Fetal heart rate patterns in postasphyxiated fetal lambs with brain damage

OBJECTIVE: We previously showed that in asphyxiated fetal lambs the duration of hypotension correlated well with the severity of histologic damage to the brain, whereas the duration of bradycardia did not. This study compares fetal heart rate patterns with the degree of histologic damage to the brain. STUDY DESIGN: Twelve chronically instrumented near-term fetal lambs were subjected to asphyxia by umbilical cord occlusion until fetal arterial pH was <6. 9 and base excess was <-20 mEq/L. An additional 4 fetuses served as sham-asphyxia controls. Fetal heart rate (from electrocardiogram), arterial blood pressure, fetal breathing movements, and electrocorticogram were continuously monitored before, during, and for 72 hours after asphyxia. Fetal brain histologic features were categorized as mild (group 1, n = 5), moderate (group 2, n = 4), and severe (group 3, n = 3). Long-term fetal heart rate variability expressed as amplitude range was assessed visually every 5 minutes from 30 minutes before asphyxia until 2 hours of recovery and at 6, 12, 24, 48, and 72 hours of recovery. RESULTS: Long-term fetal heart rate variability amplitude decreased from 32 +/- 17 beats/min (mean +/- SEM) preocclusion to 4 +/- 13 beats/min at the end of occlusion (P <.001) without significant differences among the 3 groups. During 10 to 45 minutes of recovery, the long-term variability of group 1 was significantly greater than that of groups 2 and 3. At 24 to 72 hours of recovery, the long-term variability of groups 1 and 2 was significantly higher than that of group 3, which was almost 0. The "checkmark" and sinusoidal fetal heart rate patterns were observed during the recovery period in groups 2 and 3. CONCLUSIONS: Decreased long-term fetal heart rate variability and the "checkmark" and sinusoidal fetal heart rate patterns were indicators of the severity of asphyxial histologic damage in the fetal brain.     

Dexamethasone and fetal heart rate variation

OBJECTIVE: To determine the effect of maternal administration of dexamethasone on fetal heart rate and its variation. DESIGN: Retrospective analysis of computerised data derived from cases studied over three years. SETTING: High risk pregnancy unit, John Radcliffe Hospital, Oxford. SUBJECTS: Twenty-eight pregnant women, at 27 to 32 weeks of gestation, to whom dexamethasone was given to accelerate pulmonary maturation in the expectation of preterm delivery. METHODS: Dexamethasone (two doses of 12 mg intramuscularly, 12 h apart) was given on 51 occasions at weekly intervals (one to four occasions per patient). Complete data were available for cardiotocograph analysis from computerised measurement of fetal heart rate variables for two days before and four days after dexamethasone and, in 19 women, measurements of umbilical arterial flow velocity waveforms before and after dexamethasone. RESULTS: In 10 pregnancies without fetal distress there was a highly significant (P < 0.01) transient rise in short term fetal heart rate variation after dexamethasone administration, from means (SE) 6.4 (0.28) to 9.8 (0.4) ms. In 18 pregnancies with subsequent delivery for fetal distress (abnormal fetal heart rate pattern) and high umbilical arterial resistance index [mean 0.93 (0.06 SE)], the rise in short term fetal heart rate variation was less (P < 0.01), from mean (SE) 5.4 (0.26) to 6.1 (0.48) ms. In a further case of discordant twin pregnancy, the larger twin continued to respond to dexamethasone administrations with a rise in fetal heart rate variation for five weeks; the smaller twin, with maintained tachycardia and reduced umbilical arterial end-diastolic flow velocity, failed to respond after the first two weeks. CONCLUSION: The results show that maternal dexamethasone administration normally causes a rise in fetal heart rate variation for up to a day. This rise is reduced in pre-eclampsia or intrauterine growth retardation, associated with a reduction in umbilical flow, perhaps because of a consequential lower concentration of steroid in the fetus. The results contrast with those for betamethasone which has been reported to reduce fetal heart rate variation.     

