Fetal heart rate variability changes during brief repeated umbilical cord occlusion in near term fetal sheep.

OBJECTIVE: To determine whether changes in fetal heart rate variation during repeated umbilical cord occlusions reflect evolving cardiovascular compromise in near term fetal sheep. DESIGN: Fetal heart rate variation, fetal mean arterial pressure, electroencephalogram (EEG) and acid-base status were measured during one minute umbilical cord occlusions, repeated either every five minutes (1:5 group) or every 2.5 minutes (1:2.5 group) for four hours or until mean arterial pressure fell below 20 mmHg for two successive occlusions. SAMPLE: Fourteen chronically instrumented fetal sheep, mean gestation 126.3 (2.6) days. RESULTS: Cord occlusion caused variable decelerations with initial sustained hypertension. In the 1:5 occlusion group mean arterial pressure remained elevated throughout, with little change in acid-base status (pH = 7.34 (0.07), base deficit = 1.3 (3.9) after 4 hours) and no significant change in fetal heart rate variation. In contrast, in the 1:2.5 group from the third occlusion there was progressive hypotension during occlusions, severe progressive metabolic acidaemia (pH 6.92 (0.1), base deficit 17.0 mmol/L (4.7) after the last occlusion) and marked EEG suppression (P < 0.01). Fetal heart rate variation increased with the onset of occlusions (P < 0.05) and then progressively fell with continued occlusions. During the last 30 minutes of occlusions, fetal heart rate variation was severely suppressed in four, but increased in two fetuses, while all six fetuses developed overshoot-instability of fetal heart rate and mean arterial pressure following each occlusion. CONCLUSIONS: Acute progressive asphyxia was typically associated with an immediate, transient increase in fetal heart rate variation. Subsequently variation became suppressed in only two-thirds of fetuses during terminal acidaemia and hypotension. Fetal heart rate overshoot-instability may be a useful marker of fetal decompensation following variable decelerations.     

Fetal arterial pressure and heart rate changes in surviving and non-surviving immature fetal sheep following brief repeated total umbilical cord occlusions

OBJECTIVE: To compare the neonatal outcome (survival, intraventricular hemorrhage and bronchopulmonary dysplasia) of inborn and outborn very-low-birth-weight infants accounting for sociodemographic, obstetric and perinatal variables. STUDY DESIGN: Ninety-one premature infants with birth weights of 750-1250 g delivered between 1990 and 1994 in a hospital providing neonatal intensive care were compared with 76 premature babies delivered in a referring hospital. In the statistical analysis, variables with a statistically significant association with the outcome variables and dissimilar distributions in the two hospitals were identified and entered together with the hospital of birth as explanatory variables in a logistic regression. RESULTS: No statistically significant differences between the outcome variables of the two populations examined were observed, whether before or after accounting for the covariates. The odds ratios (outborns relative to inborns) were 1.18 for mortality, 1.25 for bronchopulmonary dysplasia and 1.53 for severe intraventricular hemorrhage. In the multivariate analyses, respiratory distress syndrome was significantly associated with mortality; both low birth weight and the presence of respiratory distress syndrome were associated with the development of bronchopulmonary dysplasia; the evolvement of severe intraventricular hemorrhage was associated with respiratory distress syndrome, initial low Apgar score, advanced multiparity and delivery at the 28-29th week compared to the 23rd-27th week. Antenatal steroid administration had a protective effect. CONCLUSION: Our results concur with the notion that a tertiary center is the optimal location for delivery of the high risk neonate. Improvement in medical and nursing care prenatally and at delivery and transportation, including frequent administration of antenatal steroids and earlier administration of surfactant prior to transportation, may minimize the disadvantage of delivery in a referring hospital.     

The slope of fetal heart rate deceleration is predictive of fetal condition during repeated umbilical cord compression in sheep

The relationship between components of fetal heart rate deceleration and fetal arterial blood gas values or plasma catecholamine concentrations was investigated by repeated complete umbilical cord compression in chronically instrumented fetal lamb. Fetal arterial pH and bicarbonate levels decreased, while plasma norepinephrine and epinephrine concentrations increased more than tenfold. The slope of the descending limb of the fetal heart rate deceleration curve decreased and correlated strongly with fetal arterial pH, bicarbonate, and logarithmic plasma norepinephrine and epinephrine concentrations. Fetal arterial pH and bicarbonate levels were significantly lower in the group with lower fetal heart rate deceleration slope, and a greater plasma catecholamine concentration in this group suggested a redistribution of blood flow to vital organs. Therefore, during repeated umbilical cord compression, the fetal acid-base and hormonal state was predicted by the fetal heart rate deceleration slope. This relationship may be applicable to human fetuses in the diagnosis of fetal distress caused by umbilical cord compression during labor.     

