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.     

Ovine fetal breathing and swallowing activity in response to plasma glucose changes.

Fetal swallowing activity generally occurs simultaneously with fetal breathing movements (FBM) in sheep. The present study investigated the FBM and swallowing responses to altered fetal plasma glucose. Fetal lambs were chronically prepared with laryngeal, esophageal and diaphragm electromyogram (EMG) wires, an esophageal flow probe and vascular catheters. Beginning at 138 +/- 1 day, FBM and swallowing were monitored during control periods and in response to intravenous glucose infusions (14 mg/kg/min for 120 min) to fetuses of fed and fasted ewes. Glucose infusions to fetuses of fed ewes resulted in significant increases in fetal plasma glucose (21.2 +/- 0.7 to 40.5 +/- 1.9 mg/dl) and time breathing (46.2 +/- 6.3 to 60.0 +/- 9.5 min/2 h). In response to maternal fasting, fetal glucose levels (13.4 +/- 1.0 mg/dl) and time breathing (23.0 +/- 7.2 min/2 h) decreased significantly. Glucose infusion to fetuses of fasted ewes resulted in significant increases in time breathing (50.3 +/- 13.4 min/2 h) and diaphragmatic EMG activity (1,295 +/- 654 to 3,012 +/- 1,182 spikes/2 h). There was no change from basal levels of fetal EMG swallows (83.2 +/- 4.3 swallows/2 h) or esophageal flow (40.8 +/- 7.9 ml/2 h) in response to maternal fasting or fetal glucose infusions.     

The effect of magnesium sulfate on the behavioral activities of fetal goats

OBJECTIVES: To investigate fetal heart rate accelerations, fetal breathing movements, and fetal electrocortical activities during administration of magnesium sulfate to fetal goats. METHODS: The fetal heart rate accelerations, fetal breathing movements, and fetal electrocortical activities during 6 hours of continuous magnesium sulfate infusion into the fetal jugular vein were examined in 8 chronically instrumented fetal goats at 124-131 days of gestation. Fetal breathing movements were defined as repetitive negative fluctuations of the fetal tracheal pressure. Fetal electrocortical activities were assessed by visual analysis of periods of high-voltage and low-voltage electrocortical activities. RESULTS: Continuous infusion of magnesium sulfate for 6 hours significantly increased the fetal plasma magnesium concentration from 2.8 +/- 1.2 to 8.3 +/- 2.6 mg/dL without significant changes in fetal arterial blood gases. The incidence of fetal heart rate accelerations during magnesium infusion was significantly decreased from that found during the control periods. After 2 hours of infusion, the incidence of fetal breathing movements significantly decreased from 33.9% +/- 20.5% to 1.2% +/- 1.4% and remained at this level during the remaining 4 hours of magnesium infusion. The percentage of time that the fetuses were found to have low-voltage electrocortical activities decreased from 51.6% +/- 9.0% to 40.4% +/- 8.2% after 2 hours of infusion but recovered to 49.9% +/- 12.0% by 6 hours of magnesium infusion. CONCLUSION: We concluded that fetal magnesium sulfate administration affected fetal heart rate accelerations and fetal breathing movements continuously but electrocortical activities only temporarily during 6 hours of observations.     

Effects of reduced uterine blood flow on electrocortical activity, breathing, and skeletal muscle activity in fetal sheep

Experiments were conducted in 11 unanesthetized fetal sheep during the last third of gestation to examine the effects of prolonged, reversible reduction in uterine blood flow on fetal electrocortical activity, breathing movements, and skeletal muscle activity. With an adjustable clamp placed around the maternal common internal iliac artery, uterine blood flow was restricted for 2 hours to produce a reduction in fetal arterial oxygen saturation from 56.1% +/- 1.9% to 28.8% +/- 0.7%. When blood flow was reduced, there was a decrease in the percentage of time that fetuses spent in low-voltage electrocortical activity, from 57.5% +/- 3.0% to 37.8% +/- 3.5%, and a decrease in the incidence of both breathing movements and integrated skeletal muscle activity. Younger fetuses (110 to 121 days' gestation) demonstrated a lesser degree of reduction in breathing movements when compared with older fetuses (125 to 140 days) whereas the effects of hypoxemia on electrocortical activity became less apparent with advancing gestational age.     

