Antepartum evaluation of the pre-ejection period of the fetal cardiac cycle YUJI
The pre-ejection period (PEP) of the cardiac cycle was studied in 65 antepartum fetuses by means of a noninvasive technique which used simultaneous recordings of abdominal fetal electrocardiogram (FECG) and ultrasound fetal Doppler cardiogram (FDCG). Although most of the fetuses were products of high-risk pregnancies, 45 fetuses had ur~entful p&natal courses. The PEP’s from these fetuses demonstrated a significant positive relation&ip with gestational age (p’ < 0.01). Uterine contractions induced for antepartum We& testing of the fetus were found to prolong the PEP by approximately 9.1 per cent in five cases (four fetuses). The average PEP of an&par&urn fetuses between 38 and 40 weeks was shorter than that of intrapartum fetuws by approximately 9.5 per cent. Comparison between clinical outoome and the PEP’s of the fetuses who were born within a week after the last determination of PEP revealed a strong correlation between prol~ged PEP duration and abnormalities in the perfnatal course. (AM. J. OSSTET. GYNECOL. 132: 278, 1978.)
s Y STO LI c time intervals of the fetal cardiac cycle have recently been studied intensively by several investigators. From a ciinical standpoint, the pre-ejection period (PEP), which is defined as the interval between the onset of the Q-wave of the electrocardiogram (ECG) and the beginning of ventricular ejection, has been regarded as the most useful in evaluating the myocardial function. The results reported previously are not totally in agreement. Observations of simultaneous FECG and phonocardiographic recordings showed that both the Q-S, and SI-Sp intervals were rel-
From the Department Angeles County-University Medical Center.
and Gynecology, of Southern California
Supported in part by Grant HD-06406Jrom Institute.~ of Health, United States Public Received
the National Health Seroice.
requests: Vu. Murata, M.D., Department of Obstetrics and Gynecology, 1240 N. Mission Rd., Los Angeles, California 90033.
address: Department of Obstetrics and Kagoshima Municipal Hospital, Kagoshima,
atively constant over a wide range of heart rates during labor. In this study, prolongation of Q-S, was found in only one severely distressed fetus.’ Organ and coworkers,* using simultaneous recordings of FECG and ultrasound Doppler cardiogram (DCG), measured an average PEP of 70 ? 10 msec. in intrapartum human fetuses. Shortening of the PEP was observed during hypoxia in fetal lambs, whereas umbilical cord occlusion produced lengthening of the PEP as measured by ECG and arterial pressure tracings.3 These same patterns of change in PEP during acute hypoxia and cord compression were observed in human fetuses during labor from FECG-DCG recordings.J A preliminary study from our laboratory of intraparturn human fetuses by FECG-DCG recordings demonstrated that the PEP duration increased with gestational age, and that the average PEP of normal fetuses between 38 and 40 weeks of gestation was 70 * 2.38 msec. Also, prolongation of PEP was observed in eight fetuses with abnormal heart rate patterns during labor.” Systematic studies of PEP in chronically instrumented fetal rhesus monkeys demonstrated that the PEP increased with advancing fetal age and with increasing systolic and diastolic blood pressure.’ The PEP showed strong inverse linear correlation with fetal OOOZ-9378/781190278+07$00.70/0
(1. 5’. Mosbv
Antepartum evaluation of PEP
Fig. 1. Simultaneous
recording (bottom). F, Fetal QRS complex; and opening; Ao, AC, Semilunar
of abdominal M, maternal
fetal ECG (top) and fetal Doppler QRS complex; MC, MO, atrioventricular
signah (filtered) valve closure
valve opening and closure.
arterial pH. The PEP also increased significantly during nonacidemic hypoxia, although the magnitude of the change was less than with acidosis.‘j Attempts have been made to process the data at real time speed as a step toward clinical application of the PEP,‘, ’ however, these have been limited to human intrapartum fetuses or animal fetuses from which direct FECG could be obtained. Although the feasibility of studying fetal systolic time intervals using abdominal fetal ECG and DCG recordings has been demonstrated,s, ” studies of the PEP of antepartum human fetuses relative to subsequent fetal outcome have not been reported.
