Indicators of Neuronal Insult in Newborns of COVID-19 Positive Mothers.

Study Overview
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Brief Summary
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The coronavirus disease (COVID- 19) is now a global pandemic that was first reported in China (Wuhan) in December of 2019. Multiple placental abnormalities including fetal and maternal vascular malperfusion have been described in pregnant women infected with (COVID- 19). To date, there are far fewer reports about the specific effects of (COVID- 19) in the newborns delivered for (COVID- 19) positive mothers.

Detailed Description
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COVID-19 in pregnant women has important impacts on perinatal and neonatal outcomes. Authors reported positive COVID infection in neonates born to COVID-19 positive mother. The finding of a recent study suggested that intrauterine or intrapartum transmission is possible and recommended for further investigation. Furthermore, reports showed newborns of COVID-19 positive mother that suffered from catastrophic sequelae of hypoxic ischemic encephalopathy (HIE). These events could be attributed to COVID-19 positive status of the mother. Neuron specific enolase is a biomarker for neuronal injury and synaptic dysfunction and have been correlated with tissue damage in different experimental models. The increased serum levels of neuron specific enolase are associated with the clinical outcome in patients with anoxic encephalopathy. Neuron specific enolase can be a candidate for a diagnostic/prognostic biomarker for neuroinflammation in COVID-19. Additionally, the cytokines are candidate biomarkers after hypoxic-ischemic injury. Macrophage migration inhibitory factor (MIF) is a multifunctional protein that has been identified as proinflammatory cytokine and activates the production of inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, interleukin-6, and interferon. Macrophage migration inhibitory factor plays a central role in controlling the inflammatory and immune response, which may be of particular importance during the development of organ dysfunction in COVID-19 patients. Furthermore, it carries out the apoptosis of the cells. Significant increase of neuronal apoptosis and caspase-3 expression was demonstrated in the brain of neonatal mice exposed to hypoxic injury. There are a limited number of studies investigating the effect of the pandemic period on the brain of the newborns. With this study, we aim to determine the impact of the COVID-19 outbreak on the neuronal functions in the neonates. The current study searches for a diagnostic/prognostic biomarker for neuroinflammation in neonate born to COVID-19 positive mothers.

Official Title
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Macrophage Migration Inhibiting Factor, Enolase and Caspase-3 as Indicators of Neuronal Insult in Newborns of COVID-19 Positive Mothers.

Conditions
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COVID-19 Pandemic

Intervention / Treatment
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* Genetic: Gene Expression


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The following inclusion criteria will be used (all necessary): Covid-19 positive mothers, term newborn (>37 completed gestational weeks), free from severe malformations. All infants will be examined generally, systemically and neurologically at birth for clinical assessment of HIE if present and for detection of outcome of these neonates. Exclusion Criteria: free from severe malformations

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 2 Days

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Control<br>A total of 20 term newborn infants with a median gestational age of 40 weeks (range: 37-42 weeks) will be selected from the Gynecology and Obstetrics Hospital (Assiut University). All control infants should have an Apgar score of > 9 at 1, 5, and 10 minutes. | Genetic: Gene Expression<br>* the expression of specific CNS enzyme (enolase), proinflammatory cytokines MIF and apoptotic marker caspase-3 in the umbilical blood of infants delivered for Covid positive mothers.<br>|
| Study group<br>Thirty newborn infants born for Covid-19 positive mothers will be prospectively included in this study. The diagnosis of hypoxia will made based on Apgar score, clinical signs present during the first hours of life and acid-base status. The following inclusion criteria will be used (all necessary): Covid-19 positive mothers, term newborn (>37 completed gestational weeks), free from severe malformations. All infants will be examined generally, systemically and neurologically at birth for clinical assessment of HIE if present and for detection of outcome of these neonates. | Genetic: Gene Expression<br>* the expression of specific CNS enzyme (enolase), proinflammatory cytokines MIF and apoptotic marker caspase-3 in the umbilical blood of infants delivered for Covid positive mothers.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the expression of specific CNS enzyme (enolase), proinflammatory cytokines MIF and apoptotic marker caspase-3 in the umbilical blood of infants delivered for Covid positive mothers. | RNA extraction Reverse Transcription polymerase chain reaction (RT-PCR) analysis: | one month |