He Di, Yan Qi, Uppal Karan, Walker Douglas I, Jones Dean P, Ritz Beate, Heck Julia E
Department of Epidemiology, Fielding School of Public Health, 650 Charles E. Young Drive, Box 951772, Los Angeles, CA, 90095-1772, USA.
Division of Pulmonary, Allergy and Critical Care Medicine, Clinical Biomarkers Laboratory, School of Medicine, Emory University, Atlanta, GA, USA.
Metabolomics. 2025 Feb 20;21(2):30. doi: 10.1007/s11306-025-02225-3.
Maternal tobacco smoking in the perinatal period increases the risk for adverse outcomes in offspring.
To better understand the biological pathways through which maternal tobacco use may have long-term impacts on child metabolism, we performed a high-resolution metabolomics (HRM) analysis in newborns, following an untargeted metabolome-wide association study workflow.
The study population included 899 children without cancer diagnosis before age 6 and born between 1983 and 2011 in California. Newborn dried blood spots were collected by the California Genetic Disease Screening Program between 12 and 48 h after birth and stored for later research use. Based on HRM, we considered mothers to be active smokers if they were self- or provider-reported smokers on birth certificates or if we detected any cotinine or high hydroxycotinine intensities in newborn blood. We used partial least squares discriminant analysis and Mummichog pathway analysis to identify metabolites and metabolic pathways associated with maternal tobacco smoking.
A total of 26,183 features were detected with HRM, including 1003 that were found to be associated with maternal smoking late in pregnancy and early postpartum (Variable Importance in Projection (VIP) scores > = 2). Smoking affected metabolites and metabolic pathways in neonatal blood including vitamin A (retinol) metabolism, the kynurenine pathway, and tryptophan and arachidonic acid metabolism.
The smoking-associated metabolites and pathway perturbations that we identified suggested inflammatory responses and have also been implicated in chronic diseases of the central nervous system and the lung. Our results suggest that infant metabolism in the early postnatal period reflects smoking specific physiologic responses to maternal smoking with strong biologic plausibility.
围产期母亲吸烟会增加后代出现不良后果的风险。
为了更好地理解母亲吸烟可能对儿童代谢产生长期影响的生物学途径，我们按照非靶向代谢组全关联研究工作流程，对新生儿进行了高分辨率代谢组学（HRM）分析。
研究人群包括899名6岁前未被诊断患有癌症且于1983年至2011年在加利福尼亚出生的儿童。加利福尼亚遗传疾病筛查项目在出生后12至48小时收集新生儿干血斑并储存以供后续研究使用。基于HRM，如果母亲在出生证明上自述或由医护人员报告为吸烟者，或者我们在新生儿血液中检测到任何可替宁或高羟基可替宁强度，我们就认为其为现吸烟者。我们使用偏最小二乘判别分析和Mummichog通路分析来识别与母亲吸烟相关的代谢物和代谢途径。
通过HRM共检测到26,183个特征，其中1003个被发现与孕期晚期和产后早期母亲吸烟有关（投影变量重要性（VIP）得分>=2）。吸烟影响新生儿血液中的代谢物和代谢途径，包括维生素A（视黄醇）代谢、犬尿氨酸途径以及色氨酸和花生四烯酸代谢。
我们识别出的与吸烟相关的代谢物和通路扰动表明存在炎症反应，并且也与中枢神经系统和肺部的慢性疾病有关。我们的结果表明，出生后早期婴儿的代谢反映了对母亲吸烟的特定生理反应，具有很强的生物学合理性。
