台灣懷孕婦女及新生兒暴露塑化劑與血清中甲狀腺功能影響之相關性研究

Relationship of urinary concentrations of 9 phthalate metabolites with serum thyroid hormones in pregnant women and their newborns in Taiwan

蘇聖雯(Sheng-Wen Su)

指導教授 ： 吳登強

高雄醫學大學/醫學院/醫學研究所/碩士(2013年)

摘要

背景與目的: 越來越多的動物和流行病學研究說明，在環境中的化學物質可以影響調節甲狀腺賀爾蒙的功能。然而，懷孕的婦女與新生兒方面目前只有少數研究報導了塑化劑暴露對甲狀腺功能的影響。本研究目的是想了解台灣地區孕婦暴露塑化劑的風險和他們的甲狀腺荷爾蒙濃度，並探討其新生兒臍帶血中甲狀腺荷爾蒙濃度與產婦塑化劑暴露之相關性。
材料與方法: 本研究分析了281對孕婦和新生兒。我們對每一位孕婦做問卷訪視，也收集了他們在孕晚期的尿液和分娩時的血液樣本及臍帶血樣本。運用液相層析串聯質譜儀（LC-ESI-MS/MS）分析尿液樣本中九種塑化劑代謝物的濃度（MEHP、MEOHP、MEHHP、MiBP、MnBP、MEP、MBzP、MMP、MiNP）。運用酵素免疫分析(EIA)與化學發光免疫分析（CLIA）檢測孕婦靜脈血和新生兒臍帶血中甲狀腺荷爾蒙（TSH、T4、T3、Free T4）。此外，我們藉由DEHP代謝物濃度計算回推其台灣孕婦DEHP的暴露量。
結果:
（1） 我們研究發現，使用玻璃和塑膠容器(5號pp材質)收集並檢測尿液中塑化劑的代謝物濃度，其結果發現兩種容器收集存放尿液並不會影響塑化劑代謝物的濃度。
（2） 我們調整了孕婦年齡、生產前BMI、懷孕週數、孕婦血清中TSH濃度後發現，孕婦尿液中MBzP和MEP濃度與新生兒臍帶血中TSH濃度呈負相關。（MBzP: β = -3.04，P= 0.003；MEP: β= -2.01，
P <0.05）。
（3） 應用公式計算出孕婦每日攝入DEHP（E-DA和CSMU）的中位數分別是1.86 μg/kg bw/day 和 2.20 μg/kg bw/day (creatinine 計算) 以及 3.78μg/kg bw/day 和 4.00 μg/kg bw/day (尿液體積計算)。
結論: 本研究結果發現，儲存尿液方式無論是使用玻璃或塑膠容器(5號pp材質)所測得尿液中的鄰苯二甲酸酯代謝物的濃度是相似的。此外我們發現，新生兒臍帶血中的TSH濃度與孕婦尿液中MBzP和MEP的濃度有顯著的負相關，但目前MBzP和MEP是如何影響甲狀腺的功能目前仍還不清楚。未來還需要進一步研究以闡明其作用機制。

關鍵字

鄰本二甲酸脂類 ； 甲狀腺賀爾蒙

並列摘要

Background and Objective: A growing number of animal and epidemiological studies have indicated that environmental chemicals can interrupt the regulation of thyroid function. However, only a few studies were reported the effects of phthalates exposure on thyroid function in pregnant women and their newborns. The present study was to investigate the association between maternal phthalate exposures and their thyroid hormones, and cord thyroid hormones in their newborns from the general population in Taiwan.
Methods: A total of 281 maternal and infant pair were recruited and analyzed. Pregnant women were interviewed by a standardized questionnaire, and we also collected their urine and blood samples at third trimester and cord blood samples at delivery. Nine phthalate metabolites (MEHP, MEOHP, MEHHP, MiBP, MnBP, MBzP, MEP, MMP, and MiNP) in urine samples were determined by liquid chromatography/ electrospray tandem mass spectrometry (LC-ESI-MS/MS). Serum thyroid hormones of pregnant women and cord thyroid hormones (TSH, Free T4, T3 and T4) of newborns were measured by enzyme immunoassay (EIA) and Chemoluminescence Immunoassay (CLIA). In this study, we used two different models for the calculation of the daily DEHP intake by pregnant women.
Results:
(1) Urine analysis found that either glass or plastic containers to the phthalate metabolites concentrations (MEOHP, MEHHP, MEHP, MBzP, MnBP, MEP, MMP, MiBP) were not significant differences (All p values > 0.05, Wilcoxon signed rank test)
(2) After adjusting for age, pre-BMI, gestational age, TSH (mother) and other phthalate metabolites of the participants, urinary MBzP and MEP levels showed a negative association with TSH. (TSH: β= -3.04, P=0.003 for MBzP: β= -2.01, P<0.05 for MEP).
(3) The median of the daily DEHP intake for all investigated pregnant women (E-Da and CSMU) were 1.86 μg/kg bw/day and 2.20 μg/kg bw/day of low volume and 3.78μg/kg bw/day and 4.00 μg/kg bw/day of high volume.Conclusion: This study found that levels of phthalate metabolites measured in urine stored in glass containers were similar to which stored in plastic containers. We found that levels of TSH in new born were significantly negatively associated with urinary MBzP and MEP levels, but how MBzP and MEP affects thyroid function is unclear. Further studies are needed to elucidate the mechanism of action and to investigate whether any other factors related to DBzP and DEP exposure alter the thyroid function.

並列關鍵字

urinary phthalate metabolites ； thyroid hormones ； cord blood ； pregnant women

參考文獻

Adibi, J. J., R. Hauser, et al. (2009). "Maternal Urinary Metabolites of Di-(2-Ethylhexyl) Phthalate in Relation to the Timing of Labor in a US Multicenter Pregnancy Cohort Study." Am J Epidemiol 169(8): 1015-1024.

Adibi, J. J., F. P. Perera, et al. (2003). "Prenatal exposures to phthalates among women in New York City and Krakow, Poland." Environmental Health Perspectives 111(14): 1719-1722.

Adibi, J. J., R. M. Whyatt, et al. (2008). "Characterization of phthalate exposure among pregnant women assessed by repeat air and urine samples." Environmental Health Perspectives 116(4): 467-473.

Anderson, W. A. C., L. Castle, et al. (2001). "A biomarker approach to measuring human dietary exposure to certain phthalate diesters." Food Additives and Contaminants 18(12): 1068-1074.

Boas, M., H. Frederiksen, et al. (2010). "Childhood Exposure to Phthalates: Associations with Thyroid Function, Insulin-like Growth Factor I, and Growth." Environmental Health Perspectives 118(10): 1458-1464.