Reitsma Stéphanie E, Barsoum Julia R, Hansen Kirk C, Sassin Alexa M, Dzieciatkowska Monika, James Andra H, Aagaard Kjersti M, Ahmadzia Homa K, Wolberg Alisa S
Department of Pathology and Laboratory Medicine and UNC Blood Research Center, University of North Carolina School of Medicine, Chapel Hill, NC.
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, The George Washington University School of Medicine and Health Science, Washington DC.
Am J Obstet Gynecol. 2025 Feb;232(2):220.e1-220.e18. doi: 10.1016/j.ajog.2024.04.050. Epub 2024 May 6.
Postpartum hemorrhage is difficult to predict, is associated with significant maternal morbidity, and is the leading cause of maternal mortality worldwide. The identification of maternal biomarkers that can predict increased postpartum hemorrhage risk would enhance clinical care and may uncover mechanisms that lead to postpartum hemorrhage.
This retrospective case-control study employed agnostic proteomic profiling of maternal plasma samples to identify differentially abundant proteins in controls and postpartum hemorrhage cases.
Maternal plasma samples were procured from a cohort of >60,000 participants in a single institution's perinatal repository. Postpartum hemorrhage was defined as a decrease in hematocrit of ≥10% or receipt of transfusion within 24 hours after delivery. Postpartum hemorrhage cases (n=30) were matched by maternal age and delivery mode (vaginal or cesarean) with controls (n=56). Mass spectrometry was used to identify differentially abundant proteins using integrated peptide peak areas. Statistically significant differences between groups were defined as P<.05 after controlling for multiple comparisons.
By study design, cases and controls did not differ in race, ethnicity, gestational age at delivery, blood type, or predelivery platelet count. Cases had slightly but significantly lower predelivery and postdelivery hematocrit and hemoglobin. Mass spectrometry detected 1140 proteins, including 77 proteins for which relative abundance differed significantly between cases and controls (fold change >1.15, P<.05). Of these differentially abundant plasma proteins, most had likely liver or placental origins. Gene ontology term analysis mapped to protein clusters involved in responses to wound healing, stress response, and host immune defense. Significantly differentially abundant proteins with the highest fold change (prostaglandin D2 synthase, periostin, and several serine protease inhibitors) did not correlate with predelivery hematocrit or hemoglobin but identified postpartum hemorrhage cases with logistic regression modeling revealing good-to-excellent area under the operator receiver characteristic curves (0.802-0.874). Incorporating predelivery hemoglobin with these candidate proteins further improved the identification of postpartum hemorrhage cases.
Agnostic analysis of maternal plasma samples identified differentially abundant proteins in controls and postpartum hemorrhage cases. Several of these proteins are known to participate in biologically plausible pathways for postpartum hemorrhage risk and have potential value for predicting postpartum hemorrhage. These findings identify candidate protein biomarkers for future validation and mechanistic studies.
产后出血难以预测，与孕产妇的严重发病相关，是全球孕产妇死亡的主要原因。识别能够预测产后出血风险增加的母体生物标志物将改善临床护理，并可能揭示导致产后出血的机制。
这项回顾性病例对照研究采用对母体血浆样本进行无偏倚的蛋白质组分析，以识别对照组和产后出血病例中丰度有差异的蛋白质。
从单一机构围产期储存库中超过60000名参与者的队列中采集母体血浆样本。产后出血定义为产后24小时内血细胞比容下降≥10%或接受输血。产后出血病例（n = 30）按产妇年龄和分娩方式（阴道分娩或剖宫产）与对照组（n = 56）进行匹配。使用质谱法通过整合肽峰面积来识别丰度有差异的蛋白质。在控制多重比较后，组间具有统计学意义的差异定义为P <.05。
根据研究设计，病例组和对照组在种族、民族、分娩时的孕周、血型或产前血小板计数方面没有差异。病例组产前和产后的血细胞比容和血红蛋白略低但有显著差异。质谱法检测到1140种蛋白质，其中77种蛋白质在病例组和对照组之间的相对丰度有显著差异（倍数变化>1.15，P <.05）。在这些丰度有差异的血浆蛋白中，大多数可能起源于肝脏或胎盘。基因本体术语分析映射到参与伤口愈合反应、应激反应和宿主免疫防御的蛋白质簇。倍数变化最高的显著丰度有差异的蛋白质（前列腺素D2合酶、骨膜蛋白和几种丝氨酸蛋白酶抑制剂）与产前血细胞比容或血红蛋白无关，但通过逻辑回归模型识别产后出血病例，显示受试者工作特征曲线下面积良好至优秀（0.802 - 0.874）。将产前血红蛋白与这些候选蛋白结合使用可进一步改善产后出血病例的识别。
对母体血浆样本进行无偏倚分析，识别出了对照组和产后出血病例中丰度有差异的蛋白质。其中几种蛋白质已知参与了与产后出血风险生物学上合理的途径，对预测产后出血具有潜在价值。这些发现确定了候选蛋白质生物标志物，以供未来进行验证和机制研究。
