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Fetal habituation to vibroacoustic stimulation in uncomplicated postterm pregnancies
European Journal of Obstetrics & Gynecology and Reproductive Biology 97 (2001) 178±182
Fetal habituation to vibroacoustic stimulation in uncomplicated postterm pregnancies Cathelijne F. van Heterena,*, P. Focco Boekkooia, Rikke H.M. Schiphorsta, Henk W. Jongsmaa, Jan G. Nijhuisb a
Department of Obstetrics and Gynecology, University Medical Centre Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands b Department of Obstetrics and Gynecology, University Hospital of Maastricht, Maastricht, The Netherlands Received 14 August 2000; received in revised form 19 October 2000; accepted 18 November 2000
Abstract Objectives: Testing of fetal habituation to repeated vibroacoustic stimulation might give additional information concerning the fetal condition and central nervous system (CNS) functioning in postterm pregnancies. This study is designed to investigate whether healthy postterm fetuses are able to habituate and if so, if the habituation pattern of postterm fetuses differs from that of term fetuses. Study design: Twenty women with an uncomplicated pregnancy beyond 41 weeks gestational age (GA) participated, and 37 women with a GA between 37 and 40 weeks served as controls. The vibroacoustic stimulus was repeatedly applied to the maternal abdomen above the fetal legs for a period of 1 s every 30 s. A fetal trunk movement within 1 s of stimulus application was considered a positive response. Lack of response to four consecutive stimuli indicated habituation. The habituation rate is de®ned as the number of stimuli applied before the fetus stopped responding. Data were compared using Mann±Whitney U test. Results: Of the 18 postterm fetuses in which the presence or absence of habituation could be established, 14 habituated and four persisted in responding. Twenty-six of the 32 term fetuses, in which the presence or absence of habituation could be established, habituated and six persisted in responding. The habituation rate varied widely in postterm (median of eight stimuli, quartile ranges of 6 and 18) as well as in term fetuses (median of 9.5 stimuli, quartile ranges of 6 and 15). There was no difference in median habituation rate between postterm and term fetuses. Conclusion: The ongoing maturation of the CNS in the last weeks of pregnancy appears not to be re¯ected in the fetal habituation pattern. Furthermore, the interfetal variability in habituation of healthy postterm fetuses is such that testing of habituation appears not to be suitable for the identi®cation of the fetus at risk for an adverse neonatal outcome. # 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Fetal habituation; Vibroacoustic stimulation; Postterm pregnancy
1. Introduction Prolongation of pregnancy beyond term is accompanied by an increase in perinatal mortality and morbidity [1±3] and adequate fetal monitoring is indicated. Assessment of the biophysical pro®le seems to be the best way to evaluate fetal well-being in a postterm pregnancy because a variety of fetal parameters (fetal heart rate (FHR), amount of amniotic ¯uid, fetal breathing, body movements and fetal tone) are observed [4]. The primary disadvantage of scoring the biophysical pro®le is the risk for a false-positive test with subsequent needless interventions as well the risk for a falsenegative test result that can result in fetal morbidity or
* Corresponding author. Tel.: 31-243616801; fax: 31-243541194. E-mail address: [email protected] (C.F. van Heteren).
mortality. Another disadvantage is the time required to perform the test and the need for an experienced sonographer. Current research on the use of fetal testing has focused on the re®nement of testing protocols and the application of new methods to improve the positive predictive value of fetal testing in postterm pregnancies [5]. Testing of fetal habituation to repeated vibroacoustic stimulation might give additional information concerning the fetal condition and functioning of the fetal central nervous system (CNS). Habituation is the decrease, and eventual cessation, of response that follows repeated application of the same stimulus. Habituation can be seen as a basic form of learning that requires an intact functioning of the CNS [6]. Studies in persons with various disorders of the CNS reveal that the habituation pattern of these persons is different from that of persons without these disorders [7±11]. Pediatricians use this habituation phenomenon to assess newborns for various pathological conditions of the CNS [12].