The PR interval-fetal heart rate relationship during repetitive umbilical cord occlusions in immature fetal sheep

OBJECTIVE: To evaluate the relationship of the PR interval and fetal heart rate during repetitive umbilical cord occlusions in immature sheep fetuses. STUDY DESIGN: In seven chronically cannulated immature sheep fetuses [gestational age 90.6 days (mean)], we analyzed continuous fetal electrocardiogram recordings during repetitive cord occlusions for 2 out of every 5 min until fetal mean arterial pressure dropped to 50% of baseline value. PR interval-fetal heart rate correlation coefficients (Pearson) was measured on consecutive blocks of 2.5 min. R-values of the baseline and the repetitive occlusion period were compared by Fisher's exact test. RESULTS: Repetitive cord occlusions resulted in acidosis and hypotension. Two fetuses died at the end of the repetitive occlusion period. Four out of seven fetuses showed a significant change from a negative relationship between the PR interval and fetal heart rate during baseline to a predominantly positive relationship during the repetitive occlusion period. CONCLUSION: In immature fetal sheep, a change from a negative relationship between the PR interval and fetal heart rate to a predominantly positive relationship between the PR interval and fetal heart rate was observed in four out of seven fetuses following the initiation of repetitive umbilical cord occlusions.     

ST waveform changes during repeated umbilical cord occlusions in near-term fetal sheep

OBJECTIVE: This study was undertaken to determine whether changes in the fetal ST waveform during repeated umbilical occlusion reflect the development of hypotension and acidosis.Study Design: Chronically instrumented, near-term fetal sheep received 1-minute total umbilical cord occlusion either every 5 minutes for 4 hours (1:5 group, n = 8), or every 2.5 minutes until blood pressure fell <20 mm Hg on 2 successive occlusions (1:2.5 group, n = 8). RESULTS: Umbilical cord occlusion caused variable decelerations, with sustained hypertension in the 1:5 group and little change in acid-base status (pH = 7.34 +/- 0.07 after 4 hours). In contrast, the 1:2.5 group showed progressive hypotension and metabolic acidemia (pH 6.92 +/- 0.1 after the final occlusion). There was a marked increase in ST waveform height during occlusions; this increase was greater in the 1:2.5 group (P <.001), but there was overlap between the groups. ST waveform height between occlusions was significantly higher in the 1:2.5 group (P <.001) until negative and biphasic ST waveforms developed in these fetuses between occlusions in the final 30 minutes. CONCLUSION: ST waveform elevation occurs during umbilical cord occlusions but only crudely reflects the severity of hypoxia. Interocclusion waveform height may be a better reflection of the severity of hypoxia. The appearance of biphasic and negative waveforms between occlusions may be a useful marker for severe decompensation.     

Depression of uterine blood flow during total umbilical cord occlusion in sheep

The effect of total umbilical cord occlusion upon maternal blood flow in the internal iliac and median uterine arteries was studied in eight chronically instrumented pregnant sheep. Occlusion of the umbilical cord was performed with an inflatable balloon occluder around the total cord. Blood flow was measured with electromagnetic flow transducers. Total umbilical cord occlusion of short duration (mean 40.1 s) caused a significant decrease in blood flow in the maternal internal iliac and median uterine arteries at the end of the occlusion to respectively 93.9% and 91.7% of the control values.The decrease in internal iliac and median uterine artery blood flow is attributed to an elevated fetal capillary pressure in the placenta, leading to an increased fetal placental tissue pressure which in turn compresses the maternal placental capillaries, resulting in a heightened vascular resistance and a decrease in uterine blood flow.     

Fetal cerebral energy metabolism and electrocardiogram during experimental umbilical cord occlusion and resuscitation

Objective.?The purpose of this experimental study was to elucidate alterations in fetal energy metabolism in relation to ECG changes during extreme fetal asphyxia, postnatal resuscitation and the immediate post-resuscitatory phase.

Study design.?Five near-term fetal sheep were subjected to umbilical cord occlusion until cardiac arrest followed by delivery, resuscitation and postnatal pressure-controlled ventilation. Four sheep served as sham controls and were delivered immediately after ligation of the umbilical cord. Fetal ECG was analysed online for changes of the ST segment. Fetal metabolism was monitored by intracerebral and subcutaneous microdialysis catheters.

