Timofeeva Angelika V, Fedorov Ivan S, Nikonets Anastasia D, Tarasova Alla M, Balashova Ekaterina N, Degtyarev Dmitry N, Sukhikh Gennady T
National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician Kulakov V.I., 117997 Moscow, Russia.
Int J Mol Sci. 2024 Dec 11;25(24):13309. doi: 10.3390/ijms252413309.
Despite the increasing number of placenta accreta spectrum (PAS) cases in recent years, its impact on neonatal outcomes and respiratory morbidity, as well as the underlying pathogenetic mechanism, has not yet been extensively studied. Moreover, no study has yet demonstrated the effectiveness of antenatal corticosteroid therapy (CT) for the prevention of respiratory distress syndrome (RDS) in newborns of mothers with PAS at the molecular level. In this regard, microRNA (miRNA) profiling by small RNA deep sequencing and quantitative real-time PCR was performed on 160 blood plasma samples from preterm infants (gestational age: 33-36 weeks) and their mothers who had been diagnosed with or without PAS depending on the timing of the antenatal RDS prophylaxis. A significant increase in hsa-miR-199a-3p and hsa-miR-382-5p levels was observed in the blood plasma of the newborns from mothers with PAS compared to the control group. A clear trend toward the normalization of hsa-miR-199a-3p and hsa-miR-382-5p levels in the neonatal blood plasma of the PAS groups was observed when CT was administered within 14 days before delivery, but not beyond 14 days. Direct correlations were found among the hsa-miR-382-5p level in neonatal blood plasma and the hsa-miR-199a-3p level in the same sample (r = 0.49; < 0.001), the oxygen requirements in the NICU (r = 0.41; = 0.001), the duration of the NICU stay (r = 0.31; = 0.019), and the severity of the newborn's condition based on the NEOMOD scale (r = 0.36; = 0.005). Logistic regression models based on the maternal plasma levels of hsa-miR-199a-3p and hsa-miR-382-5p predicted the need for cardiotonic therapy, invasive mechanical ventilation, or high-frequency oscillatory ventilation in newborns during the early neonatal period, with a sensitivity of 95-100%. According to the literary data, these miRNAs regulate fetal organogenesis via IGF-1, the formation of proper lung tissue architecture, surfactant synthesis in alveolar cells, and vascular tone.
尽管近年来胎盘植入谱系（PAS）病例数量不断增加，但其对新生儿结局和呼吸系统发病率的影响以及潜在的发病机制尚未得到广泛研究。此外，尚无研究在分子水平上证明产前皮质类固醇治疗（CT）对预防PAS母亲新生儿呼吸窘迫综合征（RDS）的有效性。在这方面，通过小RNA深度测序和定量实时PCR对160份来自早产儿（胎龄：33 - 36周）及其母亲的血浆样本进行了微小RNA（miRNA）分析，这些母亲根据产前RDS预防的时间被诊断为患有或未患有PAS。与对照组相比，患有PAS母亲的新生儿血浆中hsa-miR-199a-3p和hsa-miR-382-5p水平显著升高。当在分娩前14天内进行CT治疗时，观察到PAS组新生儿血浆中hsa-miR-199a-3p和hsa-miR-382-5p水平有明显的正常化趋势，但超过14天则没有。在新生儿血浆中hsa-miR-382-5p水平与同一样本中的hsa-miR-199a-3p水平之间（r = 0.49；<0.001）、新生儿重症监护病房（NICU）中的氧气需求量之间（r = 0.41； = 0.001）、NICU住院时间之间（r = 0.31； = 0.019）以及基于NEOMOD量表的新生儿病情严重程度之间（r = 0.36； = 0.005）发现了直接相关性。基于母亲血浆中hsa-miR-199a-3p和hsa-miR-382-5p水平的逻辑回归模型预测了新生儿在新生儿早期需要强心治疗、有创机械通气或高频振荡通气，敏感性为95 - 100%。根据文献数据，这些miRNA通过胰岛素样生长因子-1（IGF-1）调节胎儿器官发生、适当肺组织结构的形成、肺泡细胞中表面活性剂的合成以及血管张力。