0301-2115/01/$ ± see front matter # 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 3 0 1 - 2 1 1 5 ( 0 0 ) 0 0 5 4 3 - 1
C.F. van Heteren et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 97 (2001) 178±182
Several studies on fetal habituation have been published [13±17]. Although the methodologies used varied widely, these studies all reveal that normal fetuses are able to habituate to repeated external stimulation. Studies in compromised or chromosomally abnormal fetuses demonstrate that the habituation pattern of these fetuses is different from that of normal fetuses [18,19]. Testing the fetal ability to habituate to repeated stimulation could also be helpful in identifying the fetus at risk for hypoxia. In fetal sheep as well as in human fetuses, fetal hypoxia resulted in either more rapid habituation or a failure to habituate compared to normoxic controls [20,21]. It is of importance to know whether habituation could be useful to identify the fetus at risk in the postterm period. Before such a study can be undertaken, it is essential to gain knowledge about the habituation pattern of normal postterm fetuses. This study was therefore designed to investigate whether healthy postterm fetuses are able to habituate to repeated stimulation and if so, if the habituation pattern of postterm fetuses differs from that of term fetuses. 2. Subjects and method Twenty healthy postterm pregnant women (study group) were recruited at the University Medical Center Nijmegen in the Netherlands. All had an uncomplicated pregnancy and were sent to the hospital by their primary health care midwife for fetal surveillance because of prolonged pregnancy. Thirty-seven healthy pregnant women (control group) were recruited from a low-risk obstetric population for a study of fetal habituation in normal term fetuses. Both studies were approved by the hospitals ethical committee and all participants gave their written informed consent. Inclusion criteria were: (1) gestational age (GA) beyond 41 completed weeks for the postterm study group and GA between 37 and 40 completed weeks for the term control group (pregnancies were dated using the last menstrual period or by early ultrasound when dates were uncertain), (2) no maternal medical or obstetric complications, (3) single fetus without apparent structural or chromosomal anomalies and with an expected birth weight above the 10th centile, (4) adequate amniotic ¯uid volume as assessed by ultrasound, (5) no maternal use of alcohol, drugs or medication other than vitamins and/or iron. All studies were performed by the same examiner in a darkened, quiet room between 4 and 7 p.m. The women were placed in a semi-recumbent position. The stimuli were produced by a fetal vibroacoustic stimulator (Corometrics model 146, Wallingford, Conn.; audible sound 20±9000 Hz, vibrations between 67 and 83 Hz, sound level 74 dB at 1 m in air). A stimulus of 1 s duration was repeatedly applied to the maternal abdomen above the fetal legs every 30 s. The fetal trunk was displayed by means of a real time ultrasound scanner (Hitachi model EUB-525, Tokyo, Japan). The FHR was recorded continuously with a cardiotocograph (Sonicaid
179
FM7, Oxford, UK) at a paper speed of 3 cm per minute. Stimuli were applied during fetal quiescence. A movement of the fetal trunk within 1 s of application of the stimulus was considered to be a positive response. Response decrement was noted as a changing from a more intense to a less intense response pattern with successive trials. Habituation was considered to be established if the fetus responded regularly to the repeated stimuli. The data from experiments in which the fetuses showed alternate responses and nonresponses to repeated stimulation were excluded from the analysis because the habituation pattern was deemed to be uniterpretable. A response decrement was noted as a tendency to change from a more intense to a less intense response pattern with successive trials. A lack of response to four consecutive stimuli was taken to indicate habituation. We allowed a maximum of 24 stimuli in each habituation procedure. However, a minimum of four additional stimuli would be necessary to show habituation if a fetus was still responding to the 21st stimulus. We therefore stopped stimulating if a fetus persisted in responding to the 21st stimulus. The habituation rate was de®ned as the number of stimuli applied before a fetus stopped responding. The entire procedure was repeated 10 min after the ®rst test to investigate whether the fetus habituated more rapidly to the second series of stimuli. The outcome of each pregnancy was examined for birth weight, GA at delivery, Apgar scores, umbilical artery blood pH, and the presence of