產前多種暴露與七歲兒童智力: 各種統計分析方法比較

Abstract

ﰀ 背景: 生活之中暴露到很多種的環境汙染物,產前暴露目前大部分文獻都是針對單一物 質作探討,多種環境汙染物質暴露對兒童智力的影響到目前為止還沒有研究過。 目的:評估母親產前環境化學物質的暴露和孩子到 7 歲時智力之間的關聯。 ﰀ 材料與方法: 採用 Taiwan Birth Panel Study (TBPS)前瞻性的出生世代追中研究,收案地點是台 灣北部的兩家醫院和兩家診所,時間在 2004 到 2005 年收案完成,總共收了 486 個樣本,測量臍帶血重金屬(Cd, As, Pb, Hg, Mn, Cu, Se, Zn),鄰苯二甲酸鹽 (MEP,MnBP,MBzP,MEHP,MECPP,MCMHP,MINP),全氟碳化物(PFOA, PFNA, PFOS, PFUA),農藥(Flucythrinate, Cypermethrin, Chlorpyrifos),苯酚 (BPA,NP,OP)和尼古丁。為了評估 7 歲兒童的智力成果,全面魏氏智力量 表第四版(WISC-IV)被使用,其表示全量表智商(FSIQ),言語理解指數(VCI), 知覺推理指數(PRI) ,工作記憶指數(WMI)和處理速度指數(PSI)。我們 使用了多重插補的方法來計算遺失的暴露值,再採用 Partial Least Squares (PLS) 偏最小平方法以及其他各種的統計分析方法來看多種環境化學汙染物對智力的 影響,包括 Factors analysis method 因素分析方法和 Stepwise selection method 逐 步選擇方法以及 Elastic net selection method 彈力網選擇方法,並對各個方法進行 比較。 ﰀ 結果: Least Squares (PLS) 偏最小平方法中,高濃度的 BPA, OP, PFNA, PFUA 和 Cu 暴露會對智力造成影響,其中 BPA, PFNA 和 Cu 有顯著的不良影響。經過 校正之後 BPA 影響全量表智商(FSIQ)(β:-1.54; 95% CI:-3.04, -0.04),言 語理解指數(VCI)(β:-1.91; 95% CI:-3.43, -0.40),知覺推理指數(PRI) (β:-1.94; 95% CI:-3.58, -0.31);PFNA 影響處理速度指數(PSI)(β:-2.45; 95% CI:-4.03, -0.88); Cu 影響工作記憶指數(WMI)(β:-22.30; 95% CI:- 43.41, -1.19)與 FSIQ 呈負相關; Factors analysis method 因素分析方法在暴露濃度 中第三分位的酚類(β - 7.78; 95%CI:-12.27, -3.29)與 FSIQ 呈負相關; Stepwise selection method 逐步選擇方法中,PFOS,PFUA,BPA 和 OP 對 FSIQ 影響較大; Elastic net selection method 彈力網選擇方法可以看出 BPA 對 FSIQ 是影響最大的 變項。 ﰀ 結論: 出生前暴露於多種化學物質當中,BPA,PFNA 和 Cu 在 7 歲時智力會受到不良 的影響,在多種方法之中LeastSquares(PLS) 偏最小平方法和Elasticnetselection method 彈力網選擇方法對多種環境暴露的分析是比較適合的方法。

ﰀ Background: Prenatal exposure to environmental pollutant has been associated with detrimental effects to neurodevelopment. However, the effects of mixtures between intelligence in childhood have not been studied. Aims: To evaluate the associations between pre- and perinatal biomarker concentrations of environmental pollutants and child intelligence at 7 years of age. ﰀ Methods: The mother-child pairs enrolled in a Taiwan Birth Panel Study (TBPS) at a medical center in Taipei from May 2004 to January 2005. We collected their cord blood for measuring heavy metals (Cd, As, Pb, Hg, Mn, Cu, Se, Zn), phthalates (MEP, MnBP, MBzP, MEHP, MECPP, MCMHP, MiNP), perfluroalkyl chemicals (PFOA, PFNA, PFOS, PFUA), pesticide (Flucythrinate, Cypermethrin, Chlorpyrifos), phenols (BPA, NP, OP) and Cotinine. To assess the intelligence outcome in children at 7 year-old, Comprehensive the Wechsler intelligence scale 4th edition (WISC-IV) were used, whose indicates full scale IQ (FSIQ), verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI) and processing speed index (PSI). We used a multiple imputation approach to impute the missing exposure values. We estimated the associations between environment pollutants and IQ scores in Partial Least Squares (PLS) Regression and we also compared various statistical analysis methods, included factors analysis method, stepwise selection method, and elastic net selection method. ﰀ Results: The higher concentrations of BPA, OP, PFNA, PFUA and Cu were associated with children’s IQ. The significances were observed as BPA in Full-Scale IQ Score ( FSIQ ) (β:-1.54; 95% CI:-3.04, -0.04), Verbal Comprehension (VCI)(β:-1.91; 95 % CI:-3.43, -0.40), Perceptual Reasoning (PRI)(β:-1.94; 95% CI:-3.58, - 0.31); PFNA in Processing Speed (PSI)(β:-2.45; 95% CI:-4.03, -0.88); Cu in Working Memory (WMI)(β:-22.30; 95% CI:-43.41, -1.19)inversely associated with FSIQ; in factors analysis method factor analysis method in the exposure concentrations of phenolic third quintile (β - 7.78; 95% CI: -12.27, -3.29) was negatively correlated with FSIQ; in stepwise selection method PFOS, PFUA , BPA and OP were more impact on FSIQ; in elastic net selection method can be seen that BPA was the most impact on FSIQ . ﰀ Conclusions: Prenatal exposure to BPA, PFNA, and Cu were adversely associated with intelligence at age of 7 years in our study population. The PLS modeling approach and elastic net may prove useful for similar environmental epidemiology analyses of multiple exposures.