Maternal-Fetal Electrophysiology Modelling: Sensitivity Analysis of Input Parameters on Fetal ECG Morphology

Ludovica Cicci1, Sian Chivers2, Antonio de Marvao3, Gernot Plank4, John Simpson2, Catherine Williamson1, Steven Niederer1
1Imperial College London, 2Evelina London Children's Hospital, 3King's College London, 4Medical University of Graz


Abstract

Aims: Non-invasive fetal electrocardiography (fECG) is a promising clinical tool yet extracting and interpreting the fetal signal remains challenging. This study performed sensitivity analysis (SA) of a maternal-fetal ventricular electrophysiology (EP) model to identify which pregnancy-related parameters most strongly influence fECG morphology.

Methods: The anatomical model was reconstructed from one maternal-fetal MRI at 38 gestational weeks. Ventricular activity was simulated for 5 seconds using the pseudo-bidomain formulation, coupling the adult ToR-ORd-dynCl and fetal-adjusted ten Tusscher-Panfilov ionic models (maternal/fetal heart rate of 60/134 bpm) with a fascicular-based model for the His-Purkinje system (HPS). Abdominal signals were recorded at four electrode locations and the fECG was extracted using independent component analysis (namely, multi-channel FastICA). SA considered 29 inputs – fetal myocardial conductivities, fetal ionic conductances, fetal HPS root locations, and the conductivity of the amniotic fluid, blood pools, maternal organs, and subcutaneous fat – varied independently (±50% or within physiological bounds). Sensitivities were quantified from finite-difference slopes between bound simulations, and normalised indices ranked parameter influence across all seven outputs considered.

Results: Fetal myocardial and blood pool conductivities were the primary determinants of QRS amplitude and duration. Ionic conductances, particularly the inward rectifier potassium current, dominated T-wave amplitude and QTc. Sodium channel conductance was the strongest driver of overall morphology changes, accounting for 48% and 68% of total normalised sensitivity pre- and post-extraction, respectively. Among fetal HPS parameters, only the apico-basal coordinates had non-negligible effects.

Conclusion: This study identified 18 of 29 parameters with negligible influence on the fECG, which can therefore be fixed, reducing model complexity for calibration. This is a necessary step toward patient-specific calibration from clinically acquired fECG, as only a limited number of parameters can realistically be constrained. Generalisability across gestational age, fetal position and orientation will require a larger virtual cohort.