Patients and methods Simultaneous recordings of FECG and FDCG were obtained from antepartum patients. Suction cup electrodes were placed on the maternal abdomen and positioned to obtain the clearest FECG signals. These signals were amplified by a Tektronix physiologic monitor and were recorded on magnetic tape together with the FDCG obtained from a Kretz MCG-2 (2 MHz) fetal pulse detector. Following the technique previously described, the tapes were subsequently played back at an eight-fold increase in speed through the appropriate filters into an ink-writing recorder (Elema Mingograph Model No. 21 B). The effective paper speed of this recorder was 50 mm. per second. The PEP was measured manually as the distance from the onset of the QRS complex on the FECG to the onset of the semilunar valve opening signal (Ao) on the FDCG (Fig. 1). The means and standard deviations of the R-R intervals and PEP’s were calculated from 20 fetal cardiac cycles in each determination. The measurements were
of pregnancy No. of
Complication Diabetes menitus (all classes) Pre-eclampsia Chronic hypertension Rh isoimmunization Suspected fetal distress Suspected intrauterine growth Fetal arrhythmia
Previous poor obstetrical history Prolonged pregnancy (>42 Premature labor Systemic lupus erythmatosus Cardiac failure Suspected amnionitis
25 6 6 5 5 4 3 3 3 2 1 1 1
made on portions of the record obtained when no uterine contractions were present. The patients from whom either clear FECG or DCG could not be obtained were not included in the study. Approximately 19 per cent of the patients in whom recordings were attempted fell into this category. Ninety-one satisfactory determinations of the fetal PEP were obtained from 65 antepartum patients. Most of these patients were being followed and treated in special-care clinics or as inpatients because of one or another complication of their pregnancies (Table I). All were subsequently delivered in Los Angeles County-university of Southern California Medical Center. FECG-DCG recordings were usually performed immediately before contraction stress testing (CST)“; hsvever, three determinations were made immediately after the CST and four patients had measurements performed both just before and immediately following the CST. The technique for recording and measuring
October 1 Obster.
1. 1978 C;)nrw.
Fig. 2. Correlation between the PEP and gestational age of fetuses with normal outcome. Multiple determinations on individual fetuses at different gestational weeks are connected by lines. @= values obtained immediately after contraction stress testing of the fetus.
m r 39
Fig. 3. Correlation between the PEP and gestational age of fetuses with normal outcome. The shaded area shows the normal range of the PEP defined by fifth and ninety-fifth percentiles. Dots signify mean values for individual gestational weeks. PEP was exactly the same whether the measurement preceded or followed the CST. The results of the PEP studies were not available to the physicians involved in patient management. Fetal heart rate monitoring was performed on most of the fetuses by an indirect technique (phonocardiogram or Doppler ultrasound) during the antepartum CST, and also by a continuous direct technique (fetal electrode and intrauterine catheter) during the intrapartum period. The abnormal group of fetuses in this study consisted of the fetuses who developed late decelerations either antepartum or intrapartum and/or who subsequently had complicated neonatai courses. The fetuses who had uneventful antepartum, intrapar-
turn, and neonatal courses were selected to determine the normal range of the PEP in relation to gestational age. Gestational age was calculated from the first day of the last menstrual period, if this agreed with clinic4 findings and immediate neonatal findings. If all of these were not in agreement, the gestation&l age was estimated from the newborn examination. In analyzing the relationship between the duration of PEP and fetal-neonatal outcome, only fetuses who had at least one determination of the PEP within a week before the date of delivery were considered. Three patients with fetal arrhythmias were excluded from both the determination of normal PEP in relation to gestational age and the correlation of PEP duration
Fig. 4. PEP’s from 14 fetuses who had prolonged PEP’s and/or abnormal perinatal courses. One patient (A. B.) who had a stillbirth with a PEP of 89.9 msec. is excluded because of uncertain gestational week.
with fetal outcome. All of these arrhythmias were thought to be premature atria1 contractions, and none of these fetuses showed any recognizable change in QRS configuration or duration.
