Stratmann Marlene, Özel Fatih, Marinopoulou Maria, Lindh Christian, Kiviranta Hannu, Gennings Chris, Bornehag Carl-Gustaf
Department of Health Sciences, Karlstad University, Karlstad, Sweden.
Department of Organismal Biology, Uppsala University, Uppsala, Sweden.
J Expo Sci Environ Epidemiol. 2024 Dec 19. doi: 10.1038/s41370-024-00739-x.
Endocrine disrupting chemicals (EDCs) can cross the placenta and thereby expose the fetus, which may lead to developmental consequences. It is still unclear which chemicals are of concern regarding neurodevelopment and specifically behaviour, when being exposed to a mixture.
The objective is to determine associations between prenatal exposure to EDCs and behavioural difficulties. Furthermore, we investigated sex-specific associations and determined chemicals of concern in significant regressions.
Associations between prenatal exposure to EDCs (both as single compounds and their mixtures) and behavioural outcomes using the Strengths and Difficulties Questionnaire (SDQ) were estimated in 607 mother-child pairs in the Swedish Environmental Longitudinal, Mother and Child, Asthma and Allergy (SELMA) study. Levels for chemical compounds were measured in either urine or serum (median of 10 weeks of gestation). Associations were estimated for the total SDQ score (quasipoisson regression) and a 90th percentile cut-off (logistic regression). Exposure for EDC mixtures (phenols, phthalates, PFAS and persistent chlorinated) was studied using weighted quantile sum (WQS) regression with deciles and with and without repeated holdout validation techniques. The models were adjusted for selected covariates.
The odds for behavioural difficulties increased in girls with higher chemical exposures (OR 1.77, 95% CI 1.67, 1.87) using the full sample and borderline for the validation set (OR 1.31, 95% CI 0.93, 1.85) with 94/100 positive betas in the 100 repeated holdout validations. Chemicals of concern for girls are mostly short-lived chemicals and more specifically plasticizers. No pattern of significant associations was detected for boys.
There is an indication of increased behavioural difficulties for girls in the SELMA population with higher exposure to mixtures of EDCs. Using the repeated holdout validation techniques, the inference is more stable, reproducible and generalisable. Prenatal exposure to mixtures of environmental chemicals should be considered when assessing the safety of chemicals.
Growing evidence points towards a "mixture effect" where different environmental chemicals might act jointly where individual compounds may be below a level of concern, but the combination may have an effect on human health. We are constantly exposed to a complicated mixture pattern that is individual for every person as this mixture depends on personal choices of lifestyle, diet and housing to name a few. Our study suggests that prenatal exposure to EDCs might adversely affect the behaviour of children and especially girls. Hence, risk assessment needs to improve and sex-specific mechanisms should be included in assessments.
内分泌干扰化学物质(EDCs)可穿过胎盘,从而使胎儿暴露其中,这可能导致发育后果。当暴露于混合物中时,究竟哪些化学物质会对神经发育尤其是行为产生影响仍不清楚。
确定产前暴露于EDCs与行为问题之间的关联。此外,我们研究了性别特异性关联,并在显著回归中确定了相关化学物质。
在瑞典环境纵向母婴哮喘与过敏研究(SELMA)中,对607对母婴进行了研究,估计产前暴露于EDCs(包括单一化合物及其混合物)与使用长处和困难问卷(SDQ)得出的行为结果之间的关联。在妊娠10周时采集尿液或血清样本测量化合物水平。对总SDQ得分(拟泊松回归)和第90百分位数临界值(逻辑回归)进行关联估计。使用加权分位数和(WQS)回归结合十分位数以及有无重复留出验证技术研究EDC混合物(酚类、邻苯二甲酸盐、全氟辛烷磺酸和持久性氯化物)的暴露情况。模型针对选定的协变量进行了调整。
在全样本中,化学物质暴露水平较高的女孩出现行为问题的几率增加(比值比1.77,95%置信区间1.67, 1.87),在验证集中接近临界值(比值比1.31,95%置信区间0.93, 1.85),在100次重复留出验证中有94/100的正β值。与女孩相关的化学物质大多是短效化学物质,尤其是增塑剂。未在男孩中检测到显著关联模式。
有迹象表明,在SELMA人群中,暴露于较高水平EDC混合物的女孩行为问题有所增加。使用重复留出验证技术,推断结果更稳定、可重复且具有普遍性。在评估化学物质安全性时,应考虑产前暴露于环境化学物质混合物的情况。
越来越多的证据指向一种“混合物效应”,即不同的环境化学物质可能共同起作用,其中单个化合物可能低于关注水平,但它们的组合可能对人类健康产生影响。我们持续暴露于复杂的混合物模式中,这种模式因人而异,因为它取决于生活方式、饮食和住房等个人选择等多种因素。我们的研究表明,产前暴露于EDCs可能对儿童尤其是女孩的行为产生不利影响。因此,风险评估需要改进,评估中应纳入性别特异性机制。