Vagal contributions to fetal heart rate variability: an omics approach

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: multistate time irreversibility asymmetry index (AsymI), detrended fluctuation analysis (DFA) alpha(1), Kullback-Leibler permutation entropy (KLPE) and scale-dependent Lyapunov exponent slope (SDLE alpha). 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.