Results Five pairs of PEP determinations were obtained both immediately before and after a CST from four fetuses who subsequently showed normal courses during the perinatal period. The R-R intervals of the FECG were shortened by approximately 6.2 per cent after the CST in four of the five cases; however, the change was not statistically significant (0.5 > p > 0.1 by paired t test). The PEP was prolonged consistently after the CST in all five cases. The prolongation was approximately 9.1 per cent and the change was statistically significant (0.05 > p > 0.02 by paired t test). In spite of the complications of pregnancies, there were 45 patients (63 determinations) whose fetuses were retrospectively considered to be normal. The PEP’s from these fetuses are shown in Fig. 2 plotted against the corresponding gestational ages. Three PEP values taken only after CST are indicated by double circles. The PEP’s from the fetuses who had two or more determinations are connected by lines. Although five fetuses showed shortening of PEP with advancing gestational age, the over-all tendency is a linear prolongation of the PEP with increasing duration of pregnancy (PEP = 1.52 x gestational weeks + 4.08, r = 0.73, n = 63, p < 0.01 (Fig. 3). The weekly increment of the PEP was calculated
to be 1.8 2 2.4 msec. (mean + 1 SD.) from the 11 normal fetuses who had two or more PEP determinations, excluding two values obtained immediately after the CST. Fig. 3 represents mean, and fith and ninety-fifth percentiles of the PEP’s in each week of gestation from 33 to 40 weeks, defining the 90 per cent confidence limits of the PEP’s as a shaded area. Forty patients were delivered within a week after the last PEP determination. The PEP’s from 12 fetuses revealed prolongation above the ninety-fifth percentile for the appropriate gestational age. The PEP’s ,from these 12 fetuses and from three fetuses who showed an abnormal outcome in spite of the normal PEP values are illustrated in Fig. 4. One patient whose fetus showed a markedly prolonged PEP of 89.9 msec. and subsequently was stillborn was not included in this figure because of its uncertain gestational age. More detailed information from these 15 fetuses is listed in Table II. The summarized results of correlations between the duration of PEP and fetal outcome are given in Table III. There was a highly significant association between prolongation of PEP antepartum and subsequent abnormalities in the antepartum, intrapartum, or neonatal course (p < 0.001 by Fisher exact probability test). Four determinations from three fetuses with arrhythmia exhibited a consistent tendency: the PEP was markedly prolonged after the short R-R interval and was normal or slightly shortened after the long R-R interval. The PEP durations following the R-R intervals
Table II. Detailed Fetus No.
A. Fetuses with broloneed 1 D. Hen.‘ 61.78
-.-- -- ._.._
Mode of delivery
scme 5 min
for gest. age,
prolonger1 nronatal acidosis.
Spontaneous vaginal C/S C/S
Spontaneous vaginal C/S C/S
C. Al. R. 0.
C. Ar. L. w.
None CST (+)
CST (+) None
M. P. A. L.
Table III. Antepartum
Normal Late deceleration
B. Fetuses with nwmnl PEP and afmonnai 13 Z. M. 60.81 35
reactive FHR Rh (-), Zone III None Late deceleration
Late deceleration in Iate labor
Fetal d&tress PEP
transfusion Hypoglycemia RDS, h y[xxension, heart murmur Normal Normal
Small for gest. age, h~poxemia and actdosis, hypoglycemia Hypoglycemia Neonatal deathRDS Antepartum death
CST (+) CST (+)
Markedly de pressed hypecalcemia PDA, RDS. sacral ageneais Hct. 18. exchange
corresponding to the baseline FHR fell between following the short and long R-R intervals.
