評估多氯聯苯與重金屬暴露對新生兒出生結果與神經行為發展之影響

Abstract

背景： 多氯聯苯與重金屬之暴露與許多健康效應有關。一般大眾因其在環境上具持久性與生物累積性而可能長期暴露到這兩大類污染物。在台灣，多氯聯苯已於2001年禁止使用，重金屬則廣泛使用於日常生活或工業製程。儘管多氯聯苯和重金屬在禁用與限制使用的情況下，仍有流行病學研究表明，產前暴露於多氯聯苯和重金屬可能會將這些污染物傳遞給新生兒並影響其出生結果。在台灣，並無研究同時利用臍帶血追蹤其新生兒體內多氯聯苯、重金屬濃度。產前暴露於多氯聯苯、重金屬對其新生兒健康影響、新生兒神經行為發展之間的關聯性仍不清楚。因此，本研究的目的將檢測臍帶血中多氯聯苯、重金屬濃度，藉以探討新生兒體內暴露情形。觀察臍帶血中多氯聯苯、重金屬濃度是否對新生兒之出生之身長、體重、頭圍以及神經行為發展有所影響。 材料和方法： 研究對象為居住在台灣彰化縣和雲林縣的100對母子對。藉由問卷調查收集100位母親，包括母親年齡、母親身體質量指數、懷孕週數，與100位新生兒之基本資料，包括新生兒性別、新生兒胎次。其出生結果部分，我們收集了出生體重、出生身長、出生頭圍。為了評估新生兒一歲前之神經行為發展，我們使用中文版新生兒神經行為評估量表 (The Neonatal Neurobehavioral Examination- Chinese Version，NNE-C)以了解孩童之神經發育狀況，其量表包含肌肉張力與動作型態、原始反射、行為反應3大項目，共27題。並且使用嬰兒氣質評估問卷 (Infant Temperament Questionnaire，ITQ)以評估對內外在刺激的反應方式，其問卷包含 活動量、規律性、趨避性、適應性、反應強度、情緒本質、堅持度、注意力分散度、反應閾9大項目，共95題。 生物檢體的部分，我們收集這100位新生兒之臍帶血的血清樣本。藉由氣相色譜-負離子化學電離-四極桿質譜儀 (GC-NICI-qMS)分析其臍帶血血清中 PCB28、PCB60、PCB66、PCB74、PCB99、PCB105、PCB118、PCB126、PCB138、PCB146、PCB153、PCB156、PCB170、PCB177、PCB178、PCB180、PCB183、PCB187、PCB194、 IV PCB199、PCB201、PCB206、PCB209等23種多氯聯苯異構物之濃度。透過感應耦合電漿質譜儀 (ICP-MS)分析 釩、鉻、錳、鎳、砷、鎘、鉛等7種重金屬之濃度。 利用多元線性迴歸了解產前多氯聯苯、重金屬暴露分別對於新生兒出生結果、神經行為和氣質的影響。並利用加權迴歸分析 (WQS regression model)了解產前多氯聯苯、重金屬暴露對於新生兒出生結果、對其神經行為發展、氣質影響之主要貢獻污染物。上述統計分析皆校正母親之年齡、身體質量指數、懷孕週數與嬰兒之性別及胎次。 結果： 分析結果發現100位新生兒臍帶血血清樣本中，有PCB138、PCB153、PCB156、PCB170、PCB177、PCB180、PCB187、PCB194、PCB201等9種多氯聯苯異構物與釩、鉻、錳、鎳、砷、鎘等6種重金屬，其可偵測率高於50%，我們進一步探討這些污染物之濃度與其對出生結果與神經行為發展之相關性。 其中濃度前三高之多氯聯苯異構物依序為PCB138、PCB153、PCB180 (17.28±16.84、11.50±15.12、8.09±14.10 pg/g wet weight)。濃度前三高之重金屬依序為錳、鎳、鉻 (9.38±2.66、4.88±2.28、2.93±1.65μg/L)。在出生結果部分，與出生體重呈顯著負相關有PCB153、PCB156、PCB170、PCB177、PCB180、PCB187、PCB194等7種多氯聯苯異構物，與出生頭圍呈顯著負相關有PCB153、PCB156、PCB177、PCB180、PCB187、PCB194、PCB201等7種多氯聯苯異構物。在神經行為發展部分，與原始反射 (primitive reflexes)呈顯著負相關為PCB153。在氣質問卷部分，與活動量 (activity level)呈顯著負相關為PCB177。與規律性項目 (rhythmicity)呈顯著負相關為PCB153。與適應性項目 (adaptability)呈顯著負相關為PCB180和鉻。與反應強度項目 (intensity of reaction)呈顯著正相關為PCB180、錳和鎳。 WQS結果發現，在出生結果部分，造成新生兒出生體重下降之主要貢獻者依序為PCB177、PCB156、PCB194、PCB180，造成新生兒出生頭圍減少之主要貢獻者依序為PCB156、PCB177、PCB201、PCB153。在氣質問卷部分，使活動量 (activity level)下降之主要貢獻者為鉻，使反應強度 (intensity of reaction)增強之主要貢獻者為錳。 V 結論： 與新生兒之出生體重下降及頭圍減少皆具相關性有PCB153、PCB156、PCB177、PCB180、PCB187、PCB194等6種多氯聯苯異構物。PCB153與新生兒神經行為發展遲緩具相關性。PCB153、PCB177、PCB180等3種多氯聯苯異構物和鉻、錳、鎳、鎘等4種重金屬之暴露會影響其新生兒氣質發展。在多氯聯苯禁用多年後，仍可以觀察到其暴露對新生兒之影響，建議未來進一步探討其可能暴露來源並追蹤其可能造成之健康影響。

