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Biomedicines
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Advanced Research in Early Pregnancy Loss and Other Pregnancy Complications
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Advanced Research in Early Pregnancy Loss and Other Pregnancy Complications

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 9231

Special Issue Editor

Prof. Dr. Chi Chiu Wang

E-Mail Website
Guest Editor
Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Shatin, Hong Kong
Interests: reproductive medicine (endometriosis, miscarriage, implantation failure, polycystic ovary syndrome); developmental biology (redox control, gene dosage); maternal medicine (preeclampsia, gestational diabetes mellitus); fetal medicine (fetal hypoxia, preterm, fetal growth restriction)
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Early pregnancy is a complex process involving a series of maternal endocrinological, metabolic, immunological, hematological, cellular, and molecular adaptations. These alternations are critical in establishing a dynamic homeostatic environment for embryo implantation, endometrium decidualization, placentation, and fetal development.

Accumulated evidence has shown that the disruption of this delicately modulated homeostasis will cause implantation failure, insufficient decidualization, and defective placentation, leading to abnormal fetal growth or even fetal demise. Clinical manifestations include biochemical pregnancy and spontaneous miscarriage primarily occurring in the first trimester of gestation, generally categorized as pregnancy loss. Correspondingly, late gestation stages may exhibit complications such as fetal growth restriction, preeclampsia, fetal death, and preterm birth.

Nearly half of pregnancy losses and associated complications remain unexplained. Tragically, many patients often experience recurrence. With recent advancements in biomedicine, omics, and molecular and single-cell techniques, growing innovations have unveiled the underlying mechanisms, particularly regarding maternal adaptations and maternal–fetal interactions. These scientific breakthroughs hold translational promise for clinical application and practice in prediction, diagnosis, monitoring, and treatment for better pregnancy outcomes, attracting great interest from clinicians, caretakers, scientists, pharmaceutical companies, patients, and their families.

This Special Issue will focus on the latest research advances and updates in early pregnancy loss and complications. We welcome high-quality studies exploring the underlying mechanisms of pregnancy loss, including studies on signaling pathways and cellular functions, animal studies, and translational studies with potential clinical applications. By consolidating diverse research perspectives, this Special Issue aims to enhance the understanding and management of these critical conditions, ultimately improving maternal–fetal health.

Prof. Dr. Chi Chiu Wang
Guest Editor

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • pregnancy loss
  • miscarriage
  • implantation failure
  • fetal growth restriction
  • preeclampsia
  • fetal death
  • preterm birth
  • pathology
  • pathogenesis
  • mechanism

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Published Papers (6 papers)

