Effects of acute hypoxemia on fetal movement in the fetal lamb

Chronically instrumented pregnant models were established using 5 Dorset-Rambouillet pregnant ewes with gestational age between 120 and 138 days. Observation of fetal movements were started on the 3rd postoperative day or later when recovery from the surgery to the physiological condition was confirmed by maternal and fetal biophysical parameters. Fetal movements were observed using real-time ultrasound equipment with linear-array transducer placed on the maternal abdomen. Observation encompassed the control period which lasted one hour followed by an experimental period of fetal hypoxemia created by decreasing maternal FIO2. Observation was also continued during the recovery period when the mother was re-exposed to room air. Maternal and fetal samples were periodically obtained during these periods. Frequency of fetal movements was studied in 10 minute periods under the control and hypoxemic conditions. All fetuses exhibited movements during the control period, ranging 1-42 movements/10 minutes, the mean incidence being 16.9 movements/10 minutes. During fetal hypoxemia (average PaO2 decrease: 8.6 mmHg), fetal movements were significantly reduced to 5.5 movements/10 minutes with complete cessation in some cases. In 4 animals which exhibited complete cessation of both fetal movement (FM) and fetal breathing movement (FBM), FBM disappeared before FM, and reappearance of FM was following by FBM during recovery from hypoxemia.     

The pattern of breathing of fetal sheep in graded hypoxia

We examined the effects on fetal breathing movements (FBM) and electrocortical activity (ECoG) of maintaining fetal arterial PO2 (PaO2) at 16.9 +/- 1.9 mmHg for 20 min in unanaesthetized, chronically instrumented fetal sheep in utero at 122-132 days gestation. In 82% of trials, a pattern of regular FBM occurred characterised by its large (35 +/- 7 mmHg) excursions in tracheal pressure and its low frequency (ca. 3 per min) compared to the irregular FBM occurring during normoxia (ca. 5 mmHg and ca. 90 per min, respectively) (PaO2 ca. 23 mmHg). The occurrence of FBM in mild hypoxia was independent of the ECoG state of the fetus and it also occurred in fetuses in which the carotid sinus nerves and cervical vagosympathetic trunks had been sectioned bilaterally. Reducing PaO2 to between 16 and 11 mmHg produced a cessation of FBM, as reported by other workers. The FBM in mild hypoxia were distinct from 'gasping', which occurs only when PaO2 was reduced to much lower levels. The FBM in mild hypoxia are discussed in terms of central respiratory mechanisms excited by hypoxia, as opposed to the well-documented mechanisms which inhibit FBM in more intense hypoxia.     

Amniotic gas values and acid-base status during acute maternal hyperoxemia and hypoxemia in the early fetal sheep

OBJECTIVE: This study was undertaken to determine amniotic fluid gas values and acid-base balance during maternal hyperoxemia and hypoxemia in early pregnancy. STUDY DESIGN: Anesthetized sheep (n = 12) in early and mid pregnancy (0.3 to 0.5 gestation) were subjected to hyperoxemia followed by hypoxemia. Amniotic fluid PO (2), pH, PCO (2), bicarbonate concentration, and base excess were monitored continuously with a multiparameter Paratrend (Diametrics Medical Inc, St Paul, Minn) sensor and compared between 0.3 and 0.5 gestation. RESULTS: During maternal normoxemia all parameters were constant. At all gestational ages maternal hyperoxemia caused no changes apart from a rapid increase in amniotic fluid PO (2) (P <.001). Maternal hypoxemia led to a reduced amniotic fluid PO (2) (P <.001), whereas the PCO (2) and the bicarbonate concentration increased (P <.001). Changes in amniotic fluid gas values and acid-base balance were more pronounced at 0.3 gestation than at 0.5 gestation. Amniotic fluid Po(2) responded earlier to maternal hyperoxemia than to hypoxemia (9. 5 vs 14.3 minutes; P <.001). During hypoxemia maternal PaCO (2) changed faster than did amniotic fluid PCO (2) (P <.001). CONCLUSIONS: Acute maternal hypoxemia during early pregnancy was quickly reflected in amniotic fluid gas values and acid-base balance, whereas hyperoxygenation induced the quickest changes in amniotic fluid PO (2). The metabolic effects of maternal hyperoxemia and hypoxemia were also more pronounced during early pregnancy than at mid pregnancy.     

