Behavioural states: concomitants, clinical implications and the assessment of the condition of the nervous system

Behavioural states do exist in the human fetus. These states have been called 1F to 4F and resemble states 1 to 4 in the neonate. States 1F and 2F are similar to 'non-REM sleep' or 'quiet sleep' and 'REM-sleep' or 'active sleep', respectively. The fetus spends most of the time in these two states. Each state can be characterized by a particular combination of 3 variables: presence or absence of fetal eye movements and body movements, and fetal heart rate patterns A, B, C and D. From about 36 wk these combinations can be recognized during longer periods without interruptions, and with clear state-transitions. At 32 wk a certain linkage between the three variables is already present but a step-wise increase can be seen between 36 and 38 wk. Fetal breathing, mouthing movements and fetal voiding are state concomitants. Breathing movements are much more regular during state 1F than during state 2F, while the incidence is increased in 2F. It is demonstrated that knowledge of fetal behavioural states is necessary for an adequate interpretation of the fetal heart rate patterns. The concept of behavioural states may be useful for the early detection of disturbances of the developing fetal nervous system. It is therefore concluded that further studies on fetal behaviour have to be 'standardized' for behavioural states.     

Fetal mouth movements during behavioural states 1F and 2F

The aim of this study was to investigate the characteristics of mouth movements during behavioural states 1F (quiet sleep) and 2F (active sleep) in the near term human fetus. Thirty-six women participated. Fetal heart rate and fetal movements were recorded for 2 hours continuously. Videotapes with enclosed periods 1F and 2F were replayed to record fetal mouth movements in detail. During 1F, regular mouthing movements dominated (present in 74%), while jaw opening, yawn and grimace were only observed in 5 to 16% of the recordings. Tongue protrusion was not observed in 1F. In all 2F periods jaw opening was present (100%), while tongue protrusion, yawn and grimace were also frequently observed. Regular mouthing was observed in 2F in only two fetuses. For regular mouthing and sucking, onset-to-onset intervals of clusters, cluster duration, and number and frequency of movements within clusters were calculated. In all aspects the differences between these two types of movement were statistically significant. Within the clusters of regular mouthing a decline in the mouthing frequency was found. The data on fetal regular mouthing correspond with observations in the neonate.     

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.     

Computerized assessment of fetal behavioral states

Fetal heart rate and fetal movements provide information on the fetal condition. In the near term human fetus, four behavioural states have been described based upon heart rate patterns and presence or absence of eye and body movements. For our studies concerning fetal physiology as well as the influence of maternal antiepileptic medication and the effects of intrauterine growth retardation on the fetal condition, we developed a computerized system for acquisition and storage of fetal heart rate signals and observed fetal movements. Fetal heart rate is recorded using a commercially available monitor combined with a home-made computer interface. Fetal movements are observed using two real-time ultrasound units. The observers handle keyboards to mark occurrence and duration of various types of fetal movements, and pedals to mark the visibility of the observed part of the fetal body. Keyboards and pedals are scanned by the computer. Special techniques are used to store heart rate and movement signals in an efficient way. Three experts determine fetal heart rate patterns by application of a Delphi group opinion procedure. Fetal behavioral states are identified by the computer using the results of the Delphi procedure, and performing the so-called extended automatic window procedure. This procedure identifies periods of presence and periods of absence of fetal eye and body movements, and incorporates the loss of visibility of the ultrasound images during the recording session. Fetal heart rate variability indices and distributions of fetal movements can be computed in the context of the fetal behavioral state concept.     

Human fetal mouthing movements: a potential biophysical variable for distinguishing state 1F from abnormal fetal behavior; report of 4 cases

In late pregnancy, when fetal behavioural states are well developed, human fetuses spend about one third of their time in a quiescent state, 1F. In healthy fetuses biophysical tests often appear suboptimal if recording happens to occur in this state, and as a result prolonged recording may be necessary. We have examined fetal mouthing movements during state 1F in 65 fetuses beyond 36 weeks, with and without risk factors, but in whom there was no immediate evidence of compromise. We found that periodic rhythmical mouthing movements were a characteristic feature of state 1F, occurring in 93.0% of episodes, when the fetal mouth was visible. This compares favourably with variables of the biophysical profile, which were less likely to be satisfactory in state 1F - fetal breathing 53.8%, fetal movements 46.2%, fetal heart rate 69.2%, and overall biophysical score of 8 or 10, 60.0%. We identified objective evidence of fetal compromise (of various aetiologies) in four other fetuses of the same gestational age, and mouthing movements were absent in all four.     

