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Prematurity-Related Ventilatory Control: Role in Respiratory Outcomes (Pre-Vent-BioLINCC)

Objectives

To develop a predictive model of short-term respiratory outcomes in extremely preterm infants, based on quantitative analysis of neonatal ICU cardiorespiratory monitoring data.

Background

Preterm birth is a major cause of infant mortality and morbidity worldwide and a leading contributor to disability. Abnormal control of breathing is common in preterm infants and usually manifests as apnea, intermittent hypoxemia, bradycardia, and periodic breathing. Extremely preterm infants may also have impaired gas exchange caused by respiratory distress syndrome and subsequent bronchopulmonary dysplasia. The combination of apnea and lung disease often leads to more prolonged episodes of intermittent hypoxia. Such chronic intermittent hypoxia is associated with worse short-term outcomes (e.g., increased respiratory support, retinopathy of prematurity) and neurodevelopmental impairment that are difficult to predict in the neonatal ICU (NICU). The contribution of abnormal control of breathing to respiratory outcomes has not been determined. The Pre-Vent study was initiated to analyze cardiorespiratory continuous waveform monitoring data to delineate mechanisms of immature ventilatory control in preterm infants and identify predictive markers.

Participants

Infants less than 29 weeks gestational age with continuously archived cardiorespiratory monitoring data were included. 717 total infants were evaluated.

Design

Pre-Vent was an observational multicenter prospective cohort study. Clinical data collected included respiratory support, medications, and co-morbidity data. Physiologic data consisted of variables extracted from cardiorespiratory monitoring data and quantified by count of events per day and duration per event. The extracted variables were apnea (≥20 seconds), periodic breathing (wavelet transform using a five-breath template), intermittent hypoxia events with oxygen saturation <80% as measured by pulse oximetry, intermittent hypoxia events with oxygen saturation <90% as measured by pulse oximetry, and bradycardia (<80bpm for 5 seconds or longer).

Infants discharged prior to 40 weeks post-menstrual age or inpatient infants at 40 weeks post-menstrual age had a favorable outcome if they were not on respiratory support or respiratory medications. Infants discharged prior to 40 weeks post-menstrual age or inpatient infants at 40 weeks post-menstrual age had an unfavorable outcome if they were on respiratory medications and/or respiratory support, or deceased.

Conclusions

The major findings of this study were that mathematical models based on cardiorespiratory bedside monitoring can identify alterations in physiologic measures that are independently associated with unfavorable respiratory outcomes in extremely preterm infants. Both physiologic and clinical variables contributed to good prediction models, with the contribution by physiologic variables increasing with postnatal age (Ambalavanan N, Weese-Mayer DE, Hibbs AM, et al. Am J Respir Crit Care Med. 2023;208(1):79-97.), (Weese-Mayer DE, Di Fiore JM, Lake DE, et al. Pediatr Res. 2024;95(4):1060-1069).

Data Access

NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions.

Access to Biospecimens is through the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC). Biospecimens from Pre-Vent include DNA. Please note that use of biospecimens in genetic research is subject to a tiered consent.