Increased Levels of Hsa-miR-199a-3p and Hsa-miR-382-5p in Maternal and Neonatal Blood Plasma in the Case of Placenta Accreta Spectrum
Authors: Timofeeva Angelika V. , Fedorov Ivan S. , Nikonets Anastasia D. , Tarasova Alla M. , Balashova Ekaterina N. , Degtyarev Dmitry N. , Sukhikh Gennady T. 
Published: October 2024

Despite the increasing number of placenta accreta spectrum (PAS) cases in recent years, its im-pact on neonatal outcomes and respiratory morbidity has not yet been extensively studied. In this context, it is crucial to understand the underlying mechanisms of neonatal complications. Moreover, no study has yet demonstrated the effectiveness of antenatal corticosteroid therapy (CT) for prevention of the respiratory distress syndrome (RDS) in newborns of mothers with PAS at the molecular level. In this regard, miRNA profiling was performed on 160 blood plasma sam-ples from preterm infants (gestational age 33–36 weeks) and their mothers diagnosed with or without PAS. The samples with PAS were categorized into groups: without antenatal RDS prophylaxis, and with CT admin-istered either 2–7 days, 7–14 days, or more than 14 days before delivery. These groups were compared to a control group without PAS in the absence of antenatal CT. Deep sequencing was conducted using the NEB-Next® Multiplex Small RNA Library Prep Set for Illumina® on the NextSeq 500/550 platform, followed by validation by quantitative real-time PCR. A significant increase in hsa-miR-199a-3p and hsa-miR-382-5p levels was observed in the blood plasma of newborns with PAS (placenta accreta and increta) compared to the control group. In maternal blood, hsa-miR-199a-3p levels were markedly higher than hsa-miR-382-5p. The timing of antenatal CT significantly influenced the levels of hsa-miR-199a-3p and hsa-miR-382-5p in neonatal plasma from mothers with placenta accreta or increta. A clear trend toward normalization was observed when CT was administered within 14 days before delivery, particularly in the seven days before delivery, but not beyond 14 days. Among newborns with PAS, higher levels of hsa-miR-382-5p were significantly associated with increased Neomod scale severity scores of 2, 4, and 5 compared to a score of 0. Additional-ly, a direct correlation was found between hsa-miR-382-5p level in neonatal plasma and hsa-miR-199a-3p level in the same sample (r = 0.49; p = 0.0001), oxygen requirements in the NICU (r = 0.41; p = 0.0016), duration of NICU stay (r = 0.31; p = 0.019), and the severity of the newborn’s condition based on the NEOMOD scale (r = 0.36; p = 0.0051). Logistic regression mod-els based on 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 ventila-tion in newborns during the early neonatal period, with a sensitivity of 95-100%. It was con-cluded that elevated circulating levels of miRNAs, hsa-miR-199a-3p and hsa-miR-382-5p, in ma-ternal and fetal blood are crucial in the development of respiratory and cardiac complications in newborns from pregnancies affected by PAS. These miRNAs regulate surfactant synthesis in al-veolar cells, fetal organogenesis via IGF-1, the formation of proper lung tissue architecture, and vascular tone.