Braxton Hicks' contractions and motor behavior in the near-term human fetus

The transient relationship between Braxton Hicks' contractions and fetal motor behavior was studied in 14 healthy nulliparous women near term. Two-hour recordings of fetal heart rate and uterine contractions and of real-time scanning for fetal body movements, breathing, and eye movements were made. The recordings were divided into state 1F and non-state 1F. Braxton Hicks' contractions were not influenced by fetal behavioral states and state changes were not related to these contractions. Fetal body movements did not stimulate contractions, but contractions coincided with a specific clustering of body movements during the ascending part of contractions. Breathing was clustered during the descending part of short-lasting contractions but decreased gradually during the long-lasting ones. Heart rate variation was increased during contractions.     

Human fetal breathing activity during electively induced labor at term.

Human fetal breathing movements were measured during the first stage of electively induced labor in 20 healthy term pregnancies. Fetuses made breathing movements 25.6% of the time during a 1 hour control period and breathing decreased significantly to 8.3% during latent-phase labor and further decreased to 0.8% during active labor (P less than 0.001). Patterns of increased fetal breathing activity accompanied by increased gross fetal body movements and increased fetal heart rate variability for periods of 20 to 60 minutes out of every 1.0 to 1.5 hours were observed, and the intermittent patterns of increased body movement and heart rate variability continued throughout the first stage of labor despite the decrease in fetal breathing activity during latent- and active-phase labor. It will be important to account for rest activity patterns when interpreting variability of heart rate during labor. The absence of fetal breathing activity during electively induced labor at term is not a clinical indicator of fetal ill health.     

The role of carbon dioxide in the generation of human fetal breathing movements

To determine the role of carbon dioxide in the generation of fetal respiratory movements, the effect of induced maternal hypocapnia and hypercapnia on fetal breathing movements, gross body movements, and fetal heart rate was studied in 12 healthy pregnant women near term. Patients were studied for a 1-hour control period breathing room air followed by four randomized 15-minute study periods with patients breathing either room air, a prepared gas mixture with 2% or 4% carbon dioxide, or undergoing controlled hyperventilation as determined by monitoring end-tidal PCO2. The percentage of time fetal breathing movements correlated significantly with maternal end-tidal PCO2 (r = 0.62, p less than 0.01), increasing with maternal breathing of 2% and 4% carbon dioxide and decreasing with maternal hyperventilation. Fetal gross body movements, fetal heart rate, and fetal heart rate variability showed no significant changes. It is concluded that as in adults, the carbon dioxide level in fetuses is an important stimulus for the generation of respiratory movements, acting independent of a change in behavioral state. It is hypothesized that tonic carbon dioxide level input is an important determinant of fetal respiratory center drive, but little or no phasic carbon dioxide input exists because of continuous placental excretion, thus resulting in the episodic occurrence of breathing movements with changes in the fetal behavioral state.     

Quantitative analysis of fetal behavioural patterns with real-time sonography and the actocardiograph

Fetal heart rate patterns, isolated and clustered fetal movements, fetal eye and breathing movements were analysed simultaneously and semiquantitatively in 20 uncomplicated pregnancies in accordance with the classification of fetal behavioural states by Nijhuis and with the aid of two ultrasound scanners and the actocardiograph. According to our own definition state 1 F, 2 F, 3 F and 4 F were observed in 29, 34, 8, and 14% of the registration time. In 15% no state could be identified. Using only the actocardiograph state 1 F, 2 F and 4 F could be identified in around 75%. Periods without a state diagnosis could not be assessed by the actocardiograph alone. The combination of the actocardiograph and one ultrasound scanner for the observation of fetal eye movements reached a similar diagnostic accuracy as the polygraphic monitoring with two ultrasound scanners.     

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.     

The fetal behavioural states: an ultrasonic study

In order to accurately detect the fetal behavioural state, we simultaneously measured fetal heart rate and multiple fetal activities in 27 healthy pregnant women at 38 to 40 weeks of gestation. We ultrasonically identified gross body movements, breathing movements and micturition. Analysis of fetal heart rate allowed us to distinguish two different patterns of fetal behaviour: active and quiet phases. The frequency distribution of the analysed fetal events was significantly different in these two phases. These data suggest that a complete biophysical profile of the fetus is effective in differentiating behavioural states and may improve the predictive accuracy of fetal heart rate analysis alone.     

