There is growing interest in the role of extracellular vesicles (EVs) in neonatal pathology. This study aimed to characterise circulating EVs following preterm birth. This single-centre prospective observational study included cord and postnatal plasma from preterm (n = 101) and full-term infants (n = 66). EVs were analysed using nanoparticle tracking analysis, flow cytometry, proteomics and procoagulant activity assay. We found changes in the concentration, size, cellular origin and proteomic content of circulating EVs in preterm infants during perinatal adaptation. To understand if these changes were related to prematurity or normal adaptation to extrauterine life, they were also investigated in term infants. There was a dramatic increase in the concentration of small and large EVs on Day 3 in the preterm group; specific subsets of platelet (CD42b+ and CD62P+), endothelial (VEGFR2) and tissue factor EVs were elevated. Differentially expressed proteins relating to haemostasis, pulmonary physiology and immunity were identified between Day 1 and 3 in preterm infants. These changes have never previously been described in a large cohort of preterm infants and differ from healthy term infants. These findings have major implications for future neonatal EV studies, particularly the timing of sample collection. Further work is required to understand the clinical implications of this unique EV profile following preterm birth.

Conway SPHERE Research Group Conway Institute University College Dublin Dublin Ireland

Department of Haematology Mater Misericordiae University Hospital Dublin Ireland

Department of Haematology Rotunda Hospital Dublin Ireland

Department of Health and Life Sciences University of Liverpool Liverpool UK

Department of Laboratory Medicine Rotunda Hospital Dublin Ireland

Department of Neonatology Liverpool Women's Hospital Liverpool UK

Department of Neonatology Rotunda Hospital Dublin Ireland

Department of Paediatrics Royal College of Surgeons in Ireland Dublin Ireland

Institute of Pathological Physiology 1st Faculty of Medicine Charles University Prague Czech Republic

School of Population Health Royal College of Surgeons in Ireland Dublin Ireland

Zobrazit více v PubMed

Amelio, G. S. , Provitera L., Raffaeli G., et al. 2022. “Endothelial Dysfunction in Preterm Infants: The Hidden Legacy of Uteroplacental Pathologies.” Frontiers in Pediatrics 10: 1041919. PubMed PMC

Andrew, M. , Paes B., Bowker J., and Vegh P.. 1990. “Evaluation of an Automated Bleeding Time Device in the Newborn.” American Journal of Hematology 35, no. 4: 275–277. PubMed

Andrew, M. , Paes B., Milner R., et al. 1987. “Development of the Human Coagulation System in the Full‐Term Infant.” Blood 70, no. 1: 165–172. PubMed

Andrew, M. , Paes B., Milner R., et al. 1988. “Development of the Human Coagulation System in the Healthy Premature Infant.” Blood 72, no. 5: 1651–1657. PubMed

Arraud, N. , Linares R., Tan S., et al. 2014. “Extracellular Vesicles From Blood Plasma: Determination of Their Morphology, Size, Phenotype and Concentration.” Journal of Thrombosis and Haemostasis 12, no. 5: 614–627. PubMed

Awad, H. A. , Tantawy A. A., El‐Farrash R. A., Ismail E. A., and Youssif N. M.. 2014. “CD144+ Endothelial Microparticles as a Marker of Endothelial Injury in Neonatal ABO Blood Group Incompatibility.” Blood Transfusion = Trasfusione Del Sangue 12, no. 2: 250–259. PubMed PMC

Benjamini, Y. , and Hochberg Y.. 1995. “Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing.” Journal of the Royal Statistical Society Series B (Methodological) 57, no. 1: 289–300.

