Computer-assisted analysis of fetal movements in intrauterine growth retardation (IUGR)

Early Human Development 51 (1998) 137–145

Computer-assisted analysis of fetal movements in intrauterine growth retardation (IUGR) A. D’Elia*, M. Pighetti, G.F. Moccia, P. Di Meo Department of Obstetrics and Gynecology, Federico II University Medical School, Naples, Italy Received 3 March 1997; received in revised form 23 September 1997; accepted 28 October 1997

Abstract A quantitative analysis of various fetal activities (mouth, eye and gross body movements) was made in 10 IUGR human fetuses. The aim of the study was to see whether IUGR fetuses move differently to normal fetuses. Each real-time ultrasound recording lasted 1 h and the analysis of various activities was carried out during replay of video recordings by means of a specially designed computer program. The following aspects have been investigated: (1) incidence, duration and interval for each of the fetal activities described; (2) the relationship between incidence, duration and interval for each single activity; (3) the correlations between the different activities. The results were compared with a group of 10 fetuses from normal pregnancies. On quantitative evaluation no clear effects due to uncomplicated IUGR could be detected except for median duration of eye movements, which turned out to be longer in the IUGR group. The evaluation of correlations between the characteristics (incidence, duration and interval) of each activity showed a positive correlation between incidence and duration of mouthing movements in the IUGR group, not found in the normal group. The study of the correlation between different fetal activities has shown an inverse correlation between mouthing and other activities in the normal fetuses, not found in the IUGR group. We conclude that in mildly affected fetuses with no evidence of hypoxia, there are no quantitative differences compared to normal fetuses in terms of the motility studied. The only differences found were in relation to the performance of such activities and they could reflect a dysfunction of the central nervous system resulting from a metabolic disturbance.  1998 Elsevier Science Ireland Ltd. Keywords: Fetal movements; Movement quality and quantity; Intra-uterine growth retardation

*Corresponding author. Via Pietravalle, 85, 80131 Napoli, Italy. Tel.: 1 39 81 7462967 / 5453503; fax: 1 39 81 7462903 / 7462967. 0378-3782 / 98 / $19.00  1998 Elsevier Science Ireland Ltd All rights reserved. PII S0378-3782( 97 )00108-4

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1. Introduction Fetal spontaneous motor activity is an expression of neural function. The analysis of fetal activity is thus very important to evaluate the health condition of the fetus in utero. Several studies have been performed on IUGR, as this pathology is a good model for studying the effects of hypoxia on fetal motor activity. In this situation there is a chronic reduction of nutrients and oxygen to the fetus which leads to a reduction of the cerebral mass with specific histological and biochemical alterations [1,7,8]. However, how these conditions can induce certain functional alterations is still poorly understood. Some authors [12] could not find evidence of hypoxia in many cases of IUGR. In 1985, Van Vliet et al. [18] found a delayed onset of behavioural states in IUGR fetuses, which depended on the incapacity of the fetus ‘to synchronize the state variables’. The authors concluded that these effects were the expression of a CNS dysfunction, even in the presence of mild hypoxia. In the same year (1985) Bekedam et al. [2] identified a lower incidence of movements in IUGR than in normal fetuses. However, they showed a considerable interindividual variability and a large overlap between the two groups and had thus no clinical significance. Sival et al. [16,17] observed no quantitative but only qualitative differences in the movements between normal and IUGR fetuses. They concluded that qualitative evaluation of general movements in the fetus is a sensitive method that can evaluate the neurological condition [14], and thus be successfully applied to cases of serious IUGR [16]. In our study we have evaluated the possible differences between normal and IUGR fetuses through the quantitative analysis of three types of fetal activities: mouth, eye and gross body movements. These activities were chosen because they are fundamental components of the fetus sleep–wakefulness cycles [9,10,13,19].

2. Patients We studied two groups of patients (Tables 1 and 2): (1) 10 fetuses of uncomplicated pregnancy submitted to ultrasound observation at the 38th week; (2) 10 fetuses with IUGR in women suffering from EPH gestosis, submitted to one ultrasound observation between the 34th and the 38th week. The parents of all the patients gave their informed consent. Exclusion criteria were: congenital malformations or chromosomal defects, alcohol or drug addiction, type I diabetes mellitus, smoking, and intrauterine infections. The selection criteria for the newborns were: (1) Apgar score at birth ( $ 7 at the 5th min); (2) complications in the neonatal period and / or the need for the newborns to be transferred to a neonatal intensive care unit (NICU). The newborns in the first group were all delivered normally with birth-weights above the 25th percentile, in two cases a Caesarean section was performed for cephalo-pelvic disproportion. The amount of amniotic fluid was normal. All the newborns in the IUGR study group were delivered by Caesarean section after

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Table 1 Clinical data of the normal group Case no.

