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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Autophagy, Mitophagy, Inflammation and Plasmatic Concentration of Melatonin in Newborn With Metabolic Acidosis at Birth

Conditions
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Neonatal Encephalopathy, Cell Damage, Metabolic Acidosis, Inflammation

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 15 Minutes
Maximum Age: 6 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MILD NE<br>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 Plasma levels of melatonin, Atg5, Parkin, Pink1, inflammatory cytokines will be evaluated | |
| ISOLATED METABOLIC ACIDOSIS<br>gestational age > 35 weeks and weight > 1800 gr evidence of base excess > 12 mmol/L or pH < 7,0 at initial blood gas analyses Normal Sarnat&Sarnat neurological evaluation Plasma levels of melatonin, Atg5, Parkin, Pink1, inflammatory cytokines will be evaluated | |
| HEALTY CONTROLS<br>gestational age > 35 weeks and weight > 1800 gr Normal blood pH or base excess Plasma levels of melatonin, Atg5, Parkin, Pink1, inflammatory cytokiness will be evaluated | |

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change from baseline Parkin and Pink1 Plasma concentration at 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 | birth, 72 hours, 7 days of life | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mild neonatal encephalopathy, birth asphyxia, metabolic acidosis, Autophagy, Mitophagy, inflammation