Influence of maternal hyperoxia or hypercarbia on the hemodynamics of the placenta and fetal brain

Pregnant rabbits were subjected to inhalation of different gases, and the changes in placental blood flow (PBF), fetal heart rate (HR), and fetal cerebral blood flow (CBF) associated with the changes in maternal blood gas levels were studied. The results are given below. In maternal hyperoxia, maternal blood pressure (BP) was not much influenced and PBF remained unchanged or was slightly decreased when the PCO2 level was not varied or when it was lowered. In contrast, not only maternal BP but also PBF was increased when the PCO2 level was elevated. In the absence of a conspicuous increase in PCO2, neither fetal HR nor CBF varied, regardless of PBF. Both maternal BP and PBF were increased in mild to moderate maternal hypoxia (PO2 greater than 40 mmHg) and decreased in severe hypoxia (PO2 less than 30 mmHg). The decreasing trend of fetal HR or CBF was strengthened as maternal hypoxia was intensified. An obvious decrease in either parameter was observed in severe maternal hypoxia (PO2 less than 30 mmHg). Fetal HR and CBF were well maintained. in hypoxic dams with increased PBF as compared with those with unchanged or decreased PBF. The higher the PCO2 level or the lower the pH value, the more was fetal bradycardia that was apt to occur, even in a mildly hypoxic state.     

The influence of maternal oxygen inhalation for 30 to 60 minutes on fetal oxygenation

Healthy parturients with uterine displacement received oxygen inhalation before and during spinal anesthesia for elective cesarean section. Oxygen was administered through a mask (group OH2 : 20 cases) or via a nasal cannula (group OH1: 20 cases) for 33 to 69 minutes. All patients were in the right lateral position prior to spinal block and were in the left tilt after the anesthesia. The fetal blood-gas values were relatively evaluated among the OH2, OH1 and OH groups which received oxygen via a cannula for 9 to 17 minutes. The maternal artery PO2 values for the OH2 group (the mean: 491.7 +/- 61.4mmHg) were significantly higher than those for the OH1 and OH groups (244.5 +/- 28.0 and 225.0 +/- 62.9mmHg, respectively). The umbilical vein PO2 (46.1 +/- 7.5mmHg) and SO2 (87.6 +/- 6.3%) of the OH2 group were also significantly greater than those of the other groups (PO2: 36.1 +/- 4.1mmHg, SO2: 77.3 +/- 6.0% in the OH1 group and PO2: 37.5 +/- 6.4mmHg, SO2: 77.6 +/- 10. 3% in the OH group, respectively). The Apgar scores and both the maternal and fetal acid-base values for all groups were excellent. The umbilical vein to artery PO2 and SO2 gradients of the OH2 group were significantly greater than those of the other groups. It is emphasized that maternal hyperoxia with uterine displacement improves fetal oxygenation without adversely affecting the fetal acid-base state, even if it is excessive and maintained for 60 minutes.     

Magnesium sulfate and fetal plasma concentrations of epinephrine, norepinephrine, and vasopressin in response to acute hypoxemia in goats

OBJECTIVE: We measured fetal plasma concentrations of epinephrine, norepinephrine, and vasopressin during acute hypoxemia in goats and tested whether hypermagnesemia altered these endocrine responses. METHODS: Five chronically catheterized goat fetuses at 124-129 days' gestation were used. After 4 hours of infusion (magnesium or vehicle as controls), 30 minutes of hypoxemia was induced by infusing nitrogen gas through a maternal tracheal catheter. Fetal plasma concentrations of epinephrine, norepinephrine, and vasopressin were measured before and during hypoxemia. Both magnesium sulfate and vehicle infusions were performed in each animal. Repeated-measures analysis of variance (ANOVA) and two-way ANOVA with post hoc test were used to determine statistical significance. RESULTS: During hypoxemia, fetal PO(2) decreased significantly from 30 to 14 mmHg with no significant changes in fetal pH or PCO(2) in both groups. Fetal heart rate was reduced significantly by hypoxemia, but to a lesser extent in the magnesium group (change in decrease in fetal heart rate: 41 beats per minute [bpm] in controls versus 26 bpm with magnesium). Mean blood pressure did not change significantly during hypoxemia in both groups. Fetal plasma concentrations of epinephrine, norepinephrine, and vasopressin significantly increased from the prehypoxemic values both with magnesium and in controls. There were no significant differences in these hormone concentrations between magnesium and the controls. CONCLUSION: Magnesium sulfate had no effect on fetal plasma concentrations of vasopressin, epinephrine, and norepinephrine during acute hypoxemia.     