Bertagnolli, M. , Xie L. F., Paquette K., et al. 2018. “Endothelial Colony‐Forming Cells in Young Adults Born Preterm: A Novel Link Between Neonatal Complications and Adult Risks for Cardiovascular Disease.” Journal of the American Heart Association 7, no. 14: e009720. PubMed PMC

Campello, E. , Spiezia L., Radu C. M., et al. 2015. “Circulating Microparticles in Umbilical Cord Blood in Normal Pregnancy and Pregnancy With Preeclampsia.” Thrombosis Research 136, no. 2: 427–431. PubMed

Crump, C. , Winkleby M. A., Sundquist K., and Sundquist J.. 2011. “Risk of Hypertension Among Young Adults Who Were Born Preterm: A Swedish National Study of 636,000 Births.” American Journal of Epidemiology 173, no. 7: 797–803. PubMed PMC

Dai, J. , Zhou Q., Chen J., Rexius‐Hall M. L., Rehman J., and Zhou G.. 2018. “Alpha‐Enolase Regulates the Malignant Phenotype of Pulmonary Artery Smooth Muscle Cells Via the AMPK‐Akt Pathway.” Nature Communications 9, no. 1: 3850. PubMed PMC

Danesh, A. , Inglis H. C., Abdel‐Mohsen M., et al. 2018. “Granulocyte‐Derived Extracellular Vesicles Activate Monocytes and Are Associated With Mortality in Intensive Care Unit Patients.” Frontiers in Immunology 9: 956. PubMed PMC

Doni, A. , Parente R., Laface I., et al. 2021. “Serum Amyloid P Component Is an Essential Element of Resistance Against Aspergillus Fumigatus.” Nature Communications 12, no. 1: 3739. PubMed PMC

Engan, B. , Engan M., Greve G., Vollsæter M., Hufthammer K. O., and Leirgul E.. 2021. “Vascular Endothelial Function Assessed by Flow‐Mediated Vasodilatation in Young Adults Born Very Preterm or With Extremely Low Birthweight: A Regional Cohort Study.” Frontiers in Pediatrics 9: 734082. PubMed PMC

Gairdner, D. , Marks J., and Roscoe J. D.. 1952. “Blood Formation in Infancy. Part II. Normal Erythropoiesis.” Archives of Disease in Childhood 27, no. 133: 214–221. PubMed PMC

Go, H. , Maeda H., Miyazaki K., et al. 2020. “Extracellular Vesicle miRNA‐21 Is a Potential Biomarker for Predicting Chronic Lung Disease in Premature Infants.” American Journal of Physiology. Lung Cellular and Molecular Physiology 318, no. 5: L845–L851. PubMed

Grosshaupt, B. , Muntean W., and Sedlmayr P.. 1997. “Hyporeactivity of Neonatal Platelets Is Not Caused by Preactivation During Birth.” European Journal of Pediatrics 156, no. 12: 944–948. PubMed

Guo, B. , and Yuan Y.. 2017. “A Comparative Review of Methods for Comparing Means Using Partially Paired Data.” Statistical Methods in Medical Research 26, no. 3: 1323–1340. PubMed

Hamburger, S. A. , and McEver R. P.. 1990. “GMP‐140 Mediates Adhesion of Stimulated Platelets to Neutrophils.” Blood 75, no. 3: 550–554. PubMed

Hermansen, M. C. 2001. “Nucleated Red Blood Cells in the Fetus and Newborn.” Archives of Disease in Childhood—Fetal and Neonatal Edition 84, no. 3: F211–F215. PubMed PMC

Howie, S. R. 2011. “Blood Sample Volumes in Child Health Research: Review of Safe Limits.” Bulletin of the World Health Organization 89, no. 1: 46–53. PubMed PMC

Huang, S. , Tang Z., Wang Y., et al. 2020. “Comparative Profiling of Exosomal miRNAs in human Adult Peripheral and Umbilical Cord Blood Plasma by Deep Sequencing.” Epigenomics 12, no. 10: 825–842. PubMed

Hujacova, A. , Sirc J., Pekarkova K., et al. 2021. “Large Platelet and Endothelial Extracellular Vesicles in Cord Blood of Preterm Newborns: Correlation With the Presence of Hemolysis.” Diagnostics (Basel) 11, no. 8: 1316. PubMed PMC

