塑化劑暴露與青春期前期兒童過重及肥胖之影響

Abstract

背景: 內分泌干擾物質如塑化劑(鄰苯二甲酸酯)常被廣泛的使用在我們的日常生活中，舉凡塑膠物品的製作，藥物的包裝等。而塑化劑也被認為具有類似內分泌賀爾蒙的功能會影響孩童青春期的進展，有研究指出在人體也可能有致肥胖的能力(obesogenic)。兒童肥胖的比例逐年來逐步上升，國人塑化劑的暴露對於青春期前期兒童過重與肥胖的影響卻仍不明朗。 目標: 對青春期前期之學童進行塑化劑暴露與肥胖關聯性之研究 方法: 我們使用 Taiwan Birth Panel Study (TBPS) 出生世代研究在2013至2014年的追蹤訪查資料進行分析。共有200位孩童參與本追蹤計畫，我們針對青春期前期孩童進行研究探討，有41位過重與肥胖孩童與109位正常體位孩童進行後續分析。參與者接受身體理學檢查，家庭問卷調查以及生物檢體檢測。共收集血液與尿液的檢體進行後續分析。塑化劑的暴露以尿液中塑化劑代謝產物做參考依據，以此反映體內之暴露濃度。尿液之塑化劑代謝物使用極致液態串聯質譜儀進行檢測 (UHPLC-MS/MS) (Sciex QTRAP® 6500 System, MA, USA)，並且以尿液中肌酐酸濃度進行校正，且取對數轉換使塑化劑濃度資料呈標準化分布。兒童過重與肥胖標準以身體質量指數 (Body mass index, BMI) 當作參考指標，依世界衛生組織公佈之兒童生長曲線標準定義是否過重或肥胖，並以此兒童生長曲線常模換算 BMI z-score 進行分析。統計方法使用線性迴歸和邏輯式迴歸模式檢測相關性。此外又針對男女性別與青春期前期的孩童進行分層分析。 結果: 在12項塑化劑代謝產物檢測中，以尿液中的MEP數值與所有青春期前期孩童過重或肥胖進行邏輯式迴歸分析，發現無統計學上顯著差異 (Adjusted OR=1.49, 95% CI=0.97, 2.3)，但針對青春期前期男童進行分層分析，較高濃度的MEP與過重或肥胖具有統計上顯著相關(Adjusted OR=1.64, 95% CI=1.01, 2.65)，MEP對於青春期前期女童孩童過重與肥胖則無顯著影響。尿液中的MEP數值與孩童BMI z-score進行線性迴歸分析，發現於所有青春期前期孩童有顯著正相關 (Adjusted β=0.22, 95% CI=0.03, 0.4)。另行性別分層分析，較高濃度的MEP與BMI z-score僅在青春期前期男童有顯著正相關(Adjusted β=0.36, 95% CI=0.08, 0.63)，於青春期前期女童則無顯著相關 (Adjusted β=0.05, 95% CI= - 0.14, 0.25 )。 結論: 此研究發現於青春期前期兒童過重和肥胖與塑化劑之暴露有性別上的差異，塑化劑暴露 (MEP) 對於青春期前期男童的BMI z-score 上升有正相關，後續還需要進一步追蹤了解其對兒童健康之長期影響。

Background Endocrine disrupting chemicals (EDCs) such as phthalates are widely used in daily activities. Phthalates may be related with advanced puberty development in children. The prevalence of pediatric obesity are also increased in recent years. Phthalates are believed to be obesogenic. In Taiwan, the impact of phthalate exposure on pediatric overweight and obesity (OWO) still remained unclear. Objective To investigate the association between pediatric overweight or obesity and phthalate exposures in children at pre-puberty stage. Methods We analyzed information of 200 children with clinical data obtained from Taiwan Birth Panel Study (TBPS). The definition of overweight or obesity is based on the body mass index (BMI) references for children and BMI z-score by WHO references. We analyzed the effect of phthalate on children at pre-puberty stage. There were 41 overweight or obese children and 109 in normal status children enrolled to this study. Urine phthalate concentrations were measured by ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC–MS/MS) (Sciex QTRAP® 6500 System, MA, USA). Urinary phthalate metabolites values were adjusted with urine creatinine level and log-transformed. Linear and logistic regression was used to explore the associations between pediatric overweight or obesity and phthalate exposure. Results After adjustment for gender, maternal pre-pregnancy BMI, body weight change during pregnancy, family annual income, maternal education status, preterm birth, daily hours of watching television, weekly frequency of exercise activities and frequency of probiotics usage, monoethyl phthalate (MEP) was positively associated with increased BMI z-score in male children at pre-puberty stage (Adjusted OR=1.64, 95% CI=1.01, 2.65). MEP was also positively associated with overweight or obesity in male pre-puberty children (Adjusted β=0.36, 95% CI=0.08, 0.63). Conclusions We found that MEP was associated with increment of BMI z-score and pediatric overweight or obesity during pre-puberty stage, particularly in boys. Our finding suggests that the effect of overweight and obesity due to phthalate exposures is associated with gender differences. Longitudinal follow up study is warranted to investigate the long term effect of phthalate exposure on childhood health.