Gestational age (weeks) at:

1 2 3 4 5 6 7 8 9 10

registration

delivery

38 38 39 38 38 39 38 38 39 39

40 40 40 41 38 40 39 40 40 39

Delivery

Sex

Weight (g)

Apgar 19, 59

SD SD SD CS SD SD SD SD SD CS

F M F M F F M M M F

3950 3800 2840 4030 3350 3610 3450 3500 4050 3750

8,10 9,10 8,9 8,10 8,9 8,9 8,9 8,9 9,10 9,10

suspected fetal hypoxia with birth-weights under the 10th percentile. The amount of amniotic fluid was slightly too low in four cases and very low in the remaining six. Three of the newborns in the IUGR group manifested minor neurological symptoms after birth (slight hypertonia or hypotonia), while no such symptoms were detected in the normal group. The Apgar score was normal also in IUGR fetuses; only five fetuses with minor metabolic problems were transferred to the NICU. After 1 year all the newborns underwent a standard examination, and all had a normal neurological examination.

3. Methods The observation method and the procedure for processing the data obtained were the same for both groups. Each fetus underwent a 60-min ultrasound observation using a 3.5-MHz linear transducer placed to give a parasagittal scan that included the upper thorax, the mouth Table 2 Clinical data of the IUGR group Case no.

1 2 3 4 5 6 7 8 9 10

Gestational age (weeks) at: registration

delivery

37 37 35 34 33 35 37 31 31 36

38 39 35 34 34 37 38 36 35 37

Delivery

Sex

Weight (g)

Apgar 19, 59

NICU

CS CS CS CS CS CS CS CS CS CS

M F M M F M M F F M

1690 1880 1700 1250 1500 2170 2150 2080 2030 2000

5,7 8,9 5,8 1,7 8,9 8,9 8,9 7,8 9,10 5,8

Yes Yes Yes Yes Yes No No No No No

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and at least one orbit. All the recordings were made between 1.00 and 3.00 p.m., with the patients lying in a comfortable semirecumbent position. The ultrasound images thus obtained were recorded on videotape for subsequent analysis. Cardiotocography was conducted at the same time using Hewlett-Packard equipment [6], and a Doppler evaluation of umbilical artery was also performed. The results of the cardiotocography and the Doppler evaluation were in the normal range. The fetal activities observed were the following: 1) Mouth movements such as mouthing (MM). One episode of mouthing movements consisted of the appearance (start) of a series of associated jaw and tongue movements until their disappearance (end). 2) Other mouth movements (OMM), including opening and closing of the mouth, swallowing, protrusion of the tongue, etc. Each single activity was recorded from the moment when the mouth opened (start) until it closed again (end). 3) Eye movements (EM): one eye movement was considered as the movement of the lens from an initial position (start) to another position (end), indicating a change of the position. 4) Gross body movements (BM): we considered one movement from the start to the end of a movement involving the fetus whole body and / or limbs, during a variable period of time. Two observers recorded mouthing, other mouth, eye and gross body movements, by entering the data, as it is recorded, into a personal computer via a keyboard. The software program used allows data storage and displays an actogram of the moment in which the various movements occurred (Fig. 1). These data were included in a database from which we calculated for each activity and for each patient: 1) incidence (number of movements per hour); 2) duration (time between start and end of the single movement; 3) interval (time between the start of one movement and the start of the subsequent movement. The incidence data (number of movements), duration (s) and interval (s) were then used to calculate median, lower quartile, upper quartile, interquartile range, relative duration and incidence for each type of movement studied in both normal and IUGR groups.

Fig. 1. Actogram of the various fetal activities.

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Moreover, for each patient, the observation time was subdivided into consecutive 3-min epochs during which the incidence of each movement, the correlation between different activities and the prevalence between mouthing and other activities were calculated. The following statistical analyses were employed: 1) non-parametric test (Wald– Wolfowitz) for unpaired data in order to evaluate the differences for incidence, duration and interval between the two groups studied. 2) Correlation tests (Spearman rank test) to assess the correlation between incidence, duration and interval for each activity in the normal and the IUGR group. 3) Correlation tests (Spearman rank test) to assess the correlation between the various activities over the 60-min observation of the normal and the IUGR group. Differences yielding at P # 0.05 were considered significant (two-tailed).

