Vagal contributions to fetal heart rate variability: an omics approach

Abstract

Objective: Fetal heart rate variability (fHRV) is an important indicator of health and disease, yet its physiological origins, neural contributions, in particular, are not well understood. We aimed to develop novel experimental and data analytical approaches to identify fHRV measures reflecting the vagus nerve contributions to fHRV. Approach: In near-term ovine fetuses, a comprehensive set of 46 fHRV measures was computed from fetal pre-cordial electrocardiogram recorded during surgery and 72 h later without (n = 24) and with intra-surgical bilateral cervical vagotomy (n = 15). Main results: The fetal heart rate did not change due to vagotomy. We identify fHRV measures specific to the vagal modulation of fHRV: multiscale time irreversibility asymmetry index (AsymI), detrended fluctuation analysis (DFA) α1, Kullback–Leibler permutation entropy (KLPE) and scale-dependent Lyapunov exponent slope (SDLE α). Significance: We provide a systematic delineation of vagal contributions to fHRV across signal-analytical domains which should be relevant for the emerging field of bioelectronic medicine and the deciphering of the ‘vagus code’. Our findings also have clinical significance for in utero monitoring of fetal health during surgery.Key points•Fetal surgery causes a complex pattern of changes in heart rate variability measures with an overall reduction of complexity or variability.•At 72 h after surgery, many of the HRV measures recover and this recovery is delayed by an intrasurgical cervical bilateral vagotomy.•We identify HRV pattern representing complete vagal withdrawal that can be understood as part of ‘HRV code’, rather than any single HRV measure.•We identify HRV biomarkers of recovery from fetal surgery and discuss the effect of anticholinergic medication on this recovery.