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 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 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 210 References REFERENCES References 211 Abboud S, Barkai G, Mashiach S, Sadeh D Quantification of the foetal electrocardiogram using averaging technique Comput Biol Med 1990; 20(3): 147-55 Abboud S, Alaluf A, Einav S, Sadeh D Real-time abdominal foetal ECG recording using a hardware correlator Comput Biol Med 1992; 22(5): 325-35 Abe K, Hamada H, Chen YJ, Abe A, Watanabe H, Fujiki Y, Yoshikawa H, Murakami T, Horigome H Successful management of supraventricular tachycardia in a fetus using fetal magnetocardiography Fetal Diagn Ther 2005; 20(5): 459-62 Agelink MW, Malessa R, Weisser U, Lemmer W, Zeit T, Majewski T, Klieser E Alcoholism, peripheral neuropathy (PNP) and cardiovascular autonomic neuropathy (CAN) J Neurol Sci 1998; 161(2): 135-42 Agelink MW, Malessa R, Baumann B, Majewski T, Akila F, Zeit T, Ziegler D Standardized tests of heart rate variability: normal ranges obtained from 309 healthy humans, and effects of age, gender, and heart rate Clin Auton Res 2001; 11(2): 99-108 Akselrod S, Gordon D, Ubel FA, Shannon DC, Berger AC, Cohen RJ Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control Science 1981; 213(4504): 220-2 Alcalay M, Izraeli S, Wallach-Kapon R, Tochner Z, Benjamini Y, Akselrod S Paradoxical pharmacodynamic effect of atropine on parasympathetic control: a study by spectral analysis of heart rate fluctuations Clin Pharmacol Ther 1992; 52(5): 518-27 Ali-Melkkila T, Kaila T, Antila K, Halkola L, Iisalo E Effects of glycopyrrolate and atropine on heart rate variability Acta Anaesthesiol Scand 1991; 35(5): 436-41 Allen MC, Donohue PK, Dusman AE The limit of viability neonatal outcome of infants born at 22 to 25 weeks' gestation N Engl J Med 1993; 329(22): 1597-601 10 Amer-Wahlin I, Hellsten C, Noren H, Hagberg H, Herbst A, Kjellmer I, Lilja H, Lindoff C, Mansson M, Martensson L, Olofsson P, Sundstrom A, Marsal K Cardiotocography only versus cardiotocography plus ST analysis of foetal electrocardiogram for intrapartum foetal monitoring: a Swedish randomised controlled trial Lancet 2001; 358(9281): 534-8 11 Amer-Wahlin I, Bordahl P, Eikeland T, Hellsten C, Noren H, Sornes T, Rosen KG ST analysis of the foetal electrocardiogram during labor: Nordic References 212 observational multicenter study J Matern Foetal Neonatal Med 2002; 12(4): 260-6 12 Amer-Wahlin I, Ingemarsson I, Marsal K, Herbst A Foetal heart rate patterns and ECG ST segment changes preceding metabolic acidaemia at birth BJOG 2005; 112(2): 160-5 13 Agelink MW, Malessa R, Weisser U, Lemmer W, Zeit T, Majewski T, Klieser E Alcoholism, peripheral neuropathy (PNP) and cardiovascular autonomic neuropathy (CAN) J Neurol Sci 1998; 161(2): 135-42 14 Akselrod S, Gordon D, Ubel FA, Shannon DC, Berger AC, Cohen RJ Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control Science 1981; 213(4504): 220-2 15 Akselrod S, Gordon D, Madwed JB, Snidman NC, Shannon DC, Cohen RJ Hemodynamic regulation: investigation by spectral analysis Am J Physiol 1985; 249(4 Pt 2): H867-75 16 Akselrod S, Karin J, Hirsch M Computerized detection of foetal ECG from maternal abdominal signal In: Computers in Cardiology 1987; Washington, USA IEEE Computer Society Press, Los