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Published online November 1, 2005
PEDIATRICS Vol. 116 No. 5 November 2005, pp. 1070-1074 (doi:10.1542/peds.2004-2461)
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Heart Rate Characteristics: Novel Physiomarkers to Predict Neonatal Infection and Death

M. Pamela Griffin, MD*, Douglas E. Lake, PhD{ddagger}, Eric A. Bissonette, MS§, Frank E. Harrell, Jr, PhD||, T. Michael O'Shea, MD, J. Randall Moorman, MD{ddagger}

Departments of * Pediatrics
{ddagger} Internal Medicine and the Cardiovascular Research Center
§ Health Evaluation Sciences, University of Virginia Health System, Charlottesville, Virginia
|| Department of Biostatistics, Vanderbilt University, Nashville, Tennessee
Department of Pediatrics, Wake Forest School of Medicine, Winston-Salem, North Carolina

Objective. Monitoring of regulated physiologic processes using physiomarkers such as heart rate variability may be important in the early diagnosis of subacute, potentially catastrophic illness. Early in the course of neonatal sepsis, there are physiomarkers of reduced heart rate variability and transient decelerations similar to fetal distress. The goal of this study was to determine the degree of increased risk for sepsis, urinary tract infection (UTI), and death when these abnormal heart rate characteristics (HRC) were observed.

Methods. We monitored 1022 infants at 2 tertiary care NICUs, 458 of whom were very low birth weight. We calculated an HRC index from validated regression models relating mathematical features of heart rate time series and histograms to episodes of illness. We calculated the risks for adverse events of sepsis, UTI, and death for infants stratified by HRC measurements.

Results. Compared with infants with low-risk HRC measurements, infants with high-risk HRC measurements had 5- to 6-fold increased risk for an adverse event in the next day and 3-fold increased risk in the next week. Laboratory tests that were relevant to infection added information to HRC measurements. Infants with both high-risk HRC and abnormal laboratory tests had 6- to 7-fold increased risk for an adverse event in the next day compared with infants who had neither.

Conclusion. HRC are noninvasively monitored physiomarkers that identify infants in the NICU who are at high risk for sepsis, UTI, and death.

Key Words: infant • mortality prediction • sepsis • urinary tract infections • physiomarker

Abbreviations: HRC, heart rate characteristics • UTI, urinary tract infection • UVA, University of Virginia • HR, heart rate • WFU, Wake Forest University • CONS, coagulase-negative Staphylococcus • NICHD, National Institute of Child Health and Human Development • VLBW, very low birth weight

Accepted Feb 4, 2005.


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