538 - Early factors associated with cardiorespiratory instability at near term corrected age in preterm infants

Publication Number: 3519.538

Nelson Claure, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United States; Eduardo H. Bancalari, University of Miami, MIAMI, FL, United States; Douglas Lake, University of Virginia, Charlottesville, VA, United States; Jiaxing Qiu, University of Virginia School of Medicine, Charlottesville, VA, United States; Katherine Nash. Krahn, University of Virginia, Charlottesville, VA, United States; Anna Maria Hibbs, UH Rainbow Babies & Children's Hospital, Cleveland, OH, United States; Juliann Di Fiore, Case Western Reserve University School of Medicine, clevelaned, OH, United States; Richard Martin, Case Western Reserve University School of Medicine, Cleveland, OH, United States; Namasivayam Ambalavanan, University of Alabama School of Medicine, Birmingham, AL, United States; Waldemar Carlo, University of Alabama School of Medicine, Birmingham, AL, United States; James S. Kemp, Washington University in St. Louis School of Medicine, St Louis, MO, United States; Zachary A. Vesoulis, Washington University School of Medicine, St. Louis, MO, United States; Debra E. Weese-Mayer, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, United States; Aaron Hamvas, Lurie Children's Hospital / Northwestern University, Chicago, IL, United States; Casey Rand, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, United States; Phyllis A.. Dennery, The Warren Alpert Medical School of Brown University, Providence, RI, United States; Karen Fairchild, University of Virginia School of Medicine, Charlottesville, VA, United States

Background: Extreme preterm infants often show persisting cardiorespiratory instability when they reach near term corrected age. This can delay NICU discharge. The risk factors and the role of early exposure to intermittent hypoxemia (IH) and hyperoxemia (IHOX) have not been established.

Objective: To evaluate the association between IH and IHOX exposure over the first 6 w on cardiorespiratory instability (apnea, bradycardia, or IH) at 35-36 wks PMA in a multicenter cohort of preterm infants of ≤28 wks gestational age (GA).

Design/Methods: 429 preterm infants, who were alive at 36 wks PMA and had SpO2 data recorded from wk 1 to 36 wks PMA were included (Table 1).
IH and IHOX were quantified as: Daily IH80 frequency and episode duration (SpO2 < 80% ≥10s), daily IHOX frequency and episode duration (SpO2 ≥98% with O2>21%) over wks 1-2 and 3-6.
Four endpoints were defined as top quartile (TQ) of daily 1) apnea frequency (≥20s, off ventilator), 2) apnea frequency or caffeine, 3) bradycardia frequency (HR < 100 bpm), and 4) IH90 frequency (SpO2 < 90% ≥10s) at 35 0/7 - 36 6/7 w PMA. For each endpoint, statistical models by multivariate generalized estimating equations (GEE) adjusted for demographics, clinical factors, sibling clusters and prior history of the same event (apnea or bradycardia during wks 3-6).

Results: IH80 episode duration over wks 1-2, IHOX episode duration over wks 3-6, male sex, and apnea frequency over wks 3-6 were associated with increased risk for TQ of apnea at 35-36w PMA (Table 2).
IHOX episode duration over wks 3-6, maternal hypertension, BW < 10th-tile, culture proven sepsis, and apnea frequency over wks 3-6 were associated with increased risk whereas GA and IH80 frequency over wks 3-6 with reduced risk for TQ of apnea or caffeine at 35-36w PMA (Table 3).
IH80 episode duration over wks 1-2, increased IHOX frequency over wks 3-6, and bradycardia frequency over wks 3-6 were associated with increased risk for TQ of bradycardia at 35-36w PMA (Table 4).
IH80 frequency and episode duration, and IHOX episode duration over wks 3-6 were associated with increased risk for TQ of IH90 at w 35-36 PMA (Table 5).

Conclusion(s): In this cohort of preterm infants of ≤28 wks GA, early exposure to IH and IHOX was associated with higher risk for cardiorespiratory instability (apnea, bradycardia or IH90) when they reached 35-36 wks PMA. These associations suggest negative effects of early IH or IHOX, additive to their intrinsic instability, on respiratory control and autonomic function at term corrected age.
Supported by NIH/NHLBI grants U01 HL133708, U01 HL133643, U01 HL133704, U01 HL133536, U01 HL133689, U01 HL133700.

Table 1: Demographics, prenatal and postnatal clinical variables
Data are reported as mean ± SD or number (%)

Tables 2 and 3
GEE: Generalized estimating equations, IH: Intermittent hypoxemia, IHOX: Intermittent hyperoxemia,
SpO2: arterial oxygen saturation by pulse oximetry, CI: Confidence Interval.
Gestational age, race, ethnicity, maternal hypertension, chorioamnionitis, Apgar score at 5 min < 5,
and culture proven sepsis were not significantly associated with the top quartile for apnea during 35-36 w PMA.
Race, ethnicity, chorioamnionitis, and Apgar score at 5 min < 5 were not significantly associated
with the top quartile for apnea or caffeine during 35-36 w PMA.

Tables 4 and 5
GEE: Generalized estimating equations, IH: Intermittent hypoxemia, IHOX: Intermittent hyperoxemia,
SpO2: arterial oxygen saturation by pulse oximetry, CI: Confidence Interval.
Gestational age, race, ethnicity, birth weight < 10th percentile, maternal hypertension, chorioamnionitis,
Apgar score at 5 min < 5, and culture proven sepsis were not significantly associated with the top quartile for
bradycardia daily frequency during 35-36 w PMA.
Gestational age, ethnicity, birth weight < 10th percentile, maternal hypertension, chorioamnionitis,
Apgar score at 5 min < 5, and culture proven sepsis were not significantly associated with the top quartile for IH90 daily frequency (SpO2 < 90% for ≥10s) during 35-36w PMA.