To editor: The human fetal membrane (amniochorionic membrane) is a remarkable fetal-derived structure that occupies the innermost layer of the uterus and functions as a vital interface between the developing fetus and the maternal environment. This complex, two-layer system comprises an inner amniotic layer—a specialized epithelium enveloping the amniotic cavity—and an outer chorion layer, which is connected to the maternal decidua through a specialized extracellular matrix (ECM) scaffold.1,2 The unique structure of the ECM, defined by collagen fibers encapsulated within proteoglycan-rich hydrogels, provides mechanical elasticity and supports cell-to-cell interactions via embedded amniotic mesenchymal cells.1,2 While the amniotic regulates the dynamic changes occurring within the amniotic cavity, the chorion maintains immune privilege at the maternal-fetal interface, thereby ensuring gestational homeostasis.1,2 Beyond its structural role, the fetal membrane coordinates fundamental developmental processes, including placental morphogenesis, protection of the fetus from inflammatory injury, and bidirectional signaling between mother and fetus.3 Accumulating evidence indicates that membrane dysfunction can lead to severe pregnancy complications, such as spontaneous preterm birth and preterm prelabor rupture of membranes.3 Despite the vital importance of the fetal membranes throughout pregnancy, research on the maternal-fetal interface has often emphasized the placenta. This focus has resulted in a significant gap in the understanding of the mechanisms underlying the pathophysiology of the amniochorionic membrane. Consequently, it is essential to systematically analyze the trends and conceptual developments within fetal membrane research. To bridge this knowledge gap, we employed advanced bibliometric analysis methods to map the landscape of fetal membrane research. These methods incorporate sophisticated algorithms that maintain research accuracy and mitigate bias when processing massive volumes of literature.4 We conducted a comprehensive bibliometric assessment of the field using the Web of Science Core Collection (WoSCC) database. Our analysis began with a macro perspective to grasp the overall picture and examine current publishing trends, global contributions, institutional partnerships, interdisciplinary connections, and emerging thematic clusters. We subsequently focused on current research frontiers and predicted future research priorities, followed by targeted discussion and analysis. This multifaceted approach provides both a retrospective summary and forward-looking guidance to advance the science of fetal membranes. Materials and methods Data collection All literature data were sourced from the WoSCC. Searches were conducted using the advanced search mode in the WoSCC with the “Exact Search” option. After comprehensive searching and repeated validation of synonyms, near-synonyms, and related terms, the final search expression was determined as: TS = (embryolemma*) or TS = (“fetal membrane*”) or TS = (“embryonic membrane*”) or TS = (“foetal membrane*”) or TS = (fetal NEAR/5 membrane) or TS = (fetalmembranes) or TS = (fetal NEAR/5 membranes) or TS = (chorioamnion*) or TS = (“amniotic membrane*”) or TS = (amnion) or TS = (entoptygma). This retrieved all literature related to fetal membranes from the database’s publication inception (1998) to March 14, 2025. The literature screening process and inclusion/exclusion criteria are shown in Supplementary Fig. 1, https://links.lww.com/MFM/A135. Following this screening, 10,967 articles were obtained. Bibliometric analysis The number of annual publications, the distribution of countries/regions, the distribution of authors, and the dynamic evolution of keywords were analyzed. Keywords were extracted from the “keyword” section of the published articles. Three tools were selected to improve the integration of analytical data and present the results visually. CiteSpace 6.4.r1 was used to detect keyword bursts to track the evolution of research hotspots. VOSviewer was used to build cooperation networks among countries, institutions, and authors, as well as keyword co-occurrence networks. SCImago Graphica was used to visualize the international cooperation network by integrating geospatial data. Results Global annual publications on fetal membranes: general statistics Research articles on fetal membranes indexed in the database date back to 1998, with 272 publications recorded in that year, indicating that important findings were being reported from the outset. A total of 10,967 articles related to fetal membranes were published between 1998 and 2025. Since 1998, research activity in this field has steadily increased, with a notable rise in annual publications between 2019 and 2020 (Supplementary Fig. 2, https://links.lww.com/MFM/A135). During this period, the growth rate reached 12.40%, with publication volume peaking between 2020 and 2022, when more than 500 articles were published annually. Despite a slight decline over the past two years, publication levels remain elevated. The citation rate of fetal membrane research remains stable and robust, peaking between 2020 and 2021 with more than 9000 citations per year. Between 1998 and 2024, these publications were cited 143,952 times, with an average of 13.22 citations per article (Supplementary Fig. 2, https://links.lww.com/MFM/A135). The sustained citation levels and high publication volume indicate that fetal membrane research remains a subject of ongoing exploration. Analysis of the most influential countries, institutions, and authors Distribution of