Research a New Predictive Marker of Intraventricular Hemorrhage in Very Preterm Infants

The most frequent complications in premature infants are neurological complications: intracranial hemorrhages and white matter lesions. In Epipage 2 study the incidence of severe intraventricular hemorrhages remains stable. Severe hemorrhages are associated with neurological sequelae.

A recent study in humans and in animals shows the role of the complex formed by plasminogen activator (t-PA) and its inhibitor (PAI-1) in the induction of vascular fragility via stromelysin (MMP-3). FIBRINAT study in Rouen University Hospital showed a rate of complex t-PA-PAI1 probably very high in preterm infants. An other factor maturation PDGF-C induced by t-PA is associated with the vascular embrittlement. Among the few genetic factors associated with cerebral palsy include 2 SNP of PAI-1 gene and one SNP in the gene of endothelial NO synthase.

The hypothesis is that a high rate of the complex t-PA-PAI-1 in cord blood could be a high risk of intracranial hemorrhage in preterm infants and provide predictive of their occurrence. The rates of MMP-3, PDGF-C and PAI-1 free in cord blood, and the polymorphism of PAI-1 gene and eNOS could separately or associated with the main criterion to identify predictive of hemorrhages.

The main objective is to search a rate difference of the complex t-PA-PAI-1 in cord blood of preterm infants (before 30 weeks of gestation) that would predict intracranial hemorrhage coming in the first days of life.

The secondary objectives are

* Evaluate potential marker risk of high levels of MMP-3, PAI-1 free, and PDGF-CC
* Search in both groups the presence of alleles -675G4 / G5 and 11053 (G / T) of the PAI-1 gene and -922 (A / G) of the eNOS gene.

  120 preterm infants will be included before 30 weeks of gestation with precise inclusion and exclusion criteria during a period of 3 years.

Patients will be divided into two groups according to whether they will or not showed intracranial hemorrhage (detected by ultrasound J5-J7).

The complex rate tPA-PAI-1, PAI-1 free, MMP-3 and PDGF-C will be measured. The comparison between the two groups will be carried out using statistical tests. Comparison of the presence of the alleles -675 4G and 11053T the PAI-1 gene or -922G eNOS gene between the two groups will be performed.

The demonstration of this hypothesis would permit to identify children from birth in whom the immediate implementation of preventive treatment of bleeding is desirable.


Eligibility Criteria:
Inclusion Criteria:

* Alive preterm infants between 24 weeks gestation and 29 weeks and 6 days
* Infants of both sexes
* Children whose parents signed a free and informed consent after oral information by one of the study investigators
* Exact term (pregnancy onset evaluated by the craniocaudal length or the date of the puncture in a medical assisted reproduction)
* Children with social protection

Exclusion Criteria:

* Maternal taking of antiplatelet therapy or anticoagulation within 48 hours of birth
* Acquired maternal disease constituting a risk factor for neonatal hemorrhage
* Constitutional maternal disease constituting a risk factor for neonatal hemorrhage
* Severe fetal malformation
* Cesarean birth after diagnosis of hydrocephalus detected in utero
* Minors parents
* History of mental disease,or sensory abnormality of one of the parents, which can lead to confusion about the study