Division of Maternal-Fetal Medicine and Obstetrics, Department of Obstetrics and Gynecology, Stanford University, Stanford, CA, USA.
Division of Maternal-Fetal Medicine and Obstetrics, Department of Obstetrics and Gynecology, Stanford University, Stanford, CA, USA.
Eur J Obstet Gynecol Reprod Biol. 2024 Sep;300:224-229. doi: 10.1016/j.ejogrb.2024.07.026. Epub 2024 Jul 19.
Recent studies have suggested that pregnancy accelerates biologic aging, yet little is known about how biomarkers of aging are affected by events during the peripartum period. Given that immune shifts are known to occur following surgery, we explored the relation between mode of delivery and postpartum maternal leukocyte telomere length (LTL), a marker of biologic aging.
Postpartum maternal blood samples were obtained from a prospective cohort of term, singleton livebirths without hypertensive disorders or peripartum infections between 2012 and 2018. The primary outcome was postpartum LTLs from one blood sample drawn between postpartum week 1 and up to 6 months postpartum, measured from thawed frozen peripheral blood mononuclear cells using quantitative PCR in basepairs (bp). Multivariable linear regression models compared LTLs between vaginal versus cesarean births, adjusting for age, body mass index, and nulliparity as potential confounders. Analyses were conducted in two mutually exclusive groups: those with LTL measured postpartum week 1 and those measured up to 6 months postpartum. Secondarily, we compared multiomics by mode of delivery using machine-learning methods to evaluate whether other biologic changes occurred following cesarean. These included transcriptomics, metabolomics, microbiomics, immunomics, and proteomics (serum and plasma).
Of 67 included people, 50 (74.6 %) had vaginal and 17 (25.4 %) had cesarean births. LTLs were significantly shorter after cesarean in postpartum week 1 (5755.2 bp cesarean versus 6267.8 bp vaginal, p = 0.01) as well as in the later draws (5586.6 versus 5945.6 bp, p = 0.04). After adjusting for confounders, these differences persisted in both week 1 (adjusted beta -496.1, 95 % confidence interval [CI] -891.1, -101.1, p = 0.01) and beyond (adjusted beta -396.8; 95 % CI -727.2, -66.4. p = 0.02). Among the 15 participants who also had complete postpartum multiomics data available, there were predictive signatures of vaginal versus cesarean births in transcriptomics (cell-free [cf]RNA), metabolomics, microbiomics, and proteomics that did not persist after false discovery correction.
Maternal LTLs in postpartum week 1 were nearly 500 bp shorter following cesarean. This difference persisted several weeks postpartum, even though other markers of inflammation had normalized. Mode of delivery should be considered in any analyses of postpartum LTLs and further investigation into this phenomenon is warranted.
最近的研究表明，怀孕会加速生物衰老，但人们对围产期事件如何影响衰老生物标志物知之甚少。鉴于手术后免疫状态会发生变化，我们探讨了分娩方式与产后母亲白细胞端粒长度（LTL）之间的关系，LTL 是生物衰老的一个标志物。
2012 年至 2018 年间，从无高血压疾病或围产期感染的足月、单胎活产的前瞻性队列中获得产后母亲血液样本。主要结局是产后 1 周至产后 6 个月内从解冻的冷冻外周血单核细胞中测量的一个血液样本的产后 LTL，使用实时定量 PCR 以碱基对（bp）为单位进行测量。多变量线性回归模型比较了阴道分娩与剖宫产分娩之间的 LTL，调整了年龄、体重指数和初产妇身份作为潜在混杂因素。分析在两个相互排斥的组中进行：产后第 1 周测量 LTL 的组和产后 6 个月内测量 LTL 的组。其次，我们使用机器学习方法比较了分娩方式的多组学，以评估剖宫产是否会导致其他生物学变化。这些包括转录组学、代谢组学、微生物组学、免疫组学和蛋白质组学（血清和血浆）。
在 67 名纳入的人中，50 名（74.6%）进行了阴道分娩，17 名（25.4%）进行了剖宫产。剖宫产产后第 1 周的 LTL 明显缩短（5755.2bp 剖宫产与 6267.8bp 阴道分娩，p=0.01），较晚的样本也是如此（5586.6 与 5945.6bp，p=0.04）。在调整了混杂因素后，这一差异在产后第 1 周（调整后的 β-496.1，95%置信区间[CI] -891.1，-101.1，p=0.01）和以后（调整后的 β-396.8；95% CI -727.2，-66.4，p=0.02）仍存在。在 15 名还具有完整产后多组学数据的参与者中，在转录组学（无细胞 [cf]RNA）、代谢组学、微生物组学和蛋白质组学中，阴道分娩与剖宫产分娩的特征存在预测性，但在经过假发现率校正后，这些特征并不存在。
剖宫产术后产妇产后第 1 周的 LTL 缩短近 500bp。这种差异在产后数周内持续存在，尽管其他炎症标志物已经恢复正常。在分析产后 LTL 时应考虑分娩方式，需要进一步研究这一现象。