The FHR variability of "Shiba goats" in acute hypoxic state

Fetal heart rate variability in an experimentally induced acute hypoxic state was investigated using chronically prepared fetal goats. FHR variability was calculated using a microcomputer with the R-R intervals of the direct fetal ECG signal measured with a peak detector. The accuracy of the peak detector was 0.1 msec. The formula for FHR variability was as follows: (Formula: see text) A fetal acute hypoxic state was induced by maternal inhalation of a gas mixture low in O2 concentration. The fetal condition was evaluated by blood gas analysis of the fetal carotid artery. In mild fetal hypoxemia due to the maternal inhalation of a gas mixture including 8-10% of O2, both STV and LTV were increased at 10-20 minutes after the beginning of the experiment. Subsequently, both were decreased at 30-40 minutes, but maintained a level higher than that of the control. When severe fetal hypoxemia was induced by the maternal inhalation of the gas mixture containing 4-6% of O2, both STV and LTV increased at 10-20 minutes after induction, then decreased to a level lower than that of the control at 30-40 minutes. No significant difference in fetal PO2 was observed between the 10-20 min. period and the 30-40 min. period of the severe hypoxemic state. But significant differences in pH and BE values were found when the 10-20 min. period and the 30-40 min. period were compared. When data showing the fetal arterial pH and BE to be significantly lower than those of the control at 30-40 min. of the severe hypoxemic state were excluded, significant negative correlations were found between PO2 and STV and between PO2 and LTV . It appeared that FHR variability, both STV and LTV , would increase during the acute hypoxemic state and that they would decrease to a level lower than that of the control after metabolic acidosis occurred due to continuing hypoxemia.     

Fetal breathing movements and maternal exercise.

Earlier statements that fetal breathing movements (FBM) are sensitive to changes in the fetal homeostasis prompted the study of the effect of maternal exercise on FBM and fetal heart rate. Forty women in the last trimester of gestation were subjected to a work load (80 W) for 5 min on a bed ergometer cycle; in 30 of them FBM were recorded by A-mode ultrasound, and in 10, the fetal heart rate was monitored by continuous ultrasound. Maternal blood pressure, pulse rate, blood pH and pCO2, and transcutaneous pO2 were also followed. The FBM showed a transient marked increase in incidence immediately after the end of the exercise. No changes in basal level or in baseline variability of the fetal heart rate were found in the recovery period after work. Some possible causes of the observed FBM alterations are discussed. The findings imply that, after this particular form of stress, FBM are a more sensitive indicator of the physiological state of the fetus than the fetal heart rate.     

Alteration of fetal oxygenation and responses to acute hypoxemia by increased myometrial contracture frequency produced by pulse administration of oxytocin to the pregnant ewe from 96 to 131 days' gestation.

