Oxygenation Instability and Maturation of Control of Breathing in Premature Infants

Premature infants present with significant oxygenation instability in the form of frequent spontaneous episodes of hypoxemia during the first weeks after birth. These infants are also exposed to hyperoxemia.

The objective of this study is to determine the extent to which exposure to frequent episodes of hypoxemia and hyperoxemia in extreme premature infants during the early stages of their evolving lung disease is associated with altered maturation and function of their respiratory control system.

This study is part of the Prematurity-Related Ventilatory Control (Pre-Vent): Role in Respiratory Outcomes Clinical Research Centers (CRC) (U01) cooperative program of the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH).

Study Overview

• Status: Completed
• Conditions: Infant,Premature
• Intervention / Treatment: Other: Assessment of oxygenation instability; Other: Determination of mechanisms of hypoxemia episodes; Other: Assessment of respiratory instability; Other: apneic threshold of CO2; Other: Assessment of peripheral chemoreceptor function; Other: Assessment of central chemo-receptor function

Detailed Description

Most extreme premature infants present with respiratory failure due to altered lung function compounded by breathing instability due to an immature respiratory control function.

Premature infants present with significant oxygenation instability in the form of frequent spontaneous episodes of hypoxemia during the first weeks after birth. As a result, these infants receive oxygen supplementation but this is often excessive and these infants are also exposed to hyperoxemia. The extent to which these episodes of hypoxemia or the exposure to hyperoxemia impact on the maturation and function of the control of breathing system in extreme premature infants during the evolving stages of their respiratory disease is unknown. This is a prospective study that will systematically evaluate such association in extreme premature infants.

The main objective of this study is to determine the extent to which exposure to frequent episodes of hypoxemia and hyperoxemia in extreme premature infants during the early stages of their evolving lung disease is associated with altered maturation and function of their respiratory control system.

This study is part of the Prematurity-Related Ventilatory Control (Pre-Vent): Role in Respiratory Outcomes Clinical Research Centers (CRC) (U01) cooperative program of the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH).

• Study Type: Observational
• Enrollment (Actual): 70

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • NICU at Holtz Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Preterm infants admitted to the neonatal intensive care unit will be screened and will be considered eligible for inclusion if they fulfill all of the following inclusion and none of the exclusion criteria.

Description

Inclusion Criteria:

• Premature infants born at 23 0/7- 28 6/7 weeks gestational age
• Postnatal age up to equivalent to 36 weeks postmenstrual age
• Requiring supplemental oxygen and/or receiving mechanical ventilation, CPAP, nasal ventilation or nasal cannula

Exclusion Criteria:

• Severe congenital anomalies that may affect life expectancy or pulmonary or neurosensory development
• Severe CNS pathology that may alter respiratory control function

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peripheral chemoreceptor control of breathing function	Ventilatory response to oxygen (Dejours test)	at 32 weeks corrected postmenstrual age
Peripheral chemoreceptor control of breathing function	Ventilatory response to oxygen (Dejours test)	at 36 weeks corrected postmenstrual age
Central chemoreceptor control of breathing function	Ventilatory response to carbon dioxide	at 32 weeks corrected postmenstrual age
Central chemoreceptor control of breathing function	Ventilatory response to carbon dioxide	at 36 weeks corrected postmenstrual age
Change in peripheral chemoreceptor control of breathing function	Ventilatory response to oxygen (Dejours test)	Change from 32 to 36 weeks postmenstrual age
Change in central chemoreceptor control of breathing function	Ventilatory response to carbon dioxide	Change from 32 to 36 weeks postmenstrual age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilatory stability - Apnea frequency	Frequency of apnea episodes per hour	at 32 and 36 weeks corrected postmenstrual age
Ventilatory stability - Periodic breathing density	Percent of time with periodic breathing	at 32 and 36 weeks corrected postmenstrual age
Ventilatory stability - Time series analysis of inter-breath interval	Tail slope of the log-scaled probability density function of the inter-breath time series	at 32 and 36 weeks corrected postmenstrual age
Mechanisms of episodic hypoxemia	Classify etiology of episodes of hypoxemia as central, obstructive, or mixed apnea or active exhalation based on measurements of respiratory inductance plethysmography, esophageal pressure	at 32 and 36 weeks corrected postmenstrual age
Apneic CO2 threshold in central apnea	Carbon dioxide level change at onset of central apnea	at 32 and 36 weeks corrected postmenstrual age
Apneic CO2 threshold during mechanical ventilation	Carbon dioxide level change at onset of central apnea with stepwise increase in ventilator rate	at 32 and 36 weeks corrected postmenstrual age

Collaborators and Investigators

• Sponsor: University of Miami
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Nelson Claure, University of Miami; Principal Investigator: Eduardo Bancalari, University of Miami; Principal Investigator: Deepak Jain, University of Miami

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2018
• Primary Completion (Actual): November 1, 2023
• Study Completion (Actual): November 1, 2023

Study Registration Dates

• First Submitted: February 6, 2018
• First Submitted That Met QC Criteria: February 19, 2018
• First Posted (Actual): February 26, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 17, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Premature Birth
• Other Study ID Numbers: 20161114; U01HL133689 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No