Behavioural states in growth-retarded human fetuses

Behavioural state observations were carried out on 12 fetuses which subsequently had birthweights below the 10th percentile. Their gestational ages at the time of study ranged from 32 to 40 weeks. Real-time ultrasound scanning was used to detect fetal body and eye movements, and the fetal heart rate was continuously recorded using a clinical fetal monitor. None of these fetuses was severely acidemic or depressed at birth. Findings in the growth-retarded fetuses were compared with those obtained in the fetuses of 14 low risk nulliparae and 14 low risk multiparae by means of the same techniques (van Vliet et al. (1985) Early Hum. Dev., 12, 121-135.; Nijhuis et al. (1982) Early Hum. Dev., 6, 177-195). The appearance of states seemed to be delayed in the growth-retarded fetuses. States were present in only three of eight growth-retarded fetuses studied at 40 weeks, whereas only one of 16 low risk fetuses did not show states at this age. Also at 40 weeks, the proportion of discordant association of the state variables was increased in the growth-retarded fetuses in comparison to the low risk group. There were no consistent differences between the two groups in the occurrence of defined combinations of parameters of the state variables at earlier ages. The growth-retarded fetuses showed differences in the quality and quantity of somatic motility in comparison to low risk fetuses of equivalent gestational age. These observations suggest that some aspects of central nervous system function are disturbed in growth-retarded fetuses, even in the absence of fetal distress.     

Are there behavioural states in the human fetus?

The aim of this study was to search for the existence of behavioural states in the human fetus and to describe their developmental course. In a longitudinal study, 14 low-risk fetuses were studied at 2-week intervals from 32 weeks of gestation onward. Fetal body movements as well as fetal eye movements, visualized by means of real-time ultrasonic imaging, and fetal heart rate patterns, recorded by means of a cardiotocograph, were used as state variables.At 38 and 40 weeks, four distinct behavioural states, named states 1F through 4F and corresponding respectively to states 1 through 4 of the neonate, could be identified. That these constellations of parameters represented true behavioural states was demonstrated by the stability of association of parameters for prolonged periods and by the simultaneity of change of parameters at state transitions. There is evidence for episodes of wakefulness in the fetus. Before 36 weeks, cycles were present in each of the state variables, and combinations of parameters typical of particular states were observed. However, the relatively short durations of these combinations and the lack of simultaneity of change in the three state variables support the conclusion that these periods of coincidence occurred by chance and did not represent organized behavioural states.     

Coincidence of behavioural state parameters in the human fetus at three gestational ages

The fetal behavioural state concept was used to study fetal rest-activity cycles in normal pregnancies at gestational ages of 32 and 38 weeks. In addition, it was investigated if clustering of fetal movements was already present in recordings obtained at 20 weeks. At 20 weeks, 17 periods lasting longer than 3 min were found in which fetal body movements were absent. The mean duration of these periods was 4.0 +/- 0.8 min. On the basis of random scattering of movements on a time axis, it appeared unlikely that these periods of inactivity occurred by chance alone. At 32 and 38 weeks, data on body movements were combined with data on eye movements and the FHR pattern. At 32 weeks, true fetal behavioural states were not found. The average coincidence of 1F to 4F was 58%, while only 23% was to be expected if state parameters had fulfilled state criteria purely by chance. At 38 weeks, coincidence of 1F to 4F had increased to 80% (P less than 0.001). Expected coincidence purely by chance was 30%. True fetal behavioural states were found in 17 out of 35 recordings. For transitions from 1F into 2F, the FHR changed relatively early, i.e. as first or second parameter, while for the reverse transitions it changed relatively late (P less than 0.05). There was no clearly preferred sequence for body and eye movements within transitions.     