OBJECTIVES: This study examined the effects of increased myometrial contracture frequency from 96 to 131 days' gestation on ovine fetal oxygen transport and physiologic response to acute hypoxemia. STUDY DESIGN: Ten pregnant ewes received either saline solution (control, n = 5) or long-term administration of oxytocin (600 microU. kg-1. min-1) in 5-minute pulses every 20 minutes to the maternal jugular vein beginning at 96 days' gestation (n = 5). Maternal tracheal tubes, fetal carotid artery and jugular vein catheters, and electrocorticographic and electromyographic electrodes were placed with the animals under halothane general anesthesia at 122 days' gestation. At 131 days' gestation fetal hypoxemia was induced for 1 hour. Maternal and fetal arterial blood gas samples were obtained at 60, 15, and 5 minutes before the start of hypoxemia and at 5, 10, 20, 30, 40, 60, and 120 minutes after the start of hypoxemia. RESULTS: Baseline PO2 before hypoxemia was significantly lower and oxygen content was significantly higher in fetuses in the long-term oxytocin group than in control fetuses. At the end of hypoxemia the fetal pH, oxygen saturation, and oxygen content were significantly higher in the long-term oxytocin group than in the control group, although PO2 did not differ between groups. The fetal blood oxygen dissociation curve was shifted to the left in the long-term oxytocin group. During hypoxemia the absolute fetal blood pH was higher and the blood pH variation was lower in long-term oxytocin group than in the control group. Lower baseline and hypoxia-induced fetal plasma cortisol concentrations were observed in fetuses in the long-term oxytocin group than in fetuses of control ewes. CONCLUSION: Increased contracture frequency during a period of 35 days shifts the fetal oxygen dissociation curve toward the left and alters fetal response to acute hypoxemia.     

Fetal breathing movements and maternal hyperoxia in the growth retarded fetus

Summary. The effect on fetal breathing movements (FBM) of maternal breathing of 50% oxygen was examined. The procedure caused a two-fold rise in maternal arterial Po₂ and did not alter FBM in normal pregnancy. In pregnancy complicated by intrauterine growth retardation (IUGR) a substantial increase in the incidence of FBM was recorded during hyperoxia (control 29.8.3.9%, hyperoxia 68.2+3.6). No such change was observed in pregnancies where IUGR was suspected but not proven at delivery.     

Endocrinological and Biophysical Responses to Further Reduction in Oxygenation Following Sustained Hypoxemia in Fetal Goats

Objective: The purpose of this study was to determine fetal endocrinological and biophysical responses to the further reduction in oxygenation following prolonged nonacidemic hypoxemia in fetal goats.

Methods: Seven further hypoxic experiments were performed after prolonged (24-h) nonacidemic hypoxemia, caused by an infusion of nitrogen into the maternal trachea and by reducing uterine arterial blood flow in four chronically instrumented goat fetuses at 123–131 days' gestation. We measured arginine vasopressin, adrenocorticotropic hormone, cortisol, and cathecolamines as endocrinological parameters. Fetal heart rate, fetal blood pressure, and fetal breathing movement were observed as biophysical parameters.

Results: Fetal arterial pO₂ was significantly decreased from 27.0± 1.2 mmHg (control) to 18.0 ± 0.7 mmHg and 11.3 ± 1.3 mmHg at the end of the prolonged hypoxemia and the further hypoxia, respectively. The further hypoxia induced reductions in fetal heart rate, increases in fetal blood pressure, and a series of gasping. Arginine vasopressin and cathecolamines were elevated significantly by the further hypoxia. Although adrenocorticotropic hormone and cortisol were increasingly elevated, they did not reach a significant level.

Conclusions: Some specific fetal responses—excessive elevations of fetal cathecolamines, arginine vasopressin, accompanied with fetal gasping—were observed during further severe hypoxia.     

Studies on the measurement of fetal breathing movement by the impedance method (author's transl)

Fetal breathing movements (FBM) were detected without any invasion by recordings of impedance (IMP) variance on the maternal abdominal wall, where the FBM were visible through the myometrium and maternal abdominal wall. FBM was clearly shown by the IMP method in some modification. This IMP recordings consisted in several elements of maternal respiration and pulsation, fetal movements, FBM, etc. FBM elements on IMP recordings appeared to be in clear spike waves and these were identified as the FBM. Considering of the result of fetal respirotachogram utilizing of IMP recordings, FBM did not seemed to be regular movements. Fetal "hiccup' movements were shown as large biphasic spike waves on IMP recordings. FBM were accurately recognized by the separation of the FBM elements from FBM-IMP recordings by utilizing of the analogical subtractive amplifier system. FBM-IMP signals from the data recorder was dealt with the fast Fourier transformation (FFT) utilizing by the mini-computer system and frequency analysis of them was carried out. From the results of FFT passing through the infinite impulse response digital band-pass filter system, the only FBM elements were separately obtained.     

