臺灣中部出生世代之兒童青春期發展與鄰苯二甲酸酯暴露間的相關性

Abstract

背景：鄰苯二甲酸酯常用作塑化劑，儘管已有一些關於其對生殖系統影響的研究，說明其可能會影響兒童的青春期發展，鄰苯二甲酸酯仍廣泛應用於各種日常用品中。本研究探討了胎兒和兒童期鄰苯二甲酸酯的暴露與其青春期發展之間的相關性。 方法：於2000年12月1日至2001年11月30日之間建立一出生世代，並收集孕婦第三孕期的尿液樣本來評估母親暴露於鄰苯二甲酸酯的情況。其胎兒在出生後接受追蹤，並在8歲、11歲、14歲、17歲和21歲進行體格檢查，以監測青春期發展。兒童的尿液樣本也在2歲、5歲、8歲、11歲、14歲、17歲和21歲時收集。主要鄰苯二甲酸酯代謝物的尿液濃度——如單甲基鄰苯二甲酸酯（MMP）、單乙基鄰苯二甲酸酯（MEP）、單丁基鄰苯二甲酸酯（MBP）、單苯基鄰苯二甲酸酯（MBzP）、單2-乙基己基鄰苯二甲酸酯（MEHP）、單（2-乙基-5-羥基己基）鄰苯二甲酸酯（MEHHP）、單（2-乙基-5-氧代己基）鄰苯二甲酸酯（MEOHP）、單正丁基鄰苯二甲酸酯（MnBP）、單異丁基鄰苯二甲酸酯（MiBP）、單異壬基鄰苯二甲酸酯（MiNP）、單（2-羧甲基己基）鄰苯二甲酸酯（MCMHP）和單（2-乙基-5-羧基戊基）鄰苯二甲酸酯（MECPP）—— 使用液相色譜-串聯質譜測量。生殖發展測量包括男女的骨齡、男孩的睾丸大小和陰莖長度，以及女孩的子宮大小和卵巢體積。應用廣義線性混合模型（GLMM）和基於群組的軌跡建模（GBTM）來估計重複測量之連續變項之間的相關性。 結果：在女生的部分我們觀察到塑化劑的暴露與青春期的延遲有顯著相關，另外也發現塑化劑的暴露與子宮相關的參數較低有顯著的相關，在男生的結果我們也觀察到骨齡與實際年齡的比值可能會受到塑化劑暴露的影響。然而在兩個性別中，不同的成長軌跡間的塑化劑暴露均未顯示顯著的差異。 結論：特定時間點的鄰苯二甲酸酯暴露可能會影響兒童青春期的生殖發展；然而仍需進一步研究，擴大樣本規模並延長追蹤時間，以確立這種關聯的因果關係。

Background: Phthalates are commonly used as plasticizers, and although there have been studies on their effects on the reproductive system, indicating that they may impact children's pubertal development, phthalates continue to be widely used in various everyday products. This study investigates the correlation between fetal and childhood exposure to phthalates and pubertal development. Methods: A population-based birth cohort was created between December 1, 2000, and November 30, 2001, with maternal phthalate exposure assessed through urine samples collected during the third trimester of pregnancy. The children exposed to phthalates in utero were followed up to monitor pubertal development, with physical examinations conducted at ages 8, 11, 14, 17, and 21. Urine samples from the children were also collected at ages 2, 5, 8, 11, 14, 17, and 21. The urinary concentrations of key phthalate metabolites—such as monomethyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), Mono-n-butyl phthalate (MnBP), Mono-isobutyl phthalate (MiBP), Mono-isononyl phthalate (MiNP), Mono(2- carboxymethyl hexyl) phthalate (MCMHP), and Mono(2-ethyl-5-carboxypentyl) phthalate (MECPP)—were measured using liquid chromatography coupled with tandem mass spectrometry. The reproductive development measurements included bone age for both genders, testicle size and penis length for boys, uterus size, and ovarian volume for girls. Generalized Linear Mixed Models (GLMM) and Group-Based Trajectory Modeling (GBTM) were applied to estimate the associations between repeated continuous outcomes. Results: In girls, we observed a significant association between phthalate exposure and delayed puberty. Additionally, phthalate exposure was significantly correlated with lower uterus-related parameters. In boys, we also found that the ratio of bone age to chronological age might be influenced by phthalate exposure. However, in both genders, phthalate exposure did not show significant differences across different growth trajectories. Conclusion: Phthalate exposure at certain time points may influence the reproductive development of children during puberty; however, further studies should be with a larger sample size and longer follow-up periods to conduct the causal nature of this association.