Computer-assisted assessment of the fetal biophysical profile

The biophysical profile assesses fetal heart rate, breathing movements, fetal body movements, amniotic fluid volume, and fetal tone. In the past, these data have been scored by an arbitrary, unweighted system. While this approach is useful in detecting major anomalies and oligohydramnios, both static observations, the dynamic variables (fetal heart rate, fetal breathing movements, and fetal body movements) have added little information beyond that of an extended nonstress test alone. We have evaluated an alternative biophysical assessment system, modeled after extended physiologic studies, which not only acquires dynamic fetal variables simultaneously but, with computer assistance, quantifies the biophysical information. With an ADR 4000/L scanner, a Hewlett-Packard 8040 A monitor, and a specially programmed IBM microcomputer, we studied 100 normal term fetuses during 60-minute epochs. Each gestation had normal amniotic fluid volume and fetal tone. Normative values for the dynamic variables, expressed as means +/- SD were: fetal heart rate, 137 +/- 6.3 bpm; incidence of fetal breathing movements, 25.0% +/- 17.3%; rate of fetal breathing movements, 46.0 +/- 9.4 breaths/min; total fetal breathing movements, 823 +/- 61; incidence of fetal body movements, 8.5% +/- 3.9%; accelerations (greater than 15 bpm, 15 seconds), 14.1 +/- 6.3. We conclude that this approach is practicable, respects the biologic cycles of fetal behavior, and provides a basis for population standards and sequential study of the same fetus.     

Effects of narcotic drugs on fetal behavioral activity: acute methadone exposure

The effects of acute methadone exposure on fetal behavioral activity were investigated in 10 unanesthetized fetal lamb preparations. Fetal behavioral activity was interpreted indirectly from the electrocorticogram (ECoG), electromyogram, electrooculogram, blood pressure, heart rate (FHR), and breathing movements (FBMs) of the fetus. Methadone infusion to the mother (5 micrograms/kg/min) resulted in a suppression of all synchronized ECoG activity, and an increase in FBM, FHR, eye movements, nuchal tone, and body movements. Similar effects were observed when 10% of the dose was given directly to the fetus. These results demonstrate that methadone acts directly om the fetus to suppress both quiet sleep and rapid eye movement sleep and results in a "hyperactive" state that has previously been shown to be associated with a 20% increase in fetal oxygen consumption.     

Fetal breathing movements and the response to carbon dioxide in patients on methadone maintenance

Fetal breathing movements were monitored on six methadone maintenance patients and ten healthy control patients, studied while breathing room air and while breathing a prepared gas mixture with 5% carbon dioxide, both before and 2 hours after either the usual daily dose of methadone or a diet drink. There was no difference before and after the diet drink in control patients, who showed a significant increase in the incidence of fetal breathing movements from 37.1% +/- 5.9% (SEM) on room air to 69.4% +/- 2.8% while breathing 5% carbon dioxide (p less than 0.01). In the patients studied on room air before receiving methadone, fetal breathing movements were significantly decreased from those of the control group, 4.7% +/- 1.2% (p less than 0.01), with a further decrease when studied after receiving methadone, 1.3% +/- 0.7%. Fetal breathing movements did increase significantly in response to 5% carbon dioxide both before and after receiving methadone; however, in both instances the incidence was significantly less that that of the control group. The findings of the present study on methadone subjects demonstrate that abnormal function of the respiratory control network is evident in utero, which may be predictive of subsequent neonatal respiratory development.     

Cerebral Blood Flow and Metabolism in Ovine Fetuses During Asphyxia Resulting in Seizures

