Diminished vagal tone is a predictive biomarker of necrotizing enterocolitis-risk in preterm infants

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background: Necrotizing enterocolitis (NEC) is an acute neonatal inflammatory disease which may lead to intestinal necrosis, multisystem failure, and death. Currently, NEC is diagnosed by a combination of laboratory and radiographic tests conducted a posteriori i.e., when NEC is already clinically significant. Given the acute onset and rapid progression of NEC, a non-invasive biomarker that allows early detection of patients at risk is required as a matter of urgency. We evaluated whether the high frequency (HF) component of heart rate variability (HRV), a measure of vagal efferent tonic cholinergic activity may be used as a predictive biomarker for NEC-risk before the onset of clinical disease. Methods: In this prospective study, stable preterm (gestational age 28-35 weeks) infants had HRV power spectra analyzed from surface electrocardiogram waveforms taken at rest on day 5-8 of life. We used regression modeling to determine the utility of HF-HRV in predicting NEC. Key Results: HF-HRV power was 21.5 ± 2.7 and 3.9 ± 0.81 ms2 in infants that remained healthy and those that later developed stage 2+ NEC, respectively (p < 0.001). Nine of 70 enrolled infants developed NEC. The ROC discriminated a HF-HRV value of 4.68 ms2 predictive for developing NEC with a sensitivity and specificity of 89% and 87%, and positive and negative predictive value of 50% and 98%, respectively. With predictive regression modeling, the risk (odds ratio) of developing NEC was 10 per every one SD decrease in HF-HRV. Conclusions & Inferences: Our preliminary data indicate that HF-HRV may serve as a potential, non-invasive predictive biomarker of NEC-risk in NICU infants. Prognostic identification of infants at risk for necrotizing enterocolitis (NEC) is required as a matter of urgency. We tested the hypothesis that the high frequency (HF) component of heart rate variability (HRV) representative of vagal tone and the cholinergic anti-inflammatory reflex may be used in infants as a predictive biomarker for NEC-risk before the onset of clinical NEC. Spectral analysis of surface electrocardiogram was done in 'healthy' preterm infants at rest on day 5-8 of life and associated with later diagnosis of NEC. The risk (odds ratio) of developing NEC 0.5-20 days in advance of clinical symptoms was 10 per every one SD decrease in HF-HRV (vagal tone). Our preliminary data indicate that HF-HRV may serve as a potential, non-invasive predictive biomarker of NEC-risk in NICU infants.

Original languageEnglish (US)
Pages (from-to)832-840
Number of pages9
JournalNeurogastroenterology and Motility
Volume26
Issue number6
DOIs
StatePublished - Jun 2014

Fingerprint

Necrotizing Enterocolitis
Premature Infants
Biomarkers
Heart Rate
Odds Ratio
Cholinergic Agents
Infant, Newborn, Diseases
Electrocardiography
Delayed Diagnosis

All Science Journal Classification (ASJC) codes

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

Cite this

@article{69b93be9aeb14d688246ad3c47921c21,
title = "Diminished vagal tone is a predictive biomarker of necrotizing enterocolitis-risk in preterm infants",
abstract = "Background: Necrotizing enterocolitis (NEC) is an acute neonatal inflammatory disease which may lead to intestinal necrosis, multisystem failure, and death. Currently, NEC is diagnosed by a combination of laboratory and radiographic tests conducted a posteriori i.e., when NEC is already clinically significant. Given the acute onset and rapid progression of NEC, a non-invasive biomarker that allows early detection of patients at risk is required as a matter of urgency. We evaluated whether the high frequency (HF) component of heart rate variability (HRV), a measure of vagal efferent tonic cholinergic activity may be used as a predictive biomarker for NEC-risk before the onset of clinical disease. Methods: In this prospective study, stable preterm (gestational age 28-35 weeks) infants had HRV power spectra analyzed from surface electrocardiogram waveforms taken at rest on day 5-8 of life. We used regression modeling to determine the utility of HF-HRV in predicting NEC. Key Results: HF-HRV power was 21.5 ± 2.7 and 3.9 ± 0.81 ms2 in infants that remained healthy and those that later developed stage 2+ NEC, respectively (p < 0.001). Nine of 70 enrolled infants developed NEC. The ROC discriminated a HF-HRV value of 4.68 ms2 predictive for developing NEC with a sensitivity and specificity of 89{\%} and 87{\%}, and positive and negative predictive value of 50{\%} and 98{\%}, respectively. With predictive regression modeling, the risk (odds ratio) of developing NEC was 10 per every one SD decrease in HF-HRV. Conclusions & Inferences: Our preliminary data indicate that HF-HRV may serve as a potential, non-invasive predictive biomarker of NEC-risk in NICU infants. Prognostic identification of infants at risk for necrotizing enterocolitis (NEC) is required as a matter of urgency. We tested the hypothesis that the high frequency (HF) component of heart rate variability (HRV) representative of vagal tone and the cholinergic anti-inflammatory reflex may be used in infants as a predictive biomarker for NEC-risk before the onset of clinical NEC. Spectral analysis of surface electrocardiogram was done in 'healthy' preterm infants at rest on day 5-8 of life and associated with later diagnosis of NEC. The risk (odds ratio) of developing NEC 0.5-20 days in advance of clinical symptoms was 10 per every one SD decrease in HF-HRV (vagal tone). Our preliminary data indicate that HF-HRV may serve as a potential, non-invasive predictive biomarker of NEC-risk in NICU infants.",
author = "Doheny, {K. K.} and C. Palmer and Browning, {K. N.} and P. Jairath and D. Liao and F. He and Travagli, {R. A.}",
year = "2014",
month = "6",
doi = "10.1111/nmo.12337",
language = "English (US)",
volume = "26",
pages = "832--840",
journal = "Neurogastroenterology and Motility",
issn = "1350-1925",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Diminished vagal tone is a predictive biomarker of necrotizing enterocolitis-risk in preterm infants

AU - Doheny, K. K.

