Maturation of cardioventilatory physiological trajectories in extremely preterm infants

Abstract

Background: In extremely preterm infants, persistence of cardioventilatory events is associated with long-term morbidity. Therefore, the objective was to characterize physiologic growth curves of apnea, periodic breathing, intermittent hypoxemia, and bradycardia in extremely preterm infants during the first few months of life.

Methods: The Prematurity-Related Ventilatory Control study included 717 preterm infants <29 weeks gestation. Waveforms were downloaded from bedside monitors with a novel sharing analytics strategy utilized to run software locally, with summary data sent to the Data Coordinating Center for compilation.

Results: Apnea, periodic breathing, and intermittent hypoxemia events rose from day 3 of life then fell to near-resolution by 8-12 weeks of age. Apnea/intermittent hypoxemia were inversely correlated with gestational age, peaking at 3-4 weeks of age. Periodic breathing was positively correlated with gestational age peaking at 31-33 weeks postmenstrual age. Females had more periodic breathing but less intermittent hypoxemia/bradycardia. White infants had more apnea/periodic breathing/intermittent hypoxemia. Infants never receiving mechanical ventilation followed similar postnatal trajectories but with less apnea and intermittent hypoxemia, and more periodic breathing.

Conclusions: Cardioventilatory events peak during the first month of life but the actual postnatal trajectory is dependent on the type of event, race, sex and use of mechanical ventilation.

Impact: Physiologic curves of cardiorespiratory events in extremely preterm-born infants offer (1) objective measures to assess individual patient courses and (2) guides for research into control of ventilation, biomarkers and outcomes. Presented are updated maturational trajectories of apnea, periodic breathing, intermittent hypoxemia, and bradycardia in 717 infants born <29 weeks gestation from the multi-site NHLBI-funded Pre-Vent study. Cardioventilatory events peak during the first month of life but the actual postnatal trajectory is dependent on the type of event, race, sex and use of mechanical ventilation. Different time courses for apnea and periodic breathing suggest different maturational mechanisms.

Figure 1.

The frequency (number of events/day) and exposure (number of minutes/day) of apnea events by chronological age, postmenstrual age, and gestational age. Top Row. Data plotted by chronological age are shown in A. and by postmenstrual age in D. Within A. and D., apnea frequency is shown on the left and apnea exposure is shown on the right. Infants are grouped by gestational age as noted in the within-figure key. Days with mechanical ventilation were excluded from apnea and periodic breathing quantifications. Due to the high rate of mechanical ventilation in the 22 to 24 gestational age infants, values were not available during the first 5 weeks of life in this youngest infant cohort. Middle Row. B. and E. show heat maps in which each colored row represents an individual infant, sorted by gestational age on the y-axis. Dark blue indicates 0 or few events while orange indicates a high incidence of events, with the actual number of events shown in the corresponding color code on the right Y-axis of each heat map. Black indicates no available data (days on mechanical ventilation were excluded for apnea and periodic breathing heat maps and also denoted in black). Grey haystack at the right indicates data truncation when an infant reached 36 weeks 6 days postmenstrual age. Yellow color indicates a higher frequency or exposure of events. The right edges of the heat maps plotted by chronological age (A.) are irregular because of varying times of death or discharge. The left edges of the heat maps plotted by postmenstrual age (B.) are irregular because of varying times of birth. Bottom Row. C. and F. shows results for the entire cohort as the median (double blue line), 25^th (dotted line), 75^th (dot and dashed line) and 90^th (dashed line) percentiles.

Figure 2.

The frequency (number of events/day) and exposure (number of minutes/day) of periodic breathing events by chronological age, postmenstrual age, and gestational age. See Figure 1 for further details of each row. Yellow is more prominent at the bottom of the heat map signifying that less premature infants have more periodic breathing than more premature infants.

Figure 3.

The frequency (number of events/day) and exposure (number of minutes/day) of intermittent hypoxemia less than 80% events by chronological age, postmenstrual age, and gestational age. See Figure 1 for further details of each row. Yellow is less prominent at the bottom of the heat map signifying that less premature infants have more IH <80% than more premature infants.

Figure 4.

The frequency (number of events/day) and exposure (number of minutes/day) of intermittent hypoxemia less than 90% events by chronological age, postmenstrual age, and gestational age. See Figure 1 for further details of each row. Similar to IH <80%, yellow is less prominent at the bottom of the heat map signifying that less premature infants have more IH <90% than more premature infants.

Figure 5.

The frequency (number of events/day) and exposure (number of minutes/day) of bradycardia events by chronological age, postmenstrual age, and gestational age. See Figure 1 for further details of each row.

Figure 6.

A. The median frequency (number of events/day) (upper row) and exposure (minutes/day) (lower row) of apnea, periodic breathing, intermittent hypoxemia less than 80% and less than 90% and bradycardia events by sex and chronological age. B. The median frequency (number of events/day) (upper row) and exposure (minutes/day) (lower row) of apnea, periodic breathing, intermittent hypoxemia less than 80% and less than 90% and bradycardia events by race and chronological age.