Severe fetal asphyxia can cause neurologic damage, but little is known about cerebral oxidative metabolism under these conditions. This study was designed to measure cerebral blood flow and oxygen consumption during severe global asphyxia in fetal sheep, asphyxiated to the point at which seizure activity subsequently occurred. Six sheep were chronically instrumented with fetal electrodes, fetal and maternal vascular catheters, and an adjustable occluder on the maternal common hypogastric artery. Measurements were made of fetal arterial blood gases, blood pressure, heart rate electrocorticogram (ECoG), nuchal muscle electromyogram (EMG), and regional blood flow (radioactive microspheres) during control, and at 30 and 60 min after complete occlusion of the maternal hypogastric artery. The ECoG became isoelectric, and the fetuses developed a marked respiratory and metabolic acidosis, the pH falling to 6.99 ± 0.03, the pCO₂ rising to 73 ± 11 mm Hg, and base excess falling to ?16 ± 1 mEq/L at 60 min of occlusion. Control fetal arterial blood pressure was 52 ± 9 mm Hg and did not change significantly with asphyxia at 60 min. Cerebral cortical blood flow was 127 ± 54 ml/100 g/min at control, and 204 ± 130 ml/100 g/min at 60 min of asphyxia. Cerebral oxygen consumption was 201 ± 50 μM/100 g/min at control, and 76 ± 57 μM/100 g/min at 60 min of asphyxia (P < 0.05), i.e., 45% of control. All 6 fetuses had episodic seizure activity based on ECoG and nuchal EMG activity, beginning 50 ± 47 min after release of the occluder. This seizure activity continued for 24-36 h. This study shows that 60 min of asphyxia associated with suppressed ECoG activity and severe acidosis induced neuronal damage, manifesting as seizure activity, and that this occurred when cerebral oxidative metabolism was reduced to ≤50% of control.     

Effects of induction of labor with prostaglandin E2 on fetal breathing and body movements: controlled, randomized, double-blind study.

OBJECTIVE: To evaluate the effects of prostaglandin (PG) E2, given for induction of labor at term, on fetal breathing and body movements. METHODS: Eighteen women with term pregnancies, mild gestational hypertension, intact membranes, and unripe cervices who were not in labor participated in this study. After a 60-minute baseline ultrasound examination of fetal chest and body movements, recorded on videotape, the patients were randomly assigned to either 3 mg intravaginal PGE2 tablets or controls (placebo intravaginal tablets). Following tablet insertion and a 3-hour observation time, a second 60-minute ultrasound recording of fetal movements was taped. The videotape recordings were interpreted according to the total amount of time occupied by fetal body movements and fetal breathing movements. RESULTS: There was a total of 2180 minutes of ultrasound tape recordings, with 136.2 minutes of fetal body movements (6.2%) and 207.8 minutes of fetal breathing movements (9.5%). Mean (+/- standard deviation) observation times per patient before and after tablet insertion were 60.3 +/- 1.2 and 56.4 +/- 1.2 minutes for the PGE2 group and 60.1 +/- 1.3 and 60.4 +/- 1.1 minutes for the control group. Three hours after PGE2 insertion, there were significant decreases in the percentage of time occupied by body movements (7.8 +/- 3.1 versus 3.4 +/- 2.0%; P < .003) and breathing movements (10.6 +/- 8.6 versus 3.9 +/- 2.3%; P < .007). Three hours after tablet insertion, there were statistically significant decreases in the percentage of time occupied by body movements (P < .025) and breathing movements (P < .01) between the control and study groups. CONCLUSION: Induction of labor with intravaginal PGE2 tablets inhibits fetal body and breathing movements. The effects could be due to direct action on the fetus or indirect effects of PGE2 (through uterine contraction and/or endogenous PG).     

Effects of multiple-dose maternal ethanol infusion on fetal cardiovascular and brain activity in lambs

Ethanol (2 gm/kg of maternal body weight administered in four equal doses of 0.5 gm/kg over 5 hours) was infused intravenously into nine chronically prepared pregnant ewes between 124 and 137 days' gestation. The data demonstrated a dose-response relationship between fetal arterial ethanol concentrations and the incidence of fetal breathing movements. Suppression of normal fetal electrocortical activity occurred at a low ethanol concentration and returned to control values at a time of very high arterial ethanol concentrations. This experimental model of a binge drinking episode further supports the hypothesis that ethanol suppresses fetal breathing movements by a direct central mechanism rather than indirectly by alteration of electrocortical activity.     

