Multicentre study of fetal cardiac time intervals using magnetocardiography.

OBJECTIVE: A database with reference values of the durations of the various waveforms in a magnetocardiogram of fetuses in uncomplicated pregnancies is assessed. This database will be of help to discriminate between pathologic and healthy fetuses. A fetal magnetocardiogram is a recording of the magnetic field in a location near the maternal abdomen and reflects the electric activity within the fetal heart. It is a non-invasive method, which can be used with nearly 100% reliability from the 20th week of gestation onward. DESIGN: Durations of the waveforms were assembled from averaged magnetocardiograms and statistically processed. SETTING: Fetal magnetocardiograms were measured with different magnetocardiographs. All measurements were carried out in magnetically shielded rooms. SAMPLE: Fetal magnetocardiograms were obtained for 582 healthy patients. METHOD: The durations of the waveforms were extracted from fetal magnetocardiograms measured at the cooperating centres. The variables collected included the duration of the P-wave, the PR interval, the PQ interval, the QRS complex, the QT interval and the T-wave and QTc value. The results were compared with values extracted from electrocardiograms of fetuses measured via electrodes attached to the maternal abdomen, from electrocardiograms measured during labour using a scalp electrode, and from electrocardiograms recorded in newborns, that were found in the literature. MAIN OUTCOME MEASURES: Values of the durations are given as a function of gestational age including the regression line as well as the bounds marking the 90%, 95% and 98% prediction interval. RESULTS: The durations of the P-wave, the PR interval, the QRS complex, the QT interval and QTc value increase linearly with gestational age. The durations of the PQ interval and the T-wave are independent of fetal age. CONCLUSION: The values found agree with those found in the literature. The scatter of the data is wide due to the variation in normal physiology, the measuring system and signal processing and the subjectivity of the researcher. However, the system can define normal ranges and may be used in diagnosis.

High temporal resolution dynamic contrast MRI in a high risk group for placenta accreta.

Antenatal diagnosis of placenta accreta with MR is not easy even now because T2-weighted images (T2WI) cannot differentiate chorionic villi from decidua basalis. We performed dynamic contrast MRI to study whether trophoblastic villi could be separately demonstrated from the decidua basalis, and whether the contrast resolution between the placenta and myometrium could improve compared to T2WI. Six pregnant women with prior cesarean section were examined at 34-38 gestational weeks. Sagittal T2-weighted images with fast spin echo sequences and dynamic contrast studies with fast field echo sequence every 10-14 s after contrast injection were performed. We analyzed the enhancing pattern of the placenta and compared the contrast between placenta and myometrium. We reviewed medical records to identify complications during the placental delivery and the complications of their newborns. In the early phase after contrast enhancement, multiple foci of the strong lobular enhancement were observed in all cases. Other parts of placenta were slowly but strongly enhanced following them. We speculated that the former corresponded to intervillous space and the latter decidua basalis. The contrast between placenta and myometrium tended to be distinct near the inner cervical os on both T2WI and dynamic contrast study. On the other hand, it was indistinct in the upper part of the uterine body on T2WI despite it was clearly demonstrated on dynamic contrast study. The placentae were delivered without any complication in all cases. Although two neonates showed fetal distress, none of the infant remained any sequelae at the time of the discharge. The other four were well although one of them complicated with meconium staining. As dynamic contrast MRI can differentiate chorionic villi and decidua basalis, and can provide excellent contrast between placenta and myometrium at anywhere within the uterus, it may be a promising technique for antepartum diagnosis of the placenta accreta.

Detection of cardiac hypertrophy in the fetus by approximation of the current dipole using magnetocardiography.

