State transitions in uncomplicated pregnancies after term

Early Human Development 52 (1998) 125–132

State transitions in uncomplicated pregnancies after term J.G. Nijhuis*, M. van de Pas, H.W. Jongsma University Hospital St. Radboud, 415 Department of Obstetrics /Gynaecology, POB 9101, 6500 HB Nijmegen, Netherlands Received 24 September 1997; received in revised form 24 February 1998; accepted 3 March 1998

Abstract 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.  1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Fetal behaviour; Behavioural states; Postmaturity; Ultrasound; Fetal monitoring

*Corresponding author. Tel.: 1 31 24 3618902; fax: 1 31 24 3619036; e-mail: [email protected] 0378-3782 / 98 / – see front matter  1998 Elsevier Science Ireland Ltd. All rights reserved. PII: S0378-3782( 98 )00016-4

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1. Introduction Since the introduction of fetal behavioural states (Table 1) by Nijhuis et al. [10], their use has been advocated as a method of gaining more insight into the condition of the fetal central nervous system (CNS). Several papers have been published on fetal behaviour under various clinical conditions, such as fetal behaviour in prematurity [3,18], intra-uterine growth retardation [20], diabetes [9], anti-epileptic medication [6] and after vibro-acoustic stimulation [19,5]. Only recently, researchers became interested in fetal behavioural state transitions, i.e. the time intervals between two different behavioural states. Swartjes et al. [15], Arduini et al. [1,2] and Groome et al. [7] showed that during the last trimester, transitions have a particular sequence in which the behavioural variables change their parameter (e.g. body movements ‘present’ to ‘absent’). They all concluded that in ‘normal’ fetuses, the fetal heart rate pattern (FHRP) is the first variable to change in transitions from 1F to 2F (non-REMsleep to REM-sleep) and the last variable to change in transitions from 2F to 1F. Arduini et al. [1] showed that this sequence of change of variables does not exist in growth-retarded fetuses. Groome et al. [7] postulated that fetuses with poor state control differ in FHR–FEM (fetal eye movements) sequencing during state transitions from fetuses with relatively good state organization. They showed that fetuses with poor state control, recognized by prolonged transitional periods, loose their specific sequence of change of variables. Behavioural states are an expression of the activity of the fetal CNS [12,14] and, therefore, the absence of a specific sequence in which behavioural variables change their parameter might be an indication for a (mild) disturbance in the function of the CNS. We were interested in fetal behavioural state transitions after term. In this period, Junge [8] and Van de Pas et al. [11] already showed that the amount of state 3F and 4F (‘awake states’) increases at the expense of state 2F. However, normal fetal behaviour does not necessarily mean normal behavioural state transitions. Therefore, in the present study, we set out to investigate state transitions after 41 weeks of gestation. We wondered whether or not the duration of the transitions differed from

Table 1 State criteria represented as vectors Criteria

Body movements Eye movements FHRP

State vectors State 1F

State 2F

State 3F

State 4F

Incidental Absent A

Periodic Present B

Absent Present C

Continuous Present D

FHRP, fetal heart rate pattern. FHRP A is a stable heart rate pattern with a narrow bandwidth. FHRP B has a wider oscillation bandwidth and frequent accelerations during movements. FHRP C is stable (no accelerations), but with a wider oscillation bandwidth than that of pattern A. FHRP D is unstable, with large, longlasting accelerations that are often fused into sustained tachycardia.

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those in the term period and if there is a certain specific sequence in which the behavioural variables change their parameter.

2. Patients and methods The group of patients has been described elsewhere [11]. In short, twelve healthy women (four primiparous) with a gestational age (GA) of between 289 and 298 days ( . 41 weeks PMA) participated after giving informed consent, and after the project was granted approval of the local ethical committee. Another group of twelve healthy women (six primiparous) with a GA of between 273 and 287 days (39–41 weeks) served as controls. All pregnant women fulfilled the following criteria: single pregnancy, certain gestational age as confirmed by ultrasound examination. Exclusion criteria were hypertension, threatening premature labour and vaginal blood loss in the second and third trimester of the pregnancy. All pregnancies were uneventful. In both groups, labour was induced in three cases. In the study group, delivery was complicated by meconium-stained fluid in one case, and shoulder dystocia with fracture of the clavicula in another. In the control group, meconium staining was present in two cases. All infants were born vaginally in the vertex position, with one infant in the control group and two in the study group being delivered by vacuum or forceps. The mean birth weight in the study group was 3985 g (range 3380–4685 g) and in the control group was 3490 g (range 2825–4330 g). The study group consisted of seven males and five females, the control group of six males and six females. All neonates were born in good condition, with 5 min APGAR scores of $ 9. If measured, the pH of the umbilical artery was . 7.15 (tenth centile in our clinic [4]). On the fifth day of life, all neonates were in optimal neurological condition according to Prechtl [13]. Before the study started, an ultrasound examination was performed to exclude anomalies and to confirm normal growth and a normal amount of amniotic fluid. All studies were conducted in the afternoon between 16.00 and 22.00 h. All subjects underwent one behavioural study. We tried to make recordings of 120 min. Fetal behaviour was studied as described in detail previously [10]. Briefly, three behavioural state variables, i.e. (FEM) fetal FHRP, fetal eye and fetal body movements (FM), were recorded simultaneously using abdominal CTG equipment and two ultrasound scanners (Pie Medical 150, 3.5 MHz curved scanner and a Kontron 3.5 MHz sector scanner). Fetal eye movements were videotaped for off-line analysis and body movements were verbally recorded on the voice channel of the videotape. In this study, we did not record fetal breathing movements. Analysis of the recordings was performed after creating ‘state profiles’, as described by Nijhuis et al. [10], using a 3-min moving window technique. When the state variables fulfilled one of the specific combinations, as described in Table 1, periods were classified as coincidence 1F through 4F, respectively. The time interval between two stable periods of coincidence is called ‘no coincidence’. It was possible to draw a state diagram of all recordings and, therefore, to define the periods of ‘coincidence’ and ‘no coincidence’. If periods of no coincidence lasted for less than 3

