["The Journal of Physiology, Volume 604, Issue 13, Page 5276-5295, 1 July 2026. ", "\nAbstract figure legend Depolarization and repolarization duration analysis was conducted in preadolescent groups with IUGR and controls using a 12‐lead ECG. Principal component analysis was applied over the 12‐lead ECGs to generate spatially transformed leads better suited for robust ECG fiducial points detection. Measurements on these transformed leads revealed a 4 ms increase in QRS complex duration (QRS d$_d$) and a 2 ms increase in the Tpeak‐to‐end interval (T pe$_{pe}$) in IUGR subjects compared to controls. To investigate the rational for these findings, computational electrophysiological simulations were developed, generating globular models derived from a reference control model. Key geometrical parameter associated with IUGR, including apex‐base length, basal diameter, wall thickness and ventricular tissue volume, were modified to assess their impact on depolarization and repolarization intervals. The in silico IUGR simulations are congruent with the observed increases in QRS d$_d$ and T pe$_{pe}$, highlighting the significant influence of cardiac remodeling associated with IUGR on depolarization. On the contrary repolarization changes were not directly correlated with variations in wall thickness, underscoring a more complex relationship than the considered anatomical remodeling in IUGR‐affected hearts to explain the observed IUGR electrical activity.\n\n\n\n\n\n\n\n\n\nAbstract\nAnatomical 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 d$_d$) and a 2‐ms increase in the T peak‐to‐end interval (T pe$_{pe}$) 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 (W$\\mathcal {W}$) and ventricular tissue volume, to assess their impact on depolarization and repolarization intervals. In silico PCA leads showed increased QRS d$_d$, QRS amplitude and T pe$_{pe}$ in globular models, consistent with clinical data. Despite the QRS d$_d$ increase, the QT interval increases but is not linearly related to the W$\\mathcal {W}$ change. These findings suggest that cardiac re‐modelling primarily influences the depolarization cycle, notably QRS d$_d$, while repolarization intervals increase but are not directly related to the W$\\mathcal {W}$ 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.\n\n\n\n\n\n\n\n\n\nKey points\nIntrauterine growth restriction (IUGR) is associated with long‐term cardiovascular complications, including changes in the heart's electrical activity.\nCardiac re‐modelling as a consequence of IUGR can lead to electrical changes that can be assessed through an electrocardiogram (ECG).\nThis 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.\nComputational 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.\nBoth 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.\n\n\n"]