comment The PEP’s of the antepartum fetuses in the normal group were generally found to be shorter than those of normal fetuses of equivalent age during labor. The values obtained from antepartum and intrapartum fetuses between 38 and 40 weeks’ gestation were 63.9 * 3.7 msec. (N = 31) and 70.0 +- 2.4 msec. (N = 12),” respectively, a difference of approximately 9.5 per cent. Timing the onset of ventricular depolarization from the abdominal FECG, which does not always offer an ideal configuration of the fetal QRS complex, might be artificially responsible, in part, for
the shorter PEP measured in the antepartum fetuses. The PEP prolongation may also be due to a slight fetal hypoxia and/or acidemia caused by the uterine contractions. Consistent prolongation of PEP by approximately 9.1 per cent immediately following CST supports the latter hypothesis. The patient population studied here must also be taken into consideration. The fetuses who did not have any abnormalities have been assumed to be normal in this study. However, those fetuses were still products of complicated pregnancies. The “normal” PEP’s calculated here may in actuality represent somewhat prolonged intervals because of the maternal and feroplacental problems, or shortened ones because of adequate therapy and bed rest which possibly irnproved fetal condition. The antepartum fetuses in this study exhibited an increase in the PEP with advancing gestationat age. Wolfson and associatesI have recently reported similar findings. These observations are in keeping with our previous findings in human fetuses during 1aborJ and in longitudinal studies of fetal rhesus monkeys.B The weekly increment of the PEP from the 11 normal
Volume 132 Number3
fetuses with multiple PEP determinations was 1.8 -t 2.4 msec., which coincides fairly well with the average weekly increment of 1.5 msec. calculated from all the normal fetuses between 33 and 43 weeks’ gestation. Previous studies from our laboratory yielded a value of 2.0 msec. as the average weekly increment of the PEP from normal intrapartum human fetuses between 38 and 40 weeks’ gestation.’ The weekly increment in PEP duration in rhesus monkey fetuses during the last third of pregnancy was 1.3 msec.,6 not greatly different from the rate of increase in human fetuses. Lengthening of PEP with increasing age continues during infancy and childhood.” The relatively large standard deviation of the weekly increment in PEP (1.8 + 2.4 msec.) in the 11 fetuses studied serially results from the fact that three fetuses showed a decrease in PEP from previous values on a single occasion and one fetus exhibited a decreasing trend over three measurements. A single drop in PEP among the serial values could be explained on the basis of acute cardiovascular changes, including increased adrenergic drive of the fetal heart which may have occurred accidentally during one of the measuring sessions. The serial decrease, and indeed some of the isolated shortenings, may represent improvement in fetal condition as a result of bed rest or other therapeutic interventions. Since the standard deviation of PEP in the 20 individual cycles measured for a single determination averaged 3 msec., the weekly PEP increment of 1.8 msec. may be below the resolving ability of the present technique. This question was not studied, for we did not perform duplicate determinations on the same day or successive days in order to test reproducibility and precision. From the clinical standpoint, however, serial determinations of PEP by this method can detect a sudden significant increase in PEP, as seen in Fig. 4 (Patient D. Her.). Among 40 patients who had their last fetal PEP determination within a week of delivery, three fetuses with normal PEP values exhibited late decelerations on CST (M P., A. L.) or during labor (Z. M.). These might
be considered false-negative PEP results. The question cannot be answered for M. P. and A. L., for these fetuses were delivered by cesarean section without labor. The initial Apgar scores in these cases may have reflected the effects of anesthesia; both fetuses were scored 8 at 5 minutes. The remaining fetus, Z. M., developed mixed variable and late decelerations only after 12 hours of labor. Obviously, the fetoplacental status in this case could not have been greatly compromised. Patient L. G..may be considered a false-positive prediction. The PEP determination was performed immediately prior to a CST at 37 weeks’ gestation. Both the PEP and CST revealed abnormal results. This patient later went into spontaneous labor, and intraparturn FHR monitoring showed no ominous patterns. A possible explanation of the positive antepartum tests might be transient fetal distress due to maternal aortocaval compression. The brachial blood pressure showed a 10 mm. Hg fall in both systolic and diastolic values during the CST. A practical difficulty in using the PEP as an indicator of fetal well being antepartum is how to interpret the values of fetuses whose gestational age is not known. In these cases, the difference in PEP before and after a defined stress given to the fetus may be of use, and further investigation of this possibility is needed. The changes in PEP caused by arrhythmias have been well documented. I3 Of particular importance in the production of these changes are alterations in diastolic filling and, therefore, preload brought about by the variations in the duration of diastole. The Iluctuations in PEP duration observed in our three fetuses with arrhythmias are compatible with this mechanism in that shortened PEP’s followed the longer R-R intervals (greater preload) and the reverse. Other contributing factors may have included changes in arterial pressure (afterload) and possible asynchrony of ventricular contraction. Part of the variation in PEP may also have reflected fluctuating myocardial dysfunction due to the same abnormal circumstances which caused the arrhythmia itself.