Results.?Fetal ECG reacted on cord occlusion with an increase in the T-wave height followed by changes in intracerebral levels of oxidative parameters. Cerebral lactate/pyruvate ratio and glutamate increased to median (range) of 240 (200–744) and 34.0 (22.6–60.5) mmol/l, respectively; both parameters returned to baseline after resuscitation. Cerebral glucose decreased to 0.1 (0.08–0.12) mmol/l after occlusion and increased above baseline upon resuscitation. In subcutaneous tissue as well as blood the increase in lactate occurred with a delay compared to cerebral levels.

Conclusion.?The fetal ECG changes related to asphyxia preceded the increase in excitotoxicity as determined by increase in cerebral glutamate during asphyxia. Cerebral lactate increase was superior to subcutaneous lactate increase.     

Hemodynamic changes during complete umbilical cord occlusion in fetal sheep related to hippocampal neuronal damage

Objectives: The purpose of our study was to examine the physiologic changes caused by 10 minutes of umbilical cord occlusion in fetal sheep and to determine the correlation between fetal acidemia or cerebral ischemia and hippocampal neuronal damage. Study design: Thirteen fetal sheep were instrumented and catheterized. Carotid artery blood flow (CaF), fetal mean arterial blood pressure (FMABP), pH, PCO₂, base excess, oxygen saturation (SatO₂), and PO₂ were monitored throughout the occlusion study. Brain sections were examined for the hippocampal neuronal damage. Results: Our data showed severe ischemia (CaF: 10 ± 7 mL/min; FMABP: 29 ± 8 mm Hg) and acidemia (pH: 7.0 ± 0.05; base excess: −9.9 ± 2.4 mEq/L) at the end of occlusion. The neuronal damage score had significant correlations with ischemia and also with reperfusion, but not with the acidemic or hypoxic parameters. Conclusion: We demonstrated that the degree of hippocampal damage was correlated with the degree of ischemia and reperfusion. (Am J Obstet Gynecol 2003;188:413-8.)     

Electrocardiographic changes following umbilical cord occlusion in the midgestation fetal sheep

BACKGROUND: Clinical studies show that analysis of the fetal electrocardiographic (FECG) ST waveform at term gives important information on the myocardial response to intrapartum asphyxia. However, it is not known whether the preterm fetus responds in a similar fashion. The objective of the present study was to evaluate the FECGST response to umbilical cord occlusion in the preterm fetal sheep. METHODS: Fetal sheep at midgestation were subjected to 25 min umbilical cord occlusion (n = 7) and compared to controls (n = 5). Changes in the FECGST waveform were recorded together with arterial blood pressure, heart rate, and acid base status during the occlusion and for 3 days afterward. RESULTS: Umbilical cord occlusion resulted in immediate bradycardia (control: 187 +/- 7 bpm versus occlusion: 102 +/- 7 bpm), hypertension (control: 43.2 +/- 1.1 mmHg versus occlusion: 59.8 +/- 2.2 mmHg), and an initial increase in the T/QRS ratio (control: 0.10 +/- 0.02 versus occlusion: 0.60 +/- 0.10, P < 0.001), followed by hypotension (21.7 +/- 1.2 mmHg), normalization of the T/QRS ratio, and in some cases the development of negative T waves toward the end of the occlusion. CONCLUSIONS: These studies show that the midgestation fetal sheep has the capacity to react to umbilical cord occlusion with a significant increase in the amplitude of the ST waveform together with an augmentation of blood pressure, which then subsides as the occlusion continues. The appearance of negative ST segment appears to signify significant cardiac dysfunction. The characteristic progression of ST-waveform changes in response to umbilical cord occlusion in midgestation fetal sheep, suggests that monitoring the ST waveform may contribute clinically important information also in the preterm individual.     

Transient umbilical cord occlusion causes hippocampal damage in the fetal sheep.

OBJECTIVE: The purpose of our study was to examine the neuronal outcome after a standardized period of umbilical cord occlusion. STUDY DESIGN: The umbilical cord was clamped for 10 minutes in nine experimental and four control chronically instrumented fetal sheep. Three days later the animals were killed for histologic interpretation. Systemic, electrophysiologic, and neurohistologic effects were compared by analysis of variance. RESULTS: Clamping of the cord resulted in transient severe asphyxia, hypotension (24 +/- 5 mm Hg, p < 0.01), bradycardia (72 +/- 14 beats/min, p < 0.001), depressed electroencephalographic activity (-17 +/- 2 dB, p < 0.001), and an increase in cortical impedance. The electroencephalographic activity was depressed for 5 +/- 2 hours in spite of rapid recovery of arterial oxygen content. Neuronal loss was found in the hippocampus. Neither epileptiform electroencephalographic activity nor infarction were observed. Three animals with poor blood gas levels died during the occlusion. CONCLUSION: An isolated and brief period of umbilical cord occlusion in utero can cause predominantly hippocampal damage without persistent functional changes in cortical activity and with rapid recovery of other potential indicators of fetal asphyxia.     

