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儿童时期暴露于双酚 A 与 2 至 5 岁儿童自闭症和 ADHD 相关症状的关系:来自欧登塞儿童队列的研究

Prenatal exposure to bisphenol A and autistic- and ADHD-related symptoms in children aged 2 and5 years from the Odense Child Cohort.

机构信息

Department of Clinical Pharmacology, Pharmacy and Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark.

Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.

出版信息

Environ Health. 2021 Mar 12;20(1):24. doi: 10.1186/s12940-021-00709-y.

Abstract

BACKGROUND

Bisphenol A (BPA) is a non-persistent chemical with endocrine disrupting abilities used in a variety of consumer products. Fetal exposure to BPA is of concern due to the elevated sensitivity, which particularly relates to the developing brain. Several epidemiological studies have investigated the association between prenatal BPA exposure and neurodevelopment, but the results have been inconclusive.

OBJECTIVE

To assess the association between in utero exposure to BPA and Attention Deficit/Hyperactivity Disorder (ADHD-) symptoms and symptoms of Autism Spectrum Disorder (ASD) in 2 and 5-year old Danish children.

METHOD

In the prospective Odense Child Cohort, BPA was measured in urine samples collected in gestational week 28 and adjusted for osmolality. ADHD and ASD symptoms were assessed with the use of the ADHD scale and ASD scale, respectively, derived from the Child Behaviour Checklist preschool version (CBCL/1½-5) at ages 2 and 5 years. Negative binomial and multiple logistic regression analyses were performed to investigate the association between maternal BPA exposure (continuous ln-transformed or divided into tertiles) and the relative differences in ADHD and ASD problem scores and the odds (OR) of an ADHD and autism score above the 75th percentile adjusting for maternal educational level, maternal age, pre-pregnancy BMI, parity and child age at evaluation in 658 mother-child pairs at 2 years of age for ASD-score, and 427 mother-child pairs at 5 years of age for ADHD and ASD-score.

RESULTS

BPA was detected in 85.3% of maternal urine samples even though the exposure level was low (median 1.2 ng/mL). No associations between maternal BPA exposure and ASD at age 2 years or ADHD at age 5 years were found. Trends of elevated Odds Ratios (ORs) were seen among 5 year old children within the 3rd tertile of BPA exposure with an ASD-score above the 75th percentile (OR = 1.80, 95% CI 0.97,3.32), being stronger for girls (OR = 3.17, 95% CI 1.85,9.28). A dose-response relationship was observed between BPA exposure and ASD-score at 5 years of age (p-trend 0.06) in both boys and girls, but only significant in girls (p-trend 0.03).

CONCLUSION

Our findings suggest that prenatal BPA exposure even in low concentrations may increase the risk of ASD symptoms which may predict later social abilities. It is therefore important to follow-up these children at older ages, measure their own BPA exposure, and determine if the observed associations persist.

摘要

背景

双酚 A(BPA)是一种具有内分泌干扰能力的非持久性化学物质,用于各种消费产品。由于胎儿的敏感性较高,特别是与发育中的大脑有关,因此胎儿接触 BPA 令人担忧。几项流行病学研究调查了产前 BPA 暴露与神经发育之间的关系,但结果尚无定论。

目的

评估宫内接触 BPA 与 2 岁和 5 岁丹麦儿童注意缺陷/多动障碍(ADHD)症状和自闭症谱系障碍(ASD)症状之间的关系。

方法

在前瞻性的奥登塞儿童队列中,在妊娠 28 周时采集尿液样本测量 BPA,并根据渗透压进行调整。使用儿童行为检查表学前版(CBCL/1½-5)分别在 2 岁和 5 岁时评估 ADHD 症状和 ASD 症状,得到 ADHD 量表和 ASD 量表。使用负二项式和多变量逻辑回归分析,研究母体 BPA 暴露(连续对数转换或分为三分位数)与 ADHD 和 ASD 问题评分的相对差异以及在 658 对母子对中,2 岁时的 ASD 评分,以及在 427 对母子对中 5 岁时的 ADHD 和 ASD 评分,调整母体教育水平、母体年龄、孕前 BMI、产次和评估时儿童年龄后,ADHD 和自闭症评分高于第 75 百分位数的优势比(OR)的关系。

结果

尽管接触水平较低(中位数 1.2ng/ml),但仍在 85.3%的母体尿液样本中检测到 BPA。母体 BPA 暴露与 2 岁时的 ASD 或 5 岁时的 ADHD 之间无关联。在 BPA 暴露的第 3 三分位中,5 岁儿童的 ASD 评分高于第 75 百分位数的几率(OR)呈升高趋势(OR=1.80,95%CI 0.97,3.32),在女孩中更为明显(OR=3.17,95%CI 1.85,9.28)。在男孩和女孩中,BPA 暴露与 5 岁时的 ASD 评分之间存在剂量反应关系(p 趋势=0.06),但仅在女孩中具有统计学意义(p 趋势=0.03)。

结论

我们的研究结果表明,产前 BPA 暴露即使在低浓度下也可能增加 ASD 症状的风险,这可能预示着日后的社交能力。因此,在这些儿童年龄较大时对他们进行随访,测量他们自身的 BPA 暴露,并确定观察到的关联是否持续,这很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adce/7955642/40e5a06bbcc6/12940_2021_709_Fig1_HTML.jpg

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