Fetal Sleep Research Articles

Experimentally induced intermittent sinusoidal heart rate pattern and sleep cycle in fetal lambs

OBJECTIVE: Intermittent sinusoidal heart rate pattern, an early indicator of fetal anemia, has been speculated to have a positive correlation with fetal sleep cycles. To test this hypothesis, intermittent sinusoidal heart rate patterns were produced experimentally with arginine vasopressin in six methylatropinized fetal lambs that were demonstrating clear rapid-eye-movement and non-rapid-eye-movement sleep cycling. STUDY DESIGN: Eleven trials of arginine vasopressin infusion (40 to 160 mIU per body per minute) were performed on each of six chronically instrumented fetal lambs subsequent to parasympathetic blocking doses of methylatropine (300 to 400 μg). An intermittent sinusoidal heart rate pattern was observed in relation to fetal sleep cycles. RESULTS: Alteration between rapid-eye-movement and non-rapid-eye-movement sleep was observed in methylatropinized fetuses. In the six fetuses that showed intermittent sinusoidal heart rate patterns subsequent to arginine vasopressin infusion, the fetal heart rate tracing and fetal electrocorticogram demonstrated alternate sinusoidal pattern and reactive heart rate patterns during high- and low-voltage electrocorticogram activity, respectively. CONCLUSION: These findings support the hypothesis that fetal sleep cycling has a positive correlation with the periodic appearance of intermittent sinusoidal heart rate patterns. (AM J OBSTET GYNECOL 1994;170:1421-4.)

Experimentally induced intermittent sinusoidal heart rate pattern and sleep cycle in fetal lambs

<b>OBJECTIVE:</b> Intermittent sinusoidal heart rate pattern, an early indicator of fetal anemia, has been speculated to have a positive correlation with fetal sleep cycles. To test this hypothesis, intermittent sinusoidal heart rate patterns were produced experimentally with arginine vasopressin in six methylatropinized fetal lambs that were demonstrating clear rapid-eye-movement and non-rapid-eye-movement sleep cycling. <b>STUDY DESIGN:</b> Eleven trials of arginine vasopressin infusion (40 to 160 mlU per body per minute) were performed on each of six chronically instrumented fetal lambs subsequent to parasympathetic blocking doses of methylatropine (300 to 400 μg). An intermittent sinusoidal heart rate pattern was observed in relation to fetal sleep cycles. <b>RESULTS:</b> Alteration between rapid-eye-movement and non-rapid-eye-movement sleep was observed in methylatropinized fetuses. In the six fetuses that showed intermittent sinusoidal heart rate patterns subsequent to arginine vasopressin infusion, the fetal heart rate tracing and fetal electrocorticogram demonstrated alternate sinusoidal pattern and reactive heart rate patterns during high- and low-voltage electrocorticogram activity, respectively. <b>CONCLUSION:</b> These findings support the hypothesis that fetal sleep cycling has a positive correlation with the periodic appearance of intermittent sinusoidal heart rate patterns.

Influence of prolonged adenosine receptor blockade on fetal sleep and breathing patterns

Chronically prepared fetal sheep were subjected to 48 h infusions of theophylline, an adenosine antagonist, enprofylline, a xanthine without adenosine antagonism, or saline. Theopylline increased mean (±SD) incidence of REM sleep from49.3 ± 8.3%to57.3% ± 6.7% (p<0.02) and wakefulness from1.3 ± 1.4% to8.1 ± 7.1% (p<0.01). On the first day of theophylline infusion incidence of fetal breathing (FB) increased from37.9 ± 8.1%to53.7 ± 11.6% of total time (p<0.002) and from76.4 ± 10.2%to87.6 ± 10.3%of REM sleep (p<0.02). Diaphragmatic EMG/min increased from6.9 ± 4.0to17.3 ± 13arbitrary units(p<0.02). By the second day of infusion, FB had returned to baseline value. Enprofylline and saline had no effect. 125 μg phenyl isopropyl adenosine (PIA) i.v. caused fetal apnea that was reduced from143 ± 45.5min on the control day to39.8 ± 34.7min(p<0.001) during theophylline infusion. Enprofulline and saline had no effect, suggesting that the observed theophylline effect was due to its adenosine antagonism rather than to non-specific xanthine action. We conclude endogenous adenosine suppresses FB, but since theophylline did not alter the basic relationship between FB and REM sleep it is not primarily responsible for apnea during NREM sleep.