To determine the developmental changes in the myocardial current during fetal life, and to evaluate the clinical usefulness of magnetocardiography for prenatal diagnosis of cardiac hypertrophy or enlargement, we approximated the magnitude of the one-current dipole of the fetal heart using fetal magnetocardiography (fMCG). A total of 95 fetuses with gestational age of 20-40 wk were included in this study. fMCG was recorded with a nine-channel superconducting quantum interference device system in a magnetically shielded room. The magnitude of the dipole (Q) was calculated using an equation based on the fMCG amplitude obtained on the maternal abdomen and the distance between the maternal surface and fetal heart measured ultrasonographically. In uncomplicated pregnancies, the Q value correlated significantly with gestational age, reflecting an increase in the amount of myocardial current, i.e. myocardial mass. Moreover, the Q values in fetuses with cardiomegaly caused by various cardiovascular abnormalities tended to be higher than the normal values. Although there are some limitations of the methodology based on the half-space model, and fetal orientation may influence the magnitude of the dipole, making it smaller, fMCG recorded with a multichannel superconducting quantum interference device system is a clinically useful tool for noninvasive, prenatal, and electrical evaluation of fetal cardiac hypertrophy.

Prenatal diagnosis of QT prolongation by fetal magnetocardiogram--use of QRS and T-wave current-arrow maps.

To determine the T wave of a fetal magnetocardiogram (FMCG), we have evaluated the T/QRS ratio and obtained current-arrow maps that indicate weak currents. We measured FMCG signals for 52 normal fetuses and two abnormal fetuses with prolonged QT waves by using three superconducting quantum interference device (SQUID) systems: a nine-channel system, a 12-channel vector system and a 64-channel system. The T/QRS ratio was calculated for all the normal fetuses from the maximum magnitudes of the QRS complex and the T wave. Current-arrow maps of the QRS complex (R wave) and T wave were obtained by using the 64-channel system, and the phase differences of the total-current vectors were calculated by using the current-arrow maps. The results showed that the T/QRS ratio had a wide variability of 0.35 for the normal fetuses. However, the magnitude of the prolonged T wave was as weak as the detection limit of the SQUID magnetometer. Although the T/QRS ratios for the fetuses with QT prolongation were within the normal range (< 0.35), the weak magnitude of the prolonged T wave could be evaluated. On the other hand, by comparing the current-arrow maps of the R and T waves for the normal fetuses, we found that the maximum-current arrows were indicated as either in the same direction or in opposite directions. These patterns could be identified clearly by the phase differences. Very weak prolonged T waves for the two abnormal fetuses could be determined by using these current-arrow maps and phase differences. Consequently, although the T/QRS ratios of FMCG signals have a wide distribution, we have concluded that the current-arrow map and phase difference can be used to determine the T wave of an FMCG signal.

Magnetocardiographic determination of the developmental changes in PQ, QRS and QT intervals in the foetus.

In order to determine developmental changes in atrioventricular (PQ), ventricular depolarizing (QRS) and QT intervals of the foetal heart, we recorded foetal magnetocardiographic waveforms using a superconducting quantum interference device system in a magnetically shielded room in 150 uncomplicated foetuses of gestational age >20 wk. Recording of the QRS waveform was successful in 128 (85%) of the subjects, based on unaveraged tracings. After signal averaging of the data from these 128 cases, P waves were recognized in 102 (68%) subjects and T waves in 64 (43%). The QRS interval, ranging from 32-74 ms, showed a positive linear correlation with the gestational age, which probably reflects an increase in the number and size of myocardial cells. The PQ interval showed low correlation with the gestational age, and was rather constant, with an average value of 100 ms. The QT interval ranged from 180-302 ms, and tended to be slightly shorter during early gestation. Although the success rate of measuring the PQ and QT intervals was unsatisfactory for this methodology to prevail in a clinical setting, these values provide the basis for in utero non-invasive investigation of foetal cardiac activity by magnetocardiography.

[The risk factors of emergency coronary artery bypass grafting in the elderly].

The purpose of this study was to evaluate the risk factor of emergency coronary artery bypass grafting (CABG) in the elderly. From January 1986 to December 1998, there were 37 patients of emergency CABG in 75 years old and over. They were divided into two groups (alive: 27 patients and dead: 10 patients). The risk factors that influenced the mortality were preoperative chronic renal failure and cardiogenic shock, prolonged cardiopulmonary bypass time and aortic cross clamp time, postoperative mediasinitis and perioperative cerebrovascular accident. In conclusion, the predictors of operative mortality of emergency CABG in elderly were preoperative cardiogenic shock and renal dysfunction.