The sex-peptide gene (Acp70A) is duplicated in Drosophila subobscura

OBJECTIVE: We quantified the presence of diurnal rhythms in various computerized fetal heart rate parameters in normal pregnancies to assess their clinical relevance. STUDY DESIGN: Modified cosine analysis was applied to the outcomes of computerized analysis of continuous 24-hour fetal heart rate recordings in 26 normal pregnancies. Diurnal rhythms in maternal heart rate and plasma hormones were assessed in 15 and 17 pregnancies, respectively. Correlations between maternal and fetal rhythms were calculated. RESULTS: A significant diurnal rhythm in basal heart rate was present in 73% of the fetuses and was closely related to the maternal heart rate rhythm. Diurnal rhythms in heart rate variability, accelerations, and activity were present in only 30% to 50% of the fetuses. CONCLUSIONS: The mother entrains fetal diurnal rhythms. The normal variability in neural development may account for the absence of diurnal rhythms in some fetuses.     

5-Hydroxytryptamine1D-like receptors mediate contraction of partially depolarized rabbit renal arteries

OBJECTIVE: Our purpose was to correlate measures of Doppler-detected fetal movements with standard fetal heart rate parameters and perinatal outcomes. STUDY DESIGN: This prospective, multiinstitutional trial used the Hewlett-Packard M1350A monitor to record simultaneous fetal heart rate baseline, variability, accelerations, decelerations, and number of fetal movements, and duration and percent of total time. These data were compared at 10- and 30-minute intervals during nonstress tests and were correlated with fetal heart rate baseline parameters and maternally perceived fetal movements and with outcomes of infants delivered within 7 days of the last test. RESULTS: At six centers 1704 actocardiograms from 884 third-trimester patients were analyzed. Doppler-detected fetal movement counts, durations, and percent of total time correlated weakly with all baseline fetal heart rate parameters (all values < 0.20). All fetal movement parameters increased significantly in successive 10-minute blocks and in periods of increased or normal fetal heart rate variability compared with those with fetal heart rate variability. The sensitivity, specificity, and predictive values of the percent of total movement time were comparable to those of standard nonstress test parameters. The risk of poor perinatal outcomes after nonreactive nonstress tests was lower in cases with fetal movements than in those without. CONCLUSIONS: Doppler actocardiography may help to discriminate fetal states during antepartum testing. It may prevent inappropriate diagnosis of fetal compromise when the nonstress test is nonreactive or nonreassuring.     

A placebo-controlled comparison between betamethasone and dexamethasone for fetal maturation: differences in neurobehavioral development of mice offspring

OBJECTIVE: Our purpose was to determine whether antenatal betamethasone or dexamethasone is the preferred drug by use of neurobehavioral development assessment of exposed mice offspring. STUDY DESIGN: Thirty adult CD-1 mice were randomly assigned to one of three groups (n = 10) to be administered a single subcutaneous dose of either a placebo (0.9% sodium chloride), betamethasone (0.10 mg), or dexamethasone (0.10 mg) on day 14 (74%) of gestation. The offspring then performed a battery of sensory, motor, motivational-anxiety, cognitive, and social tasks. Data were compared with use of analysis of variance, Kruskal-Wallis, or chi2 testing where appropriate. RESULTS: The offspring from the three treatment groups were indistinguishable at birth. Dexamethasone exposure induced a brief developmental delay. Separation anxiety was increased in the dexamethasone-exposed group in the perinatal period, whereas exposure to both corticosteroids decreased anxiety in the juvenile period, continuing into adulthood among male betamethasone-exposed mice. Selective enhancement of a memory process occurred in betamethasone-exposed mice, whereas dexamethasone exposure resulted in a decrement. Socialization as to place preference while awake and asleep varied among the three treatment groups. Corticosteroid treatment did not induce significant changes in sensory, motor, motivation, and learning performances or in reproductive capability and progeny development. CONCLUSION: Subtle differences in offspring performances of neurobehavioral development tasks favored antenatal betamethasone rather than dexamethasone. This finding, along with the knowledge that dexamethasone is less potent in accelerating lung maturity in the fetal mouse, suggests that betamethasone may be the preferred corticosteroid to use when human preterm delivery is imminent.     