Intermittent sinusoidal heart rate pattern in vagotomized fetal lambs

Our aims were to investigate the relationship between the dose of arginine vasopressin and the pattern and duration of arginine vasopressin-induced sinusoidal fetal heart rate and to elucidate the correlation between intermittent sinusoidal heart rate and fetal sleep cycle. Sinusoidal heart rate pattern was induced by intravenous arginine vasopressin infusion at doses from 2 to 78 mlU/min into 11 chronically instrumented fetal lambs with bilateral cervical vagotomy. Appearance and frequency of sinusoidal heart rate, intermittent sinusoidal heart rate, and persistent sinusoidal heart rate were observed along with fetal tracheal pressure and electrooculogram. Intermittent sinusoidal heart rate response to low, medium, and high doses of arginine vasopressin appeared in 73.3%, 50.0%, and 33.3% of experiments, respectively. Intermittent sinusoidal heart rate appeared more frequently than persistent sinusoidal heart rate with lower doses (p < 0.02). When intermittent sinusoidal heart rate was induced, the incidence of sinusoidal patterns significantly increased during non-rapid-eye-movement sleep in comparison with rapid-eye-movement sleep (p < 0.01). Appearance of sinusoidal heart rate seems to be related to the dose of arginine vasopressin infused. Appearance of sinusoidal heart rate is also influenced by fetal sleep cycle; sinusoidal heart rate is more likely to appear during non-rapid-eye-movement sleep than during rapid-eye-movement sleep. These results support the hypothesis that persistent sinusoidal heart rate correlates with severity of stress.

Computerized analysis of episodic changes in fetal heart rate variation in early labor

Fetal heart rate variation in early labor was measured by computerized analysis in cyclic episodes of low or high variation in 136 women at 37 to 42 weeks' gestation. The amplitude (mean &#x0026;#x0026;#x0026;#x0026;#x0026;#x0026;#x00B1; SE) in episodes of low variation was 20.6 ± 0.4 milliseconds; in high variation it was 57.3 ± 1.1 milliseconds. The duration (mean ± SE) of low episodes (24.3 ± 1.3 minutes) was less than that of high episodes (45.1 ± 2.7 minutes) but was sometimes >1 hour. In episodes of low variation the amplitude was <5 beats/min long term in 11 % and <2.5 milliseconds (pulse intervals) short term in 8%; these measures would be predictive of intrauterine death if persistent before birth. We conclude that the use of decreased fetal heart rate variation as a diagnostic sign of acute fetal hypoxemia in labor is incorrect, because changes of this size occur randomly as a consequence of fetal sleep states. There was no significant correlation between fetal heart rate variation over the last hour of labor and umbilical arterial base deficit on delivery.

Fetal Heart Rate Changes Associated with General Anesthesia

Decreased fetal heart rate variability was noted 90 seconds after the induction of general anesthesia with sodium thiopentone and fentanyl in a patient undergoing basket extraction of a renal calculus at 30 weeks' gestation. The fetal sleep pattern lasted for 105 minutes after the anesthetic was discontinued, 45 minutes after the mother was fully awake.

Restoration of lung liquid volume following its acute alteration in fetal sheep.

1. The experiments were aimed at determining the means by which lung liquid volume is controlled in fetal sheep. Six unanaesthetized chronically catheterized fetuses between 121 and 144 days of gestation were used in experiments in which lung liquid volume was acutely reduced or increased. 2. The effects on lung liquid volume, secretion and flow in the trachea were continuously monitored until the original volume was restored. Tracheal pressure, breathing activity, electrocortical activity and laryngeal adductor muscle activity were also monitored. 3. Following a mean reduction in lung liquid volume of 54.1% (40.0 +/- 4.3 ml) there was a reduction in tracheal pressure of 1.91 +/- 0.26 mmHg. There was no change in the rate of lung liquid secretion and there was a near cessation in its rate of efflux from the trachea. Influx of liquid from the upper airway was rarely seen. 4. 5 h after its reduction, lung liquid volume had returned to control values. Tracheal pressure and the rate of liquid flow in the trachea returned to control values over 7-8 h. 5. In the hour following the reduction in lung liquid volume the incidence and amplitude of fetal inspiratory muscle electromyogram (e.m.g.) activity were reduced by 19% and 28% respectively. There was no change in laryngeal adductor muscle activity or in the duration of fetal sleep states. 6. When lung liquid volume was increased by 25.4 +/- 3.1 ml tracheal pressure increased by 2.01 +/- 0.17 mmHg. Although there was no change in the rate of liquid secretion there was a rapid efflux of liquid from the trachea principally during epochs of fetal breathing activity thus returning lung liquid volume to its control value. 7. Following the increase in lung liquid volume there were no changes in the incidence or amplitude of fetal inspiratory muscle activity, the activity of laryngeal adductor muscles or in the duration of sleep states. 8. It is concluded that following its alteration in fetal sheep lung liquid volume is restored by passive means. There was no evidence of volume-receptive neural reflexes being activated in defence of lung liquid volume.

Continuous twenty-four hour recording of the fetal cardiac rhythm during normal pregnancies

Recording the fetal cardiac rhythm (FCR) is currently the technique most widely used to assess the well being of the fetus. In view of the importance of the decisions taken on the modifications of the FCR, the authors have recorded and analysed over 24 consecutive hours 10 resting women manifesting a strictly normal pregnancy. They observed no modification in the basal cardiac frequency, very few declarations and above all, never any signs of a flat or sinusoidal rhythm. Flattening of the FCR is invariably pathological. It must not be interpreted as “fetal sleep” period, but it should intensify the surveillance.

