He Zhengting, Song Ashley Y, Schrott Rose, Feinberg Jason I, Bakulski Kelly M, Benke Kelly S, Croen Lisa A, Hertz-Picciotto Irva, Schmidt Rebecca J, Lyall Kristen, Newschaffer Craig J, Fallin M Daniele, Volk Heather E, Ladd-Acosta Christine
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
Wendy Klag Center for Autism and Developmental Disabilities, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
Environ Epidemiol. 2025 May 5;9(3):e384. doi: 10.1097/EE9.0000000000000384. eCollection 2025 Jun.
Prenatal air pollutants have been associated with adverse birth outcomes, and DNA methylation (DNAm) changes in placenta may contribute to these associations. DNAm-based epigenetic gestational age (GA) estimators are emerging biomarkers for aging/biological age that can reflect early-life exposures and predict long-term health outcomes. We leveraged 103 mother-offspring pairs from the Early Autism Risk Longitudinal Investigation cohort to assess associations between prenatal air pollution and placental epigenetic GA at birth.
Prenatal air pollution concentrations (NO, O, PM, and PM) were estimated from weekly data from monitoring stations near maternal residence and calculated for preconception and pregnancy periods. DNAm from fetal-side placenta samples was measured on Illumina HumanMethylation450 BeadChip. Epigenetic GA was computed using Lee's robust placenta clock algorithm. GA acceleration/deceleration was the residual of predicted epigenetic GA on chronologic GA, adjusted (intrinsic) or unadjusted (extrinsic) for cell type proportions. We used linear regressions to examine associations between average air pollution levels in each period and GA acceleration/deceleration, and weekly distributed lag models to examine critical exposure windows.
Higher pregnancy average O and PM exposures were associated with decelerated intrinsic (β = -0.65 and -0.79) and extrinsic GA (β = -0.69 and -0.74) at birth (per 10-unit increment). Trimester-specific analyses revealed higher O and PM exposures in trimesters 2 to 3 associated with decelerated GA at birth. Weekly distributed lag models suggested pregnancy weeks 21 to 31 and 21 to 29 were critical windows of O and PM exposures, respectively.
Prenatal air pollution exposures, especially during mid- to late-pregnancy, were associated with lower biological maturity at birth.
产前空气污染物与不良出生结局有关，胎盘DNA甲基化（DNAm）变化可能导致这些关联。基于DNAm的表观遗传胎龄（GA）估计值是新兴的衰老/生物学年龄生物标志物，可反映早期生活暴露并预测长期健康结局。我们利用来自早期自闭症风险纵向调查队列的103对母婴来评估产前空气污染与出生时胎盘表观遗传GA之间的关联。
根据母亲居住地附近监测站的每周数据估算产前空气污染浓度（NO、O、PM和PM），并计算孕前和孕期的浓度。在Illumina HumanMethylation450 BeadChip上测量胎儿侧胎盘样本的DNAm。使用Lee的稳健胎盘时钟算法计算表观遗传GA。GA加速/减速是预测的表观遗传GA在按细胞类型比例调整（内在）或未调整（外在）的实际GA上的残差。我们使用线性回归来检验每个时期的平均空气污染水平与GA加速/减速之间的关联，并使用每周分布滞后模型来检验关键暴露窗口。
较高的孕期平均O和PM暴露与出生时内在GA减速（β = -0.65和-0.79）和外在GA减速（β = -0.69和-0.74）相关（每增加10个单位）。按孕期进行的分析显示，孕2至3期较高的O和PM暴露与出生时GA减速相关。每周分布滞后模型表明，孕21至31周和21至29周分别是O和PM暴露的关键窗口。
产前空气污染暴露，尤其是在妊娠中后期，与出生时较低的生物学成熟度有关。