Chronic hyperglycemia and insulin concentrations in fetal lambs

Insulin concentrations were measured in 20 chronically instrumented fetuses of 10 sheep with alloxan-induced chronic hyperglycemia and 10 control sheep to examine if the hyperglycemia resulted in high fetal insulin concentration. Additionally, in six neonatal lambs of three chronically hyperglycemic ewes and three control sheep, insulin concentrations were measured after intravenous glucose injection. After a 2-month period of significant maternal hyperglycemia, no relationship between concentrations of fetal glucose and insulin could be detected. The mean fetal glucose concentration was 3.5 +/- 0.5 mmol/L in the hyperglycemic group and 0.6 +/- 0.1 mmol/L in the control group. Mean fetal insulin levels were 12.5 +/- 1.4 and 10.7 +/- 1.3 microU/ml, respectively. The neonatal lambs of the hyperglycemic and control ewes showed comparable concentrations of glucose and insulin after infusion of glucose. It is presumed that persistent high glucose levels depress the insulin secreting capacity of the fetal pancreas.     

Intrauterine fetal activity in at term and prolonged pregnancies

Fetal body movements and breathing movements were recorded with a real time ultrasound scanner in 26 fetuses. There were two recording periods of 25 min each, before and half and hour after maternal IV administration of 50 gr glucose. Six fetuses were at 280 days of gestation (Group A), twelve fetuses were at 294 days of gestation (group B), eight fetuses at 294 days gestation were classified as stage I postmature (group C). The incidence of fetal body movements was not significantly different in the three groups. Maternal glucose administration had no significant influence on fetal body movements in any group. On the other hand fetal breathing activity was significantly increased in all three groups after maternal glucose administration. Breathing activity was significantly greater in group A when compared to group C in both recording periods, and when compared to group B in the period which followed maternal glucose administration. It is concluded that fetal breathing activity is reduced in prolonged pregnancies.     

Effects of fetal breathing movements on umbilical venous blood flow in fetal lambs

The effects of fetal breathing movements on the blood flow pattern in the common umbilical vein were studied in six chronically instrumented fetal lambs between 106 and 143 days gestation. Umbilical venous blood flow was measured with an electromagnetic flow transducer around the intra-abdominal common umbilical vein. Fetal breathing movements were recorded by means of an intratracheal catheter. During rapid irregular breathing movements instantaneous umbilical venous blood flow showed undulations with the frequency of the breathing movements. An inspiratory movement, characterized by a fall in tracheal pressure (mean +/- S.D. = 5.3 +/- 1.7 mmHg) was accompanied by a decrease in instantaneous umbilical venous blood flow (mean +/- S.D. = 10.5 +/- 2.8%). This decrease in umbilical blood flow during inspiration was accompanied by an increase in intra-abdominal pressure. A much greater decrease (mean +/- S.D. = 40.6 +/- 18.4%) in instantaneous umbilical venous blood flow occurred during deep inspiratory efforts (mean pressure drop +/- S.D. = 15.5 +/- 4.3 mmHg), accompanied by marked increases in intra-abdominal pressure. Isolated expiratory efforts resulted in an increase in both tracheal (mean +/- S.D. = 6.3 +/- 2.6 mmHg) and intra-abdominal pressure, while umbilical venous blood flow decreased (mean +/- S.D. = 33.5 +/- 21.3%). These observations show the great influence of fetal respiratory movements on the blood flow pattern in the common umbilical vein. The changes in instantaneous umbilical venous blood flow are possibly brought about by changes in intra-abdominal pressure.     

Nuchal muscle activity at different levels of hypoxemia in fetal sheep

The effects of hypoxemia on nuchal muscle activity, a parameter of gross body movements, were studied during 12 experiments in five chronically instrumented fetal lambs. Hypoxemia was accomplished by tracheal infusion of nitrogen and did not result in significant changes in fetal arterial pH and PCO2. Fetal arterial blood gases and pH were continuously measured with an extracorporeal flow-through cuvette. Nuchal muscle activity was measured by electromyography and was expressed as the percentage of time spent moving. A decrease in fetal arterial oxygen saturation to three fourths of the initial value for 2 hours was not associated with significant changes in nuchal muscle activity. When fetal arterial oxygen saturation was further reduced for 2 hours to one half, fetal nuchal muscle activity fell significantly from 34.6% +/- 10.5% during normoxemia to 20.9% +/- 13.9% during hypoxemia. However, the most pronounced changes in fetal nuchal muscle activity occurred in the first 15 minutes after the changes in arterial oxygen saturation. A considerable transient increase in nuchal muscle activity was observed during the first 15 minutes after recovery from hypoxemia. During hypoxemia there was a relative predominance of short-lasting (less than 3 minute) movements.     