Emergence of behavioural states in fetuses of type-1-diabetic women

The aim of this study was to investigate the effects of tightly controlled maternal (type-1-)diabetes mellitus on the development of fetal behavioural states. Seventeen diabetic women, who required insulin (White's class C predominantly) and were treated with continuous subcutaneous insulin infusion (CSII) therapy, participated in the study. Adjustment to an insulin-pump occurred before conception or during early pregnancy. In all diabetic women (near-)normoglycemia was achieved during pregnancy, with glycosylated hemoglobin-values within the normal range (6-8.5%). Fifty-three 2-h recordings of fetal heart rate, uterine contractions and of real-time ultrasound scanning for fetal body movements, breathing and eye movements were obtained from the 17 fetuses. The fetuses were longitudinally studied between 32 and 40 weeks post menstrual age, at intervals of 2 weeks. The 3 state variables, fetal heart rate, body movements and eye movements, were analyzed for the presence of combinations meeting the definitions of the four fetal behavioural states. Findings in the fetuses of diabetic women were compared with those obtained from 28 low risk fetuses. The criteria of states were met in only 3 of 8 fetuses studied at 38 weeks and in one of two studied at 40 weeks. For comparison: in low risk fetuses studied at 38 and 40 weeks, states were present in 70% and 90% of the cases, respectively. This poorly developed state organization exhibited by the near term fetuses of the diabetic group, was related to maternal parity, but not to pre- or postconceptional onset of CSII-treatment. Fetuses of nulliparous diabetic women showed more often asynchrony of transitions (greater than 3 min) and interruption of periods of concordant association. This resulted in significantly higher percentages of 'no-coincidence' and in low incidence of behavioural states as compared with control fetuses of nulliparous women. In the few multiparous diabetic cases studied near term the development of fetal behavioural states was normal. We conclude therefore that, despite tight control of maternal diabetes, the development of behavioural states is disturbed in fetuses of nulliparous diabetic women.     

The relationship between the response to external light stimulation and behavioral states in the human fetus: how it differs from vibroacoustic stimulation

OBJECTIVE: To determine the effects of external light stimulation on fetal behavioral states and know the difference from those of vibroacoustic stimulation. METHODS: A flashlight and a vibroacoustic stimulator was applied directly on the maternal abdomen to determine the response of 56 normal fetuses at 36-40 weeks gestation. Fetal heart rate (FHR) and body movements were recorded using an actocardiograph, and fetal eye movements were observed using real-time ultrasonography. Using Nijhuis's criteria, the fetal behavioral states (1F-4F) were determined. FHR acceleration was considered a fetal response to the stimulations. RESULTS: The lag time between stimulation and fetal response was within 4 s. A positive response rate to the light stimulation was higher at behavioral states 2F (82%) and 3F (83%) than at state 1F (4%). Light stimulation changed the behavioral state of two of the six 3F fetuses (33%) from 3F to 4F. No change of state was observed in fetuses that were in states 1F and 2F. For vibroacoustic stimulation, fetal response was 100% positive and changes of states were observed frequently irrespective of the behavioral state before the stimulation. CONCLUSION: Fetal response to light stimulation is closely connected to fetal behavioral states and may reflect some distinct stages of the sleep-wakefulness cycle.     

Fetal behavioural states and controlled sound stimulation

The aim of this study was to investigate responses of human fetuses near term (37-42 wks) (increase/decrease of fetal heart rate and/or fetal motility) to acoustic stimuli. The study group consisted of 43 patients and the control group of 27 patients. Polygraphic recordings of 5 different fetal variables were carried out synchronously for the categorization of the actual fetal behavioural state according to Nijhuis et al. (Nijhuis, J.G., Prechtl, H.F.R., Martin, C.B., Jr. and Bots, R.S.A.M. (1982): Early Hum. Dev., 6, 177-195). Controlled acoustic stimulation was performed either with sine wave tone (2 kHz, 120 dB and 5 s duration) or modulated sine wave tone (0.5-2 kHz, 'sawtooth' modulation, 120 dB and 5 s duration). An additional group of patients received 'sham' stimulation. Overall 84 acoustic stimulations have been carried out. In 26 out of 84 stimulations (30%) a fetal response could be observed within 5 s after acoustic stimulation. In general, there were far fewer fetal responses in sleep states than in states of wakefulness. Whereas in state 1 F only 1 out of 28 acoustic stimulations was followed by an immediate fetal response, more responses were observed in state 2 F. An obvious increase in fetal reactivity to acoustic stimulation was noted in states of wakefulness (states 3 F and 4 F). Comparison between the true and sham stimulations revealed a relatively high level of spontaneous fetal activity (high variation of fetal heart rate and fetal motility) present in states 2 F and 4 F. This must be taken into account in all assessments of fetal responses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hip Joint Instability in Breech Pregnancy