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Research

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16 pages, 1529 KiB  
Article
Prediction Models for Late-Onset Preeclampsia: A Study Based on Logistic Regression, Support Vector Machine, and Extreme Gradient Boosting Models
by Yangyang Zhang, Xunke Gu, Nan Yang, Yuting Xue, Lijuan Ma, Yongqing Wang, Hua Zhang and Keke Jia
Biomedicines 2025, 13(2), 347; https://doi.org/10.3390/biomedicines13020347 - 3 Feb 2025
Viewed by 926
Abstract
Background: Preeclampsia, affecting 2–4% of pregnancies worldwide, poses a substantial risk to maternal health. Late-onset preeclampsia, in particular, has a high incidence among preeclampsia cases. However, existing prediction models are limited in terms of the early detection capabilities and often rely on costly [...] Read more.
Background: Preeclampsia, affecting 2–4% of pregnancies worldwide, poses a substantial risk to maternal health. Late-onset preeclampsia, in particular, has a high incidence among preeclampsia cases. However, existing prediction models are limited in terms of the early detection capabilities and often rely on costly and less accessible indicators, making them less applicable in resource-limited settings. Objective: To develop and evaluate prediction models for late-onset preeclampsia using general information, maternal risk factors, and laboratory indicators from early gestation (6–13 weeks). Methods: A dataset of 2000 pregnancies, including 110 late-onset preeclampsia cases, was analyzed. General information and maternal risk factors were collected from the hospital information system. Relevant laboratory indicators between 6 and 13 weeks of gestation were examined. Logistic regression was used as the baseline model to assess the predictive performance of the support vector machine and extreme gradient boosting models for late-onset preeclampsia. Results: The logistic regression model, only considering general information and risk factors, identified 19.1% of cases, with a false positive rate of 0.4%. When selecting 15 factors encompassing general information, risk factors, and laboratory indicators, the false positive rate increased to 0.7% and the detection rate improved to 27.3%. The support vector machine model, only considering general information and risk factors, achieved a detection rate of 27.3%, with a false positive rate of 0.0%. After including all the laboratory indicators, the false positive rate increased to 7.7% but the detection rate significantly improved to 54.5%. The extreme gradient boosting model, only considering general information and risk factors, achieved a detection rate of 31.6%, with a false positive rate of 1.5%. After including all the laboratory indicators, the false positive rate remained at 0.7% but the detection rate increased to 52.6%. Additionally, after adding the laboratory indicators, the areas under the ROC curve for the logistic regression, support vector machine, and extreme gradient boosting models were 0.877, 0.839, and 0.842, respectively. Conclusion: Compared with the logistic regression model, both the support vector machine and extreme gradient boosting models significantly improved the detection rates for late-onset preeclampsia. However, the support vector machine model had a comparatively higher false positive rate. Notably, the logistic regression and extreme gradient boosting models exhibited high negative predictive values of 99.3%, underscoring their effectiveness in accurately identifying pregnant women less likely to develop late-onset preeclampsia. Additionally, logistic regression showed the highest areas under the ROC curve, suggesting that the traditional model has unique advantages in relation to prediction. Full article
(This article belongs to the Special Issue Advanced Research in Early Pregnancy Loss and Other Pregnancy Complications)
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11 pages, 233 KiB  
Article
Maternal Macronutrient Intake and Associated Risk for Gestational Diabetes Mellitus: Results from the BORN2020 Study
by Antigoni Tranidou, Ioannis Tsakiridis, Emmanuela Magriplis, Aikaterini Apostolopoulou, Violeta Chroni, Eirini Tsekitsidi, Ioustini Kalaitzopoulou, Nikolaos Pazaras, Michail Chourdakis and Themistoklis Dagklis
Biomedicines 2025, 13(1), 57; https://doi.org/10.3390/biomedicines13010057 - 29 Dec 2024
Cited by 1 | Viewed by 950
Abstract
Background/Objectives: Limited evidence links maternal macronutrient intake to gestational diabetes mellitus (GDM) risk. Therefore, we evaluated these intakes both before and during pregnancy, comparing macronutrient data against the European Food and Safety Authorities’ (EFSA) Dietary Reference Values (DRVs). Methods: Data were prospectively collected [...] Read more.
