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

University Hospital of Ferrara150 enrolled

Overview

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 .

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 Type

OBSERVATIONAL

Enrollment

150

Conditions

Neonatal Encephalopathy Cell Damage Metabolic Acidosis Inflammation

Eligibility

Sex: ALLMin age: 15 MinutesMax age: 6 HoursHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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

Time frame: birth, 72 hours, 7 days of life

Secondary Outcomes

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