Maturation of cardioventilatory physiological trajectories in extremely preterm infants.

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.

Cardiorespiratory Monitoring Data to Predict Respiratory Outcomes in Extremely Preterm Infants.

Rationale: Immature control of breathing is associated with apnea, periodic breathing, intermittent hypoxemia, and bradycardia in extremely preterm infants. However, it is not clear if such events independently predict worse respiratory outcome. Objectives: To determine if analysis of cardiorespiratory monitoring data can predict unfavorable respiratory outcomes at 40 weeks postmenstrual age (PMA) and other outcomes, such as bronchopulmonary dysplasia at 36 weeks PMA. Methods: The Prematurity-related Ventilatory Control (Pre-Vent) study was an observational multicenter prospective cohort study including infants born at <29 weeks of gestation with continuous cardiorespiratory monitoring. The primary outcome was either "favorable" (alive and previously discharged or inpatient and off respiratory medications/O2/support at 40 wk PMA) or "unfavorable" (either deceased or inpatient/previously discharged on respiratory medications/O2/support at 40 wk PMA). Measurements and Main Results: A total of 717 infants were evaluated (median birth weight, 850 g; gestation, 26.4 wk), 53.7% of whom had a favorable outcome and 46.3% of whom had an unfavorable outcome. Physiologic data predicted unfavorable outcome, with accuracy improving with advancing age (area under the curve, 0.79 at Day 7, 0.85 at Day 28 and 32 wk PMA). The physiologic variable that contributed most to prediction was intermittent hypoxemia with oxygen saturation as measured by pulse oximetry <90%. Models with clinical data alone or combining physiologic and clinical data also had good accuracy, with areas under the curve of 0.84-0.85 at Days 7 and 14 and 0.86-0.88 at Day 28 and 32 weeks PMA. Intermittent hypoxemia with oxygen saturation as measured by pulse oximetry <80% was the major physiologic predictor of severe bronchopulmonary dysplasia and death or mechanical ventilation at 40 weeks PMA. Conclusions: Physiologic data are independently associated with unfavorable respiratory outcome in extremely preterm infants.

Etiology and Mechanism of Intermittent Hypoxemia Episodes in Spontaneously Breathing Extremely Premature Infants.

OBJECTIVE: To evaluate the mechanisms leading to intermittent hypoxemia (IH) episodes in spontaneously breathing extremely premature infants at 32 weeks and 36 weeks postmenstrual age (PMA). METHODS: We studied spontaneously breathing premature infants born at 23-28 weeks of gestational age who presented with IH episodes while on noninvasive respiratory support at 32 or 36 weeks PMA. Daytime recordings of arterial oxygen saturation (SpO2), esophageal pressure, respiratory inductive plethysmography of the abdomen, chest wall, and their sum were obtained during 4 hours at 32 weeks and 36 weeks PMA. IH episodes (SpO2 <90% for ≥5 seconds) and severe IH episodes (SpO2 < 80% for ≥5 seconds) were classified as resulting from apnea, active exhalation and breath holding, reduced tidal volume (VT), or reduced respiratory rate (RR) during the preceding 60 seconds. RESULTS: Fifty-one infants with a mean gestational age of 25.9 ± 1.5 weeks and a mean birth weight of 846 ± 185 g were included. Of these, 31 and 41 were included in the analysis at 32 weeks and 36 weeks PMA, respectively. At both 32 weeks and 36 weeks PMA, greater proportions of all IH episodes and severe IH episodes were associated with active exhalation and breath holding than with apnea, reduced RR, or reduced VT. The severity and duration of the IH episodes did not differ between mechanisms. CONCLUSIONS: In this group of premature infants, the predominant mechanism associated with daytime IH was active exhalation and breath holding. This etiology is more closely associated with behavioral factors than abnormal respiratory control and can have implications for prevention.

Pulse oximetry reliability for detection of hypoxemia under motion in extremely premature infants.

