The Association Between LPCAT1 Genetic Polymorphism and Stress Biomarkers in Neonatal Respiratory Distress Syndrome

Study Overview
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Brief Summary
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Aims of the Research Primary: Measure the levels of stress biomarkers in full and preterm neonates with normal and complicated pregnancies and to study the influence of delivery mode on their cord blood concentrations. Test the association between LPCAT1 genetic polymorphism and the levels of these biomarkers in neonates suffering from RDS. Study the relation between LPCAT1 genetic polymorphism and the risk/severity of neonatal respiratory distress syndrome. Secondary: 1) Help understanding the possible etiology and pathogenesis of neonatal RDS. 2) Help the possibility of early detection, diagnosis and management. 3) Help to decrease mortality and morbidity in selective cases. 4) Understand the individual variability in the susceptibility to development of pulmonary pathologies.

Detailed Description
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Neonatal respiratory distress syndrome (RDS) is caused by lung immaturity and deficiency of lung surfactant and dysfunction in preterm newborns . Surfactant is produced by type II pneumocyte that forms a bilayer of lipid over the inner surface of the alveoli. Surfactant deficiency and dysfunction lead to increased alveolar surface tension, which results in alveolar collapse and decreased lung aeration . Respiratory distress syndrome is one of the main causes of neonatal mortality . The risk of RDS increases with decreasing gestational age (GA). The incidence of RDS was estimated to be 90% in preterm neonates (GA 28 weeks or below) and to be 9% in full term neonates born at ≥38 weeks' gestation. Early diagnosis is very essential to optimize the treatment of infants with RDS. Pathogenesis The primary cause of RDS is deficiency and/or dysfunction of surfactant which is a lipoprotein complex and is vital for normal lung function. Surfactant is synthesized, stored, and secreted by the alveolar type II cells and is primarily composed of phospholipids, which constitute 80-85% of the total mass. The remaining components of surfactant includes neutral lipids (5%-10%) and proteins (10%) . Phosphatidylcholine (PC), the most abundant phospholipid species in surfactant, constitutes 80% of the total phospholipids. There are three key enzymes involved in the PC synthesis: Lysophospholipid acyltransferase (LPCAT1, Gene ID 79888), Cholinephosphotransferase (CHPT1, Gene ID 56994) and Cholinephosphate cytidylyltransferase (PCYT1B, CPCT, Gene ID 9468). LPCAT1 is the most important enzyme in biogenesis and a key enzyme in surfactant production . LPCAT1 composed of 18 exons and is located on chromosome 5p15.33. The study of the genetic polymorphisms of surfactant-lipids related gene provides significant data about individual variability in the susceptibility to development of respiratory distress syndrome. Neonatal stress biomarkers such as cardiac troponin (CTn) T, CTnI, NT-Terminal-pro-Brain Natriuretic Peptide (NT-pro-BNP), copeptin, and high sensitivity C-reactive protein (hs-CRP)have been considered as an indicator of perinatal asphyxia. Troponin is an inhibitory protein complex located on the actin filament in all striated muscle and consists of three subunits: T, C, and I. The asphyxiated neonate has elevated levels of cardiac troponin I (cTnI). cTnI is thought to be also an indicator of perinatal asphyxia . Neonates born after complicated delivery had significantly higher values of CTnT, CTnI and Copeptin than those born after uncomplicated delivery. The gender influence on copeptin releases . The gestational age, birth weight and duration of active labor, and membrane rupture have significant effect on hs-CRP levels.

Official Title
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The Association Between LPCAT1 Genetic Polymorphism and Stress Biomarkers in Neonatal Respiratory Distress Syndrome

Conditions
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Neonatal Respiratory Distress

Intervention / Treatment
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* Diagnostic Test: stress biomarkers


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: neonates who are admitted in the neonatal intensive care unit in Assiut University children hospital suffering from RDS. Exclusion Criteria: The newborn will be excluded from the study when his/her parents refuses to participate or when the neonate presented with one or more of the following: Multiple congenital anomalies Severe infection Inherited metabolic disorders Any systemic disorder (hepatic, renal, cardiovascular, and endocrinal, ...etc) Malignancies Hypoxic Ischemic Encephalopathy

Ages Eligible for Study
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Minimum Age: 1 Hour
Maximum Age: 1 Month

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 |
| --- | --- |
| Cases group<br>It includes 100 neonates who are admitted in the neonatal intensive care unit in Assiut University children hospital suffering from RDS. The cases will be subdivided into subgroups according to1. Full term or preterm, 2. Type of pregnancy (normal or complicated), 3. Mode of delivery, and 4. LPCAT1 genetic polymorphism. | Diagnostic Test: stress biomarkers<br>* used to estimate the reference values of putative biomarkers of birth stress such asCTnT, CTnI, copeptin, NT-proBNP and hs-CRP in the cord blood of full term neonates<br>|
| control group<br>include 60 neonates without RDS. | Diagnostic Test: stress biomarkers<br>* used to estimate the reference values of putative biomarkers of birth stress such asCTnT, CTnI, copeptin, NT-proBNP and hs-CRP in the cord blood of full term neonates<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LPCAT1 genetic polymorphism | The LPCAT1genetic polymorphism work will be performed using an improved multiplex ligation detection reaction (iMLDR) technique .Genomic DNA from patients will be extracted from peripheral blood by DNA mini extraction kit. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The electrochemiluminescence immunoassay ECLIA: | This method will be used to estimate the reference values of putative biomarkers of birth stress CTnT in the cord blood of full term neonates | 1 month | 
| The electrochemiluminescence immunoassay ECLIA | This method will be used to estimate the reference values of putative biomarkers of birth stress hs-CRP in the cord blood of full term neonates | 2 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LPCAT 1