高氯酸鹽、硝酸鹽及硫氰酸鹽常用於工業、軍事、農業中，可能藉由生產、使用、儲存及廢棄等過程而排放至環境中，因其具有高水溶性與高穩定性之特性，易造成廣泛環境污染，民眾可能從食物、土壤、空氣及飲用水等暴露高氯酸鹽、硝酸鹽、硫氰酸鹽，其中飲食攝入被認為主要暴露途徑。過去動物實驗發現暴露於高濃度高氯酸鹽、硝酸鹽及硫氰酸鹽會抑制碘離子吸收，進而影響甲狀腺荷爾蒙之合成。懷孕初期胎兒之大腦及中樞神經發育需仰賴母體之甲狀腺荷爾蒙，懷孕婦女若因長期暴露於高氯酸鹽、硝酸鹽及硫氰酸鹽，是否影響懷孕婦女甲狀腺荷爾蒙平衡，進而影響胎胎兒發育？為近年各國流行病學研究探求之議題。但國內目前針對人體高氯酸鹽、硝酸鹽及硫氰酸鹽等甲狀腺干擾物質暴露評估與影響甲狀腺功能之研究相對較少，尤其是敏感族群（懷孕婦女及胎兒），因此亟待調查研究。
本研究自成大醫院婦產科門診招募78位懷孕婦女，並排除其他甲狀腺干擾相關之環境或職業因子暴露、遺傳疾病及已接受荷爾蒙藥物治療者，簽署人體試驗同意書後，進行問卷調查、尿液及血液樣本採集，尿液樣本進行高氯酸鹽、硝酸鹽、硫氰酸鹽及尿碘濃度量測；血液樣本量測甲狀腺荷爾蒙及相關抗體，最後探討暴露高氯酸鹽、硝酸鹽及硫氰酸鹽對其甲狀腺功能之影響情形。78位受試者平均年齡及懷孕週數分別為34歲及12週，其每孕期（第一孕期：0-16週、第二孕期：17-29週、第三孕期：30週-分娩）檢測尿液濃度結果，高氯酸鹽濃度為：9.7 vs. 12.4 vs. 16.8 μg/L、硝酸鹽濃度：330.3 vs. 370.6 vs. 374.2 mg/L、硫氰酸鹽濃度：1101.6 vs. 1998.2 vs. 1871.9 μg/L及尿碘濃度120.0 vs. 143.7 vs. 143.4 μg/L，並發現懷孕婦女之尿碘濃度均低於WHO之建議值（150 μg/L），表示懷孕婦女對碘攝取仍不足。第一孕期中受試者尿液中硝酸鹽、硫氰酸鹽、尿碘、硝酸鹽日暴露量、硫氰酸鹽日暴露量、高氯酸鹽毒性當量濃度（PEC）及甲狀腺干擾物總和濃度指標（TDC）皆顯著低於第二及三孕期濃度（P < 0.05），且隨孕期增加而濃度呈趨勢性上升（P < 0.05）。以日暴露劑量進行分組，高氯酸鹽之高暴露組，血液中T3及T4顯著低於低暴露組（P < 0.05）；硫氰酸鹽之高暴露組，尿碘濃度顯著高於低暴露組，血液中FT3濃度顯著低於低暴露組（P < 0.05）；硝酸鹽之高暴露組，尿碘濃度顯著高於低暴露組，血液中T3及FT3濃度顯著低於低暴露組（P < 0.05）。高氯酸鹽、硝酸鹽及硫氰酸鹽與尿碘濃度四者間互相呈顯著正相關（P < 0.05）。尿中硫氰酸鹽及硝酸鹽濃度與血液中FT4呈顯著負相關，而高氯酸鹽濃度與血中T4濃度呈顯著負相關（P < 0.05）。以複回歸分析並校正干擾因子（年齡、BMI、懷孕週數及尿碘濃度）後，發現尿中高氯酸鹽、硫氰酸鹽濃度、高氯酸鹽日暴露量、硫氰酸鹽日暴露量與尿碘濃度皆呈顯著正相關（β=0.40, P < 0.01；β=0.50, P < 0.01；β=0.40, P < 0.01；β=0.49, P < 0.01）。尿中硫氰酸鹽濃度及硫氰酸鹽日暴露量則與血中FT3呈顯著負相關與TSH濃度呈顯著正相關（β=-0.23, P < 0.05；β=0.35, P < 0.05；）。進一步探討高氯酸鹽、硝酸鹽及硫氰酸鹽影響甲狀腺荷爾蒙平衡之貢獻權重，發現高氯酸鹽影響血中T3及T4濃度降低之貢獻比例較高，分別為74.2及53.4 %，硝酸鹽影響血中FT4濃度之貢獻比例最大（95.9 %）。最後，在暴露源評估中，發現以日暴露量分組後，高暴露組對蔬菜及水果類之攝食量有較高之趨勢，但未達統計上顯著。
綜合以上結果，可知懷孕婦女碘攝取不足情況下，同時暴露環境中暴露高氯酸鹽、硝酸鹽及硫氰酸鹽，而抑制甲狀腺細胞對碘離子吸收，加劇影響甲狀腺荷爾蒙（FT4及FT3）之合成，其中又以高氯酸鹽及硝酸鹽影響貢獻最高。本研究為首篇同時建立懷孕婦女體內甲狀腺干擾物質（高氯酸鹽、硝酸鹽及硫氰酸鹽）之背景濃度並探討其對甲狀腺功能及尿碘濃度干擾情形，未來需增加採樣樣本並進行長期世代研究，以確認其可能影響機制。

The present study was carried to investigate the relationship between the effects of thyroid function and perchlorate, nitrate and thiocyanate exposures of the pregnant women. Seventy eight pregnant women were recruited from obstetrics and gynecology clinics in southern Taiwan. The mean maternal age and recruited gestation week were 24 years and 12 weeks, respectively. Urinary perchlorate, nitrate, thiocyanaye and iodide concentrations were 9.7 vs. 12.4 vs. 16.8 μg/L, 330.3 vs. 370.6 vs. 374.2 mg/L, 1101.6 vs. 1998.2 vs. 1871.9 μg/L and 120.0 vs. 143.7 vs. 143.4 μg/L, respectively. The pregnant women with higher daily intake of perchlorate, nitrate and thiocyanate had significantly lower serum T3, T4 and FT3 than those of the women with low daily intake (all P < 0.05). After adjustments for the confounding factors, urinary levels and daily intakes of perchlorate and thiocyanate were significantly positively associated with UIC (all P < 0.05). Urinary levels and daily intakes of thiocyanate was significantly positively associated with serum TSH and were significantly negatively associated with serum FT3 (all P < 0.05). The results of Weighted Quantile Sum (WQS) regression revealed that perchlorate contributed the highest weight to the reduction of serum T3 and T4; nitrate contributed the highest weight in the reduction of serum FT4. In addition, the women with high perchlorate daily intake consumed more vegetables and fruits. In conclusion, exposures to environment perchlorate, nitrate and thiocyanate may reduce the iodine absorption and disrupt thyroid hormones balance during pregnancy.

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