Indomethacin-induced fetal breathing: mechanism and site of action.

The mechanism and site of action of indomethacin-induced fetal breathing (FB) was investigated in 26 chronically prepared fetal lambs. Indomethacin, which preferentially blocks prostaglandin production, was infused into the fetal circulation in two stages, 60 mg in 10 min and 60 mg over 7 h. Indomethacin stimulated sleep-state independent FB that was greatly reduced or abolished by infusions of prostaglandin E2 (PGE2). Infusions of nordihydroguaiaretic acid, which preferentially blocks the synthesis of leukotrienes, had no consistent effect on either fetal sleep or breathing activity when administered alone or after indomethacin. This suggests that the characteristic FB induced by indomethacin is due to inhibition of prostaglandin synthesis (PGE2) and not due to an overproduction of leukotrienes. The indomethacin effect on FB was observed in all fetuses tested including those deprived of peripheral chemoreceptor function, vagotomy, decortication, or spinal cord section at the T1 level. Complete constriction of the ductus arteriosus for many hours had no effect on FB. We conclude that inhibition of PGE2 synthesis stimulates FB by a central mechanism other than the cortex.

The effects of myometrial activity on fetal thoracic dimensions and uterine blood flow during late gestation in the sheep.

We wished to investigate mechanisms by which non-labour contractions of the uterus influence fetal sleep states and respiratory activity during late pregnancy. The relationship between the dimensions of the fetal chest and uterine contractions was examined in 5 pregnant sheep. The dorso-ventral dimension at the level of the xiphisternum (3 fetuses) decreased, on average by 4.4-9.4% while increases of 16.6-18.7% were seen in the transverse dimension (4 fetuses). Blood flow in a middle uterine artery was monitored using a Doppler technique in 5 pregnant sheep. Non-labour uterine contractions were accompanied by mean reductions of 6.5-12.7% in blood flow. Postural adjustments by the ewe also influenced uterine blood flow. A mean increase in blood flow of 5.9-12.0% followed a change from standing to lying; standing caused a mean reduction of 5.9-11.8%. We conclude that the influence of uterine contractions on the fetus is likely to be complex, involving distortion of the body and alterations in utero-placental haemodynamics.

Fetal heart rate variability as an indicator of fetal status.

Numerous studies have shown the clinical usefulness of monitoring fetal heart rate (FHR) variability. Among the disorders associated with decreased FHR variability during labor are fetal asphyxia and acidosis and subsequent distress in the newborn. Among the factors that influence FHR variability are maternal fever, fetal immaturity, so-called fetal sleep, fetal tachycardia, and drug administration to the mother. The nonstress test, which analyzes FHR variability and accelerations of heart rate with fetal movements, may be as useful as the oxytocin challenge test for assessing FHR variability. Doppler ultrasonic cardiography exaggerates the amount of FHR variability. FHR patterns associated with progressive loss of beat-to-beat variability in the absence of maternal drug intake necessitate intervention.

Definition of sleep state in the newborn infant by heart rate analysis

The relationship of heart rate variability to sleep state was examined in 9 term newborn infants at one to three days of age. Spectral density plots of rhythmic variations in heart rate during active sleep and quiet sleep were characteristic and always distinct from each other. Heart rate and heart rate variability were significantly higher during active sleep than during quiet sleep. It was always possible to identify quiet sleep and active sleep during sleep periods by inspecting spectral density plots of the variations in heart rate. Similar relationships between heart rate variability and sleep states may exist in utero. Spectral analysis of heart rate variations may provide an indirect measurement of fetal sleep states, and such measurements might become useful in assessing fetal brain maturity and fetal well-being.

Relationship of intrauterine fetal activity to maternal sleep stage

An attempt was made to evaluate the possibility of a humoral, rather than neural, mediation of the epiphenomena of REM sleep. The exclusively systemic communication between a mother and her fetus provided a readily available preparation for an initial approach to this problem. With reference to the sleep of newborn infants, it was assumed that periods of active motility in the fetus of a sleeping mother reflected the occurrence of REM sleep in this organism. Maternal sleep was monitored by standard recording procedures, and fetal sleep was inferred from recordings of intrauterine activity. The following results were obtained from comparisons of all-night sleep records of the mother-fetus unit: (a) The fetus tends to develop a recurrent quiet-active cycle in the course of gestation. (b) Specific instances of high fetal activity frequently occur together with or in close proximity to the recurrent episodes of REM sleep in the mother. Such increases, when they occur, appear to be related to the appearance of maternal REM sleep; however, they are not a systematic feature of this sleep phase. (c) A number of potential mechanisms for a dynamic humoral communication between the two physiological units during REM sleep are discussed.