neonatal complications. Infants were followed up three months after birth by telephone interviews with one of the parents and at one year after birth by means of a questionnaire. Data were compared using Mann±Whitney U test and Wilcoxon signed-ranks matched-pairs test. A two-tailed P value of <0.05 was considered statistically signi®cant. 3. Results All postterm and term fetuses responded with a movement of the fetal trunk to at least the ®rst stimulus. In the postterm group, two fetuses (10%) and in the term group ®ve fetuses (13.5%) were excluded from analysis because irregular movement responses to the stimuli prevented determination of the habituation rate. These fetuses did not differ from the other fetuses in their respective groups in gender, presentation, birth weight, maternal weight, amniotic ¯uid volume, GA at testing and delivery, and neonatal outcome. Characteristics of the remaining 18 postterm and 32 term fetuses are shown in Table 1. From the 18 postterm fetuses in which habituation could be determined, 14 (78%) habituated in the ®rst test. Eleven of the 14 fetuses (79%) habituated more rapidly or did not respond at all in the second test, and three (21%) of them habituated after one stimulus both in the ®rst and in the second test. Four of the 18 fetuses (22%) did not habituate within 21 stimuli in the ®rst test and persisted in responding,
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C.F. van Heteren et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 97 (2001) 178±182
Table 1 Characteristics of the postterm and term groupa Postterm group (n 18) Gestational age at time of testing (week) Gestational age at delivery (week) Birth weight (g) Sex (male/female; n) a
4/7
41 (41±42) 42 (411/7±424/7) 3527 (3020±4595) 11/7
Term group (n 32) 382/7 (37±395/7) 403/7 (385/7±423/7) 3385 (2660±4070) 14/18
Data are given in medians and ranges.
but all showed response decrement. Although they persisted in responding in the ®rst test, they all habituated in the second test (after 7, 1, 1, and 1 stimulus, respectively). The median habituation rate decreased signi®cantly from eight stimuli to one stimulus in the second test (P < 0:001), meaning that fetuses habituated more rapidly in the second test. (Fig. 1a). From the 32 term fetuses in which the presence or absence of habituation could be established, 26 (81%) habituated in the ®rst test. Twenty (77%) of them habituated more rapidly or did not respond at all in the second test. In the second test, only two fetuses habituated slower, and in four habituation could not be determined due to irregular responding. Of the
32 fetuses, six fetuses (19%) did not habituate within 21 stimuli in the ®rst test and persisted in responding (four even showed no response decrement), three of them also persisted in responding in the second test and three habituated (after 15, 13 and 3 stimuli, respectively). The median habituation rate decreased signi®cantly from 9.5 to 2 stimuli in the second test (P 0:001) (Fig. 1a). There was no difference in median habituation rate in the ®rst test as well as in the second test between postterm and term fetuses (Fig. 1b). In the group of 18 postterm fetuses in which habituation could be determined, four fetuses were born macrosomic with a birthweight above the 95th centile GA. Three of these fetuses habituated (after 18, 11 and 4 stimuli, respectively), and one persisted in responding in the ®rst test. Fifteen women delivered vaginally without complications, seven at home and eight at the hospital. In three women, labor was induced because of GA beyond 42 weeks, they all delivered vaginally. Three women delivered by cesarean section, two because of intrapartum fetal distress and one due to a cephalopelvic disproportion. All infants did well after birth, with birth weights above the 10th centile for gestational age, a 5 min Apgar score 8 and an umbilical artery pH 7.10. Follow up after 3 months and after 1 year revealed that all infants developed normally. In the group of 32 term fetuses in which habituation could be established, seven (22%) were born by cesarean section for different reasons, but not for fetal distress. All infants did well after birth, with birth weights above the 10th centile for GA, a 5 min Apgar score 8 and an umbilical artery pH 7.10. Follow up at three months and at one year of age revealed no serious abnormalities in any infant. 4. Comment
Fig. 1. (a) Habituation rate of postterm and term fetuses in test 1 and test 2. Data are combined in a Box-Whisker plot (median, interquartile ranges, maximum and minimum). A habituation rate of 23 represents a persistent response. (b) Habituation rates of test 1 and test 2 in postterm and term fetuses. NS: not significant.