MRI does not change fetal cardiotocographic parameters

The aim of this study was to determine whether magnetic resonance imaging (MRI) has any effect on fetal cardiotocographic (CTG) parameters or movement incidence. Sixteen mothers were examined during the last trimester at 28-39 weeks (mean 33 weeks; SD 4) of gestation due to a suspected fetal anomaly found in antenatal ultrasonography (US). MR imaging was performed using Siemens Magnetom Vision 1.5 T equipment with a 25 mT/m peak gradient amplitude. T2-weighted images were produced with HASTE and TRUE-FISP sequences and T1-weighted images with a 2D FLASH sequence. A four-element phase-array coil was used as the receiver. Before and after MRI-examination, a computerized analysis of the fetal heart rate (FHR) was produced. Basal FHR, short-term variation (STV) and fetal movements were calculated. The mean basal FHR was 136 beats/min (SD 11.6) before, and 133 beats/min (SD 8.9) after (P = 0.158). Short-term variation was in the normal range for both CTG-tracings: mean 9.7 ms (SD 2.7) and 8.8 ms (SD 2.8) (P = 0.196). The median for fetal movements before MRI was 48/h, and after MRI 24.5/h (P = 0.98). MRI at high field strength with powerful gradients did not affect fetal heart activity or movement incidence.     

Effects of 4 hours magnesium sulfate infusion on fetal heart rate variability and reactivity in a goat model

Effects of magnesium sulfate were investigated on fetal heart rate (FHR) baseline, variability, and reactivity in goats. Six chronically catheterized fetuses of Japanese Saanen goat at 125 to 130 days' gestation (term = 147 days) were used. Magnesium sulfate was directly infused to the fetuses. Short-term variability and long-term variability were obtained according to Huey et al. The baseline, reactivity, short-term variability and long-term variability of the FHR were compared between those receiving magnesium sulfate infusions and those receiving vehicle infusions without magnesium sulfate for 4 hr. Two-way analysis of variance (ANOVA) and Duncan's multiple range test was applied for statistical significance. Four hours magnesium sulfate infusion significantly increased fetal plasma concentration of magnesium from 2.4-6.6 mg/dL, without significant changes in fetal respiratory gases and pH values. The baseline FHR was significantly decreased by magnesium infusion compared with that receiving vehicle infusion. The incidence of acceleration, short-term variability, and long-term variability during the fourth hour of magnesium infusion was also significantly decreased compared to a controlled infusion. The time spent by high amplitude phase of short-term variability and that of long-term variability were also significantly reduced. Significant correlation was obtained between the magnesium concentration and incidence of acceleration at fourth hour of magnesium infusion. Four hours infusion of magnesium sulfate significantly decreases baseline FHR, short-term variability, long-term variability, and reactivity in fetal goats at 0.85 gestation.     

Cardiotocogram compared to Doppler investigation of the fetal circulation in the premature growth-retarded fetus: longitudinal observations

It was our objective to compare computerized fetal heart rate analysis with blood flow velocity waveform analysis of the arterial and venous fetal circulation in intrauterine growth retardation. We report five illustrative cases with longitudinal observations of fetal Doppler findings and fetal heart rate between 23 and 32 weeks of gestation. Blood flow waveforms were recorded from the umbilical artery, middle cerebral artery, descending aorta, ductus venosus and inferior vena cava. Fetal heart rate was analyzed by a computer system according to the Dawes-Redman criteria. The time sequence of deterioration is described individually for each fetus. An abrupt increase in pulsatility of ductus venosus waveforms with loss of forward flow velocity during atrial contraction preceded abnormally low short-term variation of fetal heart rate. With advanced gestational age and concomitant maternal disease, we observed severe alterations of flow velocity waveforms within 12 h of normal Doppler measurements, which is in contrast to findings in the second trimester, in which severely abnormal venous waveforms were observed over a period of several weeks before intrauterine death occurred. In a fetus with terminally low short-term variation, normal venous waveforms indicated fetal well-being despite an abnormal cardiotocogram (CTG). We challenge the current concept that the CTG is the best available parameter to determine the optimal time for elective delivery of premature growth-retarded fetuses. Deterioration in ductus venosus blood flow seems to precede an abnormal CTG and thus heralds the need for delivery.     

