高氯酸鹽、硝酸鹽及硫氰酸鹽具有高水溶性及穩定性，常用於農業、軍事及工業製造上，可藉由生產、使用、儲存及廢棄過程而排放至環境中，又因其廣泛使用及具持久特性，常在環境水體、土壤、空氣及食物等介質中檢測出，民眾可透過食入、吸入及皮膚接觸等途徑暴露高氯酸鹽、硝酸鹽及硫氰酸鹽，其中飲食攝入被認為是最主要暴露的途徑。過去已有許多動物實驗及流行病學研究均指出，高氯酸鹽、硝酸鹽及硫氰酸鹽進入人體後，會競爭性抑制碘離子通過鈉轉運體，進而抑制甲狀腺荷爾蒙分泌。此外，在懷孕及哺乳期間，新生兒之大腦及中樞神經發育皆需仰賴母體之甲狀腺荷爾蒙及碘攝取，若甲狀腺荷爾蒙分泌不足，則可能影響新生兒生長及大腦發育。過去世界各國皆有較少文獻針對新生兒高氯酸鹽、硝酸鹽及硫氰酸鹽暴露與生長發育間之相關性進行探討，因此亟需進一步探討產前及產後暴露高氯酸鹽、硝酸鹽及硫氰酸鹽是否造成胎兒及新生兒之甲狀腺功能異常及生長發育遲緩。
本研究自成大醫院婦產科及南部母乳庫招募110位懷孕及哺乳期婦女及其生產之120位新生兒，於初步訪視時排除其他環境因子之職業暴露、遺傳疾病或已接受荷爾蒙治療者，簽署人體試驗同意書後，進行問卷調查、尿液、臍帶血及母乳/嬰兒配方奶樣本採集。尿液、臍帶血及母乳/嬰兒配方奶樣本皆進行高氯酸鹽、硝酸鹽、硫氰酸鹽及碘離子量測，且臍帶血樣本亦進行甲狀腺荷爾蒙檢測，此外，並計算高氯酸鹽毒性當量濃度（perchlorate equivalence concentration, PEC），最後探討懷孕婦女產前及產後暴露高氯酸鹽、硝酸鹽及硫氰酸鹽對其新生兒早期發育之影響情形。所有懷孕婦女及新生兒尿液樣本中甲狀腺干擾物質濃度均以硝酸鹽濃度最高；硫氰酸鹽次之；高氯酸鹽濃度最低，並發現懷孕婦女尿碘濃度均低於WHO之建議值（150 µg/L），而新生兒均高於WHO之建議值（100 µg/L），表示孕婦懷孕期間對碘攝取仍不足。新生兒小於一個月及六個月時，母乳中高氯酸鹽及硝酸鹽濃度均顯著高於嬰兒配方奶中濃度；硫氰酸鹽及碘離子濃度則均顯著低於嬰兒配方奶中濃度（P<0.01）。產前暴露先以懷孕婦女日暴露劑量進行分組，懷孕中後期，母體PEC之高濃度組，其新生兒胎齡、出生身長、體重及頭圍均顯著低於低暴露組（P<0.05）；母體高氯酸鹽之高暴露組，其新生兒出生身長、體重及頭圍均顯著低於低暴露組（P<0.05）；母體硝酸鹽之高暴露組，其新生兒胎齡、出生身長、體重及頭圍亦顯著低於低暴露組（P<0.05），此外，第二孕期母體硫氰酸鹽之高暴露組，其新生兒語言能力顯著低於低暴露組（P<0.05）。經creatinine校正後母體尿液中硝酸鹽及硫氰酸鹽濃度與臍帶血血清中硝酸鹽及硫氰酸鹽濃度呈顯著正相關（P<0.05）；懷孕後期，母體尿液中硫氰酸鹽濃度亦與新生兒小於一個月尿液中硫氰酸鹽濃度呈顯著正相關（P<0.05）。經校正影響因子（母親年齡、母親教育程度、新生兒性別、胎齡、多胞胎等）後之複迴歸結果發現，懷孕中後期母體硝酸鹽、尿碘濃度及PEC與其胎齡呈顯著負相關（P<0.05）；母體高氯酸鹽與出生體重呈顯著負相關（P<0.05）。神經發展部分，產前母體高氯酸鹽、硫氰酸鹽及PEC均與語言能力呈顯著負相關（P<0.05）；懷孕後期母體高氯酸鹽亦與動作能力呈顯著負相關（P<0.05）；臍帶血中，高氯酸鹽與動作能力呈邊緣性顯著負相關（P<0.1）；硫氰酸鹽與出生身長呈顯著負相關（P<0.05）；碘離子與出生頭圍呈顯著負相關（P<0.05）。進一步解析產後暴露之影響，以哺乳方式進行分組，餵食母乳之新生兒，其尿液中經creatinine校正之高氯酸鹽、硝酸鹽、尿碘濃度及PEC均顯著高於餵食配方奶之新生兒（P<0.01）；且其身長生長幅度低於餵食嬰兒配方奶之新生兒，但未達顯著差異（P<0.1）。以新生兒日暴露劑量進行分組，小於一個月時，PEC之高濃度組，其胎齡、出生身長及體重皆顯著低於低濃度組（P<0.05）；硫氰酸鹽之高暴露組，其胎齡、出生身長及體重皆顯著小於低暴露組（P<0.01）；硝酸鹽之高暴露組，其胎齡、出生身長、體重及頭圍則皆顯著小於低暴露組（P<0.01）；六個月時，僅硝酸鹽之高暴露組，其身長、體重及頭圍則皆顯著小於低暴露組（P<0.05）。最後，經校正影響因子後之複迴歸結果發現，產後六個月新生兒僅尿碘濃度與動作能力呈顯著負相關（P<0.05）。
綜合以上結果，可知與產後暴露高氯酸鹽、硝酸鹽及硫氰酸鹽相比，產前暴露甲狀腺干擾物質對於胎兒及新生兒之生長及神經發育之影響較鉅，且碘攝取充足，對甲狀腺功能具有保護作用。本研究為首篇同時探討產前及產後高氯酸鹽、硝酸鹽及硫氰酸鹽暴露對新生兒生長及神經發育之影響情形，未來需增加採樣樣本並進行長期世代研究，以確立其可能影響機制。