Fetal and neonatal heart rate changes related with the acid-base balance of umbilical cord arterial blood

The fetal heart rate (FHR) in the last 15 minutes of labor and the neonatal heart rate (NHR) in the first 15 minutes of life were recorded, and their correlation with the acid-base balance of the umbilical cord arterial blood was studied in 62 full-term infants. The one minute Apgar score was 7 or greater in all cases. The cord arterial pH was less than 7.250 in 13 neonates in the low pH group, and it was 7.250 or greater in 49 in the high pH group. FHR patterns during the last 15 minute of labor were classified into three types. The normal type was observed in 32 cases (51%), the severe variable deceleration type in 25 (40%), and the bradycardia type in 5 (9%). In the severe variable deceleration type, 10 cases in the low pH group showed a significantly longer period that of appearance than 15 in the high pH group. All fetuses that had at least one acceleration in the last 15 minutes of labor were included in the high pH group. NHR increased and reached its peak of 192bpm at 2.8 minutes after birth on the average. However, the low pH group showed a significantly higher NHR and a longer period until the peak than the high pH group. The low pH group had a higher NHR-baseline than the high pH group.     

Fetal heart rate variability and cerebral oxygen consumption in fetal sheep during asphyxia.

This study was designed to examine the relationship between fetal heart rate variability and fetal cerebral oxygen uptake. Fetal sheep were chronically prepared with catheters and electrodes to determine cerebral blood flow (microsphere method), cerebral arteriovenous oxygen difference, and the electrocardiogram. An adjustable occluder was placed on the maternal common internal iliac artery to induce fetal asphyxia by reducing uterine blood flow. Fetal heart rate variability tended to decrease in the first 11 min of asphyxia, when cerebral oxygen consumption was approximately 53% of control. Despite stable cerebral oxygen consumption and worsening metabolic acidosis, however, fetal heart rate variability progressively returned towards normal by 36 min. There was no relationship between the depression of FHR variability and the degree of reduction of cerebral oxygen consumption. Nor was there any relationship between an alteration in regional cerebral blood flow or myocardial blood flow and the return of FHR variability with increasing duration of asphyxia. We conclude that there is an association between loss of fetal heart rate variability and reduced cerebral oxygen consumption, but the reduced variability does not persist with time at this degree of reduced cerebral metabolism in fetal sheep. This appears to be at variance with human clinical experience. Among the explanations for this may be insufficiently severe asphyxia, a species difference, removal of an inhibitor to FHR variability, or progressive use of other substrates for metabolism.     

Delayed hypotension and subendocardial injury after repeated umbilical cord occlusion in near-term fetal lambs

OBJECTIVE: This study was undertaken to determine whether myocardial injury occurs after repeated intrauterine asphyxia. STUDY DESIGN: Near-term fetal sheep with implanted instrumentation underwent either sham occlusions (n = 8) or repeated brief umbilical cord occlusions (n = 12) continued until the onset of severe (<20 mm Hg) or sustained hypotension. After 3 days of recovery, the fetal hearts were perfusion fixed. RESULTS: Repeated umbilical cord occlusions led to a severe metabolic acidosis (pH, 6.84 +/- 0.09; lactate concentration, 14.1 +/- 1.5 mmol/L) with increasing hypotension during occlusions, which were terminated after 128 +/- 38 minutes. After the occlusions, the mean arterial pressure showed a delayed fall, which resolved after 12 hours. Ultrastructural examination showed evidence of subendocardial injury, with dilatation of sarcoplasmic reticulum, margination and clumping of nuclear chromatin, and mitochondrial swelling. The most severe morphologic changes, including electron-dense mitochondrial inclusions, were found in the fetuses with delayed recovery of the fetal heart rate after the final occlusion. CONCLUSION: Subendocardial injury occurs after severe repeated intrauterine asphyxia in the late-gestation fetus, and this may contribute to cardiovascular compromise and the development of late decelerations.     

Fetal heart rate changes during diabetic ketosis

A case of diabetic ketosis during pregnancy is presented in which the fetal heart rate tracing demonstrated tachycardia complicated by late and severe variable decelerations. Intravenous administration of insulin resulted in prompt abolition of the deceleration patterns. The implications of these findings are discussed.