Dexamethasone treatment of the guinea pig fetus: its effects on the incorporation of 3H-thymidine into deoxyribonucleic acid

Pregnant guinea pigs of 50 to 53 days' gestation (term 63 days) were anesthetized with ether, and their fetuses were injected intramuscularly with 30 mg of dexamethasone or sterile saline. One week later, the fetuses were injected with 3H-thymidine intramuscularly under direct vision at laparotomy; after one hour, the incorporation of thymidine into deoxyribonucleic acid (DNA was analyzed in various fetal tissues. The relative labeling of DNA was significantly depressed in the cerebral hemispheres, cerebellum, medulla oblongata, and midbrain of the treated fetuses compared to their littermate controls. The relative labeling of the DNA of lungs, kidneys, heart, and adrenals was also significantly reduced. Increasing the dose of dexamethasone produced a progressive inhibition of the incorporation of 3H-thymidine into DNA. A variable recovery from the inhibition became apparent by 14 days following exposure to dexamethasone. The evidence suggests that exposure of the fetus to dexamethasone may exert a potentially deleterious effect on fetal tissues.     

Nonstressed fetal heart rate monitoring in the antepartum period

The role of nonstressed monitoring of the fetal heart rate (HR) in determining fetal well-being during the antepartum period was assessed in 125 high-risk patients. Observations on HR, variability, and HR response to fetal movement (FM) and uterine contractions (UC) over a 30 minute period were made with an external microphone and tocotransducer. A total of 625 tests were performed; the earliest gestation tested was 28 weeks, and the latest was 46 weeks. A reactive pattern (variability greater than 6 b.p.m. and accelerations with FM) appears to be a reliable indicator of fetal well-being. All the 51 fetuses exhibiting this pattern survived. This group also had the lowest incidence of neonatal complications. On the other hand, of the babies who failed to show variability greater than 6 b.p.m. or accelerations with FM (nonreactive pattern), 40% died in the perinatal period. Thirty-five patients showed features of both a reactive and nonreactive pattern (combined pattern). Poor outcome in this group was confined to those in whom the majority of the pattern was nonreactive. An undulating HR pattern with virtually absent variability (sinusoidal pattern) was found in 20 Rh-sensitized fetuses, 50% of whom died in the perinatal period. Bradycardia and tachycardia were not found to be reliable signs of fetal distress antepartum. Of the 12 fetuses who died during observation, six showed late decelerations with spontaneous UC but all showed diminished variability. The close correlation between nonstressed patterns and neonatal outcome demonstrated by this preliminary study warrants further use of this technique for fetal evaluation.     

Heart rate variability index in congestive heart failure: relation to clinical variables and prognosis

AIM: To evaluate the clinical and prognostic value of the heart rate variability index in patients with congestive heart failure. METHODS: Sixty-four patients with chronic congestive heart failure and sinus rhythm underwent clinical assessment, 24-h ambulatory electrocardiography and echocardiography. Patients were followed for 6 to 30 months. Cardiac death or heart transplantation constituted the primary end-point of the study. RESULTS: The heart rate variability index was related to left ventricular ejection fraction (r=0.29, P=0.02) and New York Heart Association class (P=0.01). Patients with a restrictive left ventricular filling pattern had a lower heart rate variability index compared to patients with a non-restrictive pattern (26+/-11 vs 33+/-9 units, P=0.01). Patients who died (n=11) or underwent heart transplantation (n=4) had a lower heart rate variability index compared to survivors (21+/-10 vs 33+/-9 units, P<0.0001). In multivariate survival analysis, a reduced heart rate variability index was related to survival independent of parameters of left ventricular function. CONCLUSION: The heart rate variability index provides independent information on clinical status and prognosis in patients with chronic congestive heart failure.     

Doppler study of the fetal cardiac function in prolonged pregnancies

OBJECTIVE: To evaluate the association between fetal cardiac function and amniotic fluid index (AFI) in postterm fetuses, and to determine if changes in fetal cardiac function precede the occurrence of nonreassuring intrapartum fetal heart rate (FHR) patterns. METHODS: Forty-five otherwise low-risk pregnant women between 41 and 43 weeks' gestation were studied longitudinally. Gestational age was confirmed in all patients by ultrasound before 20 weeks' gestation. Each subject had two or three tests performed every 3-4 days, including a non-stress test, a biophysical profile, and Doppler studies of the aortic and pulmonic outflow tracts. Aortic and pulmonic artery flow velocity waveforms were recorded slightly distal to the valves. Peak velocity, velocity time integral, and heart rate were calculated from the flow velocity waveforms we obtained. The change in AFI and aortic and pulmonic peak velocity and [velocity time integral] x [heart rate] were calculated for each fetus. RESULTS: Labor was induced at 42 weeks' gestation in 20 patients, and 17 entered labor spontaneously. Changes in AFI, observed during the follow-up period, correlated significantly with changes in aortic peak velocity (r = 0.54, P < .01) and with aortic outflow [velocity time integral] x [heart rate] (r = 0.60, P < .001) but not with pulmonic peak velocity and [velocity time integral] x [heart rate]. The decrease in aortic peak velocity and aortic and pulmonic [velocity time integral] x [heart rate] was significantly higher (P < .01) in eight fetuses that developed a nonreassuring intrapartum FHR (reduced FHR variability, late decelerations, and severe variable decelerations) than in those who had an uneventful labor. CONCLUSION: In prolonged pregnancies, cardiac function deteriorates in fetuses that develop a nonreassuring intrapartum FHR, and the changes in the left cardiac function correlate with changes in AFI.     