Alamitos, CA, 1988; 261-4 17 Antelmi I, de Paula RS, Shinzato AR, Peres CA, Mansur AJ, Grupi CJ Influence of age, gender, body mass index, and functional capacity on heart rate variability in a cohort of subjects without heart disease Am J Cardiol 2004; 93(3): 381-5 18 Antonucci MC, Pitman MC, Eid T, Steer PJ, Genevier ES Simultaneous monitoring of head-to-cervix forces, intrauterine pressure and cervical dilatation during labour Med Eng Phys 1997; 19(4): 317-26 19 Appel ML, Berger RD, Saul JP, Smith JM, Cohen RJ Beat to beat variability in cardiovascular variables: noise or music? J Am Coll Cardiol 1989; 14(5): 1139-48 20 Arai Y, Saul JP, Albrecht P, Hartley LH, Lilly LS, Cohen RJ, Colucci WS Modulation of cardiac autonomic activity during and immediately after exercise Am J Physiol 1989; 256(1 Pt 2): H132-41 21 Arduini D, Rizzo G, Giorlandino C, Valensise H, Dell'Acqua S, Romanini C The development of fetal behavioural states: a longitudinal study Prenat Diagn 1986; 6(2): 117-24 References 241 340 Saul JP, Albrecht P, Berger RD, Cohen RJ Analysis of long term heart rate variability: methods, 1/f scaling and implications Comput Cardiol 1988; 14: 419-22 341 Sayers BM Analysis of heart rate variability Ergonomics 1973; 16(1): 1732 342 Schaffer MS, Trippel DL, Buckles DS, Young RH, Dolan PL, Gillette PC The longitudinal time course of QTc in early infancy Preliminary results of a prospective sudden infant death syndrome surveillance program J Perinatol 1991; 11(1): 57-62 343 Schechtman VL, Raetz SL, Harper RK, Garfinkel A, Wilson AJ, Southall DP, Harper RM Dynamic analysis of cardiac R-R intervals in normal infants and in infants who subsequently succumbed to the sudden infant death syndrome Pediatr Res 1992; 31: 606–12 344 Schipke JD, Pelzer M, Arnold G Effect of respiration rate on short-term heart rate variability J Clin Basic Cardiol 1999; 2: 92-5 345 Schneider U, Haueisen J, Loeff M, Bondarenko N, Schleussner E Prenatal diagnosis of a long QT syndrome by fetal magnetocardiography in an unshielded bedside environment Prenat Diagn 2005; 25(8): 704-8 346 Schroeder EB, Chambless LE, Liao D, Prineas RJ, Evans GW, Rosamond WD, Heiss G Diabetes, glucose, insulin, and heart rate variability: the Atherosclerosis Risk in Communities (ARIC) study Diabetes Care 2005; 28(3): 668-74 347 Schuit AJ, Van Amelsvoort LG, Verheij TC, Rijneke RD, Maan AC, Swenne CA, Schouten EG Exercise training and heart rate variability in older people Med Sci Sports Exerc 1999; 31(6): 816-21 348 Schwartz JB, Gibb WJ, Tran T Aging effects on heart rate variation J Gerontol 1991 ; 46(3): M99-106 349 Schwartz PJ, Pagani M, Lombardi F, Malliani A, Brown AM A cardiocardiac sympathovagal reflex in the cat Circ Res 1973; 32(2): 215-20 350 Schwartz PJ, Montemerlo M, Facchini M, Salice P, Rosti D, Poggio G, Giorgetti R The QT interval throughout the first months of life: a prospective study Circulation 1982; 66(3): 496-501 351 Schwartz PJ, Stramba-Badiale M, Segantini A, Austoni P, Bosi G, Giorgetti R, Grancini F, Marni ED, Perticone F, Rosti D, Salice P Prolongation of the References 242 QT interval and the sudden infant death syndrome N Engl J Med 1998; 338(24): 1709-14 352 Schwartz PJ, Priori SG, Dumaine R, Napolitano C, Antzelevitch C, StrambaBadiale M, Richard TA, Berti MR, Bloise R A molecular link between