Fetal ECG monitoring

Taking the challenge of fetal acidemia detection this to the bedside, my lab has developed a non-invasive approach to identify fetuses developing acidemia using multidimensional fetal HRV analyses with FDA-approved transabdominal fetal ECG (t-a fECG) monitors. Similarly, in fetal sheep model of inflammation, we showed that using such t-a fECG monitors we should be able to non-invasively detect systemic and gut fetal inflammatory response, even when it is clinically asymptomatic (no maternal signs of infection).

Further studies have shown the value of ECG-based, or more generally, precise beat-to-beat-based, heart monitoring to detect exposure to chronic stress during pregnancy, Zika virus, presence of Autism Spectrum Disorder (and other psychiatric disorders such as Conduct Disorder or Major Depression compared to Typical Conduct eight-year olds), and the origins of fetal HRV in the stochastic fluctuations of cardiac sinus node cells' ion channels as foundation for memory of chronic hypoxia in HRV.

These findings have raised many new theoretical and practical questions our lab is currently investigating. The concept of HRV code attempts to synthesize these findings across species, conditions, and health outcomes to come up with a more general formulation of how to think about HRV, well beyond the fetal HRV I started out with some 16 years ago.

1. Frasch MG et al. (2014) Correlating multidimensional fetal heart rate variability analysis with acid-base balance at birth. Physiological Measurement. 35(12):L1-L12. PMID: 25407948.

2. Durosier LD, Herry CL, Cortes M, Cao M, Burns P, Desrochers A, Fecteau G, Seely AJ, Frasch MG. Does heart rate variability reflect the systemic inflammatory response in a fetal sheep model of lipopolysaccharide-induced sepsis? Physiol Meas. 2015;36(10):2089-102. PMID: 26290042.

3. L. Garzoni, H. Liu, L.D. Durosier, et al. Can Monitoring Fetal Intestinal Inflammation Using Heart Rate Variability Analysis Signal Incipient Necrotizing Enterocolitis of the Neonate? 2015. Pediatric Critical Care Medicine. 17(4):e165-76. DOI: 10.1097/PCC.0000000000000643. PMID: 26914621.

4. Herry CL, et al. Temporal patterns in sheep fetal heart rate variability correlate to systemic cytokine inflammatory response: a methodological exploration of monitoring potential using complex signals bioinformatics. 2016. PLoS One. 21;11(4):e0153515. DOI: 10.1371/journal.pone.0153515. PMID: 27100089.

5. Frasch, MG et al. (2016). Decreased neuroinflammation correlates to higher vagus nerve activity fluctuations in near-term ovine fetuses: a case for the afferent cholinergic anti-inflammatory pathway? J of Neuroinflammation 10;13(1):103. doi: 10.1186/s12974-016-0567-x.

6. Li R, Frasch MG, Wu HT. Efficient Fetal-Maternal ECG Signal Separation from Two Channel Maternal Abdominal ECG via Diffusion-Based Channel Selection. Front Physiol. 2017. 8:277. doi: 10.3389/fphys.2017.00277.

7. C Shen, MG Frasch, HT Wu, CL Herry, M Cao, A Desrochers, G Fecteau, P Burns. Non-invasive acquisition of fetal ECG from the maternal thorax: a feasibility study and a call for open data sets. arXiv:1708.09526 [physics.med-ph] -> Dataset from this publication can be found here.

8. P. Burns, C. L. Herry, K. J. Jean, Y. Frank, C. Wakefield, M. Cao, A. Desrochers, G. Fecteau, M. Last, A. Seely, C. Faure, M.G. Frasch. The neonatal sepsis is diminished by cervical vagus nerve stimulation and tracked non-invasively by ECG: a preliminary report in the piglet model. arXiv:2002.04136 [q-bio.TO]

9. Nathan Gold, Christophe L. Herry, Xiaogang Wang, Martin G. Frasch. Fetal cardiovascular decompensation during labor predicted from the individual heart rate: a prospective study in fetal sheep near term and the impact of low sampling rate. arXiv:1911.01304 [q-bio.QM]

10. Christophe L. Herry, Helena M.F. Soares, Lavinia Schuler-Faccini, Martin G. Frasch. Evaluation of heart rate fluctuations in toddlers exposed to Zika virus during pregnancy. arXiv:1812.05259 [q-bio.QM]

11. Lobmaier, SM, Wu, H-T, Shen, C, Su, P-C, Müller, A, Berg, G, Fabre, B, Weyrich, J, Zelgert, C, Frasch, MG, Antonelli, MC. Fetus: the radar of maternal stress. In press. Archives of Gynecology and Obstetrics https://arxiv.org/abs/1902.09746

12. Christophe Herry*, Patrick Burns*, André Desrochers, Gilles Fecteau, Lucien Daniel Durosier, Mingju Cao, Andrew Seely and Martin G. Frasch. Decoding vagal contributions to fetal heart rate variability. Physiological Measurement. 2019. Jul 1;40(6):065004. doi: 10.1088/1361-6579/ab21ae. https://arxiv.org/abs/1901.06431

13. Martin G. Frasch, Chao Shen, Hau-Tieng Wu, Alexander Mueller, Raphael Bernier, Theodore Beauchaine, Emily Neuhaus. Can a composite heart rate variability biomarker shed new insights about autism spectrum disorder in school-aged children? https://arxiv.org/abs/1808.08306. In press. DOI: 10.1007/s10803-020-04467-7. Journal of Autism and Developmental Disorders.

14. Martin G. Frasch. Heart rate variability code: Does it exist and can we hack it? arXiv:2001.08264 [q-bio.TO]

15. Martin G. Frasch, Herry, CL, Niu, Y, Giussani, D. First evidence that intrinsic fetal heart rate variability exists and is affected by chronic hypoxia. https://doi.org/10.1101/242107. In press. Journal of Physiology.