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Fig. 1. Example showing a behavioural transition from coincidence 1F to 2F. FHRP (fetal heart rate pattern) was the first variable to change, FM (fetal body movements) was the second and FEM (fetal eye movements) was the last.

min they were considered to be behavioural state transitions. Analysis of these transitions was performed as described by Arduini et al. [1]. The analysis of transitions was limited to periods from 1F to 2F and 2F to 1F because of the low incidence of periods of coincidence 3F and 4F and, thus, the low number of transitions concerning coincidence 3F and 4F. In this study, we evaluated state transitions in terms of their duration, and the order in which behavioural variables change their parameter, as is illustrated in Fig. 1. For statistical analysis, we used the Mann-Whitney test and the two-tailed binomial test with random order as the null hypothesis; a P-value , 0.05 was required for significance.

3. Results

3.1. Overall characteristics of the two groups Twelve recordings in both groups were carried out at the above-mentioned gestational ages (weeks post menstrual age). Median duration of the recordings was 123 min (range 60–130 min) in the study group, and 121.5 min (66–142 min) in the control group.

3.2. Periods of coincidence and no coincidence The amount of time spent in periods of coincidence 2F decreased significantly from 73% in the control group (range 59–95%) to 57% in the study group (range 29–79%). Coincidence 3F and 4F increased in the after-term fetuses, but this increase only reached significance if these two conditions (‘wakefulness’) were combined: 5.0% (range 0–17%) in the control group and 16.8% (range 0–53%) after term. No

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Table 2 Duration(s) of transitions in the two groups of fetuses studied Control group, 39–41 weeks

Study group, . 41 weeks

Transitions 1F–2F Number Median Q1–Q3 Range

11 60 s 40–110 s 10–180 s

12 85 s 35–130 s 10–180 s

Transitions 2F–1F Number Median Q1–Q3 Range

9 60 s 40–90 s 30–100 s

11 80 s 60–90 s 10–140 s

Significance (P)

NS

NS

The median duration, the interquartile range (Q1–Q3) and the total range are given.

differences were found for coincidence 1F and no coincidence. The median (maximum) percentage of recording time for coincidence 1F was 14% (27%) in the control group, and 15% (50%) in the study group; for no coincidence, the values obtained were 6% (11%) and 6% (9%), respectively.

3.3. State transitions The number and durations of the state transitions are given in Table 2. In total, we recorded 23 transitions from 1F to 2F and 20 from 2F to 1F. There were no differences in the durations of the transitions. The median (range) duration for transitions from 1F to 2F was 85 s (10–180 s) in the study group, and 60 s (10–180 s) in the control group. Transitions from 2F to 1F lasted 80 s (10–140 s) and 60 s (30–100 s), respectively. In the study group, twelve transitional periods from 1F to 2F were recorded. FHR was the first variable to change (from pattern A to pattern B) in nine transitions (75%). No specific order was found between the other two behavioural variables (FEM and FM). In the control group, eleven transitional periods from 1F to 2F were recorded, and FHR was the first variable to change in eight transitions (73%). FM was the second variable to change, also in eight cases (Table 3). After term, eleven transitions were recorded from 2F to 1F, but the behavioural variables changed in a random order. In the control group, nine transitions were recorded; FHR was the last variable to change in six transitions (67%) (Table 4).