the sudden infant death syndrome and the long-QT syndrome N Engl J Med 2000; 343(4): 262-7 353 Schwartz PJ, Garson A Jr, Paul T, Stramba-Badiale M, Vetter VL, Wren C; European Society of Cardiology Guidelines for the interpretation of the neonatal electrocardiogram A task force of the European Society of Cardiology Eur Heart J 2002; 23(17): 1329-44 354 Schwartz PJ Stillbirths, sudden infant deaths, and long-QT syndrome: puzzle or mosaic, the pieces of the Jigsaw are being fitted together Circulation 2004; 109(24): 2930-2 355 Semrad B, Fiser B, Honzikova N Ageing and the cardiac autonomic status In: Malik M, ed Clinical guide to cardiac autonomic tests Netherlands: Kluwer Academic Publishers; 1998: 285-300 356 Shakespeare SA, Crowe JA, Hayes-Gill BR, Bhogal K, James DK The information content of Doppler ultrasound signals from the foetal heart Med Biol Eng Comput 200; 39(6): 619-26 357 Shannon DC, Carley DW, Benson H Aging of modulation of heart rate Am J Physiol 1987; 253(4 Pt 2): H874-7 358 Shapiro I, Degani S, Leibovitz Z, Ohel G, Tal Y, Abinader EG Foetal cardiac measurements derived by transvaginal and transabdominal cross-sectional echocardiography from 14 weeks of gestation to term Ultrasound Obstet Gynecol 1998; 12(6): 404-18 359 Siedner S, Kruger M, Schroeter M, Metzler D, Roell W, Fleischmann BK, Hescheler J, Pfitzer G, Stehle R Developmental changes in contractility and sarcomeric proteins from the early embryonic to the adult stage in the mouse heart J Physiol 2003; 548(Pt 2): 493-505 360 Siira SM, Ojala TH, Vahlberg TJ, Jalonen JO, Valimaki IA, Rosen KG, Ekholm EM Marked fetal acidosis and specific changes in power spectrum analysis of fetal heart rate variability recorded during the last hour of labour BJOG 2005; 112(4): 418-23 361 Simpson DM, Wicks R Spectral analysis of heart rate indicates reduced baroreceptor-related heart rate variability in elderly persons J Gerontol 1988; 43(1): M21-4 References 243 362 Singh JP, Larson MG, Tsuji H, Evans JC, O'Donnell CJ, Levy D Reduced heart rate variability and new-onset hypertension: insights into pathogenesis of hypertension: the Framingham Heart Study Hypertension 1998; 32(2): 293-7 363 Sloan RP, Shapiro PA, Bagiella E, Boni SM, Paik M, Bigger JT Jr, Steinman RC, Gorman JM Effect of mental stress throughout the day on cardiac autonomic control Biol Psychol 1994; 37(2): 89-99 364 Southern EM Foetal anoxia and its possible relation to changes in the prenatal foetal electrocardiogram Am J Obstet Gynecol 1957; 73(2): 233-47 365 Spencer JA, Badawi N, Burton P, Keogh J, Pemberton P, Stanley F The intrapartum CTG prior to neonatal encephalopathy at term: a case-control study Br J Obstet Gynaecol 1997; 104(1): 25-8 366 Spencer JAD, Samson I Suction-contact foetal scalp electrode Br J Obstet Gynaecol 1998; 105(Suppl 17): 83 367 Srinivasan K, Sucharita S, Vaz M Effect of standing on short term heart rate variability across age Clin Physiol Funct Imaging 2002; 22(6): 404-8 368 Stahle A, Nordlander R, Bergfeldt L Aerobic group training improves exercise capacity and heart rate variability in elderly patients with a recent coronary event A randomized controlled study Eur Heart J 1999; 20(22): 1638-46 369 Stein PK, Domitrovich PP, Huikuri HV, Kleiger RE; Cast Investigators Traditional and nonlinear heart rate variability are