Barandiaran Leyre Notario, Bauer Julie A, Laue Hannah E, Signes-Pastor Antonio J, Jackson Brian P, Peacock Janet L, Madan Juliette, Bellinger David C, Korrick Susan, Karagas Margaret R
Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA.
Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois Chicago, Chicago, IL, USA.
Environ Health Perspect. 2025 Jun 3. doi: 10.1289/EHP16752.
Exposure to metals and metalloids (hereafter referred to as 'metals') during gestation and early childhood may affect children's neurodevelopment. However, few studies have simultaneously evaluated the impact of exposure to both essential and non-essential metals across specific windows of exposure on children's neurodevelopmental outcomes.
To investigate whether levels of metals during gestation and the early postnatal period, individually and as a mixture, are related to child cognition at 5 years of age among participants in the New Hampshire Birth Cohort Study (NHBCS).
We followed 278 NHBCS pregnancy-offspring dyads up to approximately 5 years of age. Total arsenic (As), copper (Cu), manganese (Mn), lead (Pb), selenium (Se), and zinc (Zn) were measured in toenail samples collected from pregnant persons at ~24 to 28 weeks of gestation (representing periconception and early pregnancy), and at ~6 weeks postpartum (representing mid-pregnancy), and their infants at ~6 weeks of age (representing early infancy). Cognitive development at 5 years was assessed using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV) which includes measures of full-scale intelligence quotient (FSIQ) and five composite indices. Associations between ln-metal toenail concentrations across multiple exposure windows and the six WPPSI-IV scores were estimated through mean field variational Bayes for lagged kernel machine regression (MFVB-LKMR). Potential effect modification by other elements in the mixture as well as sex were further explored.
Biomarkers of As exposures of periconception and early pregnancy, mid-pregnancy and early infancy were associated with lower cognitive scores at 5 years of age (e.g., FSIQ: -0.16 (95% Credible Interval (CrI): -0.24, -0.08) SD change). Periconception and early pregnancy exposures to Mn and Cu were associated with higher child cognitive scores. Sex differences were observed, especially with Mn exposure, with stronger positive associations among males during periconception and early pregnancy and among females during mid-pregnancy. For Pb and Zn exposures, associations with cognitive scores differed across exposure windows, exhibiting both positive and negative associations.
By evaluating multiple essential and non-essential elements across the three previously mentioned exposure windows, we found evidence of sensitive periods of susceptibility to child cognitive measures. While results for As indicated detrimental effects, those for Cu and Mn suggested beneficial trends across all exposure windows. https://doi.org/10.1289/EHP16752.
孕期和儿童早期接触金属和类金属（以下简称“金属”）可能会影响儿童的神经发育。然而，很少有研究同时评估在特定暴露窗口期接触必需金属和非必需金属对儿童神经发育结局的影响。
在新罕布什尔州出生队列研究（NHBCS）的参与者中，调查孕期和出生后早期金属水平单独以及作为混合物与5岁儿童认知能力之间的关系。
我们追踪了278对NHBCS怀孕-后代二元组直至约5岁。在妊娠约24至28周（代表受孕前后和孕早期）、产后约6周（代表孕中期）从孕妇采集的趾甲样本中，以及在约6周龄的婴儿（代表婴儿早期）中测量总砷（As）、铜（Cu）、锰（Mn）、铅（Pb）、硒（Se）和锌（Zn）。使用韦氏学前和小学智力量表（WPPSI-IV）评估5岁时的认知发展，该量表包括全量表智商（FSIQ）和五个综合指数的测量。通过平均场变分贝叶斯滞后核机器回归（MFVB-LKMR）估计多个暴露窗口期的ln-金属趾甲浓度与六个WPPSI-IV分数之间的关联。进一步探讨混合物中其他元素以及性别的潜在效应修正。
受孕前后和孕早期、孕中期和婴儿早期的砷暴露生物标志物与5岁时较低的认知分数相关（例如，FSIQ：-0.16（95%可信区间（CrI）：-0.24，-0.08）标准差变化）。受孕前后和孕早期接触锰和铜与儿童较高的认知分数相关。观察到性别差异，尤其是锰暴露，受孕前后和孕早期男性之间以及孕中期女性之间的正相关更强。对于铅和锌暴露，与认知分数的关联在不同暴露窗口期有所不同，呈现出正相关和负相关。
通过评估上述三个暴露窗口期的多种必需和非必需元素，我们发现了儿童认知测量易感性敏感期的证据。虽然砷的结果表明有有害影响，但铜和锰的结果表明在所有暴露窗口期都有有益趋势。https://doi.org/10.1289/EHP16752 。
