背景:关于认知和神经发育结果的研究显示,与全氟烷基物质(PFAS)和有机氯的产前暴露相关的结果不一致。评估在以后的生活中持续存在的相关化学暴露的混合效应可能有助于对现实生活中的剂量反应关联进行无偏见的评估和理解。
方法:对于第四次佛兰德环境与健康研究(FLEHS)的子集,通过超高效液相色谱-串联质谱法(UPLC-MS/MS)分别在99和153-160脐带血浆样品中和15年后在青少年的外周血清中测量了四种PFAS和六种有机氯的浓度。通过连续性能测试(CPT)和Stroop测试作为潜在神经发育缺陷的指标,在14-15年测量了持续和选择性的注意力。应用分位数计算来评估产前暴露于单独和组合的PFAS和有机氯组与青春期CPT和Stroop测试中的表现之间的联合关联。随后,在具有两组协变量的混合效应模型中分析了每种化合物的个体效应.出生时和认知评估时的分析数据可以抵消出生后的暴露。
结果:在混合物分析中,PFAS和有机氯的自然对数转换值同时增加一个分位数,与CPT的平均反应时间(RT)和反应时间变异性(RTV)的减少有关(β=-15.54,95%CI:-29.64,-1.45和β=-7.82,95%CI:-14.97,-0.67),单独的PFAS与-40%,-94%CI(=β:0.60)的混合物在单一污染物模型中,这些结果证实了CPT中全氟己磺酸盐(PFHxS)与RT(β=-17.95,95%CI=-33.35,-2.69)以及六氯苯与RTV(β=-5.78,95%CI:-10.39,-0.76)之间的相关性.此外,产前暴露量高于全氟壬酸(PFNA)定量限的参与者在CPT中的RT和RTV显著较短(β=-23.38,95%CI:-41.55,-5.94和β=-9.54,95%CI:-19.75,-0.43).
结论:更高的产前暴露于PFAS混合物以及PFAS和有机氯混合物的混合物与青春期更好的持续和选择性注意力相关。这些关联似乎是由PFHxS驱动的,在评估时与暴露水平无关。
BACKGROUND: Studies on cognitive and neurodevelopmental outcomes have shown inconsistent results regarding the association with prenatal exposure to perfluoroalkyl substance (PFAS) and
organochlorines. Assessment of mixture effects of correlated chemical exposures that persist in later life may contribute to the unbiased evaluation and understanding of dose-response associations in real-life exposures.
METHODS: For a subset of the 4th Flemish Environment and Health Study (FLEHS), concentrations of four PFAS and six
organochlorines were measured in respectively 99 and 153-160 cord plasma samples and 15 years later in adolescents\' peripheral serum by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS). Sustained and selective attention were measured at 14-15 years with the Continuous Performance Test (CPT) and Stroop Test as indicators of potential neurodevelopmental deficits. Quantile g-computation was applied to assess the joint associations between prenatal exposure to separate and combined groups of PFAS and
organochlorines and performance in the CPT and Stroop Test at adolescence. Subsequently, individual effects of each chemical compound were analyzed in mixed effects models with two sets of covariates. Analytical data at birth and at the time of cognitive assessment allowed for off-setting postnatal exposure.
RESULTS: In mixtures analysis, a simultaneous one-quantile increase in the natural log-transformed values of PFAS and
organochlorines combined was associated with a decrease in the mean reaction time (RT) and the reaction time variability (RTV) in the CPT (β = -15.54, 95% CI:-29.64, -1.45, and β = -7.82, 95% CI: -14.97, -0.67 respectively) and for the mixture of PFAS alone with RT (β = -11.94, 95% CI: -23.29, -0.60). In the single pollutant models, these results were confirmed for the association between perfluorohexanesulfonate (PFHxS) with RT (β = -17.95, 95% CI = -33.35, -2.69) and hexachlorobenzene with RTV in the CPT (β = -5.78, 95% CI: -10.39, -0.76). Furthermore, the participants with prenatal exposure above the limit of quantification for perfluorononanoic acid (PFNA) had a significantly shorter RT and RTV in the CPT (β = -23.38, 95% CI: -41.55, -5.94, and β = -9.54, 95% CI: -19.75, -0.43, respectively).
CONCLUSIONS: Higher prenatal exposure to a PFAS mixture and a mixture of PFAS and
organochlorines combined was associated with better sustained and selective attention during adolescence. The associations seemed to be driven by PFHxS and were not linked to exposure levels at the time of assessment.