Limitations of the study and future directions 203 CHAPTER 12 LIMITATIONS OF THE STUDY AND FUTURE DIRECTIONS Limitations of the study and future directions 204 Clinical applications In the first half of the thesis, the foetal electrocardiogram (ECG) was recorded by a non-invasive technique via maternal abdominal electrodes, with success in elimination of noise and maternal ECG With this technique, the normal range of foetal cardiac time intervals (P wave, PR interval, QRS complex, QT interval, QTc and T wave) of normal healthy foetuses from 18 to 41 gestational weeks was established This study demonstrates that with advancements in computing technology, non-invasive techniques may provide reliable information on foetal ECG from early gestation to term In addition, the successful recording of fECG and measurement of fECG parameters during the 1st stage of labour using abdominal electrodes suggest an alternative method to the invasive scalp fECG currently in use for intrapartum foetal monitoring The results on foetal cardiac time intervals may serve as references for clinical use as a comparison to differentiate between normal and abnormal cardiac time intervals In the second half of the thesis, the heart rate variability (HRV) of normal foetuses was evaluated in temporal and spectral domains using a newly-developed system (F-EXTRACT) as well as a commercial (Nevrokard) HRV system The results demonstrated a shift of sympathovagal balance from sympathetic predominance in early gestation (at around 20 weeks of gestation) to parasympathetic predominance towards term (at around 37 weeks of gestation), which coincides with the chronological development of the sympathetic and parasympathetic nervous systems This study shows the use of spectral analysis of foetal HRV as an indirect indication Limitations of the study and future directions 205 of the development of foetal cardiac autonomic activity from 18 weeks of gestation to term Notably this is a longitudinal study of a cohort of healthy foetuses The comparison of HRV results between F-EXTRACT and Nevrokard HRV systems indicates that with the exception of foetal heart rate and mNN, the other HRV variables generated by the systems did not agree well The amount of bias between the systems were different for each HRV variable measured, but in general, the Nevrokard system produced measurements that were approximately twice the magnitude of those measured by the F-EXTRACT system The disparity between the systems was related to their system-dependent algorithms in the processing of non-sinus beats This raises important points: firstly, different HRV systems may generate very different results that should be interpreted with caution Secondly, the use of programs that lack the means to remove artifacts and ectopic beats may introduce errors that seriously affect the analysis of HRV The HRV systems manufactured for analyzing adult HRV may not be suitable for foetal HRV analysis It may be more reliable to use a HRV system that is specifically developed for foetal HRV analysis, such as F-EXTRACT, which has an inbuilt algorithm that allows the deletion and linear interpolation of erroneous beats commonly present in foetal RR-intervals Limitations of the study and future directions 206 Limitations of study/ equipment Although this study contributes valuable information to the field of non- invasive foetal ECG and to the understanding of the development of the foetal autonomic nervous system via measurement of heart rate variability, it has several limitations While it is useful to know the reproducibility of the foetal cardiac time intervals, this was not evaluated in this study However, in of the patients in which foetal ECG was recorded twice on the same day, the coefficients of variation (CV= SD/Mean x 100) for P wave duration, PR interval, QRS duration, QT interval, QTc interval, and T wave duration were 5.1%, 3.3%, 2.9%, 2.3%, 2.0% and 4.3%, respectively Reproducibility of abdominal foetal ECG techniques has not been evaluated so far However, the reproducibility of 12-lead ECG has been evaluated by 10 repeated recordings obtained from adults in the supine position, and the CV for PR interval, QRS duration, QT interval and QTc interval were observed to be 2.5%, 2.9%, 1.5% and 1.4%, respectively (Gang Y et al., 1998) Thus, the reproducibility of foetal cardiac time intervals as observed from the repeated fECG recordings was comparable (p>0.05) to that of adult 12-lead ECG High reproducibility and interobserver reliability have also been observed in foetal cardiac time intervals obtained from foetal magnetocardiography (fMCG) (Van Leeuwen P et al., 2004) Secondly, there were logistic problems in conducting this longitudinal study during antenatal visits There was some loss of data due to the following reasons: (1) Limitations