Ductus Arteriosus Closure and D-Dimer and Fibrinogen Levels

Study Overview
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Brief Summary
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The aim of this study is to investigate whether there is a relationship between echocardiographic measurements regarding closure of PDA and serum D-Dimer and Fibrinogen levels in premature infants born before 32nd gestational week and weighing less than 1500 grams.

Detailed Description
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Ductus arteriosus (DA) is located between the main pulmonary artery and descending aorta in embryonal life, with dense spiral-located smooth muscle cells in the media layer, and the intima layer is thicker than the aorta. It must be open in fetal life; in this way, the blood flowing from the right ventricle to the collapsed lungs is directed to the descending aorta. DA usually closes functionally by constriction of the media during the first three days after labor. In the second week after birth; endothelial folding, subendothelial proliferation and coagulation processes results in anatomical permanent closure. When not closed, patent ductus arteriosus (PDA) is formed resulting in shunting from aorta to pulmonary artery. Probability of patency is inversely related with birth weight. Risk of pulmonary edema, pulmonary hemorrhage, bronchopulmonary dysplasia and loss of pulmonary function increases due to increased pulmonary flow from left to right shunt. Renal, mesenteric and cranial blood supply are impaired due to reduced peripheral circulation. As a result, impaired renal function and necrotizing enterocolitis may develop. Risk of intracranial hemorrhage, cerebral hypoxia and premature retinopathy due to variable blood supply. It has been associated with increased mortality in newborns due to increased morbidity. On physical examination, hyperdynamic precordium, viable pulses and left ventricular hypertrophy are observed. Large PDAs are characterized by prominent pulmonary conus, increased pulmonary vascularization and cardiomegaly on telecardiography. Diagnosis of PDA is confirmed by echocardiography. Symptomatic PDA treatment and follow-up is mostly followed by echocardiography. Detailed echocardiographic examination can only be performed by a Pediatric Cardiologist, but it is not possible to evaluate DA at any time. It is necessary to benefit from significant changes in specific hematological parameters that may accompany DA closure in order to detect and predict these conditions. One of the main mechanisms involved in anatomic permanent closure in DA is platelet aggregation and coagulation. To the best of our knowledge, there is no study in the literature investigating whether there is a relationship between Fibrinogen and D-dimer levels and anatomical closure of DA. It is postulated that circulating fibrinogen levels will decrease and D-dimer levels increase as a by-product due to thrombosis in the lumen during DA closure. It is predicted that in infants in whom DA does not close and remain open, fibrinogen levels will be higher and D-dimer levels will be lower than infants in whom DA is closed. It is also suggested that echocardiographic DA measurements will correlate with serum Fibrinogen and D-Dimer levels. The aim of this study is to investigate whether there is a relationship between echocardiographic measurements regarding closure of PDA and serum D-Dimer and Fibrinogen levels in premature infants born before 32nd gestational week and weighing less than 1500 grams.

Official Title
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The Relationship of Ductus Arteriosus Closure and D-Dimer and Fibrinogen Levels in Premature Babies

Conditions
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Ductus Arteriosus, Patent

Intervention / Treatment
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* Diagnostic Test: Withdrawal of blood samples for D-Dimer
* Diagnostic Test: Withdrawal of blood samples for Fibrinogen
* Diagnostic Test: Echocardiographic Examination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: premature newborns born before 32nd gestational week and weighing less than 1500 grams. Exclusion Criteria: Babies with: Major congenital anomalies Chromosomal anomalies Inborn errors of metabolism Hypoxic ischemic encephalopathy Disseminated intravascular coagulation Unstable hemodynamic status Severe neonatal sepsis Who died in time frame of postnatal 14 days Patients who are not volunteered to participate

Ages Eligible for Study
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Minimum Age: 0 Days
Maximum Age: 28 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study Group<br>Premature newborns born before 32nd gestational week and weighing less than 1500 grams. | Diagnostic Test: Withdrawal of blood samples for D-Dimer<br>* Blood samples are withdrawn at birth via cord blood and at postnatal 3rd and 7th days via umbilical catheter in order to test for D-dimer levels.<br>Diagnostic Test: Withdrawal of blood samples for Fibrinogen<br>* Blood samples are withdrawn at birth via cord blood and at postnatal 3rd and 7th days via umbilical catheter in order to test for Fibrinogen levels.<br>Diagnostic Test: Echocardiographic Examination<br>* At postnatal 3rd, 7th and 14th days, Ductus Arteriosus will be echocardiographically examined to obtain calculations and confirm status of ductal patency or closure.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rise in D-dimer blood levels during Ductus Arteriosus closure from postnatal day 0 to postnatal 3rd and 7th days | It is postulated that circulating D-dimer levels will increase gradually as a by-product due to thrombosis in the lumen during DA closure from postnatal day 0 to postnatal 3rd and 7th days. It is predicted that D-dimer levels will be lower in infants in whom DA does not close than in infants whom DA is closed. Blood samples are withdrawn accordingly at birth via cord blood and at postnatal 3rd and 7th days via umbilical catheter in order to test for D-dimer levels. | postnatal 0 - 14 days | 
| Fall in Fibrinogen blood levels during Ductus Arteriosus closure from postnatal day 0 to postnatal 3rd and 7th days | It is postulated that circulating fibrinogen levels will fall gradually due to thrombosis in the lumen during DA closure from postnatal day 0 to postnatal 3rd and 7th days. It is predicted that fibrinogen levels will be higher in infants in whom DA does not close than in infants whom DA is closed. Blood samples are withdrawn accordingly at birth via cord blood and at postnatal 3rd and 7th days via umbilical catheter in order to test for fibrinogen levels. | postnatal 0 - 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ductus Arteriosus, Premature Newborn, D-Dimer, Fibrinogen