each independently associated with mortality after myocardial infarction J Cardiovasc Electrophysiol 2005; 16(1): 13-20 370 Steptoe A, Fieldman G, Evans O, Perry L Cardiovascular risk and responsivity to mental stress: the influence of age, gender and risk factors J Cardiovasc Risk 1996; 3(1): 83-93 371 Stinstra J, Golbach E, Van Leeuwen P, Lange S, Menendez T, Moshage W, Schleussner E, Kaehler C, Horigome H, Shigemitsu S, Peters MJ Multicentre study of foetal cardiac time intervals using magnetocardiography BJOG 2002; 109(11): 1235-43 372 Storck N, Ericson M, Lindblad L, Jensen-Urstad M Automatic computerized analysis of heart rate variability with digital filtering of ectopic beats Clin Physiol 2001; 21(1): 15-24 References 244 373 Strachan BK, Van Wijngaarden WJ, Sahota D, Chang A, James DK Cardiotocography only versus cardiotocography plus PR-interval analysis in intrapartum surveillance: a randomised, multicentre trial FECG Study Group Lancet 2000; 355(9202): 456-9 374 Sturm R, Muller HP, Pasquarelli A, Demelis M, Erne SN, Terinde R, Lang D Multi-channel magnetocardiography for detecting beat morphology variations in fetal arrhythmias Prenat Diagn 2004; 24(1): 1-9 375 Surkan PJ, Stephansson O, Dickman PW, Cnattingius S Previous Preterm and Small-for-Gestational-Age Births and the Subsequent Risk of Stillbirth Obstet Gynecol Surv 2004; 59(7): 493-495 376 Symonds EM Configuration of the foetal electrocardiogram in relation to foetal acid-base balance and plasma electrolytes J Obstet Gynaecol Br Commonw 1971; 78(11): 957-70 377 Symonds EM Vectorcardiography and acid-base balance in the human foetus J Obstet Gynaecol Br Commonw 1972; 79(5): 416-23 378 Symonds EM Foetal electrocardiographic monitoring: past, present and future a historical perspective J Perinat Med 1986; 14(6): 385-90 379 Symonds EM, Sahota D, Chang A Foetal electrocardiography London: Imperial College Press; 2001 380 Tapanainen JM, Thomsen PE, Kober L, Torp-Pedersen C, Makikallio TH, Still AM, Lindgren KS, Huikuri HV Fractal analysis of heart rate variability and mortality after an acute myocardial infarction Am J Cardiol 2002; 90(4): 347-52 381 Task Force Heart rate variability: standards of measurement, physiological interpretation and clinical use Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology Circulation 1996; 93(5): 1043-65 382 Taylor BJ, Williams SM, Mitchell EA, Ford RPK Symptoms, sweating and reactivity of infants who die of SIDS compared to community controls J Paediatr Child Health 1996; 32: 316–22 383 Taylor MJ, Smith MJ, Thomas M, Green AR, Cheng F, Oseku-Afful S, Wee LY, Fisk NM, Gardiner HM Non-invasive foetal electrocardiography in singleton and multiple pregnancies BJOG 2003; 110(7): 668-78 References 245 384 Taylor MJ, Thomas MJ, Smith MJ, Oseku-Afful S, Fisk NM, Green AR, Paterson-Brown S, Gardiner HM Non-invasive intrapartum fetal ECG: preliminary report BJOG 2005; 112(8): 1016-21 385 Thomaidis C, Varlamis G, Karamperis S Comparative study of the electrocardiograms of healthy fullterm and premature newborns Acta Paediatr Scand 1988; 77(5): 653-7 386 Tulppo MP, Makikallio TH, Takala TE, Seppanen T, Huikuri HV Quantitative beat-to-beat analysis of heart rate dynamics during exercise Am J Physiol 1996; 271(1 Pt 2): H244-52 387 Tulppo MP, Hautala AJ, Makikallio TH, Laukkanen RT, Nissila