Johnsen, K. B. , Gudbergsson J. M., Andresen T. L., and Simonsen J. B.. 2019. “What Is the Blood Concentration of Extracellular Vesicles? Implications for the Use of Extracellular Vesicles as Blood‐Borne Biomarkers of Cancer.” Biochimica et Biophysica Acta ‐ Reviews on Cancer 1871, no. 1: 109–116. PubMed

Jopling, J. , Henry E., Wiedmeier S. E., and Christensen R. D.. 2009. “Reference Ranges for Hematocrit and Blood Hemoglobin Concentration During the Neonatal Period: Data From a Multihospital Health Care System.” Pediatrics 123, no. 2: e333–e337. PubMed

Karlaftis, V. , Attard C., Summerhayes R., Monagle P., and Ignjatovic V.. 2014. “The Microparticle‐Specific Procoagulant Phospholipid Activity Changes With Age.” International Journal of Laboratory Hematology 36, no. 4: e41–e43. PubMed

Korbal, P. , Słomka A., Sadowska‐Krawczenko I., and Żekanowska E.. 2017. “Evaluation of Tissue Factor Bearing Microparticles in the Cord Blood of Preterm and Term Newborns.” Thrombosis Research 153: 95–96. PubMed

Kupsco, A. , Prada D., Valvi D., et al. 2021. “Human Milk Extracellular Vesicle miRNA Expression and Associations With Maternal Characteristics in a Population‐Based Cohort From the Faroe Islands.” Scientific Reports 11, no. 1: 5840. PubMed PMC

Lal, C. V. , Olave N., Travers C., et al. 2018. “Exosomal microRNA Predicts and Protects Against Severe Bronchopulmonary Dysplasia in Extremely Premature Infants.” JCI Insight 3, no. 5: e93994. PubMed PMC

Liu, L. , Johnson H. L., Cousens S., et al. 2012. “Global, Regional, and National Causes of Child Mortality: An Updated Systematic Analysis for 2010 With Time Trends Since 2000.” Lancet 379, no. 9832: 2151–2161. PubMed

Lötvall, J. , Hill A. F., Hochberg F., et al. 2014. “Minimal Experimental Requirements for Definition of Extracellular Vesicles and Their Functions: A Position Statement From the International Society for Extracellular Vesicles.” Journal of Extracellular Vesicles 3: 26913. PubMed PMC

Mar, P. K. , Galley J., Rajab A., and Besner G. E.. 2021. “Urine Extracellular Vesicle‐Derived miRNA Patterns in Infants With Necrotizing Enterocolitis.” Pediatrics 147: 923.

Mateescu, B. , Kowal E. J., van Balkom B. W., et al. 2017. “Obstacles and Opportunities in the Functional Analysis of Extracellular Vesicle RNA—An ISEV Position Paper.” Journal of Extracellular Vesicles 6, no. 1: 1286095. PubMed PMC

Matei, A. C. , Antounians L., and Zani A.. 2019. “Extracellular Vesicles as a Potential Therapy for Neonatal Conditions: State of the Art and Challenges in Clinical Translation.” Pharmaceutics 11, no. 8: 404. PubMed PMC

McCarthy, K. N. , Ryan N. C., and O'Shea D. T., et al. 2019. “Parental Opinion of Consent in Neonatal Research.” Archives of Disease in Childhood. Fetal and Neonatal Edition 104, no. 4: F409–F414. PubMed

McCoy, J. , Tichon T., and Narvey M.. 2016. “Reducing CBC Clotting Rates in the Neonatal Patient Care Areas.” BMJ Quality Improvement Reports 5, no. 1: u215456.w4946. PubMed PMC

Mestan, K. K. , Check J., Minturn L., et al. 2014. “Placental Pathologic Changes of Maternal Vascular Underperfusion in Bronchopulmonary Dysplasia and Pulmonary Hypertension.” Placenta 35, no. 8: 570–574. PubMed PMC

Milas, G. P. , Issaris V., and Niotis G.. 2023. “Pentraxin‐3 and Neonatal Sepsis: A Systematic Review and Meta‐Analysis.” Journal of Maternal‐Fetal & Neonatal Medicine 36, no. 1: 2205986. PubMed

