極低出生體重早產兒體內甲基汞濃度對神經發展之影響

The Relationship between Methylmercury Level on Early Neurodevelopment Effects in Very Low Birth Weights Preterm Infants

陳怡甄(Yi-Jhen Chen)

指導教授 ： 簡伶朱

臺北醫學大學/公共衛生暨營養學院/公共衛生學系暨研究所/碩士(2015年)

https://doi.org/10.6831/TMU.2015.00045

摘要

背景:甲基汞具人類神經毒性，兒童為易感受族群，而魚類攝取為人體甲基汞暴露的主要方式之一，魚體內豐富的ω−3多元不飽和脂肪酸卻為人體腦部發展重要營養來源。過去的研究多關心甲基汞暴露對於學齡前兒童神經發展之影響，較少研究關心甲基汞暴露對極低出生體重早產兒(Very Low Birth Weight, VLBW; 出生體重≤1500g)之影響。因此，本研究欲探討極低出生體重早產兒體內甲基汞濃度對於幼兒認知、語言、動作評估分數之影響並比較其與一般出生體重且足月兒(Normal Birth Weight, NBW; 出生體重>2500g且週產數>37週)體內甲基汞濃度之差異。
方法:本研究以預產期2010年10月起至2012年4月矯正年齡2歲之極低出生體重早產兒為研究對象，足月兒於馬偕醫院健兒門診進行收案。向研究對象之法定代理人說明目的並獲同意書後，進行問卷訪視並收集頭髮、手指甲樣本。頭髮、手指甲經清洗後、利用甲基汞蒸餾系統(Methyl Hg Distillation System)、甲基汞分析系統(MERX integrated automated MeHg analyzer)進行濃度分析，並以感應耦合電漿質譜儀(Inductively Coupled Plasma Mass Spectrometry, ICP-MS)測定鉛、鎘、砷、硒濃度。
結果:本研究共納入65名極低出生體重早產兒及87名一般出生體重且足月兒，兩組頭髮、手指甲甲基汞、砷濃度以一般出生體重且足月兒顯著較高，手指甲硒濃度以極低出生體重早產兒顯著較高。以兒童妊娠週數中位數進行分層，妊娠週數≥37週兒童神經發展評估分數皆顯著高於妊娠週數<37週兒童。將兒童量表分數以常模平均值10分區分為兩組，經年齡、性別調整後，兒童妊娠週數低且頭髮甲基汞濃度高認知、接受性語言、表達性語言、精細動作發展較不好危險對比值與信賴區間分別為高妊娠週數且低頭髮甲基汞濃度兒童的4.08倍(95% CI= 1.07-15.56)、3.84倍(95% CI= 1.07-13.84)、6.41倍(95% CI= 1.58-25.99)、6.71倍(95% CI=1.69- 26.60)，皆達趨勢顯著，顯示隨著兒童妊娠週數愈低且頭髮甲基汞濃度愈高，認知、接受性語言、表達性語言、精細動作發展愈不好，但加入基本人口學特徵、其他重金屬等多變項進行調整後，危險對比值下降且未達統計上顯著。極低出生體重早產兒妊娠週數≥29週兒童認知發展、表達性語言量表分數、語言組合、動作發展分數顯著高於妊娠週數< 29週兒童。極低出生體重早產兒頭髮甲基汞≥0.5 μg/g之兒童在認知組合、語言組合、接受性語言、表達性語言量表分數有低於頭髮甲基汞<0.5 μg/g兒童的趨勢雖未達統計上顯著。極低出生體重早產兒妊娠週數愈低且頭髮甲基汞濃度愈高之兒童認知、語言、動作組合分數、認知量表分數顯著愈低。
結論:本研究顯示較低妊娠週數相對甲基汞、其他重金屬暴露為顯著造成極低出生體重早產兒有較低發展評估分數之重要因子，但隨著妊娠週數愈低、甲基汞濃度愈高，極低出生體重早產兒神經發展分數較低的機率也較高。兒童體內甲基汞濃度則是會受海水魚類攝取、家庭社經地位、哺餵母乳時間長短影響。

關鍵字

極低出生體重早產兒 ； 一般出生體重且足月兒 ； 甲基汞 ； 頭髮 ； 手指甲 ； 貝萊嬰幼兒發展量表第三版

並列摘要

Background
Methlymercury (MeHg) is the most toxic form of mercury and children’s nervous system are sensitivity to its toxicity. Fish is the major exposure pathway of MeHg to humans because it is also concumed for its variety of proteins and omega-3 fatty acid, which are important for brain development. The neurotoxicity of MeHg to preschool children has been well documented but few have studied the neurotoxicity for very low birth weight (VLBW) preterm infants. The purpose of this study was to investigate the relationship of hair MeHg levels and nail MeHg levels to cognitive, language, and motor developments in VLBW preterm infants; the study also compares this relationship between VLBW preterm infants and children with birth weights above 2500g and gestation above 37 weeks.
Methods
The study subjects in our study collected whose estimated date of confinement (EDC) was form October 2010 to April 2012. Personal interview and biospeciment of hair and nail were conducted after participants’ informed consents were obtained. The level of MeHg in hair and nail were analyzed using a MERX system with cold vapor
atomic fluorescence spectrophotometry. The level of lead, cadmium, arsenic, and seleniumin hair and nails were analyzed by inductively coupled plasma mass spectrometry (ICP-MS).
Results
We recruited 65 VLBW preterm infants and 86 normal birth weight infants in our study. Hair MeHg, nail MeHg and nail arsenic of NBW were significantly higher than those of VLBW, but nail selenium of NBW was significantly lower than that of VLBW. The gestational age (GA) was dichotomized at ≥ 37 weeks. We found that children with lower GA and they appeared to have a lower cognitive, language and motor scores. All children were used normal average scaled scores to classify into two groups. After we adjusted age and sex, we found children with lower GA and higher hair MeHg had 4.08(95% CI= 1.07-15.56), 3.84(95% CI= 1.07-13.84), 6.41(95% CI= 1.58-25.99) and 6.71(95% CI=1.69- 26.60) folds higher risk appeared to have lower cognitive, receptive communication, expressive communication and fine motor scores. However, after adjusting the demographic characteristics, heavy metals, and other variables, we did not observe any significant difference. VLBW preterm infants with higher GA (≥ 29 weeks) had significantly higher cognitive, expressive communication and motor scores. VLBW preterm infants with higher hair MeHg (≥0.5 μg/g) had lower cognitive, language and motor scores but not significant. However we found VLBW preterm infants with lower GA and higher hair MeHg had lower cognitive, language and motor scores.
Conclusion
The study shows that lower GA was the most important risk factor for children with lower developmental performance. Increased saltwater fish consumption, low socioeconomic level, and duration of breastfeeding are critical risk factors for MeHg levels in children and may cause a lower developmental performance.

並列關鍵字

Very low birth weight preterm infants ； Normal birth weight infants ； Methylmercury ； Hair ； nail ； Bayley Scales of Infant and Toddler Development (Bayley-III)

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