Cross-Correlation of Heart Rate and Oxygen Saturation in Very Low Birthweight Infants: Association with Apnea and Adverse Events
12 May 2017
09 October 2017
15 November 2017 (eFirst)
Background Analysis of subtle vital sign changes could facilitate earlier treatment of acute inflammatory illnesses. We previously showed that high cross-correlation of heart rate and oxygen saturation (XCorr-HR-SpO2) occurs in some very low birthweight (VLBW) infants with sepsis, and hypothesized that this corresponds to apnea.
Methods In 629 VLBW infants, we analyzed XCorr-HR-SpO2 in relation to central apnea with bradycardia and desaturation (ABD), BD with or without central apnea (BD), and percent time in periodic breathing (PB) throughout the neonatal intensive care unit (NICU) stay (75 infant-years). We reviewed 100 days with extremely high XCorr-HR-SpO2 (>0.7) and control days for clinical associations. Next, we identified all cases of late-onset septicemia (LOS) and necrotizing enterocolitis (NEC) and analyzed change in XCorr-HR-SpO2 before diagnosis.
Results Mean XCorr-HR-SpO2 was ∼0.10, and increasing XCorr-HR-SpO2 was associated with increasing ABD, BD, and PB (correlation coefficients >0.93). Days with maximum XCorr-HR-SpO2 >0.7 were more likely to have an adverse event than control days (49% versus 13%). In 93 cases of LOS or NEC, there was a 67% increase in XCorr-HR-SpO2 in the 24-hour period prior to diagnosis compared with the previous day (p < 0.01).
Conclusion High XCorr-HR-SpO2 is associated with apnea and adverse events including LOS and NEC.
- 1 Stoll BJ, Hansen NI, Bell EF. , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993-2012. JAMA 2015; 314 (10) 1039-1051
- 2 Sullivan BA, Fairchild KD. Predictive monitoring for sepsis and necrotizing enterocolitis to prevent shock. Semin Fetal Neonatal Med 2015; 20 (04) 255-261
- 3 Fairchild KD, Schelonka RL, Kaufman DA. , et al. Septicemia mortality reduction in neonates in a heart rate characteristics monitoring trial. Pediatr Res 2013; 74 (05) 570-575
- 4 Moorman JR, Carlo WA, Kattwinkel J. , et al. Mortality reduction by heart rate characteristic monitoring in very low birth weight neonates: a randomized trial. J Pediatr 2011; 159 (06) 900-9006.e1
- 5 Moorman JR, Lake DE, Griffin MP. Heart rate characteristics monitoring for neonatal sepsis. IEEE Trans Biomed Eng 2006; 53 (01) 126-132
- 6 Griffin MP, Lake DE, Bissonette EA, Harrell Jr FE, O'Shea TM, Moorman JR. Heart rate characteristics: novel physiomarkers to predict neonatal infection and death. Pediatrics 2005; 116 (05) 1070-1074
- 7 Hofstetter AO, Saha S, Siljehav V, Jakobsson P-J, Herlenius E. The induced prostaglandin E2 pathway is a key regulator of the respiratory response to infection and hypoxia in neonates. Proc Natl Acad Sci U S A 2007; 104 (23) 9894-9899
- 8 Herlenius E. An inflammatory pathway to apnea and autonomic dysregulation. Respir Physiol Neurobiol 2011; 178 (03) 449-457
- 9 Siljehav V, Hofstetter AM, Leifsdottir K, Herlenius E. Prostaglandin E2 mediates cardiorespiratory disturbances during infection in neonates. J Pediatr 2015; 167 (06) 1207-13.e3
- 10 Balan KV, Kc P, Hoxha Z, Mayer CA, Wilson CG, Martin RJ. Vagal afferents modulate cytokine-mediated respiratory control at the neonatal medulla oblongata. Respir Physiol Neurobiol 2011; 178 (03) 458-464
- 11 Gauda EB, Shirahata M, Mason A, Pichard LE, Kostuk EW, Chavez-Valdez R. Inflammation in the carotid body during development and its contribution to apnea of prematurity. Respir Physiol Neurobiol 2013; 185 (01) 120-131
- 12 Lee H, Rusin CG, Lake DE. , et al. A new algorithm for detecting central apnea in neonates. Physiol Meas 2012; 33 (01) 1-17
- 13 Mohr MA, Fairchild KD, Patel M. , et al. Quantification of periodic breathing in premature infants. Physiol Meas 2015; 36 (07) 1415-1427
- 14 Fairchild K, Mohr M, Paget-Brown A. , et al. Clinical associations of immature breathing in preterm infants: part 1-central apnea. Pediatr Res 2016; 80 (01) 21-27
- 15 Patel M, Mohr M, Lake D. , et al. Clinical associations with immature breathing in preterm infants: part 2-periodic breathing. Pediatr Res 2016; 80 (01) 28-34
- 16 Fairchild KD, Lake DE, Kattwinkel J. , et al. Vital signs and their cross-correlation in sepsis and NEC: a study of 1,065 very-low-birth-weight infants in two NICUs. Pediatr Res 2017; 81 (02) 315-321
- 17 Sullivan BA, Grice SM, Lake DE, Moorman JR, Fairchild KD. Infection and other clinical correlates of abnormal heart rate characteristics in preterm infants. J Pediatr 2014; 164 (04) 775-780
- 18 Finer NN, Higgins R, Kattwinkel J, Martin RJ. Summary proceedings from the apnea-of-prematurity group. Pediatrics 2006; 117 (3, Pt 2): S47-S51
- 19 Fairchild KD, Srinivasan V, Moorman JR, Gaykema RP, Goehler LE. Pathogen-induced heart rate changes associated with cholinergic nervous system activation. Am J Physiol Regul Integr Comp Physiol 2011; 300 (02) R330-R339
- 20 Vergales BD, Paget-Brown AO, Lee H. , et al. Accurate automated apnea analysis in preterm infants. Am J Perinatol 2014; 31 (02) 157-162
- 21 Mohr MA, Vergales BD, Lee H. , et al. Very long apnea events in preterm infants. J Appl Physiol (1985) 2015; 118 (05) 558-568