Mižíková, I. , and Morty R. E.. 2015. “The Extracellular Matrix in Bronchopulmonary Dysplasia: Target and Source.” Front Med (Lausanne) 2: 91. PubMed PMC

Moore, T. , Hennessy E. M., Myles J., et al. 2012. “Neurological and Developmental Outcome in Extremely Preterm Children Born in England in 1995 and 2006: the EPICure Studies.” BMJ 345: e7961. PubMed PMC

Morley, C. J. , Lau R., Davis P. G., and Morse C.. 2005. “What Do Parents Think About Enrolling Their Premature Babies in Several Research Studies?” Archives of Disease in Childhood. Fetal and Neonatal Edition 90, no. 3: F225–F228. PubMed PMC

Morton, S. U. , and Brodsky D.. 2016. “Fetal Physiology and the Transition to Extrauterine Life.” Clinics in Perinatology 43, no. 3: 395–407. PubMed PMC

Murphy, C. A. , O'Reilly D. P., and Neary E., et al. 2020. “A Review of the Role of Extracellular Vesicles in Neonatal Physiology and Pathology.” Pediatric Research 90, no. 2: 289–299. PubMed

Ohta, M. , Koshida S., and Jimbo I., et al. 2021. “Chronological Changes of Serum Exosome in Preterm Infants: A Prospective Study.” Pediatrics International 64, no. 1: e14933. PubMed

Olin, A. , Henckel E., Chen Y., et al. 2018. “Stereotypic Immune System Development in Newborn Children.” Cell 174, no. 5: 1277–1292.e14. PubMed PMC

O'Reilly, D. , Dorodnykh D., Avdeenko N. V., et al. 2021. “Perspective: The Role of Human Breast‐Milk Extracellular Vesicles in Child Health and Disease.” Advances in Nutrition 12, no. 1: 59–70. PubMed PMC

O'Reilly, D. , Egan K., Burke O., et al. 2018. “The Population of Circulating Extracellular Vesicles Dramatically Alters After Very Premature Delivery‐ A Previously Unrecognised Postnatal Adaptation Process? Supplement.” Blood 132, no. S1: 1129.

O'Reilly, D. , Murphy C. A., and Moore C. M., et al. 2023. “Markers of Platelet Activation foR Identification of Late Onset sEpsis in infaNTs: PARENT Study Protocol.” Pediatric Research 95, no. 3: 852–856. PubMed

Owens, A. P., 3rd , and Mackman N.. 2011. “Microparticles in Hemostasis and Thrombosis.” Circulation Research 108, no. 10: 1284–1297. PubMed PMC

Pancholi, V. 2001. “Multifunctional Alpha‐Enolase: Its Role in Diseases.” Cellular and Molecular Life Sciences 58, no. 7: 902–920. PubMed PMC

Parsons, M. E. M. , McParland D., and Szklanna P. B., et al. 2017. “A Protocol for Improved Precision and Increased Confidence in Nanoparticle Tracking Analysis Concentration Measurements Between 50 and 120 Nm in Biological Fluids.” Frontiers in Cardiovascular Medicine 4: 68. PubMed PMC

Patel, M. D. , Breatnach C. R., James A. T., et al. 2019. “Echocardiographic Assessment of Right Ventricular Afterload in Preterm Infants: Maturational Patterns of Pulmonary Artery Acceleration Time Over the First Year of Age and Implications for Pulmonary Hypertension.” Journal of the American Society of Echocardiography 32, no. 7: 884–894.e4. PubMed PMC

Peinado, H. , Alečković M., Lavotshkin S., et al. 2012. “Melanoma Exosomes Educate Bone Marrow Progenitor Cells Toward a Pro‐Metastatic Phenotype Through MET.” Nature Medicine 18, no. 6: 883–891. PubMed PMC

