Papastefan Steven T, Langereis Morgan M, Redden Catherine R, Liesman Daniel R, Huerta Cassandra B, Turner Lucas E, Kang Hee Kap, Stetson Bethany T, Ott Katherine C, Marriott William S, Ito Joyceline A S, Shaaban Aimen F, Alhajjat Amir M
Department of Surgery, The Chicago Institute for Fetal Health, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.
Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.
Front Mol Biosci. 2025 Jul 23;12:1597215. doi: 10.3389/fmolb.2025.1597215. eCollection 2025.
Ultrasound-based staging systems for twin-twin transfusion syndrome (TTTS) are limited by radiologic expertise, fetal positioning, and timing of the exam, and may benefit from incorporation of objective biochemical measures for diagnosis and prognostication. microRNA expression is altered in amniotic fluid of TTTS patients, however the invasive nature of amniocentesis has precluded practical incorporation of these biomarkers into current staging systems. Therefore, we sought to assess whether non-invasive maternal plasma microRNAs can distinguish between TTTS and normal monochorionic diamniotic (MCDA) twin pregnancies.
Maternal blood samples were collected for patients with normal MCDA twin pregnancies (n = 11) or prior to selective fetoscopic laser photocoagulation (SFLP) for patients with TTTS (n = 36). Extracted microRNA from a panel of 24 microRNAs was compared between groups.
miR-26a-5p (P = 0.004), miR-222-3p (P = 0.007), and miR-145-5p (P = 0.047) were downregulated and miR-320a-3p (P = 0.005) was upregulated in the maternal plasma of TTTS patients compared to controls. miR-26a-5p, miR-320a-3p, and miR-222-3p in combination were strong predictors of TTTS on random forest modeling (area under curve = 0.905). After SFLP, all significantly dysregulated microRNAs in TTTS trended toward levels of expression observed in control MCDA twin pregnancies.
Several microRNAs are differentially expressed in maternal plasma and demonstrate strong predictive capacity for identifying twin-twin transfusion syndrome. These plasma microRNAs could provide minimally invasive means to enhance currently established ultrasound diagnostic criteria for twin-twin transfusion syndrome.
基于超声的双胎输血综合征（TTTS）分期系统受到放射学专业知识、胎儿体位和检查时机的限制，纳入客观生化指标进行诊断和预后评估可能会有所帮助。TTTS患者羊水中的微小RNA表达发生改变，然而羊膜腔穿刺术的侵入性使得这些生物标志物无法实际纳入当前的分期系统。因此，我们试图评估无创性母体血浆微小RNA能否区分TTTS和正常单绒毛膜双羊膜囊（MCDA）双胎妊娠。
收集正常MCDA双胎妊娠患者（n = 11）的母体血样，或TTTS患者（n = 36）在选择性胎儿镜激光凝固术（SFLP）前的母体血样。比较两组中从一组24种微小RNA中提取的微小RNA。
与对照组相比，TTTS患者母体血浆中miR-26a-5p（P = 0.004）、miR-222-3p（P = 0.007）和miR-145-5p（P = 0.047）下调，miR-320a-3p（P = 0.005）上调。在随机森林模型中，miR-26a-5p、miR-320a-3p和miR-222-3p联合是TTTS的强预测指标（曲线下面积 = 0.905）。SFLP后，TTTS中所有显著失调的微小RNA的表达水平趋向于对照MCDA双胎妊娠中观察到的水平。
几种微小RNA在母体血浆中差异表达，对双胎输血综合征具有很强的预测能力。这些血浆微小RNA可为增强目前已确立的双胎输血综合征超声诊断标准提供微创手段。