Effects on fetal breathing movements of maternal challenges. Cross-over study on dynamic work, static work, passive movements, hyperventilation and hyperoxygenation.

Ten women in the last trimester of a normal pregnancy were subjected to five different loads in a cross-over study. Fetal breathing movements (FBM), fetal heart rate (FHR), maternal heart rate (MHR), and mean arterial pressure (MAP), maternal transcutaneously measured pO2 (Tc-pO2), and the energy supply to the Tc-pO2 electrode were recorded continuously before, during, and after the load. Maternal capillary pH and pCO2 were measured at three representative time points. The immediate responses of the incidence of FBM to the different challenges were: increase after dynamic work (bicycle test); no change after static work (isometric muscle contraction) and passive movements; decrease after hyperventilation and hyperoxygenation. FHR was unaffected by all challenges. The FBM incidence varied in parallel with pCO2 after dynamic work and hyperventilation and inversely with the Tc-pO2 rise caused by hyperoxygenation. Maternal pH was increased after passive movements (no change in FBM) and after hyperventilation (decreased incidence of FBM), FBM seem to be more sensitive to environmental changes than is the FHR. Mechanical stimuli to the uterus were not responsible for the augmentation of FMB seen after the bicycle test. The present observations reveal the multifactorial nature of the regulation of FBM, and support the role of CO2 as a major stimulator of breathing movements also in prenatal life.     

Prediction of infection complicating premature rupture of the membranes by monitoring fetal breathing movement with ultrasound

Modified Vintzileos monitoring skill and scoring criteria of fetal biophysical profile (FBP), were used in assaying 48 patients with premature rupture of the membranes (PROM). The last determination before delivery was compared with the outcome of pregnancy. The results showed: (1) The infection rate in patients with low biophysical score (less than or equal to 7) was significantly higher than that of high score (greater than 7); (2) The infection rate in patients presenting fetal breathing movements (FBM) of greater than or equal to 60 sec. It was significantly lower than that in patients with a FBM of less than 60 sec. Infection was almost absent when FBM was present; (3) Fetal distress and neonatal asphyxia could be well predicted by FBP scoring in labor. The above suggested that FBP Scoring FBM is useful in prediction infection and the outcome of babies in patients with PROM.     

Plasma endothelin-1 and atrial natriuretic peptide levels during prolonged (24-h) non-acidemic hypoxemia in fetal goats.

OBJECTIVE: The purpose of this study was to investigate the effects of prolonged (24-h) non-acidemic hypoxemia on plasma endothelin-1 and atrial natriuretic peptide (ANP) in fetal goats. METHODS: During continuous infusion of nitrogen into the maternal trachea, fetal plasma endothelin-1 and ANP levels were measured in nine chronically instrumented goat fetuses at 117-129 days' gestation. Endothelin-1 and ANP were measured by radioimmunoassay. RESULTS: Fetal arterial pO(2) decreased significantly from 23.1 +/- 1.0 mmHg (control) to 15.2 +/- 0.9 mmHg during the first 2 h of hypoxemia and to 15.7 +/- 1.1 mmHg at the end of the experimental period of hypoxemia. The plasma endothelin-1 concentration increased from 10.6 +/- 1.9 pg/ml to 20.4 +/- 4.3 pg/ml (p < 0.05) during the first 2 h and was 19.7 +/- 2.4 pg/ml (p < 0.01) at the end of the experimental period. The plasma ANP concentration also increased, from 20.3 +/- 5.5 pg/ml to 23.0 +/- 4.7 pg/ml in the first 2 h and then to 58.0 +/- 8.8 pg/ml (p < 0.05) at the end of the experimental period. There was a significant negative correlation between fetal plasma endothelin-1 and pO(2), but no significant correlation was found between fetal plasma ANP and pO(2). CONCLUSIONS: Prolonged non-acidemic hypoxemia induces a continuous increase in fetal plasma endothelin-1 and ANP levels. Fetal plasma ANP increases time-dependently but endothelin-1 remains constant during hypoxemia.     

