Anti-Angiogenic Preeclampsia Milieu Impairs Infant Lung and Vascular Development

NCT ID: NCT02639676

Last Updated: 2022-02-24

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 292 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-02-11
• Study Completion Date: 2020-11-17

Brief Summary

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

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.

Conditions

Preeclampsia

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Group 1: Infants born to mothers with preeclampsia

Infants with expected delivery at 26+0 weeks gestation or greater .

Diffusion Lung Capacity (DLCO), Vascular Challenge, Video Imaging, Specimen Collections

Intervention Type: OTHER

Group 2: Infants born to mothers with normotensive pregnancies

Infants with expected delivery at 26+0 weeks gestation or greater.

Diffusion Lung Capacity (DLCO), Vascular Challenge, Video Imaging, Specimen Collections

Intervention Type: OTHER

Interventions

Diffusion Lung Capacity (DLCO), Vascular Challenge, Video Imaging, Specimen Collections

Intervention Type: OTHER

Eligibility Criteria

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.

• Normotensive pregnancy
• 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

• Maternal history of gestational diabetes
• Multiple gestation
• Genetic anomalies
• Chest wall abnormalities
• Chronic or Gestational hypertension
• Cardiopulmonary defects
• Infant is not viable

• Minimum Eligible Age: 26 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

Robert Tepper

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Robert S Tepper, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Locations

Riley Hospital for Children

Indianapolis, Indiana, United States

Countries

United States

Other Identifiers

R01HL1222215

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

1509123588

Identifier Type: -

Identifier Source: org_study_id