research countries Between 1998 and 2024, fetal membrane research involved scholars from 128 countries across six continents, reflecting an important global research effort. To identify leading contributors and established partnerships, we analyzed publication output and international collaboration networks. In the co-authorship analysis conducted via VOSviewer, countries were categorized into clusters represented by nodes of different colors, with the line width between nodes indicating the strength of the connection (Supplementary Fig. 3A, https://links.lww.com/MFM/A135). SCImago Graphica further illustrated these relationships by integrating publication data with a geographical layout. In this visualization, node size reflects the publication volume of a country, while the connection lines signify the extent of international partnerships (Supplementary Fig. 3B, https://links.lww.com/MFM/A135). The United States leads in productivity with 3821 articles, accounting for 27.16% of total publications, followed by China with 880 publications. Japan, the United Kingdom, and Australia also showed substantial output, with each contributing more than 600 publications. Together, these five countries account for 48.09% of global publications, indicating that they are primary drivers of fetal membrane research. Compared to other nations, these countries demonstrate higher levels of cooperation and connectivity, suggesting that their research landscapes are highly developed and provide significant regional and global insights. Distribution of research institutions A total of 728 institutions worldwide contributed to the advancement of fetal membrane research. Wayne State University ranks first with 324 publications, followed by Seoul National University with 196 and the University of Melbourne with 194. This indicates that these institutions have built a comprehensive and cohesive body of work on topics related to fetal membranes (Supplementary Fig. 3C and Supplementary Table 1, https://links.lww.com/MFM/A135). While individual productivity is high, research efforts among many institutions appear to be largely independent. In terms of institutional partnerships, bibliographic coupling analysis indicates that the University of Texas (total link strength: 431), the University of Florida (339), and Seoul National University (327) maintain the most extensive collaborative networks (Supplementary Fig. 3D, https://links.lww.com/MFM/A135). Distribution of research authors To demonstrate the activity and impact of individual researchers, the top 10 most prolific authors are listed by publication count. Roberto Romero of Wayne State University leads the list with 238 publications, followed by Sonia S. Hassan, also from Wayne State University, with 119 publications. Ramkumar Menon of the University of Texas Medical Branch at Galveston ranks third with 96 publications (Supplementary Fig. 3E and Supplementary Table 2, https://links.lww.com/MFM/A135). Through co-authorship analysis, authors were grouped and color-coded according to their temporal activity and overlaid onto the co-authorship network. In this visualization, each node corresponds to an author, node size reflects publication output, and the connections between nodes represent co-authorship relationships. The results indicate that there is little collaboration between many authors, though Roberto Romero maintains a notably extensive network of collaborative links (Supplementary Fig. 3F, https://links.lww.com/MFM/A135). Keyword analysis of fetal membrane research VOSviewer identified 1296 keywords across 10,967 articles, with 144 meeting the threshold for analysis and forming five distinct clusters (Supplementary Fig. 4A, https://links.lww.com/MFM/A135). In the keyword co-occurrence network, the connections between nodes indicate thematic relationships, where line thickness reflects the frequency of joint occurrence. Five main research themes emerged, characterized by the following prominent keywords: “pregnancy,” “chorioamnionitis,” “preterm birth,” “intrauterine infection,” and “necrosis factor alpha.” Specifically, the five most frequent keywords were “chorioamnionitis,” “premature birth,” “infection,” “intra amniotic infection,” and “interleukin-6.” A keyword co-occurrence network was also constructed using CiteSpace from the same dataset, identifying ten pivotal keywords based on thresholding: “amnion,” “chorioamnionitis,” “amniotic fluid,” “infection,” “transplantation,” “preterm birth,” “amniotic membrane transplantation,” “preterm birth,” “preterm rupture,” and “terminology” (Supplementary Fig. 4B, https://links.lww.com/MFM/A135). The publication volume within each cluster reflects the breadth and significance of research in that specific subject area, while cluster labels pinpoint key hotspots and evolving trends. By applying CiteSpace parameters for cluster analysis, ten major keyword clusters were identified and listed chronologically (IDs No.0 to No.9): No.0 extracellular matrix, No.1 amniotic fluid, No.2 corneal epithelium, No.3 reproductive performance, No.4 amniotic membrane transplantation, No.5 bronchopulmonary dysplasia, No.6 mesenchymal stem cells, No.7 amniotic membrane, No.8 cells, and No.9 preterm birth (Supplementary Fig. 4C, https://links.lww.com/MFM/A135). To clarify the evolutionary trajectory of these topics, ridge maps were used to visualize the temporal dynamics, showing the emergence and development of cluster labels over time (Supplementary Fig. 4D, https://links.lww.com/MFM/A135). Analysis of trends and future prospects in fetal membrane research Burst detection analysis of keywords