Clinical trial NCT03464396: Prematurity-Related Ventilatory Control
Official title: Physiologic Biomarkers Predicting Ventilatory Instability and Hypoxemia in Pre Mature Infants
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Respiratory Control in Premature Infants
Keywords: Periodic breathing
Apnea of prematurity
Chronic Lung disease
Prematurity
Respiratory disease
Hypoxia
Pulmonary Hypertension
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2018-03-14
Enrollment: 177
Sex: ALL
Minimum age (years): 1
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Infants admitted to the Neonatal Intensive Care Unit who are born between 24 0/7 to 28 7/8 weeks GA

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.

Eligibility criteria: 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.

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.

Primary outcomes:
measure: Respiratory phenotype based on physiologic testing
timeFrame: 36 weeks post menstrual age
Secondary outcomes:
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: James Kemp, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Coste F, Ferkol T, Hamvas A, Cleveland C, Linneman L, Hoffman J, Kemp J. Ventilatory control and supplemental oxygen in premature infants with apparent chronic lung disease. Arch Dis Child Fetal Neonatal Ed. 2015 May;100(3):F233-7. doi: 10.1136/archdischild-2014-307272. Epub 2015 Feb 25.
citation: Carroll JL, Agarwal A. Development of ventilatory control in infants. Paediatr Respir Rev. 2010 Dec;11(4):199-207. doi: 10.1016/j.prrv.2010.06.002. Epub 2010 Jul 31.