Oxygenation Instability and Maturation of Control of Breathing in Premature Infants

Study Overview
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Brief Summary
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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).

Detailed Description
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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).

Official Title
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Oxygenation Instability and Maturation of Control of Breathing in Premature Infants

Conditions
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Infant,Premature

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Assessment of oxygenation instability|Recordings of SpO2 and heart rate will be analyzed by dedicated software to obtain frequency, duration and severity of episodes of hypoxemia and hyperoxemia.|
|Other: Determination of mechanisms of hypoxemia episodes|Recordings of SpO2, heart rate, esophageal pressure, tidal volume, minute volume, respiratory rate and transcutaneous PCO2 will be analyzed to determine the prevalence, severity and duration of hypoxemia episodes produced by the different mechanisms.|
|Other: Assessment of respiratory instability|Recordings of tidal volume, minute volume and respiratory rate will be analyzed to determine frequency of apnea, periodic breathing, distribution of inter-breath intervals.|
|Other: apneic threshold of CO2|In mechanically ventilated infants the apneic threshold of CO2 will be measured by transcutaneous PCO2 following a step wise increase in ventilator rate until spontaneous breathing ceases transiently. In spontaneously breathing infants the apnea threshold of CO2 will be measured during episodes central apnea.|
|Other: Assessment of peripheral chemoreceptor function|The Dejours test will be used to assess peripheral chemoreceptor function by measuring the immediate ventilatory response to high-inspired oxygen.|
|Other: Assessment of central chemo-receptor function|Central chemo-receptor function will be assessed by measuring the ventilatory response to inspired CO2.|

What is the study measuring?
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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 |