S, Hughson RL, Huikuri HV Effects of aerobic training on heart rate dynamics in sedentary subjects J Appl Physiol 2003; 95(1): 364-72 388 Uusitalo AL, Laitinen T, Vaisanen SB, Lansimies E, Rauramaa R Physical training and heart rate and blood pressure variability: a 5-yr randomized trial Am J Physiol Heart Circ Physiol 2004; 286(5): H1821-6 389 Van Bemmel JH Detection of weak foetal electrocardiograms by autocorrelation and crosscorrelation of envelopes IEEE Trans Biomed Eng 1968; 15(1): 17-23 390 Van Iddekinge B, Hofmeyr GJ, Buchmann E Visual interpretation of the effect of maternal betamethasone administration on the foetal heart rate pattern J Obstet Gynaecol 2003; 23(4): 360-363 391 Van Leeuwen P, Lange S, Hackmann J, Klein A, Hatzmann W, Groenemeyer DH Assessment of intra-uterine growth retardation by foetal magnetocardiography In: Nenonen J, Ilmoniemi RJ, Katila T, editors Biomag 2000, Proceedings of the 12th International Conference on Biomagnetism Espoo: Helsinki Univ Technology, 2001; 23: 603-606 392 Van Leeuwen P, Lange S, Klein A, Geue D, Groenemeyer DH Dependency of magnetocardiographically determined foetal cardiac time intervals on gestational age, gender and postnatal biometrics in healthy pregnancies BMC Pregnancy Childbirth 2004; 4(1): 393 Van Leeuwen P, Lange S, Klein A, Geue D, Zhang Y, Krause HJ, Gronemeyer D Reproducibility and reliability of foetal cardiac time intervals using magnetocardiography Physiol Meas 2004; 25(2): 539-52 394 Van Hoogenhuyze D, Weinstein N, Martin GJ, Weiss JS, Schaad JW, Sahyouni XN, Fintel D, Remme WJ, Singer DH Reproducibility and relation to mean heart rate of heart rate variability in normal subjects and in patients References 246 with congestive heart failure secondary to coronary artery disease Am J Cardiol 1991; 68(17): 1668-76 395 Van Oosterom A Spatial filtering of the foetal electrocardiogram J Perinat Med 1986; 14(6): 411-9 396 Van Wijngaarden WJ, de Haan HH, Sahota DS, James DK, Symonds EM, Hasaart THM Changes in the PR interval - foetal heart rate relationship of the electrocardiogram during foetal compromise in chronically instrumented sheep Am J Obstet Gynecol 1996a; 175(3): 548-54 397 Van Wijngaarden WJ, Sahota DS, James DK, Farrell T, Mires GJ, Wilcox M, Chang A Improved intrapartum surveillance with PR interval analysis of the foetal electrocardiogram: A randomized trial showing a reduction in foetal blood sampling Am J Obstet Gynecol 1996b; 174(4): 1295-9 398 Van Wijngaarden WJ, Strachan BK, Sahota DS, James DK Improving intrapartum surveillance: an individualised T/QRS ratio? Eur J Obstet Gynecol Reprod Biol 2000; 88(1): 43-8 399 Vanderschoot J, Callaerts D, Sansen W, Vandewalle J, Vantrappen G, Janssens J Two methods for optimal MECG elimination and FECG detection from skin electrode signals IEEE Trans Biomed Eng 1987; 34(3): 233-43 400 Veerman DP, Imholz BP, Wieling W, Karemaker JM, Van Montfrans GA Effects of aging on blood pressure variability in resting conditions Hypertension 1994; 24(1): 120-30 401 Walker AM, Cannata J, Dowling MH, Ritchie B, Maloney JE Sympathetic and parasympathetic control of heart rate in unanaesthetized foetal and newborn lambs Biol Neonate 1978; 33(3-4): 135-43 402 Walker D Functional development of the autonomic innervation of the human feta l heart Biol Neonate 1975; 25: 