ABSTRACT. 222 consecutive fetuses found by ultrasound to be in breech presentation in the 33rd gestational week were followed with repeated examinations in weeks 35 and 38. Ninety-one of these fetuses persisted in breech presentation until delivery, while cephalic version occurred in 131. The frequency of hip joint instability was 21% in the breech delivered group and 1.5% in the vertex delivered group. The position of the fetal legs was established at each ultrasound examination. The intrauterine fetal attitude was classified as extended when the fetuses had extended knees and maximally flexed hips at all ultrasound examinations. This occurred in 30 breech delivered fetuses, 47% of which developed hip joint instability. Only 8% of the breech born infants with flexed legs in utero developed hip joint instability. It is concluded that instability of the hip joint is a consequence of the intrauterine attitude, rather than of the breech delivery per se.     

Quantitated fetal heart rhythm at 20, 32 and 38 weeks of gestation and dependence on rest-activity patterns.

Quantitative parameters of fetal heart rate (FHR) were automatically analysed at 20, 32 and 38 weeks of pregnancy. FHR was obtained both by the fetal ECG method and by wide range Doppler ultrasound with autocorrelation. At 32 and 38 weeks, FHR was studied in relation to fetal rest-activity according to the fetal behavioural state concept (coincidence 1F and 2F). Basal fetal heart rate was significantly higher at 20 weeks of gestation than at 32 and 38 weeks. The number of accelerations increased significantly from 20 weeks to 32 and 38 weeks for C2F periods. Parameters of FHR variability, i.e. ID, ABB, LTI indices and bandwidth, were higher during periods C2F compared to periods C1F. Lowest values of all four parameters were found at 20 weeks gestation. The ID index, which is a measure of short-term variability increased significantly between 32 to 38 (C2F). The absolute values of ID, ABB and LTI were lower for ultrasound recordings than for the fetal ECG.     

Pregnancy-induced hypertension,antihypertensive drugs and the development of fetal behavioural states

In 21 pregnancies complicated by pregnancy-induced hypertension (PIH) which was treated by antihypertensive drugs (labetalol, nifedipine), fetal behavioural recordings (quiet state, C1F; active state, C2F; no coincidence, NOC) and Doppler measurements of blood flow velocity in the umbilical artery (UA) (resistance index, RI) were made on two occasions (27–32 and 33–36 weeks of gestation). Data were compared to those of a control group of normally grown fetuses (n = 96); in 15 cases we were able to match fetuses from the study group for age (±1 week) and weight (±150 g) at birth with fetales from a control group. It was the aim of this study to investigate if there are disturbances in the development of fetal behavioural states and if possible disturbances are due to poor fetal growth or to antihypertensive therapy. Our results show that in PIH treated by antihypertensive drugs, there are disturbances in the development of fetal behavioural states with higher percentages of NOC and C1F, lower percentages of C2F, and higher UA RI values. These disturbances are mainly due to coexisting placental impairment and poor fetal growth rather than to nifedipine or labetalol therapy, although these drugs may cause some redistribution of states.     