was conducted to illustrate the dynamic trends of the most influential terms. The keyword burst plot identified the top 25 keywords based on burst duration and intensity, revealing shifting research priorities over time (Supplementary Fig. 5, https://links.lww.com/MFM/A135). “Preterm birth” exhibited the highest burst intensity from 1998 to 2025, particularly during the 1998–2002 period, highlighting its role as a central research focus. In the initial stages of the study period, prominent keywords included “preterm birth,” “messenger RNA,” “tumor necrosis factor,” “localization,” and “delivery.” As the field progressed, terms such as “surface reconstruction,” “ureaplasma urealyticum,” and “penetrating keratoplasty” became more prevalent. More recently, the research focus has shifted toward “regenerative medicine,” “perinatal outcome,” “wound healing,” “neural outcome,” and “extracellular vesicles,” reflecting current and future research trends. Discussion This bibliometric analysis provides a comprehensive overview of the fetal membrane research landscape through March 14, 2025, detailing the field’s evolution, primary research hotspots, collaborative patterns, and future trajectories. Although fetal membranes are essential for supporting and protecting the placenta and fetus during pregnancy, their full significance has historically remained under-researched. The findings indicate that there has been a steady increase in publication volume since 1998, which suggests that scientific interest is sustained and growing. While a slight decline occurred in the past two years, the overall output remains high and reflects the continued vitality of the field. Geographically, the United States and China dominate research output, a trend that underscores their established infrastructures and pivotal roles in advancing this discipline. At the institutional level, contributions from organizations such as Wayne State University and Seoul National University are particularly notable. Despite the productivity of these leading entities, the analysis reveals a pattern of largely independent research efforts, characterized by limited collaboration between authors and institutions across different countries. This finding indicates that international cooperation must be strengthened to consolidate expertise, address complex research questions more effectively, and accelerate scientific progress. Keyword analysis constituted a central component of this study and served as a rigorous tool for projecting future research directions. Our analysis identified six major thematic areas that represent the core of current and emerging research: preterm birth,5 chorioamnionitis,6 regeneration,7 therapeutic potential in wound healing,8 mother-to-fetal outcome,9 and extracellular vesicles.10 Sustained focus on traditional topics, such as chorioamnionitis and preterm birth, indicates that these areas retain their clinical significance. Concurrently, the emergence of novel fields—particularly extracellular vesicles and wound healing—implies that there has been a paradigm shift toward exploring the regenerative and therapeutic potential of fetal membranes. These six areas, summarized in Supplementary Fig. 6, https://links.lww.com/MFM/A135 and detailed in the Supplementary Materials, https://links.lww.com/MFM/A135, establish a clear roadmap for future investigations. Translating these identified hotspots into tangible clinical advancements represents the primary trajectory for future fetal membrane research. To address existing knowledge gaps and improve maternal and infant health outcomes, future studies should prioritize three key areas. First, the development of fetal membrane-specific biomarkers is essential for the early diagnosis and monitoring of conditions such as preterm birth and chorioamnionitis. Second, the exploration of advanced treatment strategies—particularly those leveraging the regenerative properties of extracellular vesicles and fetal membrane tissues—demonstrates substantial therapeutic promise. Finally, addressing the current deficit in global collaboration is necessary for harmonizing research efforts, sharing resources, and resolving the complex biological and clinical challenges within the field. In conclusion, this bibliometric analysis maps the current state of fetal membrane research and provides a strategic framework for guiding future innovation and improving patient care. Acknowledgments Tianjin Key Medical Discipline Construction Project (TJYXZDXK-3-029C). Funding This study was supported by Noncommunicable Chronic Diseases-National Science and Technology Major Project (Grant No. 2023ZD0517600), the National Natural Science Foundation of China (82001579) and the Tianjin Health Research Project (TJWJ2025MS031). Author Contributions Yongmei Shen designed the study and wrote the manuscript. Hefei Wang and Maolin Nie collected and analyzed the data. Jiasong Cao re-examined the data. Yaqi Li, Rongxin Wei, and Junli He participated in analyzing the data. Qimei Lin and Ying Chang contributed equally to this work, and both reviewed and revised the manuscript. All authors contributed to the article and approved the submitted version. Conflicts of Interest The authors declare no conflicts of interest. Data Availability The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Editor Note Ying Chang is one of the editorial board members of Maternal-Fetal Medicine. This article was subject to the journal’s standard procedures, with peer review handled independently of this editor and the associated research groups.
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