Department of Epidemiology, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Department of Epidemiology, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Int J Hyg Environ Health. 2023 Mar;248:114078. doi: 10.1016/j.ijheh.2022.114078. Epub 2022 Nov 28.
Attention-deficit/hyperactivity-disorder (ADHD) is a leading neurodevelopmental disorder in children worldwide; however, few modifiable risk factors have been identified. Organophosphate esters (OPEs) are ubiquitous chemical compounds that are increasingly prevalent as a replacement for other regulated chemicals. Current research has linked OPEs to neurodevelopmental deficits. The purpose of this study was to assess gestational OPE exposure on clinically-assessed ADHD in children at age 3 years.
In this nested case-control study within the Norwegian Mother, Father, and Child Cohort study, we evaluated the impact of OPE exposure at 17 weeks' gestation on preschool-age ADHD. Between 2007 and 2011, 260 ADHD cases were identified using the Preschool Age Psychiatric Assessment and compared to a birth-year-stratified control group of 549 children. We categorized bis(2-butoxyethyl) phosphate (BBOEP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) as values < limit of detection (LOD) (BBOEP N = 386, BDCIPP N = 632), ≥LOD but < limit of quantification (LOQ) (BBOEP N = 413; BDCIPP N = 75), or above LOQ (BBOEP N = 70; BDCIPP N = 102). Diphenyl phosphate (DPhP) and di-n-butyl phosphate (DnBP) were categorized as quartiles and also modeled with a log10 linear term. We estimated multivariable adjusted odds ratios (ORs) using logistic regression and examined modification by sex using an augmented product term approach.
Mothers in the 3rd DnBP quartile had 1.71 times the odds of having a child with ADHD compared to the 1st quartile (95%CI: 1.13, 2.58); a similar trend was observed for log10 DnBP and ADHD. Mothers with BDCIPP ≥ LOD but < LOQ had 1.39 times the odds of having a child with ADHD compared to those with BDCIPP < LOD (95%CI: 0.83, 2.31). Girls had lower odds of ADHD with increasing BBOEP exposure (log10 OR: 0.55 (95%CI: 0.37, 0.93), however boys had a weakly increased odds (log10 OR: 1.25 (95%CI: 0.74, 2.11) p-interaction = 0.01].
We found modest increased odds of preschool ADHD with higher DnBP and BDCIPP exposure.
注意力缺陷多动障碍（ADHD）是全球儿童中主要的神经发育障碍；然而，尚未确定多少可改变的危险因素。有机磷酸酯（OPEs）是无处不在的化学物质，作为其他受管制化学品的替代品，其使用越来越普遍。目前的研究已经将 OPEs 与神经发育缺陷联系起来。本研究旨在评估妊娠 17 周时 OPE 暴露对 3 岁儿童临床评估的 ADHD 的影响。
在挪威母婴队列研究中，我们进行了嵌套病例对照研究，评估了妊娠 17 周时 OPE 暴露对学龄前 ADHD 的影响。在 2007 年至 2011 年期间，使用学龄前儿童精神评估识别了 260 例 ADHD 病例，并与出生年份分层的 549 名儿童对照组进行比较。我们将双（2-丁氧基乙基）磷酸酯（BBOEP）和双（1,3-二氯-2-丙基）磷酸酯（BDCIPP）归类为低于检测限（LOD）值（BBOEP N=386，BDCIPP N=632）、LOD 但<定量限（LOQ）（BBOEP N=413；BDCIPP N=75）或高于 LOQ（BBOEP N=70；BDCIPP N=102）。磷酸二丁酯（DPhP）和磷酸二正丁酯（DnBP）被归类为四分位数，并使用对数线性项进行建模。我们使用逻辑回归估计多变量调整后的比值比（OR），并通过扩展乘积项方法检查性别修饰作用。
与第 1 四分位数相比，第 3 四分位数的 DnBP 母亲的 ADHD 儿童发生几率高 1.71 倍（95%CI：1.13，2.58）；DnBP 与 ADHD 之间也存在类似的趋势。BDCIPP≥LOD 但<LOQ 的母亲的 ADHD 儿童发生几率是 BDCIPP<LOD 的母亲的 1.39 倍（95%CI：0.83，2.31）。随着 BBOEP 暴露量的增加，女孩患 ADHD 的几率降低（log10 OR：0.55（95%CI：0.37，0.93），而男孩患 ADHD 的几率略有增加（log10 OR：1.25（95%CI：0.74，2.11），p 交互作用=0.01]。
我们发现 DnBP 和 BDCIPP 暴露量较高与学龄前 ADHD 发生几率适度增加有关。
