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

Neonatal Respiratory Distress Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04947215
• Other study ID #: Neonatal RDS
• Status: Recruiting
• Start date: August 1, 2021
• Est. completion date: July 31, 2022

Study information

• Verified date: June 2021
• Source: Assiut University
• Contact: Ahmed AEL sayed, Master
• Phone: +201063656071
• Email: drahmedabdo1986[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: July 31, 2022
• Est. primary completion date: June 30, 2022
• Gender: All
• Age group: N/A to 1 Month

Eligibility

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

Related Conditions & MeSH terms

• Hyaline Membrane Disease
• Neonatal Respiratory Distress
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn

Intervention

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

Locations

Country	Name	City	State
Egypt	Assiut university	Assiut
Egypt	Assiut University	Assiut

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

Country where clinical trial is conducted

Egypt, 

References & Publications (9)

Alemu AY, Belay GM, Berhanu M, Minuye B. Determinants of neonatal mortality at neonatal intensive care unit in Northeast Ethiopia: unmatched case-control study. Trop Med Health. 2020 Jun 3;48:40. doi: 10.1186/s41182-020-00232-9. eCollection 2020. — View Citation

De Bisschop B, Derriks F, Cools F. Early Predictors for INtubation-SURfactant-Extubation Failure in Preterm Infants with Neonatal Respiratory Distress Syndrome: A Systematic Review. Neonatology. 2020;117(1):33-45. doi: 10.1159/000501654. Epub 2019 Aug 22. — View Citation

Evers KS, Wellmann S. Arginine Vasopressin and Copeptin in Perinatology. Front Pediatr. 2016 Aug 2;4:75. doi: 10.3389/fped.2016.00075. eCollection 2016. Review. — View Citation

Ishibashi M, Takemura Y, Ishida H, Watanabe K, Kawai T. C-reactive protein kinetics in newborns: application of a high-sensitivity analytic method in its determination. Clin Chem. 2002 Jul;48(7):1103-6. — View Citation

Kim M, Porras-Gomez M, Leal C. Graphene-based sensing of oxygen transport through pulmonary membranes. Nat Commun. 2020 Feb 27;11(1):1103. doi: 10.1038/s41467-020-14825-9. — View Citation

Lin S, Ikegami M, Moon C, Naren AP, Shannon JM. Lysophosphatidylcholine Acyltransferase 1 (LPCAT1) Specifically Interacts with Phospholipid Transfer Protein StarD10 to Facilitate Surfactant Phospholipid Trafficking in Alveolar Type II Cells. J Biol Chem. 2015 Jul 24;290(30):18559-74. doi: 10.1074/jbc.M115.666701. Epub 2015 Jun 5. — View Citation

Ma H, Yan W, Liu J. Diagnostic value of lung ultrasound for neonatal respiratory distress syndrome: a meta-analysis and systematic review. Med Ultrason. 2020 Sep 5;22(3):325-333. doi: 10.11152/mu-2485. Epub 2020 Apr 15. Review. — View Citation

Rouatbi H, Zigabe S, Gkiougki E, Vranken L, Van Linthout C, Seghaye MC. Biomarkers of neonatal stress assessment: A prospective study. Early Hum Dev. 2019 Oct;137:104826. doi: 10.1016/j.earlhumdev.2019.104826. Epub 2019 Jul 27. — View Citation

Shen W, Kuang P, Wang B, Zeng Q, Chen C, Lin X. Genetic Polymorphisms of LPCAT1, CHPT1 and PCYT1B and Risk of Neonatal Respiratory Distress Syndrome among a Chinese Han Population. Pediatr Neonatol. 2020 Jun;61(3):318-324. doi: 10.1016/j.pedneo.2019.12.012. Epub 2020 Jan 3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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"
Secondary	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"