of the study and future directions 207 Four patients were lost to follow-up as they switched to other hospitals while two patients went overseas for delivery; (2) three pregnancies ended in miscarriages; (3) some patients refused foetal ECG recording during certain antenatal visits for personal reasons Various technical problems related to abdominal foetal ECG were noted As mentioned in earlier chapters, a relatively low signal-to-noise ratio of the foetal ECG was observed from 27 to 32 gestational weeks, a common finding in abdominal foetal ECG due to the thick layer of vernix present on the foetal surface during this gestational period This resulted in some loss of data during this period of time Unlike adults who are able to keep still during short-term resting ECG recordings, foetal movements are totally beyond the control of laboratory settings Sudden muscular movements cause distortions in the ECG signal and wanderings in the baseline, which may in turn introduce errors in RR-interval measurements that need to be removed by strict artifact-correction algorithms for accurate HRV analysis However, on the other hand, foetal movements are indicative of a healthy foetus with intact neural activity, and it is reassuring to obtain a CTG that shows accelerations of at least 15 beats per minute for 15 seconds or longer that often occur with foetal movements Thus, by including foetal movements in the HRV analysis, it may better reflect the true autonomic tone of the healthy foetus Limitations of the study and future directions 208 Lastly, during foetal ECG recording, Doppler ultrasound was not simultaneously applied to monitor the foetal breathing or movements It was thus not possible to associate particular bands of spectral power to foetal respiratory or physical activity Recommendations for future studies As this study has shown promising results in prenatal determination of foetal ECG, it will be useful to conduct abdominal foetal ECG recordings in foetuses with cardiac structural and electrophysiological defects as well as other conditions such intrauterine growth restriction (IUGR) where foetal cardiac development may be affected (van Leeuwen P et al., 2001; Pardi G et al., 1986) The clinical application of abdominal foetal ECG in intrapartum monitoring of foetal hypoxia can also be explored in clinical trials Since this is a non-invasive technique as opposed to the invasive foetal scalp ECG monitoring that is currently being performed during labour, abdominal foetal ECG has the potential to become a new clinical tool in the field of foetal monitoring both during the antenatal and intrapartum periods New signal processing methods can be employed to overcome the problem of low signal-to-noise ratio of the abdominal foetal ECG during the period of 27 to 32 gestational weeks The use of multiple electrodes and recording channels (Taylor MJ et al., 2003) may be a more accurate and sensitive way of capturing ECG signals However, the number of electrodes used must provide adequate maternal comfort and practicality when considering for routine clinical application Limitations 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9(2): 166-75 437 Zion AS, Bond V, Adams RG, Williams D, Fullilove RE, Sloan RP, Bartels MN, Downey JA, De Meersman RE Low arterial compliance in young African-American males Am J Physiol Heart Circ Physiol 2003; (2): H45762 250 Appendix A APPENDIX A 251 Appendix A This appendix shows additional figures of averaged foetal ECG complexes, similar to those shown in Chapter Po Po Pt Pt Qo Qo St St To To Tt Tt 252 Appendix A Po Pt Po Po Qo Pt Qo Pt Qo St St St To To Tt Tt To Tt 253 Appendix A Po Pt Pt Po Po Qo Pt St Qo Qo To St St Tt To Tt To Appendix Figure 1: Averaged foetal ECG complexes of different foetuses Subscripts o and t = onset and termination points of P, QRS and T waves Tt 254 Appendix A Po Pt St Qo To Tt (a) Po Pt Qo St To (b) Qo St (c) Tt 255 Appendix A Po Pt Qo St To Tt (d) Po Pt Qo St To Tt (e) Appendix Figure 2: Averaged foetal ECG complexes of one foetus at different gestational stages- (a) 22 weeks (b) 27 weeks (c) 29 weeks (d) 35 weeks and (e) 39 weeks Subscripts o and t = onset and termination points of P, QRS and T waves ... valuable information to the field of non- invasive foetal ECG and to the understanding of the development of the foetal autonomic nervous system via measurement of heart rate variability, it has... Influence of gestational age and foetal heart rate on the foetal mechanical PR interval J Matern Foetal Neonatal Med 2004; 15( 5): 303-3 05 47 Bonnemeier H, Richardt G, Potratz J, Wiegand UK, Brandes... rate variability in healthy subjects: effect of age and the derivation of normal ranges for tests of autonomic function Br Heart J 1986; 55 (4): 348 -54 277 O''Leary DS Autonomic mechanisms of muscle