Identification of a Pool of miRNA to Improve Early Management of Perinatal Asphyxia and Hypoxic Ischemic Encephalopathy

NCT05986994 | Unknown

• 1 other identifier: 495
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 2

Brief Summary

Hypoxic-ischemic encephalopathy is the most common cause of neurological damage in the neonatal period. It has an incidence of about 1.5-2.5% of livebirths in developed countries. It is associated with a high rate of mortality and morbidity. Major neurological outcomes such as cerebral palsy, mental retardation, learning disabilities, epilepsy occur in approximately 25% of survivors. The diagnostic and prognostic tools currently available for enrollment have limitations and additional reliable biomarkers are needed for all phases of clinical management. Sarnat staging has taken on a role in identifying those infants who may benefit from treatment of hypothermia, resulting in the need for neurological evaluation and staging within 6 hours of life. Therapeutic hypothermia is still the best therapeutic treatment. A new tool in neuroscience research is represented by micro-ribonucleic acid (microRNA) profiling. The presence of microRNAs in blood, urine and saliva and the ability to measure their levels non-invasively has opened new doors in the search for peripheral biomarkers for the diagnosis and prognosis of neurodegenerative diseases and also as possible pharmacological targets. The aim of the present study is to analyze a specific cluster of miRNAs selected from data obtained by macroarray (NGS Pannel) on the entire microRNAome in healthy newborns with normal cord arterial pH value (7.26-7.35) as control cases and in newborns with fetal metabolic acidosis with a pH threshold value lower than 7.12 of the blood gas analysis from cord arterial blood. This latter group will be further stratified into two groups, neonates who will practice therapeutic hypothermia according to current guidelines and a further group who will not practice therapeutic hypothermia. This study will make a further international contribution in evaluating and identifying the potential of microRNAs as diagnostic and prognostic biomarkers in perinatal asphyxia and hypoxic ischemic encephalopathy. Furthermore, the study aims to identify specific microRNA sequences as new possible markers to be used as an additional parameter for the enrollment of therapeutic hypothermia, especially in cases of mild hypoxic-ischemic encephalopathy.

Conditions

Hypoxic-Ischemic Encephalopathy; Asphyxia Perinatal

Keywords

newborn; microRNA; asphyxia; encephalopathy; hypothermia

Outcome Measures

Primary Outcomes (6)

• Evaluation of microRNA levels

  Quantitative characterization of microRNAs (ng/uL) in healthy neonates and neonates with metabolic acidosis at birth with or without therapeutic hypothermia and who developed hypoxic ischemic encephalopathy

  60 minutes of life

• Qualitative evaluation of microRNAs

  Characterization of the type of microRNAs in healthy neonates and neonates with metabolic acidosis at birth with or without therapeutic hypothermia and who developed hypoxic ischemic encephalopathy

  60 minutes of life

• Evaluation of microRNA levels

  Quantitative characterization of microRNAs (ng/uL) in healthy neonates and neonates with metabolic acidosis at birth with or without therapeutic hypothermia and who developed hypoxic ischemic encephalopathy

  3 hours of life

• Qualitative evaluation of microRNAs

  Characterization of the type of microRNAs in healthy neonates and neonates with metabolic acidosis at birth with or without therapeutic hypothermia and who developed hypoxic ischemic encephalopathy

  3 hours of life

• Evaluation of microRNA levels

  Quantitative characterization of microRNAs (ng/uL) in healthy neonates and neonates with metabolic acidosis at birth with or without therapeutic hypothermia and who developed hypoxic ischemic encephalopathy

  72 hours of life

• Qualitative evaluation of microRNAs

  Characterization of the type of microRNAs in healthy neonates and neonates with metabolic acidosis at birth with or without therapeutic hypothermia and who developed hypoxic ischemic encephalopathy

  72 hours of life

Secondary Outcomes (6)

• Predictive role of microRNAs

  60 minutes of life

• Predictive role of microRNAs

  60 minutes of life

• Predictive role of microRNAs

  3 hours of life

• Predictive role of microRNAs

  3 hours of life

• Predictive role of microRNAs

  72 hours of life

Study Arms (3)

Group A

15 healthy newborns with umbilical cord arterial pH between 7.26 and 7.35

Diagnostic Test: microRNA

Group B

15 newborns with metabolic acidosis at birth with umbilical cord arterial pH at birth \< 7.12 and who do not practice therapeutic hypothermia due to lack of enrollment criteria

Other: Metabolic acidosis; Diagnostic Test: microRNA

Group C

15 newborns with metabolic acidosis at birth with umbilical cord arterial pH at birth \< 7.12 and practicing therapeutic hypothermia in accordance with current guidelines

Other: Metabolic acidosis; Diagnostic Test: microRNA; Other: Hypothermia

Interventions

Metabolic acidosis OTHER

Metabolic acidosis at birth with umbilical cord arterial pH at birth \< 7.12

Group B; Group C

microRNA DIAGNOSTIC_TEST

Evaluation of microRNA levels

Group A; Group B; Group C

Hypothermia OTHER

Therapeutic induced hypothermia refers to a lowering of the central body temperature for therapeutic purposes

