L-arginine Concentrations and CPS Polymorphisms in VLBW Infants

Carbamoyl-phosphate Synthase Gene Polymorphisms Influencing Plasma L-arginine Concentrations in Preterm Infants

Plasma L-arginine concentrations are decreased in premature infants with necrotizing enterocolitis (NEC). A carbamoyl-phosphate synthetase 1 (CPS1) polymorphism has been correlated with low plasma concentrations of L-arginine in neonates (> 35 weeks of gestation). Recently Moonen et al (Pediatr Res 2007; 62(2):188-90) described a correlation between this CPS1 T1405N single nucleotide polymorphism (SNP) and the presence of NEC in VLBW infants. However there is no data about the correlation between the plasma arginine concentrations and the T1405N SNP in the CPS-1 gene in VLBW infants. In the present project we postulate that T1405N SNP in the CPS-1 gene is associated with lower plasma arginine concentrations and is also a risk factor for the development of NEC.

Study Overview

• Status: Completed
• Conditions: Infant, Very Low Birth Weight
• Intervention / Treatment: Other: blood sample and buccal swab sample

Detailed Description

Plasma L-arginine concentrations are decreased in premature infants with necrotizing enterocolitis (NEC). A C-to-A nucleotide transversion (T1405N) in the gene that encodes carbamoyl-phosphate synthetase 1 (CPS1), the rate-limiting enzyme in the urea cycle, has been correlated with low plasma concentrations of L-arginine in neonates (> 35 weeks of gestation). Recently Moonen et al (Pediatr Res 2007; 62(2):188-90) described a correlation between this CPS1 T1405N single nucleotide polymorphism (SNP) and the presence of NEC in VLBW infants. However there is no data about the correlation between the plasma arginine concentrations and the T1405N SNP in the CPS-1 gene in VLBW infants. In the present project we postulate that T1405N SNP in the CPS-1 gene is associated with lower plasma arginine concentrations and is also a risk factor for the development of NEC.

• Study Type: Interventional
• Enrollment (Actual): 477
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Mantova, Italy
    • Carlo Poma Hospital
  • Milano, Italy
    • Cattedra di Neonatologia-Università degli Studi di Milano
• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6202 AZ
      • Maastricht University Hospital
• Spain
  • Las Palmas de Gran Canaria, Spain, 35016
    • Complejo Universitario Hospitalario Insular-Materno Infantil

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 hours to 12 hours (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• VLBW infants (< 30 weeks and < 1500 gram birth weight).

Exclusion Criteria:

• Blood transfusion, enteral or parenteral protein intake, or inhaled nitric oxide administration before time of the blood sample (obtained between 6 and 12 hours after birth).
• Parents not able to give informed consent.

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VLBW between 6 and12 hours after birth; Blood sample and buccal swab sample. One blood sample (500 mL) will be obtained from each VLBW infant between 6 and12 hours after birth from an umbilical-artery or peripheral artery catheter. Additional DNA collection buccal cell samples were obtained with a sterile OmniSwab.	Other: blood sample and buccal swab sample; one blood sample (500 mL) will be obtained from each VLBW infant between 6 and12 hours after birth from an umbilical-artery or peripheral artery catheter. Additional DNA collection buccal cell samples were obtained with a sterile OmniSwab.; Other Names: OmniSwab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the association between the T1405N SNP in the CPS-1 gene and lower plasma L-arginine concentrations	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine whether the T1405N SNP in the CPS-1 gene is associated with a higher risk of NEC	4 years

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Principal Investigator: Eduardo Villamor, MD, PhD, Maastricht University Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: November 6, 2007
• First Submitted That Met QC Criteria: November 6, 2007
• First Posted (Estimate): November 7, 2007

Study Record Updates

• Last Update Posted (Estimate): October 28, 2015
• Last Update Submitted That Met QC Criteria: October 27, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Body Weight; Birth Weight
• Other Study ID Numbers: 07-2-018