Effects of thyrotropin-releasing hormone in the fetal lamb

Thyrotropin-releasing hormone causes neurobehavioral arousal and stimulates breathing in adult, newborn, and preterm experimental animals. Its effects on behavioral state, breathing, blood pressure, and heart rate were studied in the chronically instrumented late term fetal lamb. Fetal intravenous administration of thyrotropin-releasing hormone resulted in behavioral arousal with electrocortical desynchronization, increased body and eye movements, rapid and deep breathing movements, and a transient bradycardia followed by prolonged tachycardia, associated with an increase in both systolic and diastolic blood pressure. The effects were similar following intracisternal administration of thyrotropin-releasing hormone. The effects of thyrotropin-releasing hormone on behavior, but not breathing, was abolished in the presence of muscarinic blockade. Thyrotropin-releasing hormone may play a role in the modulation of central regulation of cardiovascular, respiratory, and behavioral activity in the fetus.     

Patterns of human fetal breathing activity at 34 to 35 weeks' gestational age.

Continuous measurements of human fetal breathing movements at 34 to 35 weeks' gestational age were made with an ultrasonic real-time scanner for periods of 24 hours in 11 women. A significant increase occurred in fetal breathing activity during the second and third hour following meals and this pattern apparently followed an increase in maternal plasma glucose concentration. There was a prolonged significant increase in fetal breathing activity between 0100 and 0700 hours. Increases in human fetal breathing activity accompanied by increased gross fetal body movements occurred for periods of 20 to 60 minutes out of every 1.0 to 1.5 hours of observation time. It was concluded that the percentage of time spent breathing by normal fetuses was related to time of day and maternal meals. The alternating changes of fetal activity and inactivity observed may represent biologic changes of sleep state in the human fetus in utero at 34 to 35 weeks' gestational age. It will be important to account for these three patterns of fetal breathing activity in clinical studies which examine the usefulness of fetal breathing movements in assessing fetal health.     

Longitudinal assessment of behavioural transitions in healthy human fetuses during the third trimester of pregnancy

A longitudinal study was performed on 35 healthy fetuses in order to evaluate the developmental course of behavioural transitions during the last trimester of pregnancy. A progressive decrease in the duration of transitions as a function of gestational age was evidenced for both transitions from 1F to 2F and transitions from 2F to 1F. Concerning the sequence in change of behavioural variables (fetal heart rate, fetal eye movements and fetal gross body movements) a random distribution was found until 30 weeks for 1F to 2F transitions and until 34 weeks for 2F-1F transitions. After these gestational ages fetal heart rate and fetal gross body movements respectively become the first variable to change during 1F-2F and 2F-1F transitions. Reference values for these parameters are calculated in order to provide a basis for the diagnosis of behavioural abnormalities in high risk fetuses.     

Fetal respiratory movements and their regulation

In 1972, fetal breathing movements were clinically rediscovered. Details of their episodic occurrence, frequency, inspired volume, pleural pressure, and the nearly absolute independence of fetal blood gases were investigated in animal experiments. In the human being, there is also an association between fetal breathing and sleep state: fetal breathing movements were confined almost exclusively to periods of REM sleep. The pattern of respiratory frequency changes as gestation progresses; the rates decrease as term approaches. Hardly any breathing movement can be detected during labor. The fetal respiratory centre is capable of rhythmic movements, but there is a lack of response to basic chemical stimuli from the periphery of the body. The association between fetal breathing and REM sleep implies that the connection between breathing and behaviour is already established before birth; but in the fetus, the link between breathing and metabolism is not yet forged. Throughout postnatal life this linkage predominantly regulates breathing. The difference between fetus and newborn in the reaction to chemical stimuli implies a change at birth related to the glomera cells of the carotid bodies. Under the influence of the marked increase in the sympathetic tone there is a major increase in the sensitivity of the receptor cells to oxygen deficiency immediately after birth.     

Sinusoidal heart rate pattern and an normal biophysical profile in a severely compromised fetus

A case is described in which a woman complained of weakened fetal movements, and a persistent sinusoidal heart rate pattern was demonstrated in the presence of normal fetal breathing movements, normal fetal tone, and normal amount of amniotic fluid. In view of the subjective complaints and disregarding the normal biophysical profile, termination of pregnancy was performed. A compromised, severely anemic fetus was delivered by cesarean section. The role of sinusoidal heart rate pattern and the limitations of biophysical scores as a single determinant of fetal well being are discussed.     