In this study, we investigated fetal habituation to repeated vibroacoustic stimulation in healthy postterm and term fetuses. The type of stimulus we used induced an immediate fetal movement response, to at least the ®rst stimulus, regardless of the fetal state. By using this stimulator and observing the immediate movement response to repeated stimulation, a clinician can easily distinguish between a response and a non-response and so determine fetal habituation. Ten percent of the postterm and 13.5% of the term
C.F. van Heteren et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 97 (2001) 178±182
fetuses responded irregularly to the repeated stimuli. These fetuses exhibited alternate responses and non-responses, which made determination of habituation impossible. Because the majority of the postterm and term fetuses responded consistently to each stimulus, we consider the habituation pattern of fetuses with irregular responses to be non-interpretable. To con®rm that the observed response decrement was the result of habituation rather than motor fatigue or sensory adaptation, we repeated the whole procedure within 10 min of the ®rst test. Repeated stimulation may physically exhaust the fetus so it is unable to respond or it may tire the auditory or tactile receptor which results in receptor adaptation. In real habituation, the original stimulus, when presented again, initially elicits a response but this response decreases more rapidly than when ®rst presented [22]. In our study, the habituation rate decreased signi®cantly in the second test in the postterm as well as in the term group. In fact, ®ve (28%) postterm fetuses and eight (25%) term fetuses did not respond at all to the presentation of the original stimulus within 10 min after they habituated to this stimulus. This can be explained by the fact that fetuses recognize the stimuli and habituate more rapidly to the stimuli when presented again [23]. Three postterm fetuses habituated within one stimulus in the ®rst as well as in the second test. In these fetuses an immediate startle was clearly observed within 1 s after the stimulus accompanied by an acceleration of the FHR of at least 15 bpm following the ®rst stimulus. In two fetuses FHR accelerations following consecutive stimuli were seen, whereas no movement response could be observed to these stimuli. Although FHR accelerations were observed to consecutive stimuli, we de®ned habituation only according to the movement response. But it is questionable whether this habituation after one stimulus is real habituation because there is no response decrement and no faster habituation to presentation of the original stimulus after 10 min. One of the factors that may determine the habituation rate is the degree of maturation of the fetal CNS. Groome et al. [14] examined the developmental trend in habituation of the fetal startle response to repeated vibroacoustic stimulation in normal fetuses between 28 and 40 weeks of gestation. They concluded that older fetuses habituated more rapidly than younger fetuses, with the greatest change in habituation rate between 28 and 32 weeks and 32 and 36 weeks. The ongoing maturation of the CNS in the last weeks of pregnancy, which is for example re¯ected in the change in behavioral state organization [24], appears not to be re¯ected in the fetal habituation pattern. We were unable to establish a faster habituation pattern in postterm fetuses compared with term fetuses. Leader et al. [18] used an electric toothbrush to study habituation in 112 compromised fetuses of different GA (small for GA, meconium-stained amniotic ¯uid or decreased growth velocity of the fetal biparietal diameter).