Peñas‐Martínez, J. , Barrachina M. N., Cuenca‐Zamora E. J., et al. 2021. “Qualitative and Quantitative Comparison of Plasma Exosomes From Neonates and Adults.” International Journal of Molecular Sciences 22, no. 4: 1926. http://europepmc.org/abstract/MED/33672065. PubMed PMC

Phillips, D. R. , Charo I. F., Parise L. V., and Fitzgerald L. A.. 1988. “The Platelet Membrane Glycoprotein IIb‐IIIa Complex.” Blood 71, no. 4: 831–843. PubMed

Pierro, M. , Villamor‐Martinez E., van Westering‐Kroon E., Alvarez‐Fuente M., Abman S. H., and Villamor E.. 2022. “Association of the Dysfunctional Placentation Endotype of Prematurity With Bronchopulmonary Dysplasia: A Systematic Review, Meta‐Analysis and Meta‐Regression.” Thorax 77, no. 3: 268–275. PubMed PMC

Raffaeli, G. , Tripodi A., Manzoni F., et al. 2020. “Is Placental Blood a Reliable Source for the Evaluation of Neonatal Hemostasis at Birth?” Transfusion 60, no. 5: 1069–1077. PubMed

Rajasekhar, D. , Barnard M. R., Bednarek F. J., and Michelson A. D.. 1997. “Platelet Hyporeactivity in Very Low Birth Weight Neonates.” Thrombosis and Haemostasis 77, no. 5: 1002–1007. PubMed

Roschitz, B. , Sudi K., Köstenberger M., and Muntean W.. 2001. “Shorter PFA‐100 Closure Times in Neonates Than in Adults: Role of Red Cells, White Cells, Platelets and von Willebrand Factor.” Acta Paediatrica 90, no. 6: 664–670. PubMed

Ruggeri, Z. M. , Zimmerman T. S., Russell S., Bader R., and De Marco L.. 1992. “von Willebrand Factor Binding to Platelet Glycoprotein Ib Complex.” Methods in Enzymology 215: 263–275. PubMed

Schmutz, N. , Henry E., Jopling J., and Christensen R. D.. 2008. “Expected Ranges for Blood Neutrophil Concentrations of Neonates: The Manroe and Mouzinho Charts Revisited.” Journal of Perinatology 28, no. 4: 275–281. PubMed

Schweintzger, S. , Schlagenhauf A., Leschnik B., et al. 2011. “Microparticles in Newborn Cord Blood: Slight Elevation After Normal Delivery.” Thrombosis Research 128, no. 1: 62–67. PubMed

Shi, Y. , Liu J., Zhang R., et al. 2023. “Targeting Endothelial ENO1 (Alpha‐Enolase) ‐PI3K‐Akt‐mTOR Axis Alleviates Hypoxic Pulmonary Hypertension.” Hypertension 80, no. 5: 1035–1047. PubMed

Sibikova, M. , Vitkova V., Jamrichova L., Haluzik M., Zivny J., and Janota J.. 2020. “Spontaneous Delivery Is Associated With Increased Endothelial Activity in Cord Blood Compared to Elective Cesarean Section.” European Journal of Obstetrics, Gynecology, and Reproductive Biology 251: 229–234. PubMed

Sinkin, R. A. , Roberts M., LoMonaco M. B., Sanders R. J., and Metlay L. A.. 1998. “Fibronectin Expression in Bronchopulmonary Dysplasia.” Pediatric and Developmental Pathology 1, no. 6: 494–502. PubMed

Sitaru, A. G. , Holzhauer S., Speer C. P., et al. 2005. “Neonatal Platelets From Cord Blood and Peripheral Blood.” Platelets 16, no. 3–4: 203–210. PubMed

Słomka, A. , Urban S. K., Lukacs‐Kornek V., Żekanowska E., and Kornek M.. 2018. “Large Extracellular Vesicles: Have We Found the Holy Grail of Inflammation?” Frontiers in Immunology 9: 2723. PubMed PMC

