Can Monitoring Fetal Intestinal Inflammation Using Heart Rate Variability Analysis Signal Incipient Necrotizing Enterocolitis of the Neonate?

Liu, Hai Lun; Garzoni, Luca; Herry, Christophe L.; Durosier, Lucien Daniel; Cao, Mingju; Burns, Patrick; Fecteau, Gilles; Desrochers, André; Patey, Natalie; Seely, Andrew J. E.; Fauré, Christophe; Frasch, Martin G.

doi:10.1097/pcc.0000000000000643

Cited by 25 publications

(21 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several other studies have measured autonomic tone changes among infants at risk for prematurity-related complications. In an instrumented fetal sheep model, Liu et al 19 described significant decreases in fetal HRV from 1.5 days before the onset of intestinal NEC changes. In a cohort of premature infants, Doheny et al 7 found that depressed vagal tone (HF HRV power) 7,12 in the early postnatal period (5-8 days of life) predicted later-onset NEC.…”

Section: Discussionmentioning

confidence: 99%

Changes in Autonomic Tone in Premature Infants Developing Necrotizing Enterocolitis

et al. 2018

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Changes in Autonomic Tone in Premature Infants Developing Necrotizing Enterocolitis

et al. 2018

View full text Add to dashboard Cite

show abstract

“…As positive and negative tissue controls, brain tissues from a different fetal sheep study being performed in our laboratory were run concurrently with UCO and control animals. In this study, afferent (positive control) and efferent (negative control) bilateral cervical vagus nerve stimulation (VNS) was accompanied by intravenous injection of endotoxin to trigger inflammatory response in fetal sheep near term [ 45 , 46 , 52 , 53 ]. Twelve dilutions of c-Fos antibody were tested with various antigen retrieval methods.…”

Section: Methodsmentioning

confidence: 99%

Decreased neuroinflammation correlates to higher vagus nerve activity fluctuations in near-term ovine fetuses: a case for the afferent cholinergic anti-inflammatory pathway?

Frasch

Szynkaruk

Prout

et al. 2016

J Neuroinflammation

View full text Add to dashboard Cite

BackgroundNeuroinflammation in utero may contribute to brain injury resulting in life-long neurological disabilities. The pivotal role of the efferent cholinergic anti-inflammatory pathway (CAP) in controlling inflammation, e.g., by inhibiting the HMGB1 release, via the macrophages’ α7 nicotinic acetylcholine receptor (α7nAChR) has been described in adults, but its importance in the fetus is unknown. Moreover, it is unknown whether CAP may also exert anti-inflammatory effects on the brain via the anatomically predominant afferent component of the vagus nerve.MethodsWe measured microglial activation in the ovine fetal brain near term 24 h after the umbilical cord occlusions mimicking human labor versus controls (no occlusions) by quantifying HMGB1 nucleus-to-cytosol translocation in the Iba1+ and α7nAChR+ microglia. Based on multiple clinical studies in adults and our own work in fetal autonomic nervous system, we gauged the degree of CAP activity in vivo using heart rate variability measure RMSSD that reflects fluctuations in vagus nerve activity.ResultsRMSSD correlated to corresponding plasma IL-1β levels at R = 0.57 (p = 0.02, n = 17) and to white matter microglia cell counts at R = −0.89 (p = 0.03). The insult increased the HMGB1 translocation in α7nAChR+ microglia in a brain region-dependent manner (p < 0.001). In parallel, RMSSD at 1 h post insult correlated with cytosolic HMGB1 of thalamic microglia (R = −0.94, p = 0.005), and RMSSD at pH nadir correlated with microglial α7nAChR in the white matter (R = 0.83, p = 0.04). Overall, higher RMSSD values correlated with lower HMGB1 translocation and higher α7nAChR intensity per area in a brain region-specific manner.ConclusionsAfferent fetal CAP may translate increased vagal cholinergic signaling into suppression of cerebral inflammation in response to near-term hypoxic acidemia as might occur during labor. Our findings suggest a new control mechanism of fetal neuroinflammation via the vagus nerve, providing novel possibilities for its non-invasive monitoring in utero and for targeted treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0567-x) contains supplementary material, which is available to authorized users.

show abstract

“…[ 4 – 6 ] CAP activity is reflected in fetal heart rate (FHR) variability (fHRV). [ 7 ] [ 8 ] [ 9 ] HRV measures can be derived from various signal-analytical domains such as statistical, informational, invariant or energetic. [ 8 ] [ 9 ] However, among many dozens HRV measures that have been deduced mathematically over the past several decades, it is not known a priori which fHRV measures reflect physiologically relevant processes such as inflammation.…”

Section: Introductionmentioning

confidence: 99%

Temporal Patterns in Sheep Fetal Heart Rate Variability Correlate to Systemic Cytokine Inflammatory Response: A Methodological Exploration of Monitoring Potential Using Complex Signals Bioinformatics

Herry

Côrtes

et al. 2016

PLoS ONE

Self Cite

View full text Add to dashboard Cite

Fetal inflammation is associated with increased risk for postnatal organ injuries. No means of early detection exist. We hypothesized that systemic fetal inflammation leads to distinct alterations of fetal heart rate variability (fHRV). We tested this hypothesis deploying a novel series of approaches from complex signals bioinformatics. In chronically instrumented near-term fetal sheep, we induced an inflammatory response with lipopolysaccharide (LPS) injected intravenously (n = 10) observing it over 54 hours; seven additional fetuses served as controls. Fifty-one fHRV measures were determined continuously every 5 minutes using Continuous Individualized Multi-organ Variability Analysis (CIMVA). CIMVA creates an fHRV measures matrix across five signal-analytical domains, thus describing complementary properties of fHRV. We implemented, validated and tested methodology to obtain a subset of CIMVA fHRV measures that matched best the temporal profile of the inflammatory cytokine IL-6. In the LPS group, IL-6 peaked at 3 hours. For the LPS, but not control group, a sharp increase in standardized difference in variability with respect to baseline levels was observed between 3 h and 6 h abating to baseline levels, thus tracking closely the IL-6 inflammatory profile. We derived fHRV inflammatory index (FII) consisting of 15 fHRV measures reflecting the fetal inflammatory response with prediction accuracy of 90%. Hierarchical clustering validated the selection of 14 out of 15 fHRV measures comprising FII. We developed methodology to identify a distinctive subset of fHRV measures that tracks inflammation over time. The broader potential of this bioinformatics approach is discussed to detect physiological responses encoded in HRV measures.

show abstract

Can Monitoring Fetal Intestinal Inflammation Using Heart Rate Variability Analysis Signal Incipient Necrotizing Enterocolitis of the Neonate?

Cited by 25 publications

References 34 publications

Changes in Autonomic Tone in Premature Infants Developing Necrotizing Enterocolitis

Changes in Autonomic Tone in Premature Infants Developing Necrotizing Enterocolitis

Decreased neuroinflammation correlates to higher vagus nerve activity fluctuations in near-term ovine fetuses: a case for the afferent cholinergic anti-inflammatory pathway?

Temporal Patterns in Sheep Fetal Heart Rate Variability Correlate to Systemic Cytokine Inflammatory Response: A Methodological Exploration of Monitoring Potential Using Complex Signals Bioinformatics

Contact Info

Product

Resources

About