BACKGROUND: Episodes of intermittent hypoxemia (IH) in extremely premature infants are detected by pulse oximetry (SpO2) but motion artifact can cause falsely low readings. OBJECTIVES: To evaluate the reliability of SpO2 during IH episodes associated with motion in premature infants of ≤28 weeks GA monitored with 2 pulse oximeters. METHODS: IH episodes (defined as SpO2 < 90%, >10 s and SpO2 < 80%, >10 s) were classified by an analytic tool based on distortion caused by motion in the pulse plethysmograph (Pleth) as: A (true hypoxemia), both SpO2 decreased (only one Pleth showed motion); B (false hypoxemia), one SpO2 decreased (Pleth showed motion) and the other didn't (Pleth didn't show motion); C (suspected hypoxemia), both SpO2 decreased (both Pleth showed motion); D (true hypoxemia-motion free), both SpO2 decreased (neither Pleth showed motion). RESULTS: In 24-72 h data from 20 infants of 25.4 ± 1.5 weeks GA, 14.1 ± 5.7 episodes with SpO2 < 90% and 7.9 ± 5.5 episodes with SpO2 < 80% per infant were identified. 29 ± 15% of episodes with SpO2 < 90% were type A, 1 ± 2% B, 43 ± 21% C and 27 ± 23% D, while 26 ± 22% of episodes with SpO2 < 80% were type A, 0.3 ± 1.2% B, 45 ± 29% C, and 19 ± 25% D [p < 0.001 type B vs. rest (GLM-repeated measures)]. CONCLUSION: In extremely premature infants SpO2 with motion artifact is more likely to indicate true- than false hypoxemia. IMPACT: Uncertainty on the effect of motion on SpO2 accuracy during hypoxemia episodes in premature infants can influence the caregiver's trust on SpO2 and influence their response. This study evaluated data from two pulse oximeters used simultaneously in different extremities to determine the reliability of SpO2 during motion artifact in premature infants. Data from this study showed that in extremely premature infants SpO2 is more likely to indicate true- than false hypoxemia during episodes of hypoxemia associated with motion artifact.

Effect of the Target Range on Arterial Oxygen Saturation Stability in Extremely Premature Infants.

OBJECTIVE: The aim of this study was to compare the effect of targeting arterial oxygen saturation (SpO2) in the high (93-95%) versus the low portion (90-92%) of the recommended range of 90-95% on oxygenation stability in extremely premature infants. METHODS: Premature infants of ≤28 weeks of gestational age who received a fraction of inspired oxygen (FiO2) > 0.21 after day 14 were eligible. FiO2 was adjusted by a dedicated investigator to keep SpO2 between 90-92% and 93-95% for 2 h each in random sequence. Episodes of intermittent hypoxemia (IH) were defined as SpO2 <90% for ≥10 s; severe IH episodes were defined as SpO2 <80% for ≥10 s. Hyperoxemia was defined as SpO2 >95% or >98%. RESULTS: Eighteen premature infants were enrolled. Their (mean ± SD) GA was 26 ± 1.5 w. Seven infants were on mechanical ventilation, 4 infants on nasal ventilation, and 7 infants on nasal cannula. They were on a mean FiO2 0.38 ± 0.12 at study entry. Episodes of IH and severe IH were more frequent during the low compared to the high target (36.6 [27.0-41.3] vs. 16.0 [7.8-19.0], p < 0.001; 8.4 ± 9.3 vs. 3.2 ± 4.3, p = 0.002). The proportions of time with SpO2 >95% and >98% were greater with the high target (13.9 ± 11 vs. 34.1 ± 15.4%, p < 0.001; 0.9 [0-5.7] vs. 3.4 [0.5-16.1]%, p = 0.002). CONCLUSION: In this group of extremely premature infants, targeting SpO2 at the lower portion of the recommended range resulted in more frequent episodes of IH. However, targeting the higher SpO2 range led to more hyperoxemia. This trade-off warrants further investigation.