Prematurity-Related Ventilatory Control

Completed

• Conditions: Respiratory Control in Premature Infants
• Interventions: Other: Bedside Physiology study; Other: Carotid Body Function Test; Other: Room Air Challenge; Other: Hypoxia Challenge Test; Other: Effects of Nasal Cannula Flow; Diagnostic Test: Magnetic Resonance Imaging; Diagnostic Test: Echocardiogram; Other: Blood Sample

• Registration Number: NCT03464396
• Lead Sponsor: Washington University School of Medicine

Brief Summary

The purpose of this research study is to improve our understanding of unstable breathing and heart blood flow patterns seen in premature infants. The investigator will use novel non-invasive measures to understand the determinants of these unstable breathing and heart flow patterns to potentially identify new therapies for their prevention.

Detailed Description

The investigator will look at results of breathing tests, non-invasive sound wave (ultrasound) test of the heart and blood vessel (Echocardiography), and a sample of blood to see if it is possible for early detection of breathing control and lung blood vessel dysfunction (pulmonary vascular disease) in infants that are at risk for exposure to long term low oxygen levels. A subset of infants will have a magnetic resonance Imaging study (MRI) between 37- 40 weeks gestational age (GA) or at the time of discharge, whichever comes first.

Respiratory tests include:

* Bedside Physiology Study completed at 28, 32, 36, 40, and 52 weeks GA in conjunction with the respiratory tests. A 90-minute recording will be made using standard recording equipment that includes a conventional pulse oximeter, an EEG, an airflow sampling catheter near the nose, and respiratory inductance plethysmography (RIP) bands. Standard bedside monitoring will continue during the physiologic studies

* Carotid Body Function Test completed at 32, 36, 40 and 52 weeks GA. This test is to unmask respiratory instability in response to hyperoxia.

* Challenge Test completed at 36 weeks GA.

1. Infants receiving nasal cannula flow with or without supplemental oxygen will undergo a Room Air Challenge Test.

2. Infants on RA alone will undergo a Hypoxia Challenge test.

* Effects of Nasal Cannula Flow completed at 28, 32, 36, 40 and 52 week's GA. The flow will be increased through a nasal cannula. This test is to see how flow effects the breathing pattern.

A subset of infants will have an MRI between 37-40 weeks GA or before discharge, whichever comes first. The MRI will allow the doctors to look and see if there is any injury present in the brain that can be linked to an abnormal breathing pattern called periodic breathing.

A subset of infants will have an Echocardiogram (Echo) at 32, 36 and 52 weeks GA. The Echo is performed to assess cardiac structure and function. Echocardiography is performed routinely in premature newborns in the Neonatal Intensive Care Unit (NICU). The echocardiogram will be performed at the infant bedside and will be coordinated with bedside nurse. The infant will remain on a cardio-respiratory monitor during the echocardiogram for approximately 15 minutes.

Infants that have an Echo will have a blood sample collected near the time of the Echo, 3-blood samples total. The purpose of collecting the blood sample is to detect if the Fibroblast Growth Factor (FGF2) level is elevated and possibly be a biomarker of early pulmonary hypertension in pre term infants validated with the echo.

Study Timeline

• Study First Submitted: 2018-03-07
• Study First Submitted QC: 2018-03-07
• Study First Posted: 2018-03-14
• Study Start: 2018-05-14
• Primary Completion: 2022-02-09
• Study Completion: 2022-03-09
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-30
• Last Update Posted: 2023-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 177

Inclusion Criteria

• All infants born between 24 0/7 and 28 6/7 weeks GA admitted to the Neonatal Intensive Care Unit at St. Louis Children's Hospital will be considered for enrollment.