4. Discussion In this study, we investigated behavioural state transitions from 1F to 2F and from 2F to 1F in healthy term and after-term human fetuses with a normal amount of fluid. Two groups of twelve fetuses (control and study group) were investigated. We found

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Table 3 Temporal sequence of the changes in behavioural variables, i.e. fetal heart rate pattern (FHRP), fetal eye movements (FEM) and fetal body movements (FM) during transitions from 1F to 2F in the two groups of fetuses Control group, 39–41 weeks (%)

Study group, . 41 weeks (%)

FHRP

FHRP

FEM

FM

b

1 / 12 (8)

2 / 12 (16)

First variable to change

8 / 11 (73)

Second variable to change Third variable to change

a

FEM

FM

3 / 11 (27)

0 / 11 (0)

9 / 12 (75)

0 / 11 (0)

3 / 11 (27)

8 / 11 a (73)

2 / 12 (17)

5 / 12 (42)

5 / 12 (42)

3 / 11 (27)

5 / 11 (46)

3 / 11 (27)

1 / 12 (8)

6 / 12 (50)

5 / 12 (42)

Statistical analysis was performed using the binomial test with random order (33.3% chance for each variable) as the null hypothesis ( a P 5 0.02; b P 5 0.01).

no difference in the percentage of recording time with ‘no coincidence’ between term and after-term fetuses. All fetuses were healthy and had a relatively good state control, which might imply that all fetuses had a good functioning CNS. After term, there was a significant increase in coincidence 3F and 4F (‘awake states’) at the expense of coincidence 2F, which can be seen as an ongoing development of the fetal CNS after term under optimal conditions. Obviously, in the term fetus, analysis of ‘states’ and ‘coincidence’ yields rather similar results [11]. There was no difference in the durations of the state transitions between the two groups. We showed that, in transitions from 1F to 2F, FHR is the first variable to change in both term and after-term fetuses (73 and 75% of the transitions, respectively). In transitions from 2F to 1F, no such preference could be established, either in the term or the after-term fetuses. To our knowledge, only four articles have been published concerning state transitions in the human fetus. Swartjes et al. [15] concluded that FHR is the first Table 4 Temporal sequence of the changes in behavioural variables, i.e. fetal heart rate pattern (FHRP), fetal eye movements (FEM) and fetal body movements (FM) during transitions from 2F to 1F in the two groups of fetuses Control group, 39–41 weeks (%)

Study group, . 41 weeks (%)

FHR

FEM

FM

FHR

FEM

FM

First variable to change

1/9 (11)

5/9 (61)

3/9 (28)

3 / 11 (28)

2 / 11 (18)

6 / 11 (55)

Second variable to change

2/9 (22)

1/9 (6)

6/9 (72)

4 / 11 (36)

4 / 11 (36)

3 / 11 (27)

Third variable to change

6/9 (67)

3/9 (33)

0 / 9a (0)

4 / 11 (36)

5 / 11 (46)

2 / 11 (18)

Statistical analysis was performed using the binomial test with random order (33.3% chance for each variable) as the null hypothesis ( a P 5 0.05).

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variable to change in transitions from 1F to 2F, and the last to change in transitions from 2F to 1F. In fetuses of pregnant women who used anti-epileptic medication, they found similar results. Arduini et al. [2] published similar data for normal fetuses, but in growth-retarded fetuses, they reported prolonged durations of the transitions, without a specific sequence of variables [1]. They concluded that analysis of transitions might differentiate between healthy fetuses and those affected by growth retardation. Groome et al. [7] hypothesized that fetuses with poor state control, as evidenced by extended periods of no coincidence, differ in FHR–FEM sequencing during a state transition from fetuses with relatively good state control. The fact that the specific sequence is lost in transitions from 2F to 1F might indicate a first sign of ‘suboptimality’ in the after-term fetus, similar to the that in the growth-retarded fetus [1]. This hypothesis needs further exploration because, in the controls in the present series, we could not establish a significant order, perhaps because of the low number of transitions. In our control group, FM was the second variable to change, but the value of this result remains controversial, as the very first eye movement is probably much more difficult to detect than the first body movement. Data on neonatal behavioural state transitions are scarce. Shirataki and Prechtl [16] found no leading variable during state transitions. However, they used polygraphic studies and took other variables into account. This discrepancy could also be explained by different mechanisms regulating the alteration of behavioural states during intra-uterine life. For example, fetal behaviour exhibits circadian rhythms that are lost at birth [14,17]. Based on the neonatal data, the disappearance of a specific sequence of transitions in the healthy fetus after term might also be a sign of ongoing development of the CNS rather than a sign of deterioration, similar to that of the growth-retarded fetus. Finally, we are aware of the fact that the method of recording may influence our results. The FHRP is recorded continuously, whereas body and eye movements are observed using ultrasound, and readjustments of the transducers are necessary. It is therefore possible that the very first body or eye movements are missed. An argument against this possible inadequacy of recording is that Arduini et al. [1] showed an adequate reproducibility assured by intra-individual consistency. The analysis of behavioural state transitions might allow for its application in the future to monitor the fetus at risk. Under optimal conditions, transitions are similar in both term and after-term fetuses. Whether or not it can distinguish between ‘normal’ and ‘abnormal’ fetuses in prolonged pregnancies and detect the fetus at risk in this period awaits further study.

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