胎兒及早期兒童暴露於全氟烷基物質對甲狀腺激素之影響

Abstract

研究背景：全氟以及多氟烷基物質（Per- and Polyfluoroalkyl Substances）為一種化學結構非常穩定的人造材料，因此它自1930年代被發明之後，已經長時間與我們的生活息息相關。舉凡不沾鍋、防油包材、防水衣物、防污地毯等，皆有非常高的機率添加PFAS在其表面。PFAS在環境中半衰期非常持久，此原因也連帶的影響到易感族群：懷孕婦女、胚胎以及生長中的孩童暴露後所衍生的健康效應。本研究針對產前以及孩童時期PFOS、PFOA暴露對於孩童神經、腦部生長、學習有高度相關的荷爾蒙：甲狀腺激素之間的關聯來進行分析。 研究方法：研究探討台灣出生世代研究（Taiwan Birth Panel Study 1）2004至2005年出生的187位孩童。2004及2005年收集之臍帶血中PFOS、PFOA濃度視為孩童產前暴露；2013年收集之孩童血清中PFOS、PFOA視為孩童時期暴露，並皆於此兩時期收集結構化之問卷綜合考慮母親、胎兒、孩童之健康及生活情況。分析方法運用多元線性迴歸模型分別探討產前以及孩童時期之PFOS、PFOA暴露對於孩童9歲時期甲狀腺荷爾蒙之影響。在研究最後同時探討兩個橫斷式研究。分別為臍帶血中PFAS和甲狀腺激素之關聯性；以及9歲孩童產後暴露於PFAS對於其當下甲狀腺激素之相關性。 研究結果：在校正相關干擾因子後，產前PFOS暴露和9歲孩童的甲狀腺激素T3和Free T3具有高度的正相關性，且呈現統計上的顯著（p < 0.05）；然而孩童時期PFOS之影響並未觀察到此現象。產前PFOA暴露和孩童甲狀腺激素T3和T4之間具有邊緣顯著之正相關性（p < 0.1），然而孩童時期PFOA暴露並未觀察到和甲狀腺激素之相關性。臍帶血中的橫斷式研究顯示，產前PFOS暴露和TSH間顯著正相關（p < 0.05）但與T4顯著負相關（p < 0.05）。相比於女生，男生甲狀腺激素對於產前暴露於PFOS較為敏感。9歲時期的橫斷式研究顯示，孩童產後PFOS暴露和其TSH之間呈現邊緣顯著之負相關性（p < 0.1）。在性別的分層分析，男生對於PFOS之暴露在甲狀腺激素的變化上較為敏感。 研究結論：在許多過往研究已經證實懷孕婦女之PFAS暴露會影響新生兒的甲狀腺激素高低，本追蹤型的研究更進一步的發現到胎兒時期的PFOS、PFOA暴露，相較於孩童時期暴露，於9歲孩童的甲狀腺激素有更顯著影響。此意味胚胎時期的甲狀腺發育，可能會受到母親的PFAS暴露所干擾。透過本研究結果，寄望未來計畫懷孕之婦女能夠注意自身PFAS暴露對於其孩童長遠之影響。

Background: Per- and polyfluoroalkyl substances (PFAS) are highly stable synthetic materials widely integrated into various aspects of daily life since their invention in the 1930s. They are commonly found in products such as non-stick cookware, oil-resistant packaging, waterproof clothing, and stain-resistant carpets. PFAS exhibit persistent half-life in the environment, which consequently affects susceptible populations, including pregnant women, embryos, and growing children, leading to potential health effects. This study focuses on analyzing the association between prenatal and childhood exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) and the crucial hormones correlated to neurodevelopment, brain maturation, and learning ability of children, the thyroid hormones. Methods: The study investigated 187 children born in Taiwan between 2004 and 2005 using data from the Taiwan Birth Panel Study 1. PFOS and PFOA concentrations in cord blood collected in 2004 and 2005 were considered prenatal exposure, while serum PFAS concentrations collected in 2013 were considered childhood exposure. Structured questionnaires collected data on maternal, fetal, and child living and health conditions during both periods. Multiple linear regression models were utilized to examine the impact of prenatal and childhood PFOS and PFOA exposure on thyroid hormone levels in children at the age of 9. Furthermore, this study combined the research conducted by Tsai et al, the cross-sectional analysis of PFAS exposure and thyroid hormones in cord blood. Lastly, we further analyzed the cross-sectional analysis of postnatal PFAS exposure and thyroid hormones of 9-year-old children. Results: After adjusting for relevant confounding factors, prenatal PFOS exposure showed a significantly positive correlation (p < 0.05) with thyroid hormone T3 and Free T3 levels in 9-year-old children, whereas no such association was observed with PFOS exposure during childhood. Additionally, prenatal PFOA exposure exhibited a marginally significant positive correlation (p < 0.1) with thyroid hormone T3 and T4 levels in children, although no significant association was noted with PFOA exposure during childhood. The cross-sectional study at birth revealed that prenatal exposure to PFOS was significantly positively associated with TSH level and negatively associated with T4 level (p < 0.05). Boys demonstrated a more pronounced sensitivity to the effects of prenatal PFOS exposure on thyroid hormones compared to girls. The cross-sectional study in 9-year-old children revealed a marginal negative correlation between childhood PFOS exposure and TSH levels (p < 0.1). In gender-stratified analysis, boys exhibited a higher sensitivity to PFOS exposure in thyroid hormone variations. Conclusion: While previous studies had demonstrated the impact of PFAS exposure in pregnant women on newborn thyroid hormones, this longitudinal study further indicated that prenatal PFOS and PFOA exposure significantly affected thyroid hormone levels in 9-year-old children compared to childhood exposure. This suggested that thyroid development during embryonic stages might be disrupted by maternal PFAS exposure. Considering these findings, it is recommended that future interventions prioritize initiatives to enhance awareness among pregnant women regarding the enduring implications of PFAS exposure for their offspring.