Simultaneous determination of nerisopam, a novel anxiolytic agent showing polymorphic metabolism, and its N-acetyl metabolite from human plasma by a validated high performance liquid chromatographic method

OBJECTIVE: Our goal was to determine the effect of chronic and acute umbilical-placental embolization on placental hemodynamic and fetal heart rate patterns in relation to fetal oxygenation in the near-term ovine fetus. STUDY DESIGN: Daily fetal placental embolization was performed during 10 days in 9 sheep fetuses until fetal arterial oxygen content decreased by approximately 30%. Nine control fetuses received saline solution. Mean and pulsatile umbilical blood flow, perfusion pressure, placental vascular resistance, fundamental impedance, pressure pulsatility index, and umbilical artery resistance index corrected to a fetal heart rate of 160 beats/min were measured. On day 10 both groups were acutely embolized until fetal arterial pH decreased to approximately 7.00. Fetal heart rate was measured with the Sonicaid System 8000 (Oxford Sonicaid, Oxford, United Kingdom). RESULTS: Chronic fetal placental embolization was associated with a progressive reduction in umbilical blood flow (p < 0.00001) and fetal arterial oxygen content (p < 0.001) whereas fetal heart rate patterns remained unaltered. A chronic increase in umbilical artery resistance index corrected to a fetal heart rate of 160 beats/min could be entirely explained only if the changes in umbilical artery pressure pulsatility index and the fundamental impedance were taken into account, in addition to the changes observed in placental vascular resistance. During acute embolization leading to a 50% reduction in umbilical blood flow (p < 0.0002) and a three times increase in placental vascular resistance (p < 0.0001), the most consistent change in fetal heart rate patterns related to progressive metabolic acidosis was an 84% decrease in absolute acceleration frequency (p < 0.0001) whereas short-term fetal heart rate variability remained unaltered. CONCLUSION: Changes in umbilical artery resistance index induced by chronic umbilical-placental embolization resulting in fetal hypoxemia occurred before any changes in fetal heart rate patterns were detectable. A decrease in the absolute acceleration frequency was the only component of fetal heart rate patterns related to progressive metabolic acidosis in the near-term ovine fetus.     

Vibroacoustic Stimulation of the Fetus Using a Conventional Mechanical Alarm Clock

> Objective: For more than 20 years, vibroacoustic stimulation testing (VAST) using an artificial larynx has been used worldwide when fetal heart rate monitoring produced patterns with absent or very low variability. In addition to the artificial larynx many other appliances have been used to stimulate a seemingly dormant fetus, but these have rarely been evaluated properly. In this study we tried to evaluate the use of standard mechanical wind-up alarm clocks for VAST. Methods: VAST with an alarm clock was performed successfully in 80 women with normal pregnancies from 36 weeks to term. It was tested by placing the alarm clock on the maternal abdomen just above the fetal head or on the controlateral side of the maternal abdomen to see whether position made any difference and whether coupling with ultrasound gel applied between the alarm clock and the maternal abdomen would affect the degree of fetal reaction to VAST as expressed in heart rate acceleration. Similarly, the effect of the alarm clock VAST on subjective and objective fetal movement patterns as registered by kineto-cardiotocotraphy (K-CTG) in addition to heart rate patterns was investigated. Results: All fetuses showed heart rate acceleration, an increase in heart variability, and increase in movement patterns in the 6 min after the application of alarm clock VAST. No statistically significant difference was found which would favor a particular placement of the alarm clock on the maternal abdomen or the use of ultrasound coupling gel. When K-CTG was performed, patient-perceived fetal movements as expressed with an event marker showed agreement with the machine-registered movements only when patients could see the tracing during registration and no accordance when the K-CTG was turned toward the wall during registation. Conclusion: In keeping with the ALARA principle a conventional wind-up alarm clock appears to be an inexpensive and effective alternative to the electrolarynx.     