Background/Objectives: Limited evidence links maternal macronutrient intake to gestational diabetes mellitus (GDM) risk. Therefore, we evaluated these intakes both before and during pregnancy, comparing macronutrient data against the European Food and Safety Authorities’ (EFSA) Dietary Reference Values (DRVs). Methods: Data were prospectively collected from the Greek BORN2020 epidemiologic pregnant cohort, which included 797 pregnant women, of whom 14.7% were diagnosed with GDM. A multinomial logistic regression model assessed the association between macronutrient intake and GDM, adjusting for maternal, lifestyle, and pregnancy-related factors. Results: Women with GDM had higher maternal age (34.15 ± 4.48 vs. 32.1 ± 4.89 years), higher pre-pregnancy BMI (median 23.7 vs. 22.7 kg/m2), and were more likely to smoke during mid-gestation (17.95% vs. 8.82%). Pre-pregnancy energy intake exceeding EFSA recommendations was associated with increased GDM risk (aOR = 1.99, 95%CI: 1.37–2.86). During mid-gestation, higher dietary fiber intake (aOR = 1.05, 95%CI: 1.00–1.10), higher protein intake (aOR = 1.02, 95% CI: 1.00–1.04), and higher protein percentage of energy intake (aOR = 1.08, 95%CI: 1.01–1.17) were all significantly associated with increased GDM risk. Changes from pre-pregnancy to pregnancy showed significant increases in dietary fiber intake (aOR = 1.07, 95%CI: 1.04–1.10), protein (aOR = 1.00, 95%CI: 1.00–1.01), fat (aOR = 1.00, 95%CI: 1.00–1.01), vegetable protein (aOR = 1.01, 95%CI: 1.00–1.03), animal protein (aOR = 1.00, 95%CI: 1.00–1.01), and monounsaturated fatty acid (MUFA) intake (aOR = 1.01, 95%CI: 1.00–1.02), all of which were associated with increased GDM risk. Conclusions: Energy intake above upper levels set by EFSA, as well as increased protein, MUFA, and fiber intake, although beneficial in balanced intakes, may negatively affect gestation by increasing GDM likelihood when consumed beyond requirements. Full article
(This article belongs to the Special Issue Advanced Research in Early Pregnancy Loss and Other Pregnancy Complications)
8 pages, 217 KiB  
Article
Association of LIN28B Gene Polymorphisms with Intrauterine Adhesions in Patients after Curettage Abortion
by Danting Shen, Cong Li, Shuhua Liu, Anping Lin and Bin Liu
Biomedicines 2024, 12(9), 2044; https://doi.org/10.3390/biomedicines12092044 - 9 Sep 2024
Viewed by 877
Abstract
Background/Objectives: Intrauterine adhesion (IUA) is characterized by endometrial fibrocyte hyperplasia. The LIN28B gene is associated with many proliferative diseases. However, its association with IUA is entirely unknown. We hypothesized that LIN28B gene polymorphisms are responsible for IUA susceptibility after curettage abortion. Methods [...] Read more.
Background/Objectives: Intrauterine adhesion (IUA) is characterized by endometrial fibrocyte hyperplasia. The LIN28B gene is associated with many proliferative diseases. However, its association with IUA is entirely unknown. We hypothesized that LIN28B gene polymorphisms are responsible for IUA susceptibility after curettage abortion. Methods: In this genetic association study, We genotyped two common polymorphisms (rs369065 C>T and rs314280 A>G) in 107 patients with IUA and 270 controls without IUA after curettage abortion from a Chinese population between July 2022 and May 2023 and analyzed their associations with IUA risk using multiple logistic regression models. Results: The carriers of genotype rs314280 AA of the LIN28B gene showed an increased risk of IUA (AOR [adjusted odds ratio] = 2.12, 95% CI [confidence interval] = 1.151–3.903), compared to GG+GA genotypes. Further stratification analyses showed that the deleterious role of the rs314280 AA genotype was more evident in patients with fewer than four pregnancies (AOR = 2.740, 95% CI = 1.355–5.540), fewer than two births (AOR = 2.676, 95% CI = 1.300–5.509), and fibrous (AOR = 2.082, 95% CI = 1.084–3.997) and muscular adhesions (AOR = 3.887, 95% CI = 1.116–13.540). However, the rs369065 T>C polymorphism of the LIN28B gene was not significantly associated with the occurrence of IUA. Conclusions: The rs314280 AA genotype of the LIN28B gene is associated with an increased risk of IUA in patients after curettage abortion, especially in those with fewer pregnancies or parities and higher disease severity. Our findings implicate a precise choice of clinical counseling and decision-making of IUA, thereby protecting female reproduction. Full article
(This article belongs to the Special Issue Advanced Research in Early Pregnancy Loss and Other Pregnancy Complications)

