Assessment and quantification of foetal electrocardiography and heart rate variability of normal foetuses from early to late gestational periods 5

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
1 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 1
st
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 2 systems did not agree well. The amount of bias
between the 2 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 2 systems was related to their system-dependent algorithms in the
processing of non-sinus beats.

This raises 2 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
2 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 2 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 2 repeated fECG recordings was
comparable (p>0.05) to that of adult 12-lead ECG. High reproducibility and inter-
observer 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.

3 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 of the study and future directions

209
While fMCG has shown great potential in recording the electrical activity of
the foetal heart, resulting in signals that are not affected by the vernix, it has
disadvantages of size, cost and complexity of instrumentation required. Compared to
equipment for fECG, the fMCG equipment is bulky, cumbersome and expensive, and
requires prior ultrasound location of the foetal heart. A magnetically-shielded room is
needed to perform the recording and skilled personnel are required to handle the
liquid helium which is used as a coolant. In addition, ambulatory monitoring is not

possible with fMCG and portable versions are not likely to be available in the near
future (Peters M et al., 2001). Hence, it is worthwhile to continue to pursue and
perfect the technique of abdominal fECG given the benefits shown in this study and
in other studies.
References

210












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