Limitations in equine fetal electrocardiography

Technical and interpretive limitations of equine fetal electrocardiography were evaluated in recordings obtained from 45 pregnant mares. Technical limitations were related to the small amplitude of the fetal electrocardiogram and the variability in the lead configuration providing the best recording. It was found that recording the fetal electrocardiogram at high sensitivity and high base-line fidelity in several different leads was necessary to obtain satisfactory tracings. Interpretive limitations were related in part to the small amplitude of the fetal electrocardiogram and to the marked variability in heart rate between fetuses. The great variability in normal fetal heart rate makes a diagnosis of fetal tachycardia or distress unless serial tracings are available.     

Gender does not affect fetal heart rate variation

There is a widespread but erroneous view among the lay public that there is a difference in the baseline fetal heart rate between male and female fetuses. It has been suggested that this perception might reflect an actual difference in fetal heart rate variability. Therefore, we studied the fetal heart rate variation in 79 white European women using the Sonicaid System 8002 computer. Fourty-four of the fetuses were male and 35 were female. There was no significant gender difference in any measured aspect of fetal heart rate variation.     

Increased concentrations of endothelin-1 messenger RNA in tissues and endothelin-1 peptide in plasma in septic pigs: modulation by betamethasone

OBJECTIVES: To study the expression of preproendothelin-1 messenger RNA (mRNA) in tissue after Escherichia coli lipopolysaccharide challenge and to evaluate the possible effects of betamethasone both regarding endothelin-1 production as well as hemodynamic and vascular effects during E. coli lipopolysaccharide infusion in pigs in vivo. DESIGN: Prospective trial. SETTING: Laboratory at a university medical center. SUBJECTS: Ten domestic pigs, weighing 18 to 25 kg. INTERVENTIONS: Anesthetized pigs were given continuous infusions of E. coli lipopolysaccharide (15 micrograms/kg/hr for 3 hrs), with or without prior treatment with betamethasone (0.5 mg/kg im 12 hrs before the start of the surgical preparation and 0.5/kg iv at the start of the preparation). MEASUREMENTS AND MAIN RESULTS: The E. coli lipopolysaccharide infusion evoked the characteristic cardiovascular changes observed in septic shock: decreased mean arterial pressure and cardiac output; increased heart rate and increased pulmonary vascular resistance. Large increases in both arterial plasma concentrations of endothelin-1-like immunoreactivity, as well as preproendothelin-1 mRNA concentrations in tissues, were also observed during the E. coli lipopolysaccharide infusion. Treatment with betamethasone significantly attenuated the E. coli lipopolysaccharide-induced increase in endothelin-1 plasma concentrations, whereas the increased mRNA concentrations were only slightly affected. Furthermore, betamethasone treatment also affected cardiovascular parameters, with significant attenuation of the E. coli lipopolysaccharide-induced increase in heart rate and a higher cardiac output after 60 mins of the E. coli lipopolysaccharide infusion. The urine production, which was markedly decreased during the E. coli lipopolysaccharide infusion, was significantly higher in the betamethasone-treated group compared with the control group. CONCLUSIONS: The present results indicate that the increased concentrations of endothelin-1-like immunoreactivity that are observed in septic shock may have negative effects on both cardiovascular parameters as well as renal function, which is in agreement with a possible role for endothelin-1 in the pathogenesis of septic shock.     

Causality and control: key to the experiment

Maternal betamethasone administration causes a transient but considerable reduction in fetal body and breathing movements and in fetal heart rate variation. The aim of the present prospective study was to investigate whether there is evidence of circulatory changes in fetal, placental or uterine arteries, consistent with hypoxemia. Eighteen women at risk for preterm delivery received betamethasone to enhance fetal lung maturation. Doppler studies were performed before treatment, and 24 and 72 h after the second dose of betamethasone. Blood flow velocity waveforms were obtained from both uterine arteries, umbilical arteries, fetal descending aorta, fetal renal artery, and fetal cerebral arteries. No significant changes occurred in the pulsatility index of any of these blood vessels, suggesting that the transient reduction in fetal heart rate variation and fetal body and breathing movements following maternal betamethasone administration is not mediated through fetal hypoxemia.     