AU - Palmer, C.

AU - Browning, K. N.

AU - Jairath, P.

AU - Liao, D.

AU - He, F.

AU - Travagli, R. A.

PY - 2014/6

Y1 - 2014/6

N2 - Background: Necrotizing enterocolitis (NEC) is an acute neonatal inflammatory disease which may lead to intestinal necrosis, multisystem failure, and death. Currently, NEC is diagnosed by a combination of laboratory and radiographic tests conducted a posteriori i.e., when NEC is already clinically significant. Given the acute onset and rapid progression of NEC, a non-invasive biomarker that allows early detection of patients at risk is required as a matter of urgency. We evaluated whether the high frequency (HF) component of heart rate variability (HRV), a measure of vagal efferent tonic cholinergic activity may be used as a predictive biomarker for NEC-risk before the onset of clinical disease. Methods: In this prospective study, stable preterm (gestational age 28-35 weeks) infants had HRV power spectra analyzed from surface electrocardiogram waveforms taken at rest on day 5-8 of life. We used regression modeling to determine the utility of HF-HRV in predicting NEC. Key Results: HF-HRV power was 21.5 ± 2.7 and 3.9 ± 0.81 ms2 in infants that remained healthy and those that later developed stage 2+ NEC, respectively (p < 0.001). Nine of 70 enrolled infants developed NEC. The ROC discriminated a HF-HRV value of 4.68 ms2 predictive for developing NEC with a sensitivity and specificity of 89% and 87%, and positive and negative predictive value of 50% and 98%, respectively. With predictive regression modeling, the risk (odds ratio) of developing NEC was 10 per every one SD decrease in HF-HRV. Conclusions & Inferences: Our preliminary data indicate that HF-HRV may serve as a potential, non-invasive predictive biomarker of NEC-risk in NICU infants. Prognostic identification of infants at risk for necrotizing enterocolitis (NEC) is required as a matter of urgency. We tested the hypothesis that the high frequency (HF) component of heart rate variability (HRV) representative of vagal tone and the cholinergic anti-inflammatory reflex may be used in infants as a predictive biomarker for NEC-risk before the onset of clinical NEC. Spectral analysis of surface electrocardiogram was done in 'healthy' preterm infants at rest on day 5-8 of life and associated with later diagnosis of NEC. The risk (odds ratio) of developing NEC 0.5-20 days in advance of clinical symptoms was 10 per every one SD decrease in HF-HRV (vagal tone). Our preliminary data indicate that HF-HRV may serve as a potential, non-invasive predictive biomarker of NEC-risk in NICU infants.

AB - Background: Necrotizing enterocolitis (NEC) is an acute neonatal inflammatory disease which may lead to intestinal necrosis, multisystem failure, and death. Currently, NEC is diagnosed by a combination of laboratory and radiographic tests conducted a posteriori i.e., when NEC is already clinically significant. Given the acute onset and rapid progression of NEC, a non-invasive biomarker that allows early detection of patients at risk is required as a matter of urgency. We evaluated whether the high frequency (HF) component of heart rate variability (HRV), a measure of vagal efferent tonic cholinergic activity may be used as a predictive biomarker for NEC-risk before the onset of clinical disease. Methods: In this prospective study, stable preterm (gestational age 28-35 weeks) infants had HRV power spectra analyzed from surface electrocardiogram waveforms taken at rest on day 5-8 of life. We used regression modeling to determine the utility of HF-HRV in predicting NEC. Key Results: HF-HRV power was 21.5 ± 2.7 and 3.9 ± 0.81 ms2 in infants that remained healthy and those that later developed stage 2+ NEC, respectively (p < 0.001). Nine of 70 enrolled infants developed NEC. The ROC discriminated a HF-HRV value of 4.68 ms2 predictive for developing NEC with a sensitivity and specificity of 89% and 87%, and positive and negative predictive value of 50% and 98%, respectively. With predictive regression modeling, the risk (odds ratio) of developing NEC was 10 per every one SD decrease in HF-HRV. Conclusions & Inferences: Our preliminary data indicate that HF-HRV may serve as a potential, non-invasive predictive biomarker of NEC-risk in NICU infants. Prognostic identification of infants at risk for necrotizing enterocolitis (NEC) is required as a matter of urgency. We tested the hypothesis that the high frequency (HF) component of heart rate variability (HRV) representative of vagal tone and the cholinergic anti-inflammatory reflex may be used in infants as a predictive biomarker for NEC-risk before the onset of clinical NEC. Spectral analysis of surface electrocardiogram was done in 'healthy' preterm infants at rest on day 5-8 of life and associated with later diagnosis of NEC. The risk (odds ratio) of developing NEC 0.5-20 days in advance of clinical symptoms was 10 per every one SD decrease in HF-HRV (vagal tone). Our preliminary data indicate that HF-HRV may serve as a potential, non-invasive predictive biomarker of NEC-risk in NICU infants.

UR - http://www.scopus.com/inward/record.url?scp=84901478603&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84901478603&partnerID=8YFLogxK

U2 - 10.1111/nmo.12337

DO - 10.1111/nmo.12337

M3 - Article

C2 - 24720579

AN - SCOPUS:84901478603

VL - 26

SP - 832

EP - 840

JO - Neurogastroenterology and Motility

JF - Neurogastroenterology and Motility

SN - 1350-1925

IS - 6

ER -