4. Results Our study failed to show any statistically significant difference between the normal and the IUGR group with respect to median incidence, duration and interval value of each movement. Only the median value duration of the eye movements was statistically higher in the IUGR group (P , 0.05) (Table 3). The correlation analysis between incidence, duration and interval for each movement in normal fetuses and in the IUGR group did not shown interesting data except for the mouthing activity. In fact, we have found a positive correlation between incidence and duration of mouthing movements in the IUGR group (r 5 0.95; P , 0.01) not found in the normal group. Therefore, in the IUGR, as the number of mouthing movements increases so does the total duration of the movement itself. Correlation analysis of the various activities of normal fetuses over the 60-min observation showed a statistically significant relation; there was, in fact, a positive correlation between all the activities studied except mouthing: EM and OMM (r 5 0.83), EM and BM (r 5 0.52) and OMM and BM (r 5 0.74), and a negative correlation between MM and EM (r 5 2 0.65), OMM (r 5 2 0.80) and BM (r 5 2 0.73) (Fig. 2). In fetuses affected by IUGR a positive correlation was found between EM and BM (r 5 0.47) and between OMM and BM (r 5 0.82), whereas there was no significant correlation between mouthing and other activities (Fig. 3) and between eye movements and mouth movements, especially in the IUGR fetuses staying in NICU. The data obtained in our study show that: (1) The median duration value of eye movements was longer in the IUGR group. Since there were no significant differences in the incidence of such movements between the two groups studied, it is reasonable to believe that eye movements probably last longer (or are slower) in the IUGR than in the normal group. (2) Furthermore, while we have found an inverse correlation between mouthing and other activities in the normal group, such a correlation was not found for the IUGR group. In other words, in fetuses affected by IUGR, mouthing may take place independently of the other movements studied.

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Eye movements Median

Mouthing movements

Lower

Upper

Quartile

quartile

quartile

range

Median

Other mouth movements

Lower

Upper

Quartile

quartile

quartile

range

Median

Body movements

Lower

Upper

Quartile

quartile

quartile

range

Median

Lower

Upper

Quartile

quartile

quartile

range

NUMBER OF FETAL MOVEMENTS Normal

60.5

18.0

66.0

48.0

6.0

0.0

8.5

8.5

36.5

18.0

42.5

24.5

41.0

20.0

47.5

27.5

IUGR

54.0

21.0

88.5

67.5

8.0

2.0

15.0

13.0

51.0

25.0

57.5

32.5

56.0

32.0

62.0

30.0

DURATION OF FETAL MOVEMENTS ( SEC.) Normal

1.5

1.4

2.3

0.9

1.8

0.0

2.8

2.8

2.2

0.7

3.6

2.9

7.0

2.1

11.8

9.7

IUGR

2.8

1.7

5.5

3.8

1.7

0.3

2.5

2.2

3.4

1.6

5.0

3.4

3.8

2.5

7.4

4.9

INTERVAL BETWEEN FETAL MOVEMENTS ( SEC.) Normal

27.1

13.2

31.4

18.2

21.4

0.0

22.8

22.8

49.0

37.0

52.6

15.6

43.2

27.9

54.0

26.1

IUGR

25.2

16.8

27.2

10.4

12.2

0.0

18.3

18.3

27.3

24.9

38.1

13.2

36.5

22.4

41.3

18.9

A. D’ Elia et al. / Early Human Development 51 (1998) 137 – 145

Table 3 Median incidence, duration and interval of each movement between the normal and the IUGR group

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Fig. 2. Correlation between body and mouthing movements in the normal fetuses.

Fig. 3. Correlation between body and mouthing movements in the IUGR fetuses.

5. Discussion Our results confirm those obtained by other authors [2,4,16] who found no quantitative differences in general movements between normal and IUGR fetuses, because of the great interindividual and intraindividual variability in the number of

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these movements. Our data also cover other fetal activities (eye and mouth movements) and are in agreement with results of others [15,16], since quantitative alterations of the fetal activities are observed only in altered fetal conditions such as fetal hypoxaemia [20]. In our study, all the cardiotocographic examinations were normal, as were the Doppler assessments of the umbilical artery. None of the fetuses had severe signs of fetal hypoxia: the Apgar score was good in all fetuses ( $ 7 at the 5th min); moreover, there were no problems in the neonatal period for the NICU babies either, who showed only minor metabolic problems. Follow-up at 1 year did not show any neurological dysfunctions. However, some difference, especially in the IUGR group of NICU babies does exist. Our results show that the IUGR group presents a difficult regulation of a complex activity such as mouthing. This activity was very important in the evaluation of fetal and neonatal conditions. In the fetus, Pillay and James [13] have shown an association between absence of mouthing movements and poor outcome. In the neonate, Casaer and co-workers [3,5] have shown a correlation between gestational age and efficiency of mouthing activity and a correlation with other (swallowing, cardiorespiratory control) important neonatal functions; they also found a poor neonatal outcome in neonates with poor correlation between mouthing and swallowing and cardiorespiratory control. Similarly, in IUGR fetuses we have found, with the same incidence, a longer total duration of EM: we can therefore presume that in these fetuses the slow eye movements must be more than REMs [11]. Our data are in agreement with those of van Vliet et al. on behavioural states, since they found a delay in their occurrence mainly because of the inability of the fetus to synchronize state variables [18]. We can conclude that mildly affected IUGR fetuses, with no evidence of hypoxia, show no quantitative differences compared to the normal group in terms of the fetal activities we evaluated. The only differences we detected could reflect a dysfunction of the fetal nervous system as a result of metabolic disturbance, even in the absence of hypoxia.

Acknowledgements The authors are most grateful to Miss Leonilda Mercogliano for her collaboration in statistical analysis. Our thanks are also due to Mr. Tony Cafiero for his help in software elaboration for data collection and analysis.

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