1. Goodlin, R. C., Girard, J., and Hollmen, A.: Systolic time intervals in the fetus and neonate, Obstet. Gynecol. 39: 295, 1972. 2. Organ, L. W., Bernstein, A., Rowe, I., et al.: The preejection period of the fetal heart: Detection during labor with Doppler ultrasound, AM. J. OBSTET. GYNECOL. 115: 337,
3. Organ, L. W., Milligan, J. D., Goodwin, J. W., et al.: The pre-ejection period of the fetal heart: Response to stress
in the term fetal lamb, AM. J. OBSTET. GYNECOL. 115: 337, 1973. 4. Organ, L. W., Bernstein, A., Smith, K. C., et al.: The pre-ejection period of the fetal heart: Patterns of change during labor, AM. J. OBSTET. GYNECOL. 120: 49, 1974. 5. Murata, Y., and Martin, C. B., Jr.: Systolic time intervals of the fetal cardiac cycle, Obstet. Gynecol. 44: 224, 1973. 6. Murata, Y., Martin, C. B., Jr., Ikenoue, T., and Petrie, R. H.: Cardiac systolic time intervals in fetal monkeys:
Murata et al.
1978. 7. Hon, E. H., Murata, Y., Zanini, B., et al.: Continuous microfilm display of the electromechanical intervals of the cardiac cycle, Obstet. Gynecol. 43: 722, 1974. 8. Goodlin, R. C., Hesselein, J. C., Cracker, K., and Carlson, R. G.: Fetal cardiac interval recorder, Obstet. Gynecol. 46: 69, 1975. 9. Murata, Y., Takemura, H., and Kurachi, K.: Observations of fetal cardiac motion by M-mode ultrasonic cardiography, AM. J. OBSTET. GYNECOL. 111: 287, 197 1. 10. Wolfson, R. N., Zador, I. E., Pillay, S. K., Timor-Tirtsch, I. E., and Hertz, R. H.: Antenatal Investigation of human
Most of the provisions
of the all manuscripts
fetal systolic time intervals, AM. J. OBSTET. (;YNI:I:c~~.. 129: 203, 1977. Il. Ray, M., Freeman, R. K., Pine, S.. et al.: Clinical exper1. ence with the oxytocin challenge test, Ant. ,J. OBSTEI, GYNECOL. 114: 1, 1972 12. Harris, L. C., Weissler, A. M., Manske. A. 0.. et al.: I)uration of the phase of mechanical systole in infants and children, Am. J. Cardiol. 14: 448. 1964. 13. Lewis, R. P., Leighton, R. F., Forester, W. F.. and Weiasler, A. M.: Systolic time intervals. in Weissler, A. M.. editor: Noninvasive Cardiology, New York and London. 1974, Grune 8c Stratton, Inc., pp. 301-368.
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