兒童注意力缺損過動症相關指標與塑化劑代謝物之關係探討

Abstract

研究背景：過去已有大量的研究發現，產前母親的塑化劑暴露與嬰兒的神經行為發展有負相關，然而在嬰兒出生後的塑化劑暴露與神經行為發展部分卻尚未被深入探究，且潛在的干擾因子，如：飲食習慣、環境因子等等，亦很少被納入實驗討論之中，故本研究著眼於探討嬰兒出生後的塑化劑暴露與神經行為發展之相關性，並且將飲食習慣、環境因子等干擾因子一併納入探討。 方法：本研究之參與個案來自台灣出生世代研究 (Taiwan Birth Panel study II，TBPS II；IRB No.: 201702038RINA)，此世代研究著重於探討產前及產後母親、嬰兒、及幼兒時期之健康情形與相關風險暴露；研究中使用Conners Kiddie Continuous Performance Test II (K-CPT II)評估幼兒之神經認知功能，以超高效液相層析串聯式質譜儀測量幼兒之塑化劑代謝物，並透過結構化問卷評估母親及幼兒之家庭背景、飲食情況、及環境因子等；統計部分使用單變量及多變量之線性及羅吉斯迴歸，調整潛在干擾因子，以估計塑化劑暴露與K-CPT II表現及注意力不足過動症 (Attention deficit hyperactivity disorder, ADHD)傾向之相關性。 結果：本研究共納入280對母親及幼兒。經調整干擾因子後之模型顯示，所有尿中塑化劑代謝物與K-CPT II T-scores有顯著之相關性皆為正相關，而一般而言K-CPT II T-scores越高即代表神經認知功能表現越差、ADHD的傾向越強；若針對K-CPT II中的各項目T-score作討論，顯示Hit reaction time T-score及Perseverations T-score此兩個項目於多變量線性迴歸模型之中，與最多尿中塑化劑代謝物有顯著正相關 (包含：MEP、MECPP、MCINP、MEHP)；針對尿中塑化劑代謝物作討論，則幼兒尿中Mono-carboxy-isononyl phthalate (MCINP)與最多K-CPT II T-score有顯著正相關 (包含：Detectability、Omissions、Perseverations、Hit reaction time、HRT standard deviation、HRT inter-stimulus interval change)；若針對ADHD傾向作討論，幼兒尿中Mono-benzyl phthalate (MBzP)是本研究有測量的六種塑化劑代謝物中，唯一一種於多變量羅吉斯迴歸模型中，與ADHD傾向有顯著相關之代謝物，其相關性為正相關，而有趣的是，幼兒尿中MBzP於多變量線性迴歸模型之中並未與任何K-CPT II T-score有顯著相關。 結論：本研究顯示幼兒塑化劑暴露與神經認知功能有顯著負相關、與ADHD傾向有顯著正相關，可能之因果關係及機制值得未來研究進一步探討。

Background: Although large number of studies have found that prenatal phthalate exposure was inversely associated with neurodevelopment in children, there were limited data concerning about postnatal phthalate exposure. Besides, the dietary exposure sources and environmental factors were rarely discussed within these studies. Hence, we aimed to gain a better understanding of the relationship between dietary habits, postnatal exposure to phthalates, and cognitive and behavioral development in offspring. Methods: These participants of “Taiwan Birth Panel Study II, TBPS II” were followed up in 2017 (IRB No.: 201702038RINA), which is to investigate prenatal and postnatal factors on infant and early childhood health in National Taiwan University Hospital in 2009-2012. The neurocognitive function, phthalate exposure conditions, and other covariates were assessed by Conners Kiddie Continuous Performance Test II (K-CPT II), measurement of urine phthalate metabolites, and structured questionnaires, respectively. Univariate and multivariate linear and logistic regressions were used to examine the associations between phthalate exposure, K-CPT II performance and ADHD tendency. Results: In this study, 280 paired samples with sufficient data of K-CPT II and phthalate metabolite concentrations were included, among 501 paired maternal and child samples enrolled in TBPS II. As higher T-scores generally mean poor performance, all the significant associations between urine phthalate metabolites and K-CPT II T-scores were positive associations in multivariate linear models. For K-CPT II performance variables, Hit reaction time T-score and Perseverations T-score were significantly positively-associated with the most phthalate metabolites, including MEP, MECPP, MCINP, and MEHP. For phthalate metabolites, child MCINP were significantly positively-associated with the most K-CPT II T scores, including T-scores of Detectability, Omissions, Perseverations, Hit reaction time, HRT standard deviation, and HRT inter-stimulus interval (ISI) change. In multivariate logistic models for ADHD tendency, child MBzP was the only phthalate metabolite tested that showed significantly positive association with ADHD tendency, after adjusting for covariates. Interestingly, MBzP was not significantly associated with any K-CPT II T score in the multivariate linear models. Conclusions: Our study suggested that children phthalate exposure was significantly associated with neurocognitive function inversely, and ADHD tendency positively. Further large-scale prospective studies are warranted for investigation of the causal relationships and potential mechanisms.