The objectives of present study are to explore the relationship between prenatal and postnatal perchlorate, nitrate and thiocyanate exposure and early development. 110 pregnant women and 120 neonates were recruited from obstetrics and gynecology clinics and breast milk bank of NCKU Hospital in southern Taiwan. The results showed that the concentration of urinary nitrate was the highest, followed by the urinary thiocyanate, and the urinary perchlorate. The concentrations of perchlorate and nitrate in breast milk were significantly higher than those concentration in infant formula milk(P<0.01). In contrast, the concentration of thiocyanate and iodide in breast milk were significantly lower than those concentration in infant formula milk(P<0.01). During the prenatal exposure, the maternal creatinine-adjusted urinary nitrate and thiocyanate were significantly positively associated with cord blood serum nitrate and thiocyanate(P<0.05). The maternal urinary thiocyanate in the third trimesters was also significantly positively associated with neonatal urinary thiocyanate(P<0.05). After adjusting potential confounders, maternal urinary nitrate, iodide and perchlorate equivalence concentration (PEC) in the second and third trimesters were significantly negatively associated with gestational age(P<0.05). Prenatal maternal perchlorate, thiocyanate and PEC were significantly negatively associated with the ability of language(P<0.05). Maternal perchlorate was also significantly negatively associated with the ability of motor(P<0.05). During the postnatal exposure, urinary concentration of perchlorate, nitrate, iodide and PEC of breast-fed neonates were significantly higher than formula-fed neonates (P<0.01). Body length of breast-fed neonates was lower than formula-fed neonates but showed no significant difference (P<0.1). After adjusting potential confounders, neonatal urinary iodide was significantly negatively associated with the ability of motor (P<0.05). In conclusion, the prenatal exposure to perchlorate, nitrate and thiocyanate may affect neonatal growth and neurodevelopment than postnatal exposure.

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