Prenatal diagnosis of long QT syndrome using fetal magnetocardiography.

We describe the detection of congenital long QT syndrome in a fetus at 37 weeks' gestation using magnetocardiography (MCG). The prenatal diagnosis was confirmed by standard electrocardiography (ECG) performed after birth. This is the first case report of fetal long QT syndrome detected by MCG. Fetal MCG may be useful in the prenatal diagnosis of congenital cardiac disease with abnormal ECG findings.

Sensitivity of foetal magnetocardiograms versus gestation week.

Foetal magnetocardiograms (FMCGs) were measured using a nine-channel SQUID system equipped with first-order gradiometers (60 mm baseline, 20 mm diameter). The system was installed in a magnetically shielded room in a hospital. The white noise level was less than 10 fT/square root of Hz, and FMCGs above 1 pT were detected. These results and the depth to the foetal heart were used to estimate the current dipole. The relationship between the current dipole (Q) and the gestation week (G) was calculated and the average performance was determined as Q = 18G - 295. By using the estimated foetal current dipole, the measurement limit (average value) between depth and gestation weeks was determined. When the depth from the pickup coil to the foetal heart is 50, 60, 70 and 80 mm, the first detectable gestation weeks of FMCGs above 1 pT measured by a first-order gradiometer with 60 mm baseline were determined at 21, 23, 26, and 30 weeks respectively, and the detectable gestation weeks in the case of a 30 mm baseline were determined at 22, 26, 30 and 36 weeks respectively.

[Clinical study on the intracranial arteriovenous malformation associated with pregnancy].

We studied twelve pregnancies in nine patients with arteriovenous malformation (AVM) managed at our hospital from January, 1984 to March, 1993. Three of the cases were diagnosed as subarachnoidal hemorrhage (SAH) and one as epilepsy during pregnancy. The AVM was resected surgically in two ruptured cases during pregnancy, and the fetus was delivered vaginally. In the other case of ruptured AVM delivery was by elective cesarean section. In the non-ruptured case delivery was vaginal. Two of the six patients who took an anticonvulsant developed hemolytic anemia, and one baby was born with a cleft lip and palete. We next retrospectively investigated 42 women who were followed up for AVM at the department of neurosurgery in our hospital from January, 1978 to March, 1995. Three pregnancies of a total of 46 pregnancies were complicated by a cerebral hemorrhage. The hemorrhage rate during pregnancy for women with unruptured AVM was 0.065 +/- 0.036 per person per year. There was no significant difference between the hemorrhage rate for pregnant women and that for nonpregnant women of childbearing age, and the risk for rupture of AVM was not increased in pregnancy.

[Analysis of familial aggregation of ovarian and breast cancer in patients with ovarian cancer].

In 118 patients with common epithelial ovarian tumors (carcinomas and tumors of borderline malignancy) treated at Tsukuba University Hospital and Tsukuba-Gakuen Hospital, family histories of ovarian and breast cancer were obtained from medical records or in interviews, and familial aggregation of these cancers was examined. 1. A positive family history was found in 10 patients (8.5%). The high incidences of familial ovarian cancer and ovarian cancer in patients who were previously affected with breast cancer were statistically significant. 2. Patients with serous adenocarcinoma showed a significantly greater rate of positive family history than those with mucinous adenocarcinoma. 3. No significant correlation was seen between the clinical stage and a positive family history. 4. Every patient except one with a positive family history had onset of ovarian cancer after menopause. The age at onset for familial ovarian cancer cases was younger than that for the patients' relatives who were affected previously. 5. There were 14 healthy women considered to be at high risk for ovarian cancer among 5 familial ovarian and 2 familial ovarian and breast cancer aggregations. These preliminary findings suggest that screening for early ovarian cancer should be conducted in high risk relatives of familial cancer patients and women affected with breast cancer previously. More detailed studies are needed to define the occurrence of familial or hereditary ovarian and breast cancers in Japan.

