Placental epigenetic gestational aging in relation to maternal sociodemographic factors and smoking among infants born extremely preterm: a descriptive study

Social determinants of health (SDoH) are defined as the conditions in which people are born, grow, live, work, and age. The distribution of these conditions is influenced by underlying structural factors and may be linked to adverse pregnancy outcomes through epigenetic modifications of gestational tissues. A promising modification is epigenetic gestational age (eGA), which captures ‘biological’ age at birth. Measuring eGA in placenta, an organ critical for foetal development, may provide information about how SDoH ‘get under the skin’ during pregnancy to influence birth outcomes and ethnic/racial disparities. We examined relationships of placental eGA with sociodemographic factors, smoking, and two key clinical outcomes: Apgar scores and NICU length of stay. Using the Robust Placental Clock, we estimated eGA for placental samples from the Extremely Low Gestational Age Newborns cohort (N = 408). Regression modelling revealed smoking during pregnancy was associated with placental eGA acceleration (i.e., eGA higher than chronologic gestational age). This association differed by maternal race: among infants born to mothers racialized as Black, we observed greater eGA acceleration (+0.89 week, 95% CI: 0.38, 1.40) as compared to those racialized as white (+0.27 week, 95% CI: −0.06, 0.59). Placental eGA acceleration was also correlated with shorter NICU lengths of stay, but only among infants born to mothers racialized as Black (−0.08 d/week-eGA, 95% CI: −0.12, −0.05). Together, these observed associations suggest that interpretations of epigenetic gestational aging may be tissue-specific.健康社会决定因素（Social determinants of health, SDoH）指个体出生、成长、生活、工作及衰老所处的各类环境条件。此类条件的分布受潜在结构因素影响，且可能通过妊娠组织的表观遗传修饰与不良妊娠结局产生关联。其中颇具研究前景的表观遗传标志物为表观遗传孕周（epigenetic gestational age, eGA），该指标可反映新生儿出生时的“生物学年龄”。胎盘是胎儿发育不可或缺的器官，对胎盘组织中的eGA进行检测，或可揭示健康社会决定因素如何在妊娠期间“侵入机体”，进而影响分娩结局及种族/族裔健康差异。本研究探讨了胎盘eGA与社会人口学因素、吸烟行为及两项关键临床结局（阿普加评分、新生儿重症监护病房（NICU）住院时长）之间的关联。研究依托稳健胎盘时钟（Robust Placental Clock），对极早早产新生儿队列（Extremely Low Gestational Age Newborns cohort，N=408）的胎盘样本进行eGA估算。回归模型分析结果显示，妊娠期吸烟与胎盘eGA加速（即eGA高于实际孕周）存在显著关联。该关联因母亲种族而异：在被归类为黑人种族的母亲所产婴儿中，我们观察到更显著的eGA加速（+0.89周，95% CI：0.38, 1.40），而被归类为白人种族的母亲所产婴儿的eGA加速幅度为+0.27周（95% CI：-0.06, 0.59）。胎盘eGA加速还与更短的NICU住院时长存在相关性，但这一关联仅见于被归类为黑人种族的母亲所产婴儿群体中（-0.08天/周-eGA，95% CI：-0.12, -0.05）。综上，本研究的观测结果表明，表观遗传孕周衰老的解读可能具有组织特异性。