Inflammation and Metabolic Acidosis at Birth (AGAIN: AutophaGy AcIdosis Newborn)

• Conditions: Metabolic Acidosis; Inflammation; Neonatal Encephalopathy; Cell Damage

• Registration Number: NCT03897101
• Lead Sponsor: University Hospital of Ferrara

Brief Summary

Protection of brain development is a major aim in the Neonatal Intensive Care Unit. Neonatal encephalopathy (NE) occurs in 1.8 to 7.7 infants per 1000 births. Over the last six years, several randomized control trials have demonstrated that therapeutic hypothermia reduces the rate of death or disability at 18 months of age among infants who survived. However, the neurodevelopmental outcome in milder NE not treated with hypothermia remains unclear.

A multicenter prospective observational study will be conducted to determine biological changes of mild neonatal encephalopathy who are not recruited for therapeutic hypothermia .

Detailed Description

It is a prospective observational multicenter study on 50 newborns with mild neonatal encephalopathy and metabolic acidosis at birth not qualified for therapeutic hypothermia compared to healthy controls.

Infants with metabolic acidosis at birth and evidence of mild encephalopathy graded according to Sarnat\&Sarnat neurological evaluation will be recruited to evaluate plasma concentration of melatonin and levels of Autophagy, mitophagy and inflammation.

Plasmatic changes will be compared to:

* healthy control

* infants with isolated metabolic acidosis at birth and normal neurological evaluation.

Study Timeline

• Study Start: 2019-03-01
• Study First Submitted: 2019-03-27
• Study First Submitted QC: 2019-03-29
• Study First Posted: 2019-04-01
• Primary Completion: 2019-12-31
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-24
• Last Update Posted: 2020-03-25
• Study Completion: 2020-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

• gestational age > 35 weeks and weight > 1800 gr
• Apgar score < 5 at 10 minutes o need for cardiopulmonary resuscitation at 10 minutes or evidence of base excess > 12 mmol/L or pH < 7,0 at initial blood gas analyses
• evidence of mild encephalopathy graded according to Sarnat&Sarnat neurological evaluation
• normal amplitude integrated electroencephalography

Exclusion Criteria

• suspected inborn errors of metabolism
• major chromosomal congenital defects

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
change from baseline ATG5 Plasma concentration at 7 days of life	birth, 72 hours, 7 days of life	correlation between metabolic acidosis at birth and Autophagy. ELISA test will be used to measure plasma levels of ATG5

Secondary Outcome Measures

Name	Time	Method
change from baseline Parkin and Pink1 Plasma concentration at 7 days of life	birth, 72 hours, 7 days of life	correlation between metabolic acidosis at birth and Mitophagy. ELISA test will be used to measure plasma levels of Parkin and Park1

Trial Locations

Locations (2)

University Hospital "Sant'Anna" of Ferrara; 🇮🇹 Ferrara, Italy

Infermi Hospital Rimini; 🇮🇹 Rimini, Italy