Spaull, R. , McPherson B., Gialeli A., et al. 2019. “Exosomes Populate the Cerebrospinal Fluid of Preterm Infants With Post‐Haemorrhagic Hydrocephalus.” International Journal of Developmental Neuroscience 73: 59–65. PubMed

Stoll, B. J. , Hansen N. I., Bell E. F., et al. 2010. “Neonatal Outcomes of Extremely Preterm Infants From the NICHD Neonatal Research Network.” Pediatrics 126, no. 3: 443–456. PubMed PMC

Su, S.‐A. , Xie Y., Fu Z., Wang Y., Wang J.‐A., and Xiang M.. 2017. “Emerging Role of Exosome‐Mediated Intercellular Communication in Vascular Remodeling.” Oncotarget 8, no. 15: 25700–25712. PubMed PMC

Suff, N. , Story L., and Shennan A.. 2019. “The Prediction of Preterm Delivery: What Is New?” Seminars in Fetal and Neonatal Medicine 24, no. 1: 27–32. PubMed

Teitel, D. F. , Iwamoto H. S., and Rudolph A. M.. 1990. “Changes in the Pulmonary Circulation During Birth‐Related Events.” Pediatric Research 27, no. 4 pt. 1: 372–378. PubMed

Théry, C. , Witwer K. W., Aikawa E., et al. 2018. “Minimal Information for Studies of Extracellular Vesicles 2018 (MISEV2018): A Position Statement of the International Society for Extracellular Vesicles and Update of the MISEV2014 Guidelines.” Journal of Extracellular Vesicles 7, no. 1: 1535750. PubMed PMC

Thom, C. S. , Davenport P., Fazelinia H., et al. 2023. “Quantitative Label‐free Mass Spectrometry Reveals Content and Signaling Differences Between Neonatal and Adult Platelets.” Journal of Thrombosis and Haemostasis 22, no. 5: 1447–1462. PubMed PMC

Tietje, A. , Maron K. N., Wei Y., and Feliciano D. M.. 2014. “Cerebrospinal Fluid Extracellular Vesicles Undergo Age Dependent Declines and Contain Known and Novel Non‐Coding RNAs.” PLoS ONE 9, no. 11: e113116. PubMed PMC

Tripisciano, C. , Weiss R., Eichhorn T., et al. 2017. “Different Potential of Extracellular Vesicles to Support Thrombin Generation: Contributions of Phosphatidylserine.” Tissue Factor, and Cellular Origin. Scientific Reports 7, no. 1: 6522. PubMed PMC

Ts'ao, C. H. , Green D., and Schultz K.. 1976. “Function and Ultrastructure of Platelets of Neonates: Enhanced Ristocetin Aggregation of Neonatal Platelets.” British Journal of Haematology 32, no. 2: 225–233. PubMed

Tsuzuki, Y. , Takeba Y., Kumai T., et al. 2009. “Antenatal Glucocorticoid Therapy Increase Cardiac α‐Enolase Levels in Fetus and Neonate Rats.” Life Sciences 85, no. 17: 609–616. PubMed

Tyanova, S. , Temu T., Sinitcyn P., et al. 2016. “The Perseus Computational Platform for Comprehensive Analysis of (Prote)Omics Data.” Nature Methods 13, no. 9: 731–740. PubMed

Useckaite, Z. , Ward M. P., Trappe A., et al. 2020. “Increased Extracellular Vesicles Mediate Inflammatory Signalling in Cystic Fibrosis.” Thorax 75, no. 6: 449–458. PubMed PMC

Uszyński, M. , Zekanowska E., Uszyński W., Kuczyński J., and Zyliński A.. 2011. “Microparticles (MPs), Tissue Factor (TF) and Tissue Factor Inhibitor (TFPI) in Cord Blood Plasma. A Preliminary Study and Literature Survey of Procoagulant Properties of MPs.” European Journal of Obstetrics, Gynecology, and Reproductive Biology 158, no. 1: 37–41. PubMed

van der Pol, E. , Böing A. N., Harrison P., Sturk A., and Nieuwland R.. 2012. “Classification, Functions, and Clinical Relevance of Extracellular Vesicles.” Pharmacological Reviews 64, no. 3: 676–705. PubMed

