In recent years evidence has been accumulated showing that miRNAs can act as potential biomarkers or targets for therapy of preterm birth, one of the most important problems in modern obstetrics. We have performed a prospective study of the miRNA profile in the plasma during the first and second trimesters in pregnant women with high risk of preterm birth (n = 13 cases and n = 11 controls). For the study group plasma blood samples at 9–13 weeks before diagnosis and at 22–24 weeks after start of therapy were selected. Using high-throughput sequencing technology we detected differences in the levels of 15 miRNAs (3 upregulated—hsa-miR-122-5p, hsa-miR-34a-5p, hsa-miR-34c-5p; 12 downregulated—hsa-miR-487b-3p, hsa-miR-493-3p, hsa-miR-432-5p, hsa-miR-323b-3p, hsa-miR-369-3p, hsa-miR-134-5p, hsa-miR-431-5p, hsa-miR-485-5p, hsa-miR-382-5p, hsa-miR-369-5p, hsa-miR-485-3p, hsa-miR-127-3p) (log₂(FC) ≥ 1.5; FDR ≤ 0.05) during the first trimester compared with the control (non-high-risk of preterm birth pregnant women). All downregulated miRNAs in the first trimester from the placenta-specific C14MC cluster. During the second trimester no differentially expressed miRNAs were found. Our results suggest that the miRNA profile in plasma during early pregnancy may predict a high risk of preterm birth, which is important in preventing gestational problems as early as possible.

Although circulating microRNAs (miRNAs) in maternal blood may play an important role in regulation of pregnancy progression and serve as non-invasive biomarkers for different gestation complications, little is known about their profile in blood during normally developing pregnancy. In this study we evaluated the miRNA profiles in paired plasma and serum samples from pregnant women without health or gestational abnormalities at three time points using high-throughput sequencing technology. Sequencing revealed that the percentage of miRNA reads in plasma and serum decreased by a third compared to first and second trimesters. We found two miRNAs in plasma (hsa-miR-7853-5p and hsa-miR-200c-3p) and 10 miRNAs in serum (hsa-miR-203a-5p, hsa-miR-495-3p, hsa-miR-4435, hsa-miR-340-5p, hsa-miR-4417, hsa-miR-1266-5p, hsa-miR-4494, hsa-miR-134-3p, hsa-miR-5008-5p, and hsa-miR-6756-5p), that exhibit level changes during pregnancy (p-value adjusted < 0.05). In addition, we observed differences for 36 miRNAs between plasma and serum (p-value adjusted < 0.05), which should be taken into consideration when comparing the results between studies performed using different biosample types. The results were verified by analysis of three miRNAs using qRT-PCR (p < 0.05). The present study confirms that the circulating miRNA profile in blood changes during gestation. Our results set the basis for further investigation of molecular mechanisms, involved in regulation of pregnancy, and the search for biomarkers of gestation abnormalities.

Extracellular vesicles (EVs) are double-membrane vesicles that facilitate intercellular communication and play a pivotal role in both physiological and pathological processes. A substantial body of evidence suggests that EVs play a role in the pathogenesis of various pregnancy complications. Because EVs can be detected in the peripheral blood, they are potential biomarkers for the early diagnosis of pregnancy complications and foetal developmental disorders. The majority of studies have demonstrated a correlation between alterations in the concentration of EVs and changes in their contents and the occurrence of pregnancy complications. Despite the current limitations in establishing a clear link between these findings and the pathogenesis of the disease, as well as the lack of sufficient evidence to support their use in clinical practice, it is noteworthy to highlight the potential role of specific miRNAs carried by EVs in the development of pregnancy complications. These include miR-210 and miR-136-5p for pre-eclampsia and gestational diabetes mellitus, miR-155, miR-26b-5p, miR-181a-5p, miR-495 and miR-374c for pre-eclampsia and preterm birth. The following miRNAs have been identified as potential biomarkers for preterm birth and gestational diabetes mellitus: miR-197-3p and miR-520h, miR-1323, miR-342-3p, miR-132-3p, miR-182-3p, miR-517-3p, miR-222-3p, miR-16-5p and miR-126-3p. Additionally, miR-127-3p has been linked to foetal growth restriction and preterm birth. Nevertheless, it would be premature to propose that EVs can be employed as biomarkers for pregnancy complications. Further research and the accumulation of results obtained using the methods proposed in the MISEV2023 guidelines will enable a definitive conclusion to be reached.

