在两个具有不良神经发育风险的队列中，测量的儿童胎粪中邻苯二甲酸酯暴露与 12 个月大的儿童认知功能之间的关联。
The associations between prenatal phthalate exposure measured in child meconium and cognitive functioning of 12-month-old children in two cohorts at elevated risk for adverse neurodevelopment.
机构信息
AJ Drexel Autism Institute, Drexel University, 3020 Market St, Suite 560, Philadelphia, PA, 19104, USA; Department of Epidemiology and Biostatistics, Drexel University Dornsife School of Public Health, 3215 Market Street, Philadelphia, PA, 19104, USA.
AJ Drexel Autism Institute, Drexel University, 3020 Market St, Suite 560, Philadelphia, PA, 19104, USA.
出版信息
Environ Res. 2022 Nov;214(Pt 2):113928. doi: 10.1016/j.envres.2022.113928. Epub 2022 Jul 20.
BACKGROUND
Phthalate metabolites in gestational-maternal urine represents short-term maternal exposure, but meconium, the newborn's first stool may better capture cumulative fetal exposure. We quantified phthalate metabolites in meconium from two cohorts of children at higher risk of adverse neurodevelopment and evaluated associations with their cognitive function at 12 months.
METHODS
Meconium phthalate metabolites were quantified in the Safe Passage Study (SPS), N = 720, a pregnancy cohort with high community-levels of prenatal alcohol use, and the Early Autism Risk Longitudinal Investigation (EARLI), N = 236, a high familial autism risk pregnancy cohort. EARLI also had second and third trimester (T2/T3) maternal urine for exposure assessment. Molar sum of di (2-ethylhexyl) (∑DEHP) metabolites and an anti-androgenic score (AAS) using mono-isobutyl, mono-n-butyl, monobenzyl (MBZP), and DEHP metabolites were computed. Cognitive function was assessed at 12 months using the Mullen Scales of Early Learning-Composite (ELC). Multivariable linear regression assessed associations between log-transformed metabolites and ELC. Quadratic terms explored nonlinearity and interaction terms of metabolite by child's sex examined effect modification.
RESULTS
In SPS, MBzP (β = -6.73; 95% CI: 12.04, -1.42; β = 1.95; 0.27, 3.62) and mono (2-ethyl-5-carboxypentyl), (β = -3.81; -7.53, -0.27; β = 0.93; 0.09, 1.77) had U-shaped associations with ELC. In EARLI, T2 urine mono-carboxyisononyl was associated with linear decrease in ELC, indicating lower cognitive function. Interaction with sex was suggested (P < 0.2) for several urine metabolites, mostly indicating negative association between phthalates and ELC among girls but reversed among boys. Only mono-isononyl phthalate and ∑DEHP had consistent main effect associations across matrixes and cohorts, but similar interaction with sex was observed for meconium-measured ∑DEHP, AAS, MBzP, and mono (2-ethylhexyl) in both cohorts.
CONCLUSIONS
Few phthalate metabolites were consistently associated with children's cognitive function, but a similar set of meconium metabolites from both cohorts displayed sex-specific associations. Gestational phthalate exposure may have sexually-dimorphic associations with early cognitive function in children at higher risk for adverse neurodevelopment.
背景
孕妇尿液中的邻苯二甲酸代谢物代表了短期的母体暴露，但新生儿的第一次粪便——胎便可能更好地反映胎儿的累积暴露情况。我们对两个高危神经发育不良儿童队列的胎便中的邻苯二甲酸代谢物进行了定量检测，并评估了它们与 12 个月时认知功能的相关性。
方法
我们在 Safe Passage 研究（SPS）中对 720 名孕妇进行了胎便邻苯二甲酸代谢物的定量检测，该研究队列具有社区产前酒精使用水平高的特点；在早期自闭症风险纵向研究（EARLI）中，对 236 名具有高家族性自闭症风险的孕妇进行了同样的检测。EARLI 还在妊娠的第二和第三阶段（T2/T3）采集了尿液样本进行暴露评估。使用单异丁基、单正丁基、单苄基（MBZP）和邻苯二甲酸二（2-乙基己基）酯（∑DEHP）代谢物计算了∑DEHP 代谢物的摩尔总和和抗雄激素评分（AAS）。在 12 个月时使用 Mullen 早期学习综合量表（ELC）评估认知功能。采用多元线性回归分析，评估了 log 转化代谢物与 ELC 之间的相关性。二次项用于探索非线性关系，代谢物与儿童性别的交互项用于检验效应修饰。
结果
在 SPS 中，MBzP（β=-6.73；95%CI：12.04，-1.42；β=1.95；0.27，3.62）和单（2-乙基-5-羧基戊基）（β=-3.81；-7.53，-0.27；β=0.93；0.09，1.77）与 ELC 呈 U 型关系。在 EARLI 中，T2 尿液中单羧基异壬基与 ELC 呈线性下降相关，表明认知功能较低。几种尿液代谢物的性别交互作用提示（P<0.2），表明在女孩中，邻苯二甲酸与 ELC 之间存在负相关关系，但在男孩中则相反。只有单异壬基邻苯二甲酸酯和∑DEHP 代谢物在不同基质和队列中均具有一致的主要效应相关性，但在两个队列的胎便中，∑DEHP、AAS、MBzP 和单（2-乙基己基）邻苯二甲酸酯也表现出类似的性别交互作用。
结论
很少有邻苯二甲酸代谢物与儿童的认知功能有一致的相关性，但来自两个队列的胎便中的一组类似的邻苯二甲酸代谢物表现出了性别特异性相关性。妊娠期间的邻苯二甲酸暴露可能与神经发育不良高危儿童的早期认知功能存在性别差异的相关性。
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