Zaikova EK, Kaplina AV, Petrova NA, Pervunina TM, Golovkin AS, Kostareva AA, Kalinina OV. MicroRNA-320а as a novel biomarker at preclinical stage of necrotizing enterocolitis in term neonates with congenital heart defects. World J Clin Pediatr 2025; 14(3): 103652 [DOI: 10.5409/wjcp.v14.i3.103652]
Corresponding Author of This Article
Olga V Kalinina, PhD, Professor, Department of Laboratory Medicine with Clinic, Institution of Medical Education, Almazov National Medical Research Centre, Akkuratova Street 2, Saint-Petersburg 197341, Russia. olgakalinina@mail.ru
Research Domain of This Article
Pediatrics
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Pediatr. Sep 9, 2025; 14(3): 103652 Published online Sep 9, 2025. doi: 10.5409/wjcp.v14.i3.103652
MicroRNA-320а as a novel biomarker at preclinical stage of necrotizing enterocolitis in term neonates with congenital heart defects
Ekaterina K Zaikova, Aleksandra V Kaplina, Natalia A Petrova, Tatiana M Pervunina, Alexey S Golovkin, Anna A Kostareva, Olga V Kalinina
Ekaterina K Zaikova, Alexey S Golovkin, Anna A Kostareva, Olga V Kalinina, Institute of Molecular Biology and Genetics, Almazov National Medical Research Centre, Saint-Petersburg 197341, Russia
Aleksandra V Kaplina, Natalia A Petrova, Research Laboratory of Physiology and Diseases of Newborns, Almazov National Medical Research Centre, Saint-Petersburg 197341, Russia
Tatiana M Pervunina, Institute of Perinatology and Pediatrics, Almazov National Medical Research Centre, Saint-Petersburg 197341, Russia
Olga V Kalinina, Department of Laboratory Medicine with Clinic, Institution of Medical Education, Almazov National Medical Research Centre, Saint-Petersburg 197341, Russia
Olga V Kalinina, Research Laboratory of Molecular Epidemiology and Genetics Evolution, Saint-Petersburg Pasteur Institute, Saint-Petersburg 197021, Russia
Author contributions: Zaikova EK collected the data, performed the experiments, analyzed and interpreted the data, drafted the initial manuscript; Kaplina AV contributed to the data collection process and clinical advice; Petrova NA and Pervunina TM provided clinical advice and conceptualized the study; Golovkin AS participated in data analysis and interpretation; Pervunina TM and Kostareva AA contributed to project administration and funding acquisition; Kalinina OV conceptualized the study, analyzed and interpreted the data, drafted the initial manuscript; all authors contributed to manuscript editing and approved the final version of the manuscript.
Supported by The Russian Science Foundation, No. 19-75-20076.
Institutional review board statement: This study was approved by the local institutional Ethics Committee (protocol No. 1702-21, February 15, 2021) and complied with the Helsinki Declaration.
Conflict-of-interest statement: The authors declare no competing interests.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Olga V Kalinina, PhD, Professor, Department of Laboratory Medicine with Clinic, Institution of Medical Education, Almazov National Medical Research Centre, Akkuratova Street 2, Saint-Petersburg 197341, Russia. olgakalinina@mail.ru
Received: November 26, 2024 Revised: March 6, 2025 Accepted: March 18, 2025 Published online: September 9, 2025 Processing time: 202 Days and 9.6 Hours
Abstract
BACKGROUND
Necrotizing enterocolitis (NEC) remains a prominent gastrointestinal emergency among infants, particularly term infants with congenital heart defects (CHD) being at high risk. The molecular processes that contribute to NEC have yet to be completely understood. The high mortality rates necessitate an active search for noninvasive biomarkers that can aid in the preclinical diagnosis and prognosis of NEC. MicroRNAs (miRs), which are involved in many biological processes in both health and disease, have been discovered to play an important role in regulating inflammation and immune responses via various signaling pathways.
AIM
To determine the plasma levels of miR-155, miR-221, miR-223, miR-320a, miR-451a as potential NEC biomarkers in term newborns with CHD.
METHODS
This prospective cohort study included twenty-tree term newborns with CHD who underwent cardiac surgery on the median day of life (DOL) = 7. Nine of them developed NEC (Bell’s stage IIA and IIIA) within 1 week of cardiac surgery (NEC newborns). Blood samples were collected before (median DOL = 5) and following (median DOL = 13) cardiac surgery. Levels of plasma miR-155-5p, miR-221-3p, miR-223-3p, miR-320a-3p, and miR-451a were determined using real-time polymerase chain reaction. The functional analysis was executed using the DIANA-miRPath v4.0.
RESULTS
Preoperatively, NEC newborns had significantly lower plasma levels of miR-155 (2.70-fold, P = 0.020), miR-223 (2.42-fold, P = 0.030), and miR-320a (3.62-fold, P = 0.006) than newborns without NEC. Postoperatively, miR-451a levels differed significantly between the newborn groups, showing a 4.70-fold decrease (P = 0.014) in expression when clinical NEC symptoms appeared. According to receiver operating characteristic analysis, miR-320a was found to be the most effective predictive biomarker for NEC [area under the curve (AUC) = 0.835, 63% sensitivity, 100% specificity], while miR-451a was identified as a NEC biomarker (AUC = 0.835, 85.7% sensitivity, 76.9% specificity). Preoperatively, miR-155-5p, miR-223-3p, and miR-320a-3p were differentially expressed and targeted the forkhead box O and Hippo pathways (P < 0.01).
CONCLUSION
Our study demonstrates, for the first time, that plasma miR-320a-3p levels can be used as a preclinical biomarker for NEC in term newborns with CHD.
Core Tip: The high morbidity and mortality rates associated with necrotizing enterocolitis (NEC) highlight the critical need to identify specific and sensitive biomarkers for early detection and prevention. In this study we evaluated plasma levels of microRNA (miR)-155, miR-221, miR-223, miR-320a, and miR-451a as potential NEC biomarkers in term newborns with congenital heart defects (CHD). For the first time, plasma miR-320a-3p was identified as a predictive biomarker for the risk of NEC in term newborns with CHD at the preclinical stage, and the Hippo signaling pathway may be involved in the early stages of NEC pathogenesis.