31-43 403 Wakai RT, Wang M, Pedron SL, Reid DL, Martin CB Jr Spectral analysis of antepartum foetal heart rate variability from foetal magnetocardiogram recordings Early Hum Dev 1993; 35(1): 15-24 404 Wakai RT, Wang M, Leuthold AC, Martin CB Foetal magnetocardiogram amplitude oscillations associated with respiratory sinus arrhythmia Physiol Meas 1995; 16(1): 49-54 405 Wakai RT, Lengle JM, Leuthold AC Transmission of electric and magnetic foetal cardiac signals in a case of ectopia cordis: the dominant role of the vernix caseosa Phys Med Biol 2000; 45(7): 1989-95 247 References 406 Wakai RT Assessment of foetal neurodevelopment magnetocardiography Exp Neurol 2004; 190 Suppl 1: S65-71 via foetal 407 Warren JH, Jaffe RS, Wraa CE, Stebbins CL Effect of autonomic blockade on power spectrum of heart rate variability during exercise Am J Physiol 1997; 273(2 Pt 2): R495-502 408 Watanabe T, Okamura K, Tanigawara S, Shintaku Y, Akagi K, Endo H, Yajima A Change in electrocardiogram T-wave amplitude during umbilical cord compression is predictive of foetal condition in sheep Am J Obstet Gynecol 1992; 166(1 Pt 1): 246-55 409 Weidner G, Kohlmann CW, Horsten M, Wamala SP, Schenck-Gustafsson K, Hogbom M, Orth-Gomer K Cardiovascular reactivity to mental stress in the Stockholm Female Coronary Risk Study Psychosom Med 2001; 63(6): 91724 410 Welin AK, Blad S, Hagberg H, Rosen KG, Kjellmer I, Mallard C Electrocardiographic changes following umbilical cord occlusion in the midgestation foetal sheep Acta Obstet Gynecol Scand 2005; 84(2): 122-8 411 Westerhuis M, Porath M, Mol BW, Kwee A A comparison of intrapartum automated fetal electrocardiography and conventional cardiotocography a randomised controlled study BJOG 2006; 113(9): 1103 412 Westgate JA, Harris M, Curnow JS, Greene KR Plymouth randomized trial of cardiotocogram only versus ST waveform plus cardiotocogram for intrapartum monitoring in 2400 cases Am J Obstet Gynecol 1993; 169(5): 1151-60 413 Westgate JA, Gunn AJ, Bennet L, Gunning MI, de Haan HH, Gluckman PD Do foetal electrocardiogram PR-RR changes reflect progressive asphyxia after repeated umbilical cord occlusion in foetal sheep? Pediatr Res 1998; 44(3): 297-303 414 Westgate JA, Bennet L, Brabyn C, Williams CE, Gunn AJ ST waveform changes during repeated umbilical cord occlusions in near-term foetal sheep Am J Obstet Gynecol 2001; 184(4): 743-51 415 Westgate JA, Wassink G, Bennet L, Gunn AJ Spontaneous hypoxia in multiple pregnancies is associated with early fetal decompensation and enhanced T-wave elevation during brief repeated cord occlusion in near-term fetal sheep Am J Obstet Gynecol 2005; 193(4): 1526-33 References 248 416 Wheeler T, Murrills A, Shelley T Measurement of the foetal heart rate during pregnancy by a new electrocardiographic technique Br J Obstet Gynaecol 1978; 85(1): 12-7 417 Whyte HE, Fitzhardinge PM, Shennan AT, Lennox K, Smith L, Lacy J Extreme immaturity: outcome of 568 pregnancies of 23-26 weeks' gestation Obstet Gynecol 1993; 82(1): 1-7 418 Wibbens B, Westgate JA, Bennet L, Roelfsema V, De Haan HH, Hunter CJ, Gunn AJ Profound hypotension and associated electrocardiographic changes during prolonged cord occlusion in the near term fetal sheep Am J Obstet Gynecol 2005; 193(3 Pt 1): 803-10 419 Widmark C, Hokegard KH, Lagercrantz H, Lilja H, Rosen KG