Sporadic fetal heart rate decelerations associated with electrocortical changes in fetal lambs

AIM: The purpose of this study was to determine a relationship between sporadic fetal heart rate (FHR) decelerations and fetal electrocortical changes in physiologically normal sheep fetuses. MATERIALS AND METHODS: A total of 20 experimental observations were conducted on eight chronically instrumented fetal lambs. For electrocorticogram (ECoG) recording, two stainless steel electrodes were implanted bilaterally on the fetal parietal skull. Classifications of ECoG tracings were visually divided into periods of low, high, intermediate and transitional voltage. During day and night observations, sporadic FHR decelerations related to fetal ECoG changes were counted. RESULTS: We found that 65% of the total sporadic FHR decelerations occurred in relation to fetal ECoG changes. The largest number of sporadic FHR decelerations was associated with a switch from low voltage to high voltage ECoG (37%). However, the greatest frequency of sporadic FHR decelerations occurred during intermediate ECoG periods (34%). CONCLUSION: The majority of sporadic FHR decelerations observed in physiologically normal sheep fetuses were associated with fetal ECoG changes.     

The effect of maternal hyperoxia on breathing movements, body movements and rest-activity cycles of low-risk human fetuses

The effects of maternal hyperoxia on fetal breathing and body movements, and on fetal activity state as reflected in the fetal heart rate pattern, were studied in 20 healthy gravida. Fetal breathing and trunk movements were observed by means of real-time ultrasound scanning, and the fetal heart rate was recorded continuously before, during and after 30 min of maternal oxygen inhalation by mask. Maternal transcutaneous oxygen tension (TcPO2) was measured in 9 subjects. The protocol was also carried out in ten of the gravidas with substitution of compressed air for oxygen. Maternal TcPO2 nearly doubled during oxygen breathing in the subjects in whom this was measured. There were no significant changes in the incidence of fetal breathing or trunk movements, or in the distribution of heart rate patterns, during maternal oxygen breathing. Also, no differences were observed in these variables between the oxygen and compressed-air experiments. We conclude that the normal level of fetal oxygenation does not limit fetal activity in uncomplicated pregnancies.     

Spectral analysis of fetal heart rate variability

OBJECTIVE: To assess power spectral densities and power spectrum of FHR variability in two categories of fetal activity, quiescence and breathing movements, in pregnancies complicated by diabetes mellitus or intrauterine growth retardation. MATERIAL AND METHODS: The study group included 70 women, 35 in uncomplicated pregnancies and 35 with above-mentioned complications. The spectral analysis of FHR variability in fetal quiescence or breathing activity was performed. The power spectrum was analyzed at frequencies 0-1.0 Hz. Successively, the power spectral density was calculated. It has been presented the plots of spectral densities of beat-to-beat variabilities well during breathing episodes as "no breathing". Subsequently, the power spectra were calculated in both analyzed activities and groups. RESULTS: The highest values of power spectral densities (0.118 +/- 0.025) at 0.6-0.8 Hz were found in uncomplicated pregnancies. In pregnancies complicated by diabetes mellitus (0.048 +/- 0.049) or IUGR (0.042 +/- 0.041) these values were statistically significantly. At 0.6 Hz and 0.8 Hz power spectra of FHR variability were lower in quiescence comparing to breathing activity, as well in uncomplicated as complicated pregnancies. At these frequencies power spectra during breathing movements were significantly lower in complicated pregnancies comparing to uncomplicated. COMMENTS: The results of this study confirm the usefulness of spectral analysis in the assessment of FHR variability. The observed disturbances may reflect an abnormal fetal reactivity. The evaluation of breathing and cardiovascular systems interaction allows to study indirectly the central nervous system that coordinates both activities.     

