L-arginine Concentrations and CPS Polymorphisms in VLBW Infants

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Infant, Very Low Birth Weight

Intervention / Treatment
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* Other: blood sample and buccal swab sample


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 6 Hours
Maximum Age: 12 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VLBW between 6 and12 hours after birth<br>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<br>* 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.<br>* Other names: OmniSwab;|

What is the study measuring?
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Primary Outcome Measures

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