NUOVI METODI DI ANALISI DELL'ELETTROCARDIOGRAMMA FETALE ACQUISITO PER VIA TRANS-ADDOMINALE

NEW METHODS OF ANALYSIS OF TRANS-ABDOMINALLY ACQUIRED FETAL ELECTROCARDIOGRAM Background. Our group was one of the first to apply Phase Rectified Signal Averaging (PRSA) analysis in obstetric field by analyzing fetal ECG acquired non-invasively by trans-abdominal ECG. PRSA is a new method that emphasizes quasi-periodic oscillations masked by unrelated non-stationary elements in the signal. It is robust to the non-stationarities, noise and artifacts, and, thus, this method is superior to standard methods of heart rate (HR) evaluation such as power spectral analysis. The PRSA series can be employed to quantify the “average acceleration capacity” (AAC) and “average deceleration capacity” (ADC) of the signal. When applied to HR, AAC and ADC represent an indirect integrated quantification of the activities of the sympathetic and parasympathetic autonomic systems. In a previous study, we explored the correlation between AAC and ADC and acid-base status in an in-vivo pregnant sheep model at term exposed to acute hypoxia (progressive umbilical cord occlusions)[Submitted for publication]. We also evaluated specific PRSA parameters (in particular the T value that determines the frequencies over which AAC and ADC are computed). In conclusion, our study showed the evidence of autonomic nervous system (ANS) activation in sheep fetus exposed to acute hypoxia through a computation of ACC and ADC of FHR, and proved a correlation with acid-base status biomarkers (T 2÷6 best enhanced differences among different grades of hypoxic severity, and the correlation between AAC/ADC and acid-base biomarkers was highest in that interval). Based on our preliminary results we have hypothesized that AAC and ADC might reflect more closely the homeostasis of the ANS than short-term variation (STV), and thus might be used in the monitoring of the fetal wellbeing in fetuses with intrauterine growth restriction (IUGR). Indeed, IUGR fetuses are exposed to chronic nutrient deprivation and hypoxemia that can alter ANS regulation of cardio-vascular system, and, thus, affect FHR variability. Aim of the study The aim of the study was to investigate AAC and ADC computed by PRSA analysis on fetal ECG obtained by trans-abdominal ECG in preterm IUGR (<34 weeks) fetuses, and to explore the influence of different T values on AAC and ADC computation in relation to IUGR. Relationship of AAC and ADC with STV and Doppler velocimetry parameters of utero-placental and feto-placental districts has been also evaluated. Material and methods This is a prospective longitudinal single center case-control study. Preterm IUGR (<34 weeks), n=22, were recruited at admission and monitored on daily bases until delivery by trans-abdominal fetal ECG (Monica AN24, Monica Healthcare, UK). The results of fetal ECG were blinded to the management clinicians and midwifes. Computerized CTG, Doppler velocimetry evaluation of utero-placental-fetal districts, and timing of delivery were performed according to standard hospital protocol. A control group was made of uncomplicated pregnancies matched for gestational age recruited at low risk antenatal clinic (n=37). Fetal ECG was analyzed off-line by PRSA method, and AAC and ADC were computed for T values in a range 1÷50. Differences between IUGR and healthy fetuses matched for gestational age were evaluated. In order to account for gestational age influence on ANS maturation, we divided the cohort in two sub-groups: 26-<30 weeks, and ≥30-<34 weeks, respectively. Correlation with Doppler velocimetry parameters was evaluated. Principal findings of the study 1) In the 26-<30 weeks group, except for T=1, the AAC and ADC were significantly lower in IUGR fetuses than in matched for gestational age healthy fetuses (for T values 2÷50); 2) In the ≥30-<34 weeks group, except for T 1÷3, the AAC and ADC were significantly lower in IUGR fetuses than in matched for gestational age healthy fetuses (for T values 4÷50); 3) The amplitude of the difference was higher for very early IUGR group (26-<30 weeks) than in early IUGR group (≥30-<34 weeks); 4) STV computed on fetal ECG R-R intervals from trans-abdominal ECG was lower in IUGR fetuses than in matched for gestational age healthy fetuses in 26-<30 weeks group; 5) There were no differences in STV in ≥30-<34 weeks group; 6) There was no correlation between AAC/ADC and uterine arteries mean PI; 7) When evaluating ADC correlation with other districts, there was: a significant negative correlation with umbilical artery PI, a significant positive correlation with middle cerebral artery PI, and significant positive correlation with cerebro/placental ratio, respectively; the same vas true for AAC but in opposite direction; and 8) The correlation was found to be significant in all districts in a narrow range of T values, 1÷6; 9) When considering the Doppler velocimetry districts as categorical variables (normal, pathological), there was a clear trend of lower values of AAC and ADC as Doppler parameters deteriorated, but this difference did not reach statistical significance. Conclusions In conclusion, our study showed the evidences of an ANS “functional reduction” in IUGR fetuses through a computation of ACC and ADC of FHR in comparison to healthy matched for gestational age fetuses. This was particularly true for very early IUGR group (<30 weeks). Moreover, we proved a correlation with Doppler velocimetry parameters of feto-placental districts in the same T interval in which we found the highest correlation between AAC and ADC with acid-base biomarkers (data from a previous study). Thus, we hypothesize that AAC and ADC might have a role in the management of IUGR fetuses and we proposes a choice of parameters for the computation of PRSA. Those findings put the solid ground for future clinical studies.