181
They found that fetuses in the compromised group habituated more rapidly (<9 stimuli) or more slowly (>50 stimuli), compared with normal fetuses. Only eight of the compromised fetuses, that showed a different habituation pattern, had a 5 min Apgar score less than 6. Unfortunately, neonatal outcome, except for the Apgar scores, is not reported in their study. Leader and Baillie [20] also demonstrated that reducing the amount of oxygen inspired by the mother was associated with an impaired habituation by the fetus. Thirteen of 18 fetuses of mothers that inspired air with 12% oxygen failed to habituate within 51 stimuli. Although we followed another protocol with a different stimulator than Leader et al. used, we cannot conclude that postterm fetuses that failed to habituate or habituated within one stimulus showed fetal distress or adverse neonatal outcome. In our study, in postterm fetuses, the habituation rate varied greatly. Four fetuses persisted in responding and three habituated within one stimulus. Of the four fetuses that persisted in responding in the ®rst test, two were delivered vaginally at home, one was born after induction of labor and one was delivered by cesarean section because of intrapartum fetal compromise. Of the three fetuses that habituated within one stimulus, two were born vaginally at the hospital and one by cesarean section because of cephalopelvic disproportion. Although four postterm fetuses persisted in responding in the ®rst test and three fetuses habituated very rapidly, all these fetuses did well after birth and revealed no abnormalities at the age of three months. Apparently, there are normal postterm fetuses that fail to habituate or that habituate within one stimulus. There are even normal postterm fetuses in which habituation cannot be determined due to irregular responses. From this study we conclude that, although habituation can be clearly observed in the majority of postterm fetuses, the interfetal variability in habituation performance is such that testing of habituation is not suitable for the identi®cation of the fetus at risk for an adverse neonatal outcome. In a study in a homogenous group of healthy, full-term, minimally stressed, white neonates, normative data of the habituation rate were determined [12]. Also neonates exhibit a wide variation in the habituation performance. We attempted to ®nd normative data of fetal habituation in postterm as well as in term fetuses and also found a marked interfetal variability in habituation performance. This can be in¯uenced by many factors, although we used a homogeneous group of white, healthy, and minimally stressed fetuses. This is presumably due to the overall individual difference in fetal behavior, like there is an individual difference in neonatal behavior. This means that fetal habituation appears not to be suitable as a technique to distinguish normal from abnormal fetuses, in uncomplicated postterm and term pregnancies, due to this variability in habituation performance. Studies to investigate whether or not fetal habituation can be a tool in the evaluation of the fetal condition and functioning of the CNS in compromised fetuses are needed.
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Acknowledgements The authors thank ZorgOnderzoek Netherlands (grant 283054) and the Dutch Brain Foundation, The Hague, The Netherlands for their support of this study. References [1] Naeye RL. Causes of perinatal mortality excess in prolonged gestations. Am J Epidemiol 1978;108:429±33. [2] Boyd ME, Usher RH, McLean FH, Kramer MS. Obstetric consequences of postmaturity. Am J Obstet Gynecol 1988;158: 334±8. [3] Callenbach JC, Hall RT. Morbidity and mortality of advanced gestational age: postterm or postmature. Obstet Gynecol 1979;53: 721±4. [4] Manning FA, Platt LD, Sipos L. Antepartum fetal evaluation: development of a fetal biophysical profile. Am J Obstet Gynecol 1980;136:787±95. [5] Bobby PD, Divon MY. Fetal testing in postdates. Curr Opin Obstet Gynecol 1997;9:79±82. [6] Jeffrey WE, Cohen LS. Habituation in the human infant. Adv Child Dev Behav 1971;6:63±97. [7] Gandhavadi B. Glabellar reflex habituation in mentally retarded adults. J Ment Defic Res 1982;26:271±8. [8] Hutt SJ, Hutt C. Hyperactivity in a group of epileptic (and some nonepileptic) brain-damaged children. Epilepsia 1964;5:334±51. [9] Schafer EW, Peeke HV. Down syndrome individuals fail to habituate cortical evoked potentials. Am J Ment Defic 1982;87:332±7. [10] Lader MH, Wing L. Physiological measures in agitated and retarded depressed patients. J Psychiatr Res 1969;7:89±100. [11] Gandhavadi B, Melvin JL. Electrical blink reflex habituation in mentally retarded adults. J Ment Defic Res 1985;29:49±54.