Group C

Eligibility Criteria

• Age: 35 Weeks - 42 Weeks
• Sex: all
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

All patients transferred to the Buon Consiglio Fatebenefratelli hospital will be eligible

You may qualify if:

• newborns with at least 35 weeks of gestational age
• body weight of at least 1800 g

You may not qualify if:

• Withdrawal of informed consent

Sponsors & Collaborators

• Ospedale Buon Consiglio Fatebenefratelli: lead
• Federico II University: collaborator

Study Sites (2)

Department of Neuroscience, Reproductive and Dentistry Sciences, University of Naples Federico II

Naples, 80131, Italy

RECRUITING

Department of Woman and Child, Buon Consiglio Fatebenefratelli Hospital

Napoli, 80123, Italy

RECRUITING

Related Publications (12)

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  PMID: 10763759 RESULT

• Vinciguerra A, Cepparulo P, Anzilotti S, Cuomo O, Valsecchi V, Amoroso S, Annunziato L, Pignataro G. Remote postconditioning ameliorates stroke damage by preventing let-7a and miR-143 up-regulation. Theranostics. 2020 Oct 27;10(26):12174-12188. doi: 10.7150/thno.48135. eCollection 2020.

  PMID: 33204336 RESULT

• DE Bernardo G, Riccitelli M, Giordano M, Toni AL, Sordino D, Trevisanuto D, Buonocore G, Perrone S. Does high fidelity neonatal resuscitation simulation increase salivary cortisol levels of health care providers? Minerva Pediatr (Torino). 2023 Dec;75(6):884-889. doi: 10.23736/S2724-5276.21.05873-0. Epub 2021 Jun 21.

  PMID: 34152109 RESULT

• Locci E, Bazzano G, Demontis R, Chighine A, Fanos V, d'Aloja E. Exploring Perinatal Asphyxia by Metabolomics. Metabolites. 2020 Apr 4;10(4):141. doi: 10.3390/metabo10040141.

  PMID: 32260446 RESULT

• Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007 May;39(2):175-91. doi: 10.3758/bf03193146.

  PMID: 17695343 RESULT

• De Bernardo G, De Santis R, Giordano M, Sordino D, Buonocore G, Perrone S. Predict respiratory distress syndrome by umbilical cord blood gas analysis in newborns with reassuring Apgar score. Ital J Pediatr. 2020 Feb 12;46(1):20. doi: 10.1186/s13052-020-0786-8.

  PMID: 32050997 RESULT

• Hull J, Dodd KL. Falling incidence of hypoxic-ischaemic encephalopathy in term infants. Br J Obstet Gynaecol. 1992 May;99(5):386-91. doi: 10.1111/j.1471-0528.1992.tb13754.x.

  PMID: 1622910 RESULT

• Conway JM, Walsh BH, Boylan GB, Murray DM. Mild hypoxic ischaemic encephalopathy and long term neurodevelopmental outcome - A systematic review. Early Hum Dev. 2018 May;120:80-87. doi: 10.1016/j.earlhumdev.2018.02.007. Epub 2018 Feb 26.

  PMID: 29496329 RESULT

• O'Sullivan MP, Looney AM, Moloney GM, Finder M, Hallberg B, Clarke G, Boylan GB, Murray DM. Validation of Altered Umbilical Cord Blood MicroRNA Expression in Neonatal Hypoxic-Ischemic Encephalopathy. JAMA Neurol. 2019 Mar 1;76(3):333-341. doi: 10.1001/jamaneurol.2018.4182.

  PMID: 30592487 RESULT

• Ponnusamy V, Yip PK. The role of microRNAs in newborn brain development and hypoxic ischaemic encephalopathy. Neuropharmacology. 2019 May 1;149:55-65. doi: 10.1016/j.neuropharm.2018.11.041. Epub 2019 Feb 1.

  PMID: 30716413 RESULT

• Walsh BH, Inder TE. MRI as a biomarker for mild neonatal encephalopathy. Early Hum Dev. 2018 May;120:75-79. doi: 10.1016/j.earlhumdev.2018.02.006. Epub 2018 Feb 17.

  PMID: 29463417 RESULT

• Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH, Lee MJ, Galas DJ, Wang K. The microRNA spectrum in 12 body fluids. Clin Chem. 2010 Nov;56(11):1733-41. doi: 10.1373/clinchem.2010.147405. Epub 2010 Sep 16.

  PMID: 20847327 RESULT

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain; Asphyxia; Brain Diseases; Hypothermia

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Death; Pathologic Processes; Wounds and Injuries; Body Temperature Changes

Study Officials

• Giuseppe De Bernardo, Prof

  Buon Consiglio Fatebenefratelli Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Giuseppe De Bernardo, MD

CONTACT

3357441303; pinodebtin@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: July 8, 2023
• First Posted: August 14, 2023
• Study Start: July 18, 2023
• Primary Completion: July 18, 2024
• Study Completion: July 18, 2024
• Last Updated: August 14, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)