Exercise at high temperature causes maternal hyperthermia and fetal anomalies in rats.

Hyperthermia is thought to be a teratogen in many animal species and also in humans. It has been reported that hyperthermia caused by sauna, hot tub, or fever during the early stages of pregnancy is related to an increased risk for neural tube defects. During exercise, especially in hot conditions, body temperature can also rise to fairly high levels. Thus, we can surmise that hyperthermia induced by exercise can also cause fetal malformation. To investigate this hypothesis, pregnant rats at 9 days of gestation were divided into four groups. In the first group, the animals were made to swim for 30 minutes in water at a temperature of 40.5 degrees C. In the second group, they were restrained and immersed in water for the same time at the same temperature. In the third group, the rats were forced to swim in water at 36.0 degrees C. The fourth group were controls. The core temperature of the rats was measured during these procedures. On the 18th gestational day, fetuses were extracted by cesarean section. The elevation of maternal core temperature was significantly greater in the first group than in the other groups. In the first group, 69% of fetuses had various external anomalies. No anomalies were found in the other groups. Our results show that exercise in hot conditions caused the elevation of core temperature and resulted in fetal anomalies in rats.

An evaluation of the pelvic score by the quantification theory for categorical data.

The scoring system for pelvic examination used in Tsukuba University Hospital was evaluated by the quantification theory to investigate the precision in predicting the date of labor onset. The objects of this study were 137 nulliparous gravidae and 142 multiparous gravidae who had spontaneous onset of labor at full-term. In this analysis, we used 15 categories of findings in the examination as independent variables, and as the objective variable we used the interval from the examination to the labor onset. The multiple correlation coefficients in nulliparae was 0.593 and in multiparae 0.598. The following conclusions were reached concerning the assessment of labor onset: (1) The consistency of the cervix and the engagement of the vertex in nulliparous gravidae should be given more consideration. (2) In multiparous gravidae the dilatation of the cervix and the engagement of the vertex are important factors. (3) A different scoring system should be employed for both nulliparae and multiparae.

Increased maternal plasma concentration of endothelin-1 during labor pain or on delivery and the existence of a large amount of endothelin-1 in amniotic fluid.

The concentration of endothelin-1 (ET-1) in plasma and amniotic fluid from normal pregnant women was determined by a sensitive sandwich-enzyme immunoassay system, established recently. The plasma ET-1 level increased gradually during normal pregnancy as the pregnancy advanced, the levels (0.40 +/- 0.02 pmol/l, n = 45) being significantly (p less than 0.05) higher after 29 weeks of gestation than those (0.32 +/- 0.01 pmol/l, n = 30) before 28 weeks of gestation. The plasma ET-1 level during labor pain was significantly higher (0.59 +/- 0.06 pmol/l, n = 10) than that (0.40 +/- 0.02 pmol/l, n = 45) in the 3rd trimester of pregnancy without labor pain (p less than 0.02). Moreover, a high level of ET-1 (17.38 +/- 0.25 pmol/l, n = 18) was detected in amniotic fluid on term delivery. The ET-1 level in amniotic fluid was significantly higher than the levels in maternal and umbilical cord plasma (p less than 0.001 and p less than 0.001, respectively). After delivery the maternal ET-1 level decreased gradually and 2 day postpartum ET-1 levels reached the normal non-pregnant level.

[Basic study on criteria for the reactivity of non-stress tests by means of computer simulation].

The non-stress test has become one of the most popular tests for antenatal surveillance in modern obstetrics. However, the fact that there are so many criteria for 'reactivity' in this test has made it rather difficult to interpret the results of these tests and compare them with each other. Using computer simulation of the occurrence of acceleration in fetal heart beats, the sensitivity and specificity of eight criteria which are in general use were studied. Diagnosis by Brown's criteria produced the best results for both sensitivity and specificity, but the long time necessary for this test is a drawback. However, the predictive value positive (probability of poor fetal outcome with nonreactivity) is only 62% even according to Brown's criteria when the test is done for antenatal care screening of an unrestricted population. The results of the test are far more convincing when it is reactive because the predictive value negative is more than 96%, even when strictly interpreted.