[12] Als H, Tronick E, Lester BM, Brazelton TB. The Brazelton neonatal behavioral assessment scale (BNBAS). J Abnorm Child Psychol 1977;5:215±31. [13] Madison LS, Madison JK, Adubato SA. Infant behavior and development in relation to fetal movement and habituation. Child Dev 1986;57:1475±82. [14] Groome LJ, Gotlieb SJ, Neely CL, Waters MD. Developmental trends in fetal habituation to vibroacoustic stimulation. Am J Perinatol 1993;10:46±9. [15] Shalev E, Benett MJ, Megory E, Wallace RM, Zuckerman H. Fetal habituation to repeated sound stimulation. Isr J Med Sci 1989;25: 77±80. [16] Leader LR, Baillie P, Martin B, Vermeulen E. The assessment and significance of habituation to a repeated stimulus by the human fetus. Early Hum Dev 1982;7:211±9. [17] Kuhlman KA, Burns KA, Depp R, Sabbagha RE. Ultrasonic imaging of normal fetal response to external vibratory acoustic stimulation. Am J Obstet Gynecol 1988;158:47±51. [18] Leader LR, Baillie P, Martin B, Vermeulen E. Fetal habituation in high-risk pregnancies. Br J Obstet Gynaecol 1982;89:441±6. [19] Hepper PG, Shahidullah S. Habituation in normal and Down's syndrome fetuses. Q J Exp Psychol B 1992;44:305±17. [20] Leader LR, Baillie P. The changes in fetal habituation patterns due to a decrease in inspired maternal oxygen. Br J Obstet Gynaecol 1988;95:664±8. [21] Leader LR, Smith FG, Lumbers ER, Stevens AD. Effect of hypoxia and catecholamines on the habituation rates of chronically catheterized ovine fetuses. Biol Neonate 1989;56:218±27. [22] Madison LS, Adubato SA, Madison JK, Nelson RM, Anderson JC, Erickson J, Kuss LM, Goodlin RC. Fetal response decrement: true habituation? Dev Behav Ped 1986;7:14±20. [23] van Heteren CF, Boekkooi PF, Jongsma HW, Nijhuis JG. Fetal learning and memory. Lancet 2000;356:1169±70. [24] van de Pas M, Nijhuis JG, Jongsma HW. Fetal behaviour in uncomplicated pregnancies after 41 weeks of gestation. Early Hum Dev 1994;40:29±38.
Fetal habituation to vibroacoustic stimulation in uncomplicated postterm pregnancies Cathelijne F. van Heterena,*, P. Focco Boekkooia, Rikke H.M. Schiphorsta, Henk W. Jongsmaa, Jan G. Nijhuisb a
Department of Obstetrics and Gynecology, University Medical Centre Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands b Department of Obstetrics and Gynecology, University Hospital of Maastricht, Maastricht, The Netherlands Received 14 August 2000; received in revised form 19 October 2000; accepted 18 November 2000
Abstract Objectives: Testing of fetal habituation to repeated vibroacoustic stimulation might give additional information concerning the fetal condition and central nervous system (CNS) functioning in postterm pregnancies. This study is designed to investigate whether healthy postterm fetuses are able to habituate and if so, if the habituation pattern of postterm fetuses differs from that of term fetuses. Study design: Twenty women with an uncomplicated pregnancy beyond 41 weeks gestational age (GA) participated, and 37 women with a GA between 37 and 40 weeks served as controls. The vibroacoustic stimulus was repeatedly applied to the maternal abdomen above the fetal legs for a period of 1 s every 30 s. A fetal trunk movement within 1 s of stimulus application was considered a positive response. Lack of response to four consecutive stimuli indicated habituation. The habituation rate is de®ned as the number of stimuli applied before the fetus stopped responding. Data were compared using Mann±Whitney U test. Results: Of the 18 postterm fetuses in which the presence or absence of habituation could be established, 14 habituated and four persisted in responding. Twenty-six of the 32 term fetuses, in which the presence or absence of habituation could be established, habituated and six persisted in responding. The habituation rate varied widely in postterm (median of eight stimuli, quartile ranges of 6 and 18) as well as in term fetuses (median of 9.5 stimuli, quartile ranges of 6 and 15). There was no difference in median habituation rate between postterm and term fetuses. Conclusion: The ongoing maturation of the CNS in the last weeks of pregnancy appears not to be re¯ected in the fetal habituation pattern. Furthermore, the interfetal variability in habituation of healthy postterm fetuses is such that testing of habituation appears not to be suitable for the identi®cation of the fetus at risk for an adverse neonatal outcome. # 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Fetal habituation; Vibroacoustic stimulation; Postterm pregnancy
1. Introduction Prolongation of pregnancy beyond term is accompanied by an increase in perinatal mortality and morbidity [1±3] and adequate fetal monitoring is indicated. Assessment of the biophysical pro®le seems to be the best way to evaluate fetal well-being in a postterm pregnancy because a variety of fetal parameters (fetal heart rate (FHR), amount of amniotic ¯uid, fetal breathing, body movements and fetal tone) are observed [4]. The primary disadvantage of scoring the biophysical pro®le is the risk for a false-positive test with subsequent needless interventions as well the risk for a falsenegative test result that can result in fetal morbidity or
* Corresponding author. Tel.: 31-243616801; fax: 31-243541194. E-mail address: [email protected] (C.F. van Heteren).
