Why -aVF can be used in STAN as a proxy for scalp electrode-derived signal; reply to comments by Kjellmer et al

The conclusion of our recent paper that performance of the STAN device in clinical practice is potentially limited by high false-negative and high false-positive STAN-event rates and loss of ST waveform assessment capacity during severe hypoxemia, evoked comments by Kjellmer, Lindecrantz and Rosén. These comments can be summarized as follows: 1) STAN analysis is based on a unipolar lead but the authors used a negative aVF lead, and they did not validate this methodology; 2) The fetuses used in the study were too young to display the signals that the authors were trying to detect. In response to these comments we now provide both a theoretical and an experimental underpinning of our approach. In an in vivo experiment in human we placed several electrodes over the head (simulating different places of a scalp electrode), simultaneously recorded Einthoven lead I and II, and constructed -aVF from these two frontal leads. Irrespective of scalp electrode placement, the correlation between any of unipolar scalp electrode-derived signals and constructed-aVF was excellent (≥ 0.92). In response to the second comment we refer to a study which demonstrated that umbilical cord occlusion resulted in rapid increase in T/QRS ratio that coincided with initial hypertension and bradycardia at all gestational ages which were tested from 0.6-0.8 gestation. The animals of our study were in this gestational range and, hence, our experimental setup can be used to assess STAN's quality to detect fetal hypoxia. In conclusion, we have clearly demonstrated the appropriateness of using-aVF as a proxy for a scalp electrode-derived signal in STAN in these preterm lambs. Investigation why STAN could not detect relevant ST-changes and instead produced erroneous alarms in our experimental setup is hampered by the fact that the exact STAN algorithm (signal processing and analysis) is not in the public domain.