Review

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10 pages, 453 KiB  
Review
The Impact of Amniotic Fluid Interleukin-6, Interleukin-8, and Metalloproteinase-9 on Preterm Labor: A Narrative Review
by Theodoros Karampitsakos, Despoina Mavrogianni, Nikolaos Machairiotis, Anastasios Potiris, Periklis Panagopoulos, Sofoklis Stavros, Panos Antsaklis and Peter Drakakis
Biomedicines 2025, 13(1), 118; https://doi.org/10.3390/biomedicines13010118 - 7 Jan 2025
Cited by 1 | Viewed by 970
Abstract
Background/objectives: Preterm labor is a leading cause of neonatal morbidity and mortality worldwide. Previous research has indicated that an inflammatory response or microbial invasion of the amniotic cavity is a pathological condition linked to preterm birth; hence, inflammatory markers such as metalloproteinase-9 (MMP-9), [...] Read more.
Background/objectives: Preterm labor is a leading cause of neonatal morbidity and mortality worldwide. Previous research has indicated that an inflammatory response or microbial invasion of the amniotic cavity is a pathological condition linked to preterm birth; hence, inflammatory markers such as metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and interleukin-8 (IL-8) have been utilized to predict preterm delivery. The identification of reliable biomarkers for early prediction is critical for improving maternal, fetal, and neonatal outcomes. Methods: To address this issue, a literature review has been conducted on PubMed/Medline and Scopus databases for articles investigating the possible correlation between IL6, IL8, and MMP9 and preterm labor. Results: Using a comprehensive search of the PubMed and Scopus databases, 12 studies were analyzed to identify the correlation between these biomarkers and preterm labor. Seven studies point the impact of increased IL-6 levels or polymorphisms of the gene and higher incidence of preterm labor. Two of the included studies identified the increased risk for preterm birth in elevated levels of IL-8 in amniotic fluid. Six studies highlight the increased incidence of preterm birth in women with polymorphisms of the MMP-9 gene. Conclusions: Elevated IL-6 levels and specific gene polymorphisms are strongly associated with preterm delivery risk, with IL-8 concentrations correlating with systemic inflammation and histologic chorioamnionitis. MMP-9 gene variations and protein levels showed significant predictive value for membrane rupture and labor onset. The findings emphasize integrating these biomarkers into diagnostic tools for routine prenatal care, enhancing early detection, risk stratification, and timely interventions to improve maternal and neonatal outcomes. Full article
(This article belongs to the Special Issue Advanced Research in Early Pregnancy Loss and Other Pregnancy Complications)
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17 pages, 582 KiB  
Review
Investigating the Imperative Role of microRNAs Expression in Human Embryo Implantation: A Narrative Review Based on Recent Evidence
by Anastasios Potiris, Sofoklis Stavros, Ioanna Zouganeli, Nikolaos Machairiotis, Eirini Drakaki, Athanasios Zikopoulos, Ismini Anagnostaki, Athanasios Zachariou, Angeliki Gerede, Ekaterini Domali and Peter Drakakis
Biomedicines 2024, 12(11), 2618; https://doi.org/10.3390/biomedicines12112618 - 15 Nov 2024
Cited by 3 | Viewed by 1334
Abstract
Background/Objectives: Embryo implantation is a highly complex process that requires the precise regulation of numerous molecules to be orchestrated successfully. Micro RNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play a crucial role in the regulation of embryo implantation. This [...] Read more.
Background/Objectives: Embryo implantation is a highly complex process that requires the precise regulation of numerous molecules to be orchestrated successfully. Micro RNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play a crucial role in the regulation of embryo implantation. This article aims to summarize the key findings of the literature regarding the role of miRNAs in human embryo implantation, emphasizing their involvement in critical stages such as decidualization, endometrial receptivity and trophoblast adhesion. Methods: This review includes primary research articles from the past decade. The studies utilize a range of experimental methodologies, including gene expression analysis and in vitro studies. Results: MicroRNAs, like miR-320a, miR-149, and miR30d secreted by preimplantation embryos and blastocysts significantly influence endometrial receptivity by promoting essential cellular processes, such as cell migration and trophoblast cell attachment, while others—miR17-5p, miR-193-3p, miR-372, and miR-542-3p—secreted from the endometrium regulate the decidualization phase. During the apposition and adhesion phases, miRNAs play a complex role by promoting, for example, miR-23b-3p, and inhibiting—as do miR-29c and miR-519d-3p—important biological pathways of these stages. During invasion, miR-26a-5p and miR-125-5p modulate important genes. Conclusions: This review underscores the critical impact of miRNAs in the regulation of embryo implantation and early pregnancy. The ability of miRNAs to modulate gene expression at various stages of reproduction presents promising therapeutic avenues for improving assisted reproductive technologies outcomes and addressing infertility. Further research into miRNA-based diagnostic tools and therapeutic strategies is essential to enhance our understanding of their role in reproductive health and to exploit their potential for clinical applications. Full article
(This article belongs to the Special Issue Advanced Research in Early Pregnancy Loss and Other Pregnancy Complications)
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21 pages, 2693 KiB  
Review
Apigenin as a Promising Agent for Enhancing Female Reproductive Function and Treating Associated Disorders
by Alexander V. Sirotkin and Abdel Halim Harrath
Biomedicines 2024, 12(10), 2405; https://doi.org/10.3390/biomedicines12102405 - 21 Oct 2024
Cited by 1 | Viewed by 2893
Abstract
Apigenin is an organic flavonoid abundant in some plants such as parsley, chamomile, or celery. Recently, it has been investigated for several of its pharmacological characteristics, such as its ability to act as an antioxidant, reduce inflammation, and inhibit the growth of cancer [...] Read more.
Apigenin is an organic flavonoid abundant in some plants such as parsley, chamomile, or celery. Recently, it has been investigated for several of its pharmacological characteristics, such as its ability to act as an antioxidant, reduce inflammation, and inhibit the growth of cancer cells. The purpose of this review is to provide a summary of the existing knowledge regarding the effects of apigenin on female reproductive systems and its dysfunctions. Apigenin can influence reproductive processes by regulating multiple biological events, including oxidative processes, cell proliferation, apoptosis, cell renewal and viability, ovarian blood supply, and the release of reproductive hormones. It could stimulate ovarian folliculogenesis, as well as ovarian and embryonal cell proliferation and viability, which can lead to an increase in fertility and influence the release of reproductive hormones, which may exert its effects on female reproductive health. Furthermore, apigenin could inhibit the activities of ovarian cancer cells and alleviate the pathological changes in the female reproductive system caused by environmental pollutants, harmful medications, cancer, polycystic ovarian syndrome, ischemia, as well as endometriosis. Therefore, apigenin may have potential as a biostimulator for female reproductive processes and as a therapeutic agent for certain reproductive diseases. Full article
(This article belongs to the Special Issue Advanced Research in Early Pregnancy Loss and Other Pregnancy Complications)
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