mortality. Another disadvantage is the time required to perform the test and the need for an experienced sonographer. Current research on the use of fetal testing has focused on the re®nement of testing protocols and the application of new methods to improve the positive predictive value of fetal testing in postterm pregnancies [5]. Testing of fetal habituation to repeated vibroacoustic stimulation might give additional information concerning the fetal condition and functioning of the fetal central nervous system (CNS). Habituation is the decrease, and eventual cessation, of response that follows repeated application of the same stimulus. Habituation can be seen as a basic form of learning that requires an intact functioning of the CNS [6]. Studies in persons with various disorders of the CNS reveal that the habituation pattern of these persons is different from that of persons without these disorders [7±11]. Pediatricians use this habituation phenomenon to assess newborns for various pathological conditions of the CNS [12].
0301-2115/01/$ ± see front matter # 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 3 0 1 - 2 1 1 5 ( 0 0 ) 0 0 5 4 3 - 1
C.F. van Heteren et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 97 (2001) 178±182
Several studies on fetal habituation have been published [13±17]. Although the methodologies used varied widely, these studies all reveal that normal fetuses are able to habituate to repeated external stimulation. Studies in compromised or chromosomally abnormal fetuses demonstrate that the habituation pattern of these fetuses is different from that of normal fetuses [18,19]. Testing the fetal ability to habituate to repeated stimulation could also be helpful in identifying the fetus at risk for hypoxia. In fetal sheep as well as in human fetuses, fetal hypoxia resulted in either more rapid habituation or a failure to habituate compared to normoxic controls [20,21]. It is of importance to know whether habituation could be useful to identify the fetus at risk in the postterm period. Before such a study can be undertaken, it is essential to gain knowledge about the habituation pattern of normal postterm fetuses. This study was therefore designed to investigate whether healthy postterm fetuses are able to habituate to repeated stimulation and if so, if the habituation pattern of postterm fetuses differs from that of term fetuses. 2. Subjects and method Twenty healthy postterm pregnant women (study group) were recruited at the University Medical Center Nijmegen in the Netherlands. All had an uncomplicated pregnancy and were sent to the hospital by their primary health care midwife for fetal surveillance because of prolonged pregnancy. Thirty-seven healthy pregnant women (control group) were recruited from a low-risk obstetric population for a study of fetal habituation in normal term fetuses. Both studies were approved by the hospitals ethical committee and all participants gave their written informed consent. Inclusion criteria were: (1) gestational age (GA) beyond 41 completed weeks for the postterm study group and GA between 37 and 40 completed weeks for the term control group (pregnancies were dated using the last menstrual period or by early ultrasound when dates were uncertain), (2) no maternal medical or obstetric complications, (3) single fetus without apparent structural or chromosomal anomalies and with an expected birth weight above the 10th centile, (4) adequate amniotic ¯uid volume as assessed by ultrasound, (5) no maternal use of alcohol, drugs or medication other than vitamins and/or iron. All studies were performed by the same examiner in a darkened, quiet room between 4 and 7 p.m. The women were placed in a semi-recumbent position. The stimuli were produced by a fetal vibroacoustic stimulator (Corometrics model 146, Wallingford, Conn.; audible sound 20±9000 Hz, vibrations between 67 and 83 Hz, sound level 74 dB at 1 m in air). A stimulus of 1 s duration was repeatedly applied to the maternal abdomen above the fetal legs every 30 s. The fetal trunk was displayed by means of a real time ultrasound scanner (Hitachi model EUB-525, Tokyo, Japan). The FHR was recorded continuously with a cardiotocograph (Sonicaid
179