The relationship between fetal activity and behavioral states and fetal breathing movements in normal and growth-retarded fetuses

The incidence of fetal breathing was studied during the course of behavioral state observations on 28 low-risk fetuses between 32 and 40 weeks' gestational age and on 12 growth-retarded fetuses between 36 and 40 weeks. Real-time ultrasound scanners were used to detect fetal eye, body, and breathing movements, and the fetal heart rate was recorded continuously. The mean duration of the observation sessions was 110 minutes. The mean incidence of fetal breathing was greater during periods of fetal activity (body and eye movements present, greater heart rate variability) than during quiescence (body and eye movements absent, narrowed heart rate variability) at all gestational ages studied in both low-risk and growth-retarded fetuses. During periods when one of the state variables (body movements, eye movements, heart rate pattern) was in its active condition while the other two were quiet, or the reverse, the incidence of fetal breathing was intermediate between those found when all three state variables were in agreement. After behavioral states had developed, at 38 and 40 weeks, the mean incidence of fetal breathing in the low-risk fetuses was greater during active states than during the quiet state. There was no apparent increase in the degree of linkage between fetal breathing and other expressions of fetal activity after the emergence of behavioral states.     

Effect of maternal intravenous glucose administration on fetal heart rate patterns and fetal breathing

This study was undertaken to evaluate the effect of maternal intravenous (IV) administration of glucose on fetal breathing and its associated fetal heart patterns. Sixteen healthy women at term gestation participated in the study. The outcome of each of the pregnancies was normal. Fetal breathing and fetal electrocardiograms were simultaneously recorded by real time sonography and a fetal monitor respectively, and then digitized into a microcomputer. These women were studied for a 25-minute control period, given 50 gm of glucose IV and then, 20 minutes later, restudied for an additional 25-minute period. The results indicate that fetal breathing movements lasted for 24.8 +/- 6.2 percent of the time during the control period (mean +/- SEM) and were increased to 63.2 +/- 11.5 percent following the injection of glucose (P less than 0.01). Fetal heart rate decreased during fetal breathing by 2.3 and 2.1 beats per minute, before and after glucose administration, respectively (NS). Fetal breathing was associated with increased beat-to-beat variability by 1.32 +/- 0.5 and 1.27 +/- 0.3, before and after glucose administration, respectively (NS). This study confirms previous reports that the amount of time the fetus spends making breathing movements is significantly increased following maternal glucose administration, and demonstrates that the injection of glucose does not alter the modulation of fetal heart rate and beat-to-beat variability by fetal breathing.     

Temporal changes in fetal cardiovascular, behavioural, metabolic and endocrine responses to maternally administered dexamethasone in the late gestation fetal sheep.

OBJECTIVE: To determine the primary (0-12 h) and secondary (12-24 h) effects of dexamethasone on fetal heart rate, short term heart rate variation, blood pressure, breathing movements and electrocortical activity, blood gas exchange, metabolism and adrenocortical function in the late gestation sheep fetus. DESIGN: Comparison of the effects of a single maternally administered intramuscular injection of dexamethasone (12 mg) with those of saline vehicle from 1 h before injection to 24 h post-injection. Fetal cardiovascular and behavioural parameters were recorded continuously. Fetal and maternal blood samples were taken at regular intervals for blood gas, glucose and lactate, cortisol and adrenocorticotrophin measurements. SAMPLE: Sixteen chronically instrumented singleton fetal sheep at 127-133 days of gestation (term is about 147 days). RESULTS: During the primary phase short term heart rate variation fell (P < 0.001), and this was associated with a transient fall in the incidence of fetal breathing movements, a fall in fetal heart rate and a rise in fetal blood pressure. By 12 h there was a significant increase in short term heart rate variation (P < 0.001) and a rise in fetal heart rate, but blood pressure and fetal breathing movements had returned to normal. Dexamethasone significantly reduced fetal PaO2 throughout most of the experimental period, particularly 1 h post-injection (P < 0.005). Fetal and maternal plasma cortisol and adrenocorticotrophin concentrations fell significantly from 1 h post-injection. CONCLUSIONS: The effects of dexamethasone on fetal heart rate variation are more complex than previously described with both a fall and an increase observed depending on the time at which heart rate variation was measured after injection. Dexamethasone also caused a significant fall in fetal PaO2, and although this was not to hypoxic levels in normoxic fetuses it does raise questions about the potential impact of dexamethasone on chronically hypoxic fetuses.