Local Version of the Multi-center PREVENT Study Evaluating Cardio-respiratory Instability in Premature Infants

NCT ID: NCT03655639

Last Updated: 2024-11-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 99 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-09-09
• Study Completion Date: 2026-12-31

Brief Summary

Infants who are born prematurely have immature nervous and cardiorespiratory systems. These are systems infants use to breathe, to move oxygen throughout their bodies, and to maintain safe and stable levels of oxygen and carbon dioxide. The goal of this study is to better understand how these immature systems affect long term development, such as brain, heart, and motor function (movement) with several innovative, integrated physiological measures. We hope this will allow us to begin to find better ways to help premature infants breathe and to optimize their development.

Detailed Description

The broad long-term objective is to use comprehensive state-of-the-art, high-fidelity monitoring to investigate physiological biomarkers of autonomic neurorespiratory maturation with integrated analysis of autonomic nervous system (ANS) responses in preterm infants, and to evaluate their role in ventilatory instability, bronchopulmonary dysplasia (BPD), and co-morbidities including neurodevelopment in the 1st year of life. SPECIFIC AIM 1 will establish the spectrum and developmental trajectory of ANS maturation/function using high-resolution physiologic recordings of ventilatory, cardiovascular, and cerebrovascular measures during typical daily activity (28, 32 and 36 weeks (wks) post-menstrual age (PMA)(up to 24-hour recordings) and at 3 and 12 months (mos) corrected age (CA)(4-hour recordings). Aim 1 tests the hypothesis that individual and integrated metrics of ANS function will demonstrate maturational patterns that impart resilience or vulnerability to environmental challenges. SPECIFIC AIM 2 will determine respiratory and neurodevelopmental morbidity throughout the 1st year of life using clinically applicable outcome measures and associate morbidity with ANS development and function using a Respiratory Morbidity Severity Score (RMSS), need for respiratory support, medications, or hospitalization, Bayley Scales of Infant Development III (6, 12 mos), Neurological, Sensory, Motor, Developmental Assessment (NSMDA)(3, 6, 12 mos), and early measures of evoked-auditory potentials (EAP)(28, 32, 36 wks PMA; 3, 12 mos CA) and General Movement Assessments (GMA)(28, 32, 36 wks; 3 mos). Aim 2 tests the hypothesis that infants demonstrating delayed ANS maturation or vulnerability to endogenous challenges will require more respiratory interventions and will demonstrate developmental delays in the 1st year of life. SPECIFIC AIM 3 will determine endotypes of autonomic neurorespiratory stability and maturation through trajectory analysis and integrated physiological modeling. Aim 3 tests the hypothesis that trajectory analysis will reveal 3 autonomic maturation patterns [1) "normal" maturation with ability to withstand environmental perturbations; 2) "normal" maturation without ability to withstand environmental perturbations; and 3) delayed or disordered maturation with inability to maintain physiologic stability in absence of environmental perturbations] that will be associated with severity of respiratory morbidity and neuromotor impairment at 1 year. This novel approach will establish the role of autonomic neurorespiratory maturation in stability of oxygenation throughout the 1st year of life, provide insight into BPD pathogenesis, allow prospective identification of at-risk infants, and permit development of mechanism-specific interventions with potential to impact thousands of families and billions in healthcare cost/year in the U.S., alone.

In addition to lung-independent mechanisms of respiratory dysfunction, this study aims to investigate lung-independent mechanisms of pulmonary hypertension (PH). Typically thought to be a secondary effect of primary lung structural development and/or hypoxia, up to 40% of infants with chronic respiratory dysfunction develop pulmonary hypertension (PH) and increased risk for mortality. However, we and others found that 10-30% of premature infants who develop PH did not have clinical evidence of respiratory dysfunction, suggesting pulmonary vascular mechanisms that are independent of clinically apparent respiratory disease. Multiple molecular mechanisms are postulated by which hypoxia results in PH, but preliminary data from our group and others suggest a role for Fibroblast Growth Factor 2 (FGF2) and FGF receptors 1 and 2 (FGFR1, FGFR2) signaling in the development of pulmonary vascular remodeling in PH. Thus, by serially using sensitive echocardiographic measures of Right Ventricular-Pulmonary Arterial (RV-PA) coupling, we can quantify hypoxic exposure and RV-PA axis dysfunction and we will couple these clinical measurements of FGF2 signaling. We hypothesize that recurrent hypoxic exposure of dysmature pulmonary vasculature in premature newborns results in RV-PA axis dysfunction and pulmonary hypertension that is mediated by FGF2 signaling and is independent of clinically apparent lung disease.

Conditions

Premature Birth

Study Design

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

Study Groups

Premature Birth

Premature babies born under 29 weeks gestational age, admitted into the neonatal intensive care unit within 7 days of life.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• birth between 24 and 29 weeks of gestation
• less than 1 week of age

Exclusion Criteria

• known congenital anomalies
• imminent death
• factors that preclude reliable follow-up

• Minimum Eligible Age: 24 Weeks
• Maximum Eligible Age: 29 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Northwestern Memorial Hospital

OTHER

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Ann & Robert H Lurie Children's Hospital of Chicago

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Aaron Hamvas

Role: PRINCIPAL_INVESTIGATOR

Ann & Robert H Lurie Children's Hospital of Chicago

Locations

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Northwestern Memorial Hospital

Chicago, Illinois, United States

Countries

United States

Other Identifiers

U01HL133704

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2017-1178

Identifier Type: -

Identifier Source: org_study_id