Complications endangering mother or fetus affect around one in seven pregnant women. Investigation of the genetic susceptibility to such diseases is of high importance for better understanding of the disease biology as well as for prediction of individual risk. In this study, we collected and analyzed GWAS summary statistics from the FinnGen cohort and UK Biobank for 24 pregnancy complications. In FinnGen, we identified 11 loci associated with pregnancy hypertension, excessive vomiting, and gestational diabetes. When UK Biobank and FinnGen data were combined, we discovered six loci reaching genome-wide significance in the meta-analysis. These include rs35954793 in FGF5 ($p=6.1\times {10}^{-9}$), rs10882398 in PLCE1 ($p=8.9\times {10}^{-9}$), and rs167479 in RGL3 ($p=5.2\times {10}^{-9}$) for pregnancy hypertension, rs10830963 in MTNR1B ($p=4.5\times {10}^{-41}$) and rs36090025 in TCF7L2 ($p=3.4\times {10}^{-15}$) for gestational diabetes, and rs2963457 in the EBF1 locus ($p=6.5\times {10}^{-9}$) for preterm birth. In addition to the identified genome-wide associations, we also replicated 14 out of 40 previously reported GWAS markers for pregnancy complications, including four more preeclampsia-related variants. Finally, annotation of the GWAS results identified a causal relationship between gene expression in the cervix and gestational hypertension, as well as both known and previously uncharacterized genetic correlations between pregnancy complications and other traits. These results suggest new prospects for research into the etiology and pathogenesis of pregnancy complications, as well as early risk prediction for these disorders.

Premature birth is one of the most important problems of modern obstetrics because it is a leading cause of childhood morbidity and mortality in all countries. Annually, > 1 million premature newborns worldwide die from various types of complications, and most of the survivors become disabled. Moreover, according to WHO analysis, most of these children can be saved by developing measures for the early identification of preterm births, which will provide additional time for effective intervention. Currently, available diagnostic methods do not adequately assess the risks of premature delivery owing to the low predictive value of the methods. This makes it necessary to search for predictors of preterm labor that can improve the accuracy of diagnostic techniques. The desired predictors should have a pathogenetic basis, and most importantly, they must contribute to the early detection of life-threatening premature births. The hormone relaxin could be considered to be a promising marker of premature birth because its role in the pathogenesis of premature birth is unquestionable, and the evaluation of its levels is possible during the early stages of pregnancy.

Preterm birth in multiple pregnancy is an important medical, economic and social problem. Currently, more than half of twins are born prematurely, which puts them at high risk of developing neonatal diseases causing lifelong disability and social maladjustment. In this regard, reducing the frequency of preterm multiple births is an important task of modern obstetrics. Improving perinatal outcomes of multiple pregnancies can only be achieved using the most effective measures that have a good evidence base. At the same time, numerous studies on the effectiveness of therapeutic interventions aimed at prolonging multiple pregnancies have reported contradictory results. This review included most of the randomized controlled trials of methods for the prevention and treatment of threatening preterm birth in multiple pregnancies, as available in PubMed, Google Academy, Elibrary, and the Cochrane Central Register of Controlled Trials. Thus far, studies on the use of bed rest, prophylactic tocolysis, most of the progestins, and cervical cerclage in multiple pregnancy have shown no efficacy in reducing the risk of premature birth. However, encouraging data were obtained on improving neonatal outcomes of multiple pregnancies using vaginal progesterone and an obstetric pessary, but these results require additional confirmation in larger multicenter randomized studies. Further clinical trials are needed to develop algorithms for timely diagnosis and adequate treatment of threatened preterm birth in case of multiple pregnancy, including the use of the most rational preventive and therapeutic methods that have a high evidence level.