{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:47:46Z","timestamp":1790801266704,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,4,11]],"date-time":"2014-04-11T00:00:00Z","timestamp":1397174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Necrotizing enterocolitis (<jats:styled-content style=\"fixed-case\">NEC<\/jats:styled-content>) is an acute neonatal inflammatory disease which may lead to intestinal necrosis, multisystem failure, and death. Currently, <jats:styled-content style=\"fixed-case\">NEC<\/jats:styled-content> is diagnosed by a combination of laboratory and radiographic tests conducted <jats:italic>a posteriori<\/jats:italic> i.e., when <jats:styled-content style=\"fixed-case\">NEC<\/jats:styled-content> is already clinically significant. Given the acute onset and rapid progression of <jats:styled-content style=\"fixed-case\">NEC<\/jats:styled-content>, a non\u2010invasive biomarker that allows early detection of patients at risk is required as a matter of urgency. We evaluated whether the high frequency (<jats:styled-content style=\"fixed-case\">HF<\/jats:styled-content>) component of heart rate variability (<jats:styled-content style=\"fixed-case\">HRV<\/jats:styled-content>), a measure of vagal efferent tonic cholinergic activity may be used as a predictive biomarker for <jats:styled-content style=\"fixed-case\">NEC<\/jats:styled-content>\u2010risk before the onset of clinical disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this prospective study, stable preterm (gestational age 28\u201335\u00a0weeks) infants had <jats:styled-content style=\"fixed-case\">HRV<\/jats:styled-content> power spectra analyzed from surface electrocardiogram waveforms taken at rest on day 5\u20138 of life. We used regression modeling to determine the utility of <jats:styled-content style=\"fixed-case\">HF<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HRV<\/jats:styled-content> in predicting <jats:styled-content style=\"fixed-case\">NEC<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">HF<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HRV<\/jats:styled-content> power was 21.5\u00a0\u00b1\u00a02.7 and 3.9\u00a0\u00b1\u00a00.81\u00a0ms<jats:sup>2<\/jats:sup> in infants that remained healthy and those that later developed stage 2+ <jats:styled-content style=\"fixed-case\">NEC<\/jats:styled-content>, respectively (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001). Nine of 70 enrolled infants developed <jats:styled-content style=\"fixed-case\">NEC<\/jats:styled-content>. The <jats:styled-content style=\"fixed-case\">ROC<\/jats:styled-content> discriminated a <jats:styled-content style=\"fixed-case\">HF<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HRV<\/jats:styled-content> value of 4.68\u00a0ms<jats:sup>2<\/jats:sup> predictive for developing <jats:styled-content style=\"fixed-case\">NEC<\/jats:styled-content> 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 <jats:styled-content style=\"fixed-case\">NEC<\/jats:styled-content> was 10 per every one <jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content> decrease in <jats:styled-content style=\"fixed-case\">HF<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HRV<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>Our preliminary data indicate that <jats:styled-content style=\"fixed-case\">HF<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HRV<\/jats:styled-content> may serve as a potential, non\u2010invasive predictive biomarker of <jats:styled-content style=\"fixed-case\">NEC<\/jats:styled-content>\u2010risk in <jats:styled-content style=\"fixed-case\">NICU<\/jats:styled-content> infants.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.12337","type":"journal-article","created":{"date-parts":[[2014,4,11]],"date-time":"2014-04-11T07:21:16Z","timestamp":1397200876000},"page":"832-840","source":"Crossref","is-referenced-by-count":64,"title":["Diminished vagal tone is a predictive biomarker of necrotizing enterocolitis\u2010risk in preterm infants"],"prefix":"10.1111","volume":"26","author":[{"given":"K. K.","family":"Doheny","sequence":"first","affiliation":[{"name":"Department of Pediatrics College of Medicine Pennsylvania State University Hershey PA USA"},{"name":"Division of Newborn Medicine Penn State Children's Hospital Hershey PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Palmer","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine Penn State Children's Hospital Hershey PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. N.","family":"Browning","sequence":"additional","affiliation":[{"name":"Department of Neural and Behavioral Sciences College of Medicine Pennsylvania State University Hershey PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Jairath","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine Penn State Children's Hospital Hershey PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences College of Medicine Pennsylvania State University Hershey PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"He","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences College of Medicine Pennsylvania State University Hershey PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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