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Exclusion Criteria

• Infants not likely to survive
• Infant with significant heart disease
• Infant with a significant congenital abnormalities of the central nervous system, nose, mouth lungs or ribs, or congenital diseases that affect lung growth
• Physician refusal
• Unlikely that the infant will be available for 52-week follow-up visit.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Preterm infant study visits	Room Air Challenge	Preterm infants Study Visits 1. Bedside Physiology Study at 28, 32, 36, 40, and 52 weeks GA. 2. Respiratory tests: * Carotid Body Function Test will be completed at 32, 36, 40 and 52 weeks GA * Room Air Challenge (RAC) or Hypoxia Challenge Test (HCT) will be completed at 36 weeks GA * Effects of nasal cannula flow be completed at 28, 32, 36, 40 and 52 weeks GA 3. Magnetic Resonance Imaging (MRI): Completed on a subset of infants between 37-40 weeks GA or before discharge, whichever comes first. 4. Echocardiogram (Echo): Completed at 32, 36 and 52 weeks GA 5. Blood sample: Obtained at 32, 36 and 52 weeks GA
Preterm infant study visits	Bedside Physiology study	Preterm infants Study Visits 1. Bedside Physiology Study at 28, 32, 36, 40, and 52 weeks GA. 2. Respiratory tests: * Carotid Body Function Test will be completed at 32, 36, 40 and 52 weeks GA * Room Air Challenge (RAC) or Hypoxia Challenge Test (HCT) will be completed at 36 weeks GA * Effects of nasal cannula flow be completed at 28, 32, 36, 40 and 52 weeks GA 3. Magnetic Resonance Imaging (MRI): Completed on a subset of infants between 37-40 weeks GA or before discharge, whichever comes first. 4. Echocardiogram (Echo): Completed at 32, 36 and 52 weeks GA 5. Blood sample: Obtained at 32, 36 and 52 weeks GA
Preterm infant study visits	Carotid Body Function Test	Preterm infants Study Visits 1. Bedside Physiology Study at 28, 32, 36, 40, and 52 weeks GA. 2. Respiratory tests: * Carotid Body Function Test will be completed at 32, 36, 40 and 52 weeks GA * Room Air Challenge (RAC) or Hypoxia Challenge Test (HCT) will be completed at 36 weeks GA * Effects of nasal cannula flow be completed at 28, 32, 36, 40 and 52 weeks GA 3. Magnetic Resonance Imaging (MRI): Completed on a subset of infants between 37-40 weeks GA or before discharge, whichever comes first. 4. Echocardiogram (Echo): Completed at 32, 36 and 52 weeks GA 5. Blood sample: Obtained at 32, 36 and 52 weeks GA
Preterm infant study visits	Blood Sample	Preterm infants Study Visits 1. Bedside Physiology Study at 28, 32, 36, 40, and 52 weeks GA. 2. Respiratory tests: * Carotid Body Function Test will be completed at 32, 36, 40 and 52 weeks GA * Room Air Challenge (RAC) or Hypoxia Challenge Test (HCT) will be completed at 36 weeks GA * Effects of nasal cannula flow be completed at 28, 32, 36, 40 and 52 weeks GA 3. Magnetic Resonance Imaging (MRI): Completed on a subset of infants between 37-40 weeks GA or before discharge, whichever comes first. 4. Echocardiogram (Echo): Completed at 32, 36 and 52 weeks GA 5. Blood sample: Obtained at 32, 36 and 52 weeks GA
Preterm infant study visits	Hypoxia Challenge Test	Preterm infants Study Visits 1. Bedside Physiology Study at 28, 32, 36, 40, and 52 weeks GA. 2. Respiratory tests: * Carotid Body Function Test will be completed at 32, 36, 40 and 52 weeks GA * Room Air Challenge (RAC) or Hypoxia Challenge Test (HCT) will be completed at 36 weeks GA * Effects of nasal cannula flow be completed at 28, 32, 36, 40 and 52 weeks GA 3. Magnetic Resonance Imaging (MRI): Completed on a subset of infants between 37-40 weeks GA or before discharge, whichever comes first. 4. Echocardiogram (Echo): Completed at 32, 36 and 52 weeks GA 5. Blood sample: Obtained at 32, 36 and 52 weeks GA
Preterm infant study visits	Effects of Nasal Cannula Flow	Preterm infants Study Visits 1. Bedside Physiology Study at 28, 32, 36, 40, and 52 weeks GA. 2. Respiratory tests: * Carotid Body Function Test will be completed at 32, 36, 40 and 52 weeks GA * Room Air Challenge (RAC) or Hypoxia Challenge Test (HCT) will be completed at 36 weeks GA * Effects of nasal cannula flow be completed at 28, 32, 36, 40 and 52 weeks GA 3. Magnetic Resonance Imaging (MRI): Completed on a subset of infants between 37-40 weeks GA or before discharge, whichever comes first. 4. Echocardiogram (Echo): Completed at 32, 36 and 52 weeks GA 5. Blood sample: Obtained at 32, 36 and 52 weeks GA
Preterm infant study visits	Magnetic Resonance Imaging	Preterm infants Study Visits 1. Bedside Physiology Study at 28, 32, 36, 40, and 52 weeks GA. 2. Respiratory tests: * Carotid Body Function Test will be completed at 32, 36, 40 and 52 weeks GA * Room Air Challenge (RAC) or Hypoxia Challenge Test (HCT) will be completed at 36 weeks GA * Effects of nasal cannula flow be completed at 28, 32, 36, 40 and 52 weeks GA 3. Magnetic Resonance Imaging (MRI): Completed on a subset of infants between 37-40 weeks GA or before discharge, whichever comes first. 4. Echocardiogram (Echo): Completed at 32, 36 and 52 weeks GA 5. Blood sample: Obtained at 32, 36 and 52 weeks GA
Preterm infant study visits	Echocardiogram	Preterm infants Study Visits 1. Bedside Physiology Study at 28, 32, 36, 40, and 52 weeks GA. 2. Respiratory tests: * Carotid Body Function Test will be completed at 32, 36, 40 and 52 weeks GA * Room Air Challenge (RAC) or Hypoxia Challenge Test (HCT) will be completed at 36 weeks GA * Effects of nasal cannula flow be completed at 28, 32, 36, 40 and 52 weeks GA 3. Magnetic Resonance Imaging (MRI): Completed on a subset of infants between 37-40 weeks GA or before discharge, whichever comes first. 4. Echocardiogram (Echo): Completed at 32, 36 and 52 weeks GA 5. Blood sample: Obtained at 32, 36 and 52 weeks GA

Primary Outcome Measures

Name	Time	Method
Respiratory phenotype based on physiologic testing	36 weeks post menstrual age	Categorization of subjects based on physiologic Challenge Tests into one of four respiratory phenotypes.

Trial Locations

Locations (1)

Washington University; 🇺🇸 Saint Louis, Missouri, United States