Anti-Angiogenic Preeclampsia Milieu Impairs Infant Lung and Vascular Development

Study Overview
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Brief Summary
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Pregnant mothers who develop high blood pressure and other vascular problems (preeclampsia) deliver babies with increased neonatal health problems, which include lung disease and vascular complications, later in life. Investigators will evaluate whether infants of mothers with preeclampsia have evidence for impaired development of the lungs and blood vessels.

Detailed Description
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The overall objective of this study is to determine whether the anti-angiogenic environment of preeclampsia results in pulmonary and vascular dysfunction in infants. Specifically, study investigators hypothesize that the anti- angiogenic environment of preeclampsia will impair pulmonary development and promote vascular dysfunction in infants. Furthermore, study investigators hypothesize that circulating progenitor cell (CPC) measurements in cord blood will correlate with infant pulmonary (Aim #1) and systemic vascular (Aim #2) function. Study investigators will determine whether the pro-angiogenic circulating progenitor cells (CPC) versus non-circulating progenitor cells ratio in cord blood of pregnancies complicated by preeclampsia predicts pulmonary diffusing capacity and systemic vascular dysfunction, as well as respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD). This research represents an important translational study that extends observations made in pre-clinical animal models that have clearly established a critical relationship between angiogenesis and lung development. Preliminary data strongly suggest a relationship between pro-angiogenic circulating progenitor cells (CPCs), bronchopulmonary dysplasia (BPD), and pulmonary diffusion in human infants. Investigators will evaluate whether circulating progenitor cells (CPC)s are a biomarker for developing bronchopulmonary dysplasia (BPD), investigators will relate circulating progenitor cells (CPCs) to the underlying pathophysiology, as assessed by pulmonary function testing methods that we developed for this very difficult age group to evaluate. A positive finding in the study would provide the rationale for future translational studies evaluating the therapeutic potential of circulating progenitor cells (CPCs) to stimulate lung development of premature infants, as there are currently no known therapeutic interventions that minimize or prevent the development of bronchopulmonary dysplasia (BPD). One of several approaches could be applied in the future to increase circulating progenitor cells (CPCs) in premature infants: 1) pharmacologic mobilization of pro-angiogenic cells from the bone marrow, 2) expansion of pro-angiogenic cells from an infant's cord blood for autologous infusion, and 3) transfusion of pooled pro-angiogenic cells from multiple donors.

Official Title
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The Effects of Maternal Preeclampsia on the Development of Pulmonary and Vascular Dysfunction in Infants

Conditions
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Preeclampsia

Intervention / Treatment
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* Other: Diffusion Lung Capacity (DLCO), Vascular Challenge, Video Imaging, Specimen Collections


Participation Criteria
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Eligibility Criteria
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Group 1: Infants born to mothers with preeclampsia Inclusion Criteria: Clinical diagnosis of preeclampsia per the American College of Obstetricians and Gynecologists (ACOG) Task Force on Hypertension in Pregnancy 2013 report Anticipated delivery at 26+0 weeks gestation or greater. Exclusion Criteria: Infant is not viable Cardiopulmonary defects Chest wall abnormalities Genetic anomalies Maternal history of Diabetes Mellitus Multiple gestation Group 2: Infants born to mothers with normotensive pregnancies Inclusion Criteria Normotensive pregnancy Anticipated delivery at 26+0 weeks gestation or greater. Exclusion Criteria Maternal history of gestational diabetes Multiple gestation Genetic anomalies Chest wall abnormalities Chronic or Gestational hypertension Cardiopulmonary defects Infant is not viable

Ages Eligible for Study
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Minimum Age: 26 Weeks

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1: Infants born to mothers with preeclampsia<br>Infants with expected delivery at 26+0 weeks gestation or greater . | Other: Diffusion Lung Capacity (DLCO), Vascular Challenge, Video Imaging, Specimen Collections<br> <br> |
| Group 2: Infants born to mothers with normotensive pregnancies<br>Infants with expected delivery at 26+0 weeks gestation or greater. | Other: Diffusion Lung Capacity (DLCO), Vascular Challenge, Video Imaging, Specimen Collections<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infant lung development measured by diffusion lung capacity (DLCO) |  | by month 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Airway function measured by spirometry |  | by month 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infant, Bronchopulmonary Dysplasia, Premature