Abstract Introduction: Exposure to polychlorinated biphenyls (PCBs) and heavy metals have been associated with many health effects. General population exposed to these pollutants continuously due to the nature of persistence and bioaccumulation of these pollutants. PCBs were banned in 2001, heavy metals were still widely used in Taiwan. Although the limitation and prohibition of the pollutants, several epidemiologic evidences still indicated that maternal exposure to PCBs and heavy metals may pass these pollutants to infants and impact their’ birth outcomes. However, the association between two kinds of pollutants exposure in fetus, PCBs and heavy metals, and birth outcomes and neurodevelopment are not clear in Taiwan. Therefore, the aim of this study was to investigate the association between the two groups of pollutants, PCBs and Heavy Metals, and fetus' birth outcomes and neurodevelopment in cord blood in Taiwan. Materials and Methods: Participants of this study was obtained from a cohort of 100 mother-child pairs who lived in Changhua and Yunlin counties in Taiwan. We used questionnaire to collect the data of 100 maternal participants (maternal age, maternal BMI and gestation period) and 100 fetal participants (fetus’s gender and parity). And, we collected the 100 fetal participants’ information of birth outcomes (birth weight, birth length and birth head circumference). To assess fetus’ neurodevelopmental skills before one-year-old, we used Neonatal Neurobehavioral Examination-Chinese version(NNEC) to evaluate their neonatal neurological status. The NNEC is a 27-item questionnaire designed for assessing 3 sections (tone and motor patterns, primitive reflexes and behavioral responses). In addition, we used Infant Temperament Questionnaire (ITQ) to assess fetal responsiveness to the internal and external stimuli. The ITQ consists of a 95-item questionnaire for assessing 9 temperament characteristics (activity, rhythmicity, approach, adaptability, intensity , mood, persistence, distractibility, threshold). For biospecimen, we collected 100 cord serum samples from fetal participants. The 23 PCB congeners levels (PCB28, PCB60, PCB66, PCB74, PCB99, PCB105, PCB118, PCB126, PCB138, PCB146, PCB153, PCB156, PCB170, PCB177, PCB178, PCB180, PCB183, PCB187, PCB194, PCB199, PCB201, PCB206, PCB209) in cord serum VII samples were measured by gas chromatography-negative ion chemical ionization- quadrupole mass spectrometry (GC-NICI-qMS) and the 7 kinds of heavy metals (V, Cr, Mn, Ni, As, Cd, Pb) were measured by inductively coupled plasma mass spectrometry (ICP-MS). To investigated the relationships of pollutants levels (PCBs levels and heavy metals levels) with questionnaire data (birth outcomes and neurodevelopment scales) determined by the multiple linear regression analysis. To estimate association between main contribution in a set of two groups of pollutants and fetus’ health outcomes used by Weighted Quantile Sum (WQS) regression. TheThe aboveabove mentionedmentioned modelmodels were adjusted by maternal age, maternal BMI, gestation period, fetus’s gender and parity. Results: A After analyzing the fter analyzing the cord serum samples of 100 fetal participants, the detectable rate of 9of 9 PCB congeners (PCB138, PCB153, PCB156, PCB170, PCB177, PCB180, PCB187, PCB194, PCB201) and 6 kinds of heavy metals (V, Cr, Mn, Ni, As, Cd) were higher than 50%. And we further investigated the correlation between the concentration of these pollutants and the birth outcomes and neurobehavioral development. The three highest levels of PCB congeners in descending order were PCB138, PCB153, and PCB180 (17.28±16.84, 11.50±15.12, 8.09±14.10 pg/g wet weight, respectively). The top three of the highest levels of heavy metals in descending order were Mn, Ni, Cr (9.38±2.66, 4.88±2.28, 2.93±1.65μg/L, respectively). In the birth outcomes section, the levels he levels of 7 PCB congeners (PCB153, PCB156, PCB170, PCB177, PCB180, PCB187, PCB194) were significantly negatively correlated with birth weight.. The levels The levels of 7 PCB congeners (PCB153, PCB156, PCB177, PCB180, PCB187, PCB194, PCB201) were significantly negatively correlated with head circumference. In the NNEC section, PCB153 was significantly negatively correlated with primitive reflexes. In the ITQ section, PCB177 was significantly negatively correlated with activity level. PCB153 was significantly negatively correlated with rhythmicity. PCB180 and Cr were significantly negatively correlated adaptability. PCB180, Mn and Ni were significantly positively correlated with intensity of reaction. As to WQS analysis, in birth outcomes section, the significant association between the high contribution in descending order were PCB177, PCB156, PCB194, PCB180 and decreased birth weight, and a significant negative association between the high VIII contribution in descending order were PCB156, PCB177, PCB201, PCB153 and decreased birth head circumference. And in the ITQ section, the strongest significant association between the levels of Cr and activity decline (activity level), and strongest significant association between the levels of Mn and increase of intensity of reaction. Conclusion: The exposure of 6 PCB congeners (PCB153, PCB156, PCB177, PCB180, PCB187, PCB194) were significantly associated with the decreased birth weight and birth head circumference. The exposure of PCB153 was significantly correlated to the developmental delays for fetus. The exposure of 3 PCB congeners (PCB153, PCB177, PCB180) and 4 heavy metals (Cr, Mn, Ni, Cd) were significantly associated with the change of temperament in fetus. After PCBs were banned for two decades, we still found that prenatal exposure can affect fetus’ birth outcomes and neurodevelopment, and more research is needed to clarify the possible exposure source and the adverse health effect.