The intercostal-to-phrenic inhibitory reflex in the human fetus near term

Human fetal breathing movements (FBM) differ from neonatal breathing in that they are predominantly paradoxical and are not present all the time. Respiratory pauses are common in the fetus while prolonged apneas are life-threatening in the neonate. In the latter they occur during state 2 (active sleep) when paradoxical breathing is more frequent. Then the inward movement of the thoracic wall causes spreading of the caudal ribs which may elicit an intercostal-to-phrenic inhibitory reflex (IPIR) leading to apnea. This is not the case in state 1 (quiet sleep). In the fetus similar sleep states, state 2F and 1F respectively, have been identified and we investigated if the IPIR is already present before birth and if so, if the response is different between 1F and 2F. In 21 healthy fetuses between 37 and 40 weeks, two real time scanners and a cardiotocograph were used to asses the fetal behavioural state. If FBM were present, the caudo-lateral part of the fetal thoracic wall was shortly compressed manually and the period that FBM ceased measured. During the same epoch moments of sham-stimulation, i.e. control periods without actual compression were also carried out. In 15 out of 16 fetuses with FBM in 1F, and in 19 out of 19 fetuses in 2F, compressions were immediately followed by an apnea. In contrast, moments of sham-stimulation never induced apnea, indicating that the IPIR is indeed present in both behavioural states.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vibro-acoustic stimulation of the human fetus: effect on behavioural state organization

Vibro-acoustic stimulation of the human fetus in being increasingly performed both antenatally and during labour, to differentiate between poor and good fetal health in cases of flat or otherwise suspect fetal heart rate patterns. In a controlled study we investigated the effect of the electronic artificial larynx (EAL) on fetal behavioural state organization. In 10 healthy women with normal pregnancies of 38-40 weeks of gestation, recordings of fetal heart rate, body movements and eye movements, with a duration of 120-210 min, were carried out during two consecutive days. In each fetus, 3-4 episodes of state 1F and consecutive state 2F were studied, one of which served as a control observation. EAL stimulation during state 1F was associated with excessive fetal movements and with a state change in 7 out of 9 observations (four times into 2F; three times into 4F). Stimulation during state 2F was associated with a change into 4F in four of the nine observations. On days with EAL stimulation the fetuses spent more time in state 4F or in an episode not classifiable (because of an atypical FHR pattern with tachycardia and small accelerations) than control fetuses (21% vs. 3% of time). Disorganized states or periods of state 4F sometimes lasted for more than 1 h following the stimulation. It is concluded that stimulation with the EAL induces excessive fetal movements, a prolonged tachycardia, non-physiological state changes and a disorganisation and change in the distribution of fetal behavioural states. Until more is known regarding the safety and risks of vibro-acoustic stimulation, it should not be used in a routine clinical setting.     

The blood flow velocity waveform in the fetal descending aorta: its relationship to fetal behavioural states in normal pregnancy at 37-38 weeks

In 13 normal pregnancies, the relationship between the blood flow velocity waveform at the lower thoracic level of the fetal descending aorta and fetal behavioural states at 37-38 weeks of gestation was studied. The pulsatility index (PI), as a measure of peripheral vascular resistance, was significantly lower during state 2F compared to state 1F according to the classification by Nijhuis et al. (Nijhuis, J.G. et al. (1982) Early Hum. Dev., 6, 177-195), suggesting an increased perfusion of the fetal skeletal musculature to meet the energy demand needed for the raised muscular activity during state 2F; A significant inverse relationship (P less than 0.001) was established between PI and FHR in state 2F; this was mainly determined by a significant rise in end-diastolic flow velocity (P less than 0.02). Both the behavioural state and FHR should be taken into account when evaluating flow velocity waveforms in the fetal descending aorta during the latter weeks of pregnancy.     

