# Intelligent Neonatal Sepsis Early Diagnosis System for Very Low Birth Weight Infants
## 2 The HeRO Score and the Risk of Incorrect Sepsis Diagnosis  
This section describes and discusses how the HeRO duet manages to detect the early signs of sepsis, with the aim to understand better the aspects related to the false positivity/negativity of the HeRO score. The HeRO device can analyse the infant's heart rate variability without direct contact. It acquires the heart rate data from a multi-parameter monitor connected to the infant via electrodes.  
In the literature, it is described how a reduced variability and transient decelerations of the heart rate (HR) can be present in the hours or days preceding the diagnosis of sepsis [11]. In fact, sepsis involves the proliferation of pathogens that can depress the variability of the heart rate through both direct stimulation of the vagus nerve and the release of cytokines [14; 15]. The mechanism underlying the direct vagus nerve stimulation by pathogens is not yet well known. A direct stimulation of neuronal receptors located either peripherally or at the ganglion level is hypothesised [14]. In addition, the mechanism by which cytokines (in particular interleukin 6) induce a reduced variability of HR even in the hours preceding the onset of sepsis to date is not yet clear. Interleukin 6 is supposed to induce electrophysiological changes in the myocarditis, which lead to an electrical remodelling of the heart, which could predispose to corrected QT (QIC) interval prolongation and ventricular arrhythmia. Such a mechanism would imply a compromise of the potassium channels and an enhancement of the function of the calcium channels of the cardiomyocytes with consequent prolongation of the duration of the membrane action potential of the myocarditis [16; 17].  
The reduced heart rate variability induced early in the initial stages of sepsis, often when the inflammation indexes are negative and the symptoms fade, is recorded by HeRO, which, by analysing the changes in the HR, is able to predict in advance (in the previous 24 h or even earlier) the onset of the infection episode [18]. However, there are some pathophysiological conditions beyond sepsis that can involve the release of cytokines or the stimulation of the vagus nerve and that can affect the HeRO score outcome [15]. The knowledge of these conditions can help clinicians to orient themselves by attributing a correct meaning to the HeRO score. However, the decision whether to treat the neonate with antibiotic therapy gets more difficult if considering only the HeRO score. In fact, all newborns with a positive score would be treated with antibiotic therapy with all the risks that this entails in such small infants. As an example, the results of a study conducted on 3003 VLBW neonates were reported in [PERSON] et al. [19]. The authors of this study considered two groups of neonates: one group was treated with the knowledge of the HeRO score and the second one without access to the HeRO monitor. The results showed that in the first group of infants, there was a 22% drop in mortality, which rose to 26% if we consider only ELBW. However, in the first group of newborns, an increase in deafness was observed, which could perhaps be correlated with the greater number of days of antibiotic therapy [20].