Electrophysiological characterization of pre‐adolescents born with intrauterine growth restriction: insights from clinical and computational data

Anatomical changes associated with intra-uterine growth restriction (IUGR) have been observed in different age groups and linked to cardiovascular complications. This study analysed the electrocardiogram (ECG) in pre-adolescents with severe IUGR, comparing QRS complex and T-wave biomarkers with controls. Computer simulations explored links between anatomical re-modelling and ECG biomarkers, providing insights into the potential cardiovascular risk associated with IUGR-induced re-modelling. Clinical recordings were analysed using principal component analysis (PCA) to compute spatially transformed leads, enhancing QRS complex and T-wave delineation for depolarization and repolarization assessment. Transformed leads analysis revealed a 4-ms increase in QRS complex duration (QRS <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:msub><mml:mrow></mml:mrow> <mml:mi>d</mml:mi></mml:msub> <mml:annotation>$_d$</mml:annotation></mml:semantics> </mml:math> ) and a 2-ms increase in the T peak-to-end interval (T <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:msub><mml:mrow></mml:mrow> <mml:mrow><mml:mi>p</mml:mi> <mml:mi>e</mml:mi></mml:mrow> </mml:msub> <mml:annotation>$_{pe}$</mml:annotation></mml:semantics> </mml:math> ) in IUGR subjects compared to controls. We conducted electrophysiological in silico simulations using anatomical models based on clinical IUGR data. These models, derived from a reference control, incorporated key geometric changes associated with IUGR, the apex-base length, basal diameter, wall thickness ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:semantics><mml:mi>W</mml:mi> <mml:annotation>$\mathcal {W}$</mml:annotation></mml:semantics> </mml:math> ) and ventricular tissue volume, to assess their impact on depolarization and repolarization intervals. In silico PCA leads showed increased QRS <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:msub><mml:mrow></mml:mrow> <mml:mi>d</mml:mi></mml:msub> <mml:annotation>$_d$</mml:annotation></mml:semantics> </mml:math> , QRS amplitude and T <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:msub><mml:mrow></mml:mrow> <mml:mrow><mml:mi>p</mml:mi> <mml:mi>e</mml:mi></mml:mrow> </mml:msub> <mml:annotation>$_{pe}$</mml:annotation></mml:semantics> </mml:math> in globular models, consistent with clinical data. Despite the QRS <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:msub><mml:mrow></mml:mrow> <mml:mi>d</mml:mi></mml:msub> <mml:annotation>$_d$</mml:annotation></mml:semantics> </mml:math> increase, the QT interval increases but is not linearly related to the <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:semantics><mml:mi>W</mml:mi> <mml:annotation>$\mathcal {W}$</mml:annotation></mml:semantics> </mml:math> change. These findings suggest that cardiac re-modelling primarily influences the depolarization cycle, notably QRS <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:msub><mml:mrow></mml:mrow> <mml:mi>d</mml:mi></mml:msub> <mml:annotation>$_d$</mml:annotation></mml:semantics> </mml:math> , while repolarization intervals increase but are not directly related to the <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:semantics><mml:mi>W</mml:mi> <mml:annotation>$\mathcal {W}$</mml:annotation></mml:semantics> </mml:math> increase. The study highlights the impact of geometric and volumetric changes in IUGR-related cardiac re-modelling, also emphasizing the need for further research on electrophysiological re-modelling and its effects on cardiac function. KEY POINTS: Intrauterine growth restriction (IUGR) is associated with long-term cardiovascular complications, including changes in the heart's electrical activity. Cardiac re-modelling as a consequence of IUGR can lead to electrical changes that can be assessed through an electrocardiogram (ECG). This study analysed ECGs in pre-adolescents with severe IUGR, revealing prolonged depolarization duration (QRS complex duration) and repolarization (T peak-to-end interval) compared to healthy controls. Computational models incorporating clinically observed anatomical changes, such as increased ventricular wall thickness and altered heart geometry, were used to assess their impact on electrical function, and determine whether these structural modifications contribute to the ECG alterations observed in clinical data. Both clinical data analysis and simulation findings showed significant shifts in depolarization-based biomarkers and smaller, and non-linear changes to geometrical changes, in repolarization intervals, highlighting how cardiac re-modelling in IUGR affects heart function as measured by ECG.