Real-time ultrasound observation of breathing and movements in the fetal lamb

In seven pregnant ewes with catheters chronically implanted in the fetus, real-time ultrasound observations of fetal breathing and body movements were correlated with direct measurements of fetal arterial and tracheal pressures, heart rate, and intrauterine pressure. There was excellent correlation between the ultrasound record of fetal breathing and recordings of intratracheal pressure changes even when breath amplitude was low or frequently was high. Fetal body movements (stretches, rolls, kicks) were observed during both breathing and nonbreathing periods; vigorous movements were accompanied by rapid deflections of the amniotic and tracheal pressure traces. Movement was frequently accompanied by transient increases or decreases in heart rate. The results indicate that real-time ultrasound is an accurate method for observation of fetal movement in pregnant sheep and is particularly valuable when combined with direct measurements of fetal physiologic parameters.     

Fetal behaviour in growth retardation: its relationship to fetal blood flow

The fetal behaviour of asymmetrical growth retarded fetuses was compared with that of a control group of healthy fetuses. Fetuses underwent simultaneous cardiotocographic and echographic examinations for two consecutive hours at 36-38 weeks of gestation. The distribution of gross fetal body movements, fetal breathing movements and fetal eye movements was analysed during the different fetal heart rate patterns. Furthermore, the incidence and organization of fetal behavioural states was investigated. The degree of vascular peripheral resistance was also evaluated by means of pulsed doppler ultrasonic equipment. Growth retarded fetuses were divided into two groups on the basis of the presence or absence of end diastolic flow in the fetal thoracic descending aorta. Growth retarded fetuses showed a delay in the integration of behavioural patterns and a lower coincidence of behavioural states. These findings are particularly evident in the fetuses with a severe increase of peripheral vascular resistance (absence of end diastolic flow in descending aorta). Thus, we suggest that a delay in central nervous system development is present in asymmetrical growth retarded fetuses and that there is a possible relationship of this delay to the degree of peripheral vascular resistance.     

Relationship Between Combined Fetal Biophysical Activities,Oligohydramnios, and Fetal Acid–Base Status

The purpose of this study was to determine the relationship between combined fetal biophysical activities, oligohydramnios, and fetal acid-base status at the time of testing. In a prospective study of 101 patients undergoing cesarean section before the onset of labor, a fetal biophysical profile was performed within 3 h before the cesarean section. Different combinations of fetal biophysical activities (fetal heart rate reactivity, fetal breathing movements, fetal body movements, and fetal tone) and oligohydramnios were correlated with umbilical cord blood gas and acid-base measurements (artery and vein). Fetal acidemia was defined as umbilical arterial blood pH <7.20. The group of fetuses with reactive nonstress test (NST) and/or fetal breathing present had significantly higher pH, pO₂, bicarbonate, and base excess and significantly lower pCO₂ levels compared with fetuses who had nonreactive NST, absent fetal breathing, and compromised or absent body movements and tone. These blood gas and acid-base differences were observed in both umbilical cord artery and vein. There was a significant relationship between oligohydramnios and fetal acidemia. Seven of 15 (46.6%) fetuses with oligohydramnios were acidemic and 7 of 15 (46.6%) acidemic fetuses had oligohydramnios (P = 0.0008). Fetuses with compromised or absent movements and tone had the highest incidence of acidemia (10 of 11 or 91%) and oligohydramnios (4 or 11 or 36%). The presence of oligohydramnios was associated with increased frequency of acidemia in every combination of biophysical activities. However, when all biophysical activities were absent, the frequency of acidemia was 100% regardless of the presence or absence of oligohydramnios. In conclusion, progressive loss of fetal biophysical activities is associated with increasing frequency and severity of fetal acidemia and oligohydramnios.     

Fetal behavioural states in epileptic pregnancies

Possible negative effects of maternal antiepileptic medication on fetal motility and heart rate patterns were examined at 32 and 38 wk of gestation. Fetal eye and body movements were recorded using 2 real-time ultrasound units. Comparison between pregnancies with antiepileptic medication and control pregnancies did not show marked differences in patterns of motility and heart rate. Duration of sleep states, occurrence and duration of body movements in state 2F and statistical parameters of heart rate level and heart rate variability were very similar for both groups. This preliminary study, limited to mostly combined treatment with antiepileptic drugs, could not demonstrate any obvious effect on fetal neuromuscular development from maternal antiepileptic medication.