toenail samples were collected as a biomarker to assess arsenic exposure. The Bayley scales of infant development III was used to evaluate the cognitive, language, and motor development at 6, 12, 24 months of corrected age. The level of arsenic speciation in urine was analyzed using HPLC-HG-AAS. The level of arsenic in toenails was analyzed using ICP-MS after water bath digested. Total of 60 eligible VLBW preterm infants were enrolled. The average concentration of total arsenic was 28.6 μg/g creatinine, and inorganic arsenic was 1.01 μg/L in urine. Child urine contained on average 3% inorganic arsenic, 2% monomethylarsonic acid, and 95% dimethylarsinic acid. The primary arsenic methylation index and secondary arsenic methylation index was 1.29 and 136, respectively. The average cumulative concentration of arsenic in toenails was 225 ng/g. Urinary arsenic concentrations, arsenic methylation capability index, and toenail arsenic concentration was not significantly correlated with growth development at 6 months, 1 year, and 2 yearsold. We also found that postnatanl arsenic exposure did not show significant influence on neurological development. The gestation, weight, and head circumference at birth were significantly correlated with the neurological development at 6 months, 1 year, and 2 years old. Our study results suggested that VLBW preterm children have a low-level arsenic exposure. We recommend that further study may simultaneously analyze multiple environmental contaminants such as lead, cadmium, mercury, and PCBs that may have adverse effects on neurodevelopment. To better understand the influence of arsenic exposure on neurodevelopment.

參考文獻


第七章 參考文獻
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