Sepsis is a major health problem in high-risk newborn infants in the neonatal intensive care unit (NICU), where it occurs in 25 percent of very low birth weight infants and leads to a more than doubling of mortality and a 50 percent increase in hospital stay. Our long-term objective is to test the hypothesis that detection of abnormal heart rate characteristics (HRC) with continuous non-invasive monitoring will improve care of these patients by earlier diagnosis of sepsis and other sub-acute, potentially catastrophic illnesses. We propose to advance toward this objective by completing two research aims.
In Aim 1, we will prospectively study unselected infants in a university NICU to test the hypotheses that abnormal HRC will be associated with upcoming sepsis and sepsis-like illness as defined by objective illness criteria, and that HRC adds significant independent diagnostic information about the risk of sepsis and sepsis-like illness to clinical variables of birth weight and gestational age. The clinical research design is for derivation of multivariable predictive statistical models from one set of patients followed by a validation phase using clinical data from a second set of patients.
In Aim 2, we will develop new measures of HRC that are specific to the task of early detection of neonatal sepsis. We will investigate optimum choice of parameters for sample entropy calculation, stationarity of heart rate time series using conventional and novel measures based on the empirical cumulative distribution function, and frequency domain analysis using a novel method.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM064640-01
Application #
6420485
Study Section
Special Emphasis Panel (ZRG1-CCVS (01))
Program Officer
Somers, Scott D
Project Start
2002-03-01
Project End
2005-02-28
Budget Start
2002-03-01
Budget End
2003-02-28
Support Year
1
Fiscal Year
2002
Total Cost
$308,790
Indirect Cost
Name
University of Virginia
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Sullivan, Brynne A; Grice, Stephanie M; Lake, Douglas E et al. (2014) Infection and other clinical correlates of abnormal heart rate characteristics in preterm infants. J Pediatr 164:775-80
Lake, Douglas E; Fairchild, Karen D; Moorman, J Randall (2014) Complex signals bioinformatics: evaluation of heart rate characteristics monitoring as a novel risk marker for neonatal sepsis. J Clin Monit Comput 28:329-39
Fairchild, Karen D; Schelonka, Robert L; Kaufman, David A et al. (2013) Septicemia mortality reduction in neonates in a heart rate characteristics monitoring trial. Pediatr Res 74:570-5
Moorman, J Randall; Delos, John B; Flower, Abigail A et al. (2011) Cardiovascular oscillations at the bedside: early diagnosis of neonatal sepsis using heart rate characteristics monitoring. Physiol Meas 32:1821-32
Moorman, J Randall; Rusin, Craig E; Lee, Hoshik et al. (2011) Predictive monitoring for early detection of subacute potentially catastrophic illnesses in critical care. Conf Proc IEEE Eng Med Biol Soc 2011:5515-8
Xiao, Yuping; Griffin, M Pamela; Lake, Douglas E et al. (2010) Nearest-neighbor and logistic regression analyses of clinical and heart rate characteristics in the early diagnosis of neonatal sepsis. Med Decis Making 30:258-66
Flower, Abigail A; Moorman, J Randall; Lake, Douglas E et al. (2010) Periodic heart rate decelerations in premature infants. Exp Biol Med (Maywood) 235:531-8
Cheung, Joseph Y; Rothblum, Lawrence I; Moorman, J Randall et al. (2007) Regulation of cardiac Na+/Ca2+ exchanger by phospholemman. Ann N Y Acad Sci 1099:119-34
Griffin, M Pamela; Lake, Douglas E; O'Shea, T Michael et al. (2007) Heart rate characteristics and clinical signs in neonatal sepsis. Pediatr Res 61:222-7
Cao, Hanqing; Lake, Douglas E; Ferguson 2nd, James E et al. (2006) Toward quantitative fetal heart rate monitoring. IEEE Trans Biomed Eng 53:111-8

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