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

June 23, 2021 updated by: Ahmed Abd Elrasoul Sayed, Assiut University

Aims of the Research

Primary:

  1. 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.
  2. Test the association between LPCAT1 genetic polymorphism and the levels of these biomarkers in neonates suffering from RDS.
  3. 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Observational

Enrollment (Anticipated)

160

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Egypt
      • Assiut, Egypt
        • Recruiting
        • Assiut University
        • Contact:
          • Assuit university

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 hour to 1 month (Child)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

A case-control study

Description

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:

    1. Multiple congenital anomalies
    2. Severe infection
    3. Inherited metabolic disorders
    4. Any systemic disorder (hepatic, renal, cardiovascular, and endocrinal, ...etc)
    5. Malignancies
    6. Hypoxic Ischemic Encephalopathy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Cases group
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
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
control group
include 60 neonates without RDS.
Diagnostic test: stress biomarkers
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
LPCAT1 genetic polymorphism
Time Frame: "1 year"
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:
Time Frame: "1 month"
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
Time Frame: "2 month"
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"

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

August 1, 2021

Primary Completion (Anticipated)

June 30, 2022

Study Completion (Anticipated)

July 31, 2022

Study Registration Dates

First Submitted

June 14, 2021

First Submitted That Met QC Criteria

June 23, 2021

First Posted (Actual)

July 1, 2021

Study Record Updates

Last Update Posted (Actual)

July 1, 2021

Last Update Submitted That Met QC Criteria

June 23, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Neonatal RDS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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