Umbilical artery flow velocity waveforms in fetuses dying with congenital anomalies

Absent or reversed diastolic component in umbilical artery (UA) flow velocity waveform was observed in eight fetuses with major malformations. Because of the uncorrectable fetal conditions or the parents' reluctance to terminate the pregnancy, no interventions were undertaken and eventually all eight fetuses died in utero. The interval between the abnormal waveform recording and fetal death was between 1 and 7 days (mean 3.6 days). In two fetuses with abnormal diastolic flow, analysis of umbilical vein blood obtained by ultrasound-guided sampling revealed moderately severe acidosis and hypoxia (pH 7.228 and 7.241, PCO2 47.5 and 46.9 mmHg; PO2 14.6 and 14.7 mmHg, respectively). Our observation suggests that once the diastolic component of UA flow velocity waveforms becomes absent or reversed, the fetus is in a state of hypoxia and acidosis and fetal death is impending. This limited experience may help in formulating clinical management when using UA flow velocity waveforms in the monitoring of high-risk fetuses.     

Plasma endothelin-1 and atrial natriuretic peptide levels during prolonged (24-h) non-acidemic hypoxemia in fetal goats

Objective: The purpose of this study was to investigate the effects of prolonged (24-h) non-acidemic hypoxemia on plasma endothelin-1 and atrial natriuretic peptide (ANP) in fetal goats. Methods: During continuous infusion of nitrogen into the maternal trachea, fetal plasma endothelin-1 and ANP levels were measured in nine chronically instrumented goat fetuses at 117-129 days' gestation. Endothelin-1 and ANP were measured by radioimmunoassay. Results: Fetal arterial p O 2 decreased significantly from 23.1 &#45 1.0 mmHg (control) to 15.2 &#45 0.9 mmHg during the first 2 h of hypoxemia and to 15.7 &#45 1.1 mmHg at the end of the experimental period of hypoxemia. The plasma endothelin-1 concentration increased from 10.6 &#45 1.9 pg/ml to 20.4 &#45 4.3 pg/ml ( p < 0.05) during the first 2 h and was 19.7 &#45 2.4 pg/ml ( p < 0.01) at the end of the experimental period. The plasma ANP concentration also increased, from 20.3 &#45 5.5 pg/ml to 23.0 &#45 4.7 pg/ml in the first 2 h and then to 58.0 &#45 8.8 pg/ml ( p < 0.05) at the end of the experimental period. There was a significant negative correlation between fetal plasma endothelin-1 and p O 2, but no significant correlation was found between fetal plasma ANP and p O 2 . Conclusions: Prolonged non-acidemic hypoxemia induces a continuous increase in fetal plasma endothelin-1 and ANP levels. Fetal plasma ANP increases time-dependently but endothelin-1 remains constant during hypoxemia.     

Fetal breathing and generalized fetal movements in normal antenatal patients.

Fetal breathing movements (FBM) and generalized fetal movements (GFM) were recorded for 30 minutes using a real time B-scan instrument in 46 women with uncomplicated pregnancies. FBM occurred for 10.9+/-0.9 (SE) per cent of the recording time. The time occupied by FBM was not significantly related to smoking, meal times or plasma glucose concentrations. FBM were absent during the observation period in 15 per cent of patients and present for less than 10 per cent of the time in 33 per cent of patients.     

Correlation between neonatal Apgar scores and the results of maternal and umbilical cord blood gas analysis

The correlation between the Apgar scores of 162 neonatal 1 minute after birth and the result of maternal arterial and umbilical cord blood gas analysis was studied. The results were as follows: (1) With decreasing neonatal Apgar score, the value of the pH, PO2, HCO3, TCO2 and actual base excess (ABE) of the maternal arterial and umbilical cord blood also decreased markedly, while the PCO2, except that of the maternal arterial blood, increased obviously, and mixed acid base imbalance and hypoxemia also significantly increased (P less than 0.01). (2) Of the neonates with umbilical arterial blood pH less than or equal to 7.2, the proportion of neonates with Apgar score less than or equal to 3 amounted to 100%; that with on Apgar score of 4-7, was 77.7%; And that with on Apgar score of 8-10, was 56.31%. The difference was highly significant statistically (P less than 0.01).