A very-short-term intermittency of fetal heart rates and developmental milestone

We noticed that fetal heart rates (FHR) of immature fetuses intermittently showed unstable sudden and brief falls below baseline FHR that occur over a few or several heartbeats. The frightening falls do not occur in mature fetuses. In nonlinear dynamics, the degree of such abrupt falls in time series is quantified as intermittency. We aimed to investigate the nature and maturational changes of intermittency of the FHR in normal fetuses and to present the intermittency values of normal fetuses according to gestational weeks. FHR data of 450 normal fetuses between 23 and 40 wk of gestation were studied. We performed multifractal analysis and highlighted a very-short-term intermittency (C1alpha, 4 相似文献   

Fetal motor activity in breech presentation

Intrauterine motor activity was studied in breech presenting but otherwise normal fetuses. In the first part of the study, 48 fetuses were examined in the 33rd gestational week with an objective method using four piezo-electric crystals attached to the maternal abdomen for recording fetal movements. Of the 48 fetuses, 25 remained in breech presentation until delivery, while 23 assumed the vertex presentation before birth. In the second part of the study, 63 pregnant women with breech-presenting fetuses in the 33rd gestational week subjectively recorded perceptible movements every evening. Spontaneous cephalic version occurred in 40 cases, and 23 fetuses persisted in the breech presentation until delivery. Neither in the objective nor in the subjective study were any quantitative differences in motor activity found between fetuses subsequently born in breech presentation and these born in vertex presentation.     

Growth of Japanese Fetuses -Analysis from the Viewpoint of Population and Biological Growth Curves-

In 1984, Peter Dunn postulated that infants from 28 weeks ‘gestation till 18 weeks’ postnatal age who grow normally have almost identical potential growth velocities, regardless of racial and geographic differences. He suggested that the straight line growth curve in this period could be used as a perinatal growth chart for international reference. We composed biological growth curves for Japanese fetuses by eliminating data with risk factors for fetal growth, and compared them with the curves of Dunn. Our conclusions are as follows: 1) Japanese population fetal growth curves correspond with the curve of Dunn between 28 and 38 weeks' gestation. 2) Even in ideal conditions, flattening of fetal growth after 38 weeks' gestation always occurs. 3) In the early postnatal period, infants grow with the same straight line velocity as during fetal growth between 28–38 weeks' gestation. Infants from 28 weeks' gestation to 18 weeks' postnatal age have an almost identical growth potential in spite of some degree of growth constraint in utero after 38 weeks' gestation.     

Maturation of the human fetal startle response: Evidence for sex-specific maturation of the human fetus

Despite the evidence for early fetal experience exerting programming influences on later neurological development and health risk, very few prospective studies of human fetal behavior have been reported. In a prospective longitudinal study, fetal nervous system maturation was serially assessed by monitoring fetal heart rate (FHR) responses to vibroacoustic stimulation (VAS) in 191 maternal/fetal dyads. Responses were not detected at 26 weeks gestational age (GA). Sex-specific, age-characteristic changes in the FHR response to VAS were observed by 31 weeks' GA. Males showed larger responses and continued to exhibit maturational changes until 37 weeks' GA, females however, presented with a mature FHR startle response by 31 weeks' GA. The results indicate that there are different rates of maturation in the male and female fetuses that may have implications for sex-specific programming influences.     

SYNTHESIS OF TWO COMPONENTS OF HUMAN COMPLEMENT, β1 H AND C3bINA, DURING FETAL LIFE

ABSTRACT. Adinolfi, M., Dobson, N. C. and Bradwell, A. R. (Paediatric Research Unit, The Prince Philip Research Laboratories, Guy's Hospital Medical School, London, and Immuno Diagnostic Research Laboratory, Department of Immunology, The Medical School, Birmingham, UK). Synthesis of two components of human complement, β1H and C3bINA, during fetal life. Acta Paediatr Scand, 70:705,.–The levels of β1H and C3MNA were estimated in sera from human fetuses, cord and maternal samples. Both components of complement were detected in fetuses more than 12 weeks old. The serum concentrations tended to increase with the gestational age. The mean levels of β1H and C3bINA in cord sera were near 54 and 61 % of the mean values in sera from normal adults. Elevated levels of β1H were observed in maternal sera at the end of the gestational period. When the levels of β1H and C3bINA were compared with those of two other components of complement, it was confirmed that the mean levels of C9 were low in fetal and newborn sera, while the serum concentrations of both C9 and Factor B were elevated in maternal samples. Newly synthesised β1H was detected in the culture fluids of fetal liver and peritoneal cells, as judged by the incorporation of labelled aminoaeids and the autoradiography of the specific immunoprecipi-tates in agar gel.     