Complete congenital atrioventricular block. Prenatal diagnosis and perinatal management

OBJECTIVE: To describe our experience in prenatal diagnosis and perinatal management of congenital atrioventricular heart block, as well as pacemaker treatment in the neonate. MATERIAL AND METHODS: A total of 13 fetuses are included. The diagnosis of atrioventricular dissociation was established by Doppler heart rate sample in the right atrium to show the atrial activity while the sample in the Aorta reflected the ventricular heart rate. Gestational age at diagnosis, ventricular heart rates, autoimmune maternal pathology, maternal blood tests for autoantibodies antiRo+, congenital structural heart disease, fetal hydrops, maternal medical treatment, perinatal results and pacemaker neonatal implantation are described. RESULTS: Gestational age at diagnosis ranged between 22 and 32 (mean 27.6) weeks. Ventricular heart rates ranged between 32 to 80 (mean 54) beats/min. AntiRo+ antibodies were detected in 5 mothers, and clinical systemic lupus erythematosus was found in only one. Four had congenital heart disease (2 ventricular inversion and corrected TGA, 1 complete atrio-ventricular canal and 1 tricuspid atresia). Signs of heart failure and hydrops were detected in 9 fetuses. Treatment with beta-metasona and ritodrine was administered to 7 mothers when the ventricular heart rate dropped below 60 beats/min. Intrauterine fetal death occurred in 3 fetuses with structural congenital heart disease and hydrops. Delivery was performed by cesarean section in 8 preterm fetuses (one them a twins), 3 spontaneous deliveries at term and 3 stillbirth. Postnatal pacemaker implantation was carried out in 9 newborns (3 cases with unicameral temporal right ventricle electrode and 6 cases with permanent bicameral electrodes implanted through the subclavian vein and DDD pacemaker). Follow-up of the bicameral pacemaker group was satisfactory. CONCLUSION: Persistent fetal bradycardia is the first sign to diagnose prenatal complete atrioventricular heart block. Echocardiography asses fetal haemodynamic status and may detect signs of fetal deterioration. Hydrops and further drop in the ventricular heart rate warrant urgent cesarean section and pacemaker management of the newborn.     

Immunolocalisation of P450(C17) in the fetal sheep adrenal gland during gestation and in response to ACTH and glucocorticoid administration

In sheep, increased output of cortisol from the fetal adrenal gland is critical to organ maturation and parturition. Cortisol synthesis is determined in part by the activity of P450(C17) enzyme. We have used immunohistochemistry and Western immunoblotting to examine the distribution of P450(C17) in the ovine fetal adrenal during gestation, and after ACTH or dexamethasone administration to fetuses between Days 125 and 130. The patterns were compared with changes in 3beta-hydroxysteroid dehydrogenase (3beta-HSD) localisation and levels. Adrenal tissue was obtained from four fetuses at each of Days 63-65, 100, 125-130 and term (>140 days). Further animals were chronically catheterised and infused with ACTH, dexamethasone or saline for 96 h beginning on Day 125. Immunohistochemistry for P450(C17), 3beta-HSD, and phenylethanolamine-N-methyl transferase (PNMT) was conducted using standard techniques. At Day 63-65 of pregnancy immunoreactive (ir-)P450(C17) was present in cords of cells throughout the adrenal gland. Ir-P450(C17) was reduced or was undetectable at Day 100, but had increased by Day 125-130, and was present throughout the zona fasciculata of the adrenal cortex of term animals. An increase in P450(C17) protein was also seen between Day 100 and 125 by Western blotting, and after ACTH treatment. Dexamethasone administration led to a marked reduction in ir-P450(C17) levels. In contrast, ir-3beta-HSD was present in the fetal adrenal cortex between Day 100 and term, and was less affected by ACTH or dexamethasone treatment. We conclude that P450(C17) in the fetal sheep adrenal is responsive to regulation by ACTH, and that changes in its levels correlate with previously reported alterations in patterns of cortisol output by the fetal adrenal gland.