Computer prediction of congestion in the obstetric ward.

A computer system was developed to predict congestion of the obstetric ward in the near future. The admittance and stay in the obstetric ward of every registered patient are simulated based on the table of reservation and observed data of hospital stay, and from this the number of inpatients (occupied beds) is predicted. If the expected date of confinement of every obstetric patient is put into the computer and the information on patients who have already given birth is deleted, it is possible to obtain a reasonably accurate prediction.

Non-invasive continuous fetal transcutaneous pO2 and pCO2 monitoring during labor.

Continuous measurements of fetal scalp transcutaneous pO2 (tcpO2) and pCO2 (tcpCO2) monitoring were performed for 49 patients for the purpose of the evaluation of the fetal well-being. The equipment used was transcutaneous pO2/pCO2 monitor Micro Gas 7640 (KONTRON, Switzerland), which was inserted through the vagina and attached to the fetal head with a suction ring. Blood was taken from the umbilical vessels and pO2 and pCO2 values were analyzed. The correlation coefficient between pO2 in the umbilical artery and tcpO2 was 0.78 (p less than 0.01), and that between pCO2 in the umbilical artery and tcPCO2 was 0.79 (p less than 0.01). Relationships between the transcutaneous blood gas analysis and FHR patterns were discussed. Increase of pCO2 and decrease of tcpO2 was observed in the cases of variable deceleration, not observed in the case of early deceleration. FHR patterns don't always indicate fetal condition, for example in the case of fetal arrhythmia, especially fetal bradycardia. But tcpO2 monitoring of the fetus affected fetal arrhythmia during labor aids diagnosis of fetal distress by FHR patterns, especially in the case of fetuses affected by fetal bradycardia.

Fetal heart variability indices and the accuracy of variability measurements.

Several indices of fetal heart rate variability, including short-term variability (STV) and long-term variability (LTV) were analyzed. All the STV indices studied were found to be almost identical statistically. The LTV indices of de Haan et al were the same in essence, while other LTV indices reflected only the fluctuation around the mean fetal heart rate. Analysis using a signal generator indicates that the value of the standard deviation of beat-to-beat difference (one STV index) of less than 7 msec, through the cardiotocomonitor is unreliable; if the standard deviation of beat-to-beat difference is to be measured with an accuracy of 1 msec, an accuracy of measurement of 0.11 msec is necessary even if the fetal heart beat data are sampled with a sampling interval of 1 msec.

[Management of the goat fetus in water using membrane oxygenator by V-A bypass through the cervical vessels--comparison with the A-V bypass method through umbilical vessels].

Fourteen goat fetuses were totally sustained in water by extracorporeal perfusion using a membrane oxygenator. The two groups which underwent perfusion methods may be described as follows: One was an A-V bypass through umbilical vessels which has been reported previously, and the other was a new method, a V-A bypass through cervical vessels. Ten fetuses were perfused by an A-V bypass and the longest survival time was 9 hours. Three fetuses suddenly died shortly after perfusion was started. Four fetuses were perfused by a V-A bypass and the longest survival time was 27 hours. Cardiovascular dynamics were stable from the beginning of perfusion. Autopsy revealed hepatomegaly and bloody ascites in A-V bypassed fetuses but not in the fetuses perfused by a V-A bypass. The A-V bypass through umbilical vessels resembles physiological fetal circulation, and the cannulation technique is not difficult but it needs strict control, especially in the early stages of perfusion. A V-A bypass through cervical vessels doesn't seem to be close to a physiological perfusion for fetuses and the cannulation technique is difficult. But the cardiovascular dynamics are stable, so they are employed for clinical uses in neonatal ECMO. The V-A bypass method seems to be an adequate technique for managing extremely premature fetuses in water.