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Background: Apnea of prematurity (AOP) is nearly universal among very preterm infants, but neither the apnea burden nor its clinical associations have been systematically studied in a large consecutive cohort. Methods: We analyzed continuous bedside monitor chest impedance and electrocardiographic waveforms and oxygen saturation data collected on all neonatal intensive care unit (NICU) patients <35 wk gestation from 2009 to 2014 ( n = 1,211; >50 infant-years of data). Apneas, with bradycardia and desaturation (ABDs), defined as central apnea ≥10 s associated with both bradycardia <100 bpm and oxygen desaturation <80%, were identified using a validated automated algorithm. Results: Number and duration of apnea events decreased with increasing gestational age (GA) and postmenstrual age (PMA). ABDs were more frequent in infants <31 wk GA at birth but were not more frequent in those with severe retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), or severe intraventricular hemorrhage (IVH) after accounting for GA. In the day before diagnosis of late-onset septicemia and necrotizing enterocolitis, ABD events were increased in some infants. Many infants continued to experience short ABD events in the week prior to discharge home. Conclusion: Frequency of apnea events is a function of GA and PMA in infants born preterm, and increased apnea is associated with acute but not with chronic pathologic conditions.

Background: Periodic breathing (PB) is a normal immature breathing pattern in neonates that, if extreme, may be associated with pathologic conditions. Methods: We used our automated PB detection system to analyze all bedside monitor chest impedance data on all infants <35 wk’ gestation in the University of Virginia Neonatal Intensive Care Unit from 2009–2014 ( n = 1,211). Percent time spent in PB was calculated hourly (>50 infant-years’ data). Extreme PB was identified as a 12-h period with PB >6 SDs above the mean for gestational age (GA) and postmenstrual age and >10% time in PB. Results: PB increased with GA, with the highest amount in infants 30–33 wk’ GA at about 2 wk’ chronologic age. Extreme PB was identified in 76 infants and in 45% was temporally associated with clinical events including infection or necrotizing enterocolitis (NEC), immunizations, or caffeine discontinuation. In 8 out of 28 cases of septicemia and 10 out of 21 cases of NEC, there was a >2-fold increase in %PB over baseline on the day prior to diagnosis. Conclusion: Infants <35 wk GA spend, on average, <6% of the time in PB. An acute increase in PB may reflect illness or physiological stressors or may occur without any apparent clinical event.

Background: Subtle changes in vital signs and their interactions occur in preterm infants prior to overt deterioration from late-onset septicemia (LOS) or necrotizing enterocolitis (NEC). Optimizing predictive algorithms may lead to earlier treatment. Methods: For 1,065 very-low-birth-weight (VLBW) infants in two neonatal intensive care units (NICUs), mean, SD, and cross-correlation of respiratory rate, heart rate (HR), and oxygen saturation (SpO 2 ) were analyzed hourly (131 infant-years’ data). Cross-correlation (cotrending) between two vital signs was measured allowing a lag of ± 30 s. Cases of LOS and NEC were identified retrospectively ( n = 186) and vital sign models were evaluated for ability to predict illness diagnosed in the ensuing 24 h. Results: The best single illness predictor within and between institutions was cross-correlation of HR-SpO 2 . The best combined model (mean SpO 2 , SDHR, and cross-correlation of HR-SpO 2 ,) trained at one site with ROC area 0.695 had external ROC area of 0.754 at the other site, and provided additive value to an established HR characteristics index for illness prediction (Net Reclassification Improvement: 0.205; 95% confidence interval (CI): 0.113, 0.328). Conclusion: Despite minor inter-institutional differences in vital sign patterns of VLBW infants, cross-correlation of HR-SpO 2 and a 3-variable vital sign model performed well at both centers for preclinical detection of sepsis or NEC.