Vitkova, V. , Panek M., Janec P., et al. 2018. “Endothelial Microvesicles and Soluble Markers of Endothelial Injury in Critically Ill Newborns.” Mediators of Inflammation 2018: 1975056. PubMed PMC

Wang, D. J. , Wang C. M., Wang Y. T., Qiao H., Fang L. Q., and Wang Z. B.. 2016. “Lactation‐Related MicroRNA Expression in Microvesicles of Human Umbilical Cord Blood.” Medical Science Monitor 22: 4542–4554. PubMed PMC

Watts, C. L. , Fanaroff A. A., and Bruce M. C.. 1992. “Elevation of Fibronectin Levels in Lung Secretions of Infants With respiratory Distress Syndrome and Development of Bronchopulmonary Dysplasia.” Journal of Pediatrics 120: no. 4 pt. 1: 614–620. PubMed

Weinstein, M. J. , Blanchard R., Moake J. L., Vosburgh E., and Moise K.. 1989. “Fetal and Neonatal von Willebrand Factor (vWF) Is Unusually Large and Similar to the vWF in Patients With Thrombotic Thrombocytopenic Purpura.” British Journal of Haematology 72, no. 1: 68–72. PubMed

Weiss, L. , Uhrig W., Kelliher S., et al. 2024. “Proteomic Analysis of Extracellular Vesicle Cargoes Mirror the Cardioprotective Effects of Rivaroxaban in Patients With Venous Thromboembolism.” Proteomics Clinical Applications 18, no. 4: e2300014. PubMed

Welsh, J. A. , Van Der Pol E., Arkesteijn G. J. A., et al. 2020. “MIFlowCyt‐EV: A Framework for Standardized Reporting of Extracellular Vesicle Flow Cytometry Experiments.” Journal of Extracellular Vesicles 9, no. 1: 1713526. PubMed PMC

WHO . 2018. "Preterm Birth; Key Facts 2018." WHO. https://www.who.int/news‐room/fact‐sheets/detail/preterm‐birth#cms.

Witwer, K. W. , Buzás E. I., Bemis L. T., et al. 2013. “Standardization of Sample Collection, Isolation and Analysis Methods in Extracellular Vesicle Research.” Journal of Extracellular Vesicles 2, no. 1: 20360. PubMed PMC

Xagorari, A. , Gerousi M., Sioga A., et al. 2019. “Identification of miRNAs From Stem Cell Derived Microparticles in Umbilical Cord Blood.” Experimental Hematology 80: 21–26. PubMed

Xueya, Z. , Yamei L., and Sha C., et al. 2020. “Exosomal Encapsulation of miR‐125a‐5p Inhibited Trophoblast Cell Migration and Proliferation by Regulating the Expression of VEGFA in Preeclampsia.” Biochemical and Biophysical Research Communications 525, no. 3: 646–653. PubMed

Yamada, M. , Chishiki M., Kanai Y., Goto A., and Imamura T.. 2020. “Neonatal Reticulocyte Count During the Early Postnatal Period.” Pediatrics & Neonatology 61, no. 5: 490–497. PubMed

Yáñez‐Mó, M. , Siljander P. R. M., Andreu Z., et al. 2015. “Biological Properties of Extracellular Vesicles and Their Physiological Functions.” Journal of Extracellular Vesicles 4: 27066. PubMed PMC

Yates, A. G. , Pink R. C., Erdbrügger U., et al. 2022. “In Sickness and in Health: The Functional Role of Extracellular Vesicles in Physiology and Pathology In Vivo.” Journal of Extracellular Vesicles 11, no. 1: e12190. PubMed PMC

Zhu, X. J. , Wei J. K., and Zhang C. M.. 2019. “Evaluation of Endothelial Microparticles as a Prognostic Marker in Hemolytic Disease of the Newborn in China.” Journal of International Medical Research 47, no. 11: 5732–5739. PubMed PMC