State transitions in uncomplicated pregnancies after term

A behavioural state transition is the time interval between two different behavioural states. In low-risk fetuses, the fetal heart rate pattern (FHRP) is the first variable to change in transitions from 1F to 2F (`non-REM-sleep' to `REM-sleep') and the last variable to change in transitions from 2F to 1F. This is not the case in IUGR (intra-uterine growth retardation), and absence of a specific order in which behavioural variables are changing might be an indication for a (mild) disturbance of the fetal central nervous system (CNS). We investigated whether state transitions in twelve low risk term fetuses (39–41 weeks post menstrual age, PMA; control group) differ from those in twelve uncomplicated pregnancies >41 weeks PMA (study group). All subjects underwent one behavioural study in which fetal heart rate pattern, eye and body movements were recorded simultaneously. We recorded 23 transitions from 1F to 2F and 20 from 2F to 1F. Median (range) duration for transitions from 1F to 2F was 85 (10–180) s in the study group, and 60 (10–180) s in the control group. Transitions from 2F to 1F lasted 80 (10–140) and 60 (30–100) s, respectively. In both groups, the FHRP was the first variable to change in transitions from 1F to 2F, however, in transitions from 2F to 1F, no specific order in change of variables could be demonstrated. We conclude that the study of transitions does not distinguish between the term and after term fetuses under optimal conditions. Whether or not the analysis of state transitions can be used to distinguish `normal' from `abnormal' fetuses and detect the fetus at risk after term awaits further study.     

Carbonic anhydrase in the human fetal gastrointestinal tract

Tissues from human fetuses with a gestational age of 19-26 weeks were studied by histochemical and biochemical methods. In gastric homogenates both the catalytic activity and the immunoassayable amount of carbonic anhydrase increased with gestational age. The enzyme activity and isoenzyme pattern in a fetus of 26 weeks were similar to those found in adult gastric mucosa. High enzyme activity was demonstrated histochemically in the gastric surface epithelium at a gestational age of 19 weeks. At this age, the number of stained parietal cells was low, but it increased considerably with gestational age. In all fetal gastrointestinal tissues tested there was a total lack of capillary staining for carbonic anhydrase activity, which contrasts to the clear staining found in adult tissues. The amounts of carbonic anhydrase in the small intestine were lower in the isoenzyme HCA-B than for HCA-C. Histochemically, the staining of jejunal epithelial cells in the fetuses was clearly reduced, both on the villi and in the crypts. In the ileum, single epithelial cells on the villi were distinctly stained, a finding similar to that in adult ileal epithelial cells in the fetuses was clearly reduced, both on the villi and in the crypts. In the ileum, single epithelial cells on the villi were distinctly stained, a finding similar to that in adult ileal epithelium. The colon showed the most striking differences between fetal and adult tissues, with much lower levels of both isoenzymes HCA-B and HCA-C and less staining of the epithelium in the fetal colon. Thus, the developmental pattern of carbonic anhydrase varied considerably among the intestinal tissues. The functional significance of the differences between fetal and adult tissues is only partly understood at present.     

Fetal behaviour and the sudden infant death syndrome (SIDS).

To examine whether differences in sleep maturation could be identified before birth, behavioural studies were carried out in 28 fetuses. Studies were possible in all 28 fetuses at 28 weeks, but only in 26 fetuses at 36 weeks (two fetuses delivered before 36 weeks). The risk of sudden infant death syndrome (SIDS) was determined using the Oxford SIDS scoring system. The fetuses at greater risk of SIDS had coincidence of behavioural characteristics for a significantly lower percentage of the time than those at low risk. This difference reached significance (p < or = 0.05) only at 36 weeks.