Electrocardiographic waveform changes and catecholamine responses during acute hypoxia in the immature and mature foetal lamb Am J Obstet Gynecol 1989; 160(5 Pt 1): 1245-50 420 Widmark C, Jansson T, Lindecrantz K, Rosen KG ECG waveform, short term heart rate variability and plasma catecholamine concentrations in response to hypoxia in intrauterine growth retarded guinea-pig foetuses J Dev Physiol 1991; 15(3): 161-8 421 Widmark C, Lindecrantz K, Murray H, Rosen KG Changes in the PR, RR intervals and ST waveform of the foetal lamb electrocardiogram with acute hypoxemia J Dev Physiol 1992; 18(3): 99-103 422 Woo MA, Stevenson WG, Moser DK, Middlekauff HR Complex heart rate variability and serum norepinephrine levels in patients with advanced heart failure J Am Coll Cardiol 1994; 23(3): 565-9 423 Wood NS, Marlow N, Costeloe K, Gibson AT, Wilkinson AR Neurologic and developmental disability after extremely preterm birth EPICure Study Group N Engl J Med 2000; 343(6): 378-84 424 World Health Organization International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Volume 2: Instruction Manual, World Health Organization (WHO), Geneva 1993 425 Wu MH, Hsieh FC, Wang JK, Kau ML A variant of long QT syndrome manifested as foetal tachycardia and associated with ventricular septal defect Heart 1999; 82(3): 386-8 426 Yamamoto Y, Hughson RL Coarse-graining spectral analysis: new method for studying heart rate variability J Appl Physiol 1991a; 71(3): 1143-50 References 249 427 Yamamoto Y, Hughson RL, Peterson JC Autonomic control of heart rate during exercise studied by heart rate variability spectral analysis J Appl Physiol 1991b; 71(3): 1136-42 428 Yi G, Gallagher MM, Yap YG, Guo XH, Harrison R, McDonald JT, Camm AJ, Malik M Consistency of multicenter measurements of heart rate variability in survivors of acute myocardial infarction Pacing Clin Electrophysiol 2000; 23(2): 157-64 429 Yoshimura T, Magness RR, Rosenfeld CR Angiotension II and alpha-agonist I Responses of ovine fetoplacental vasculature Am J Physiol 1990a; 259: H464-H472 430 Yoshimura T, Magness RR, Rosenfeld CR Angiotension II and alpha-agonist II Effects on ovine fetoplacental prostaglandins Am J Physiol 1990b; 259: H473-H479 431 Yumoto Y, Satoh S, Koga T, Nagata H, Nagamatsu R, Nakano H Prenatal diagnosis of slow-rate ventricular tachycardia using foetal electrocardiography Prenat Diagn 2004; 24(6): 463-7 432 Zak R Development and proliferative capacity of cardiac muscle cells Circ Res 1974; 35(2) suppl II: 17-26 433 Zarzoso V, Nandi AK Noninvasive foetal electrocardiogram extraction: blind separation versus adaptive noise cancellation IEEE Trans Biomed Eng 2001; 48(1): 12-8 434 Zaza A, Lombardi F Autonomic indexes based on the analysis of heart rate variability: a view from the sinus node Cardiovasc Res 2001; 50(3): 434-42 435 Zhuravlev YE, Rassi D, Mishin AA, Emery SJ Dynamic analysis of beat-tobeat foetal heart rate variability recorded by SQUID magnetometer: quantification of sympatho-vagal balance Early Hum Dev 2002; 66(1): 1-10 436 Ziegler D, Laux G, Dannehl K, Spuler M, Muhlen H, Mayer P, Gries FA Assessment of cardiovascular autonomic function: age-related normal ranges and reproducibility of spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses Diabet Med 1992; 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