FM7, Oxford, UK) at a paper speed of 3 cm per minute. Stimuli were applied during fetal quiescence. A movement of the fetal trunk within 1 s of application of the stimulus was considered to be a positive response. Response decrement was noted as a changing from a more intense to a less intense response pattern with successive trials. Habituation was considered to be established if the fetus responded regularly to the repeated stimuli. The data from experiments in which the fetuses showed alternate responses and nonresponses to repeated stimulation were excluded from the analysis because the habituation pattern was deemed to be uniterpretable. A response decrement was noted as a tendency to change from a more intense to a less intense response pattern with successive trials. A lack of response to four consecutive stimuli was taken to indicate habituation. We allowed a maximum of 24 stimuli in each habituation procedure. However, a minimum of four additional stimuli would be necessary to show habituation if a fetus was still responding to the 21st stimulus. We therefore stopped stimulating if a fetus persisted in responding to the 21st stimulus. The habituation rate was de®ned as the number of stimuli applied before a fetus stopped responding. The entire procedure was repeated 10 min after the ®rst test to investigate whether the fetus habituated more rapidly to the second series of stimuli. The outcome of each pregnancy was examined for birth weight, GA at delivery, Apgar scores, umbilical artery blood pH, and the presence of neonatal complications. Infants were followed up three months after birth by telephone interviews with one of the parents and at one year after birth by means of a questionnaire. Data were compared using Mann±Whitney U test and Wilcoxon signed-ranks matched-pairs test. A two-tailed P value of <0.05 was considered statistically signi®cant. 3. Results All postterm and term fetuses responded with a movement of the fetal trunk to at least the ®rst stimulus. In the postterm group, two fetuses (10%) and in the term group ®ve fetuses (13.5%) were excluded from analysis because irregular movement responses to the stimuli prevented determination of the habituation rate. These fetuses did not differ from the other fetuses in their respective groups in gender, presentation, birth weight, maternal weight, amniotic ¯uid volume, GA at testing and delivery, and neonatal outcome. Characteristics of the remaining 18 postterm and 32 term fetuses are shown in Table 1. From the 18 postterm fetuses in which habituation could be determined, 14 (78%) habituated in the ®rst test. Eleven of the 14 fetuses (79%) habituated more rapidly or did not respond at all in the second test, and three (21%) of them habituated after one stimulus both in the ®rst and in the second test. Four of the 18 fetuses (22%) did not habituate within 21 stimuli in the ®rst test and persisted in responding,
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Table 1 Characteristics of the postterm and term groupa Postterm group (n 18) Gestational age at time of testing (week) Gestational age at delivery (week) Birth weight (g) Sex (male/female; n) a
4/7
41 (41±42) 42 (411/7±424/7) 3527 (3020±4595) 11/7
Term group (n 32) 382/7 (37±395/7) 403/7 (385/7±423/7) 3385 (2660±4070) 14/18
Data are given in medians and ranges.
but all showed response decrement. Although they persisted in responding in the ®rst test, they all habituated in the second test (after 7, 1, 1, and 1 stimulus, respectively). The median habituation rate decreased signi®cantly from eight stimuli to one stimulus in the second test (P < 0:001), meaning that fetuses habituated more rapidly in the second test. (Fig. 1a). From the 32 term fetuses in which the presence or absence of habituation could be established, 26 (81%) habituated in the ®rst test. Twenty (77%) of them habituated more rapidly or did not respond at all in the second test. In the second test, only two fetuses habituated slower, and in four habituation could not be determined due to irregular responding. Of the
32 fetuses, six fetuses (19%) did not habituate within 21 stimuli in the ®rst test and persisted in responding (four even showed no response decrement), three of them also persisted in responding in the second test and three habituated (after 15, 13 and 3 stimuli, respectively). The median habituation rate decreased signi®cantly from 9.5 to 2 stimuli in the second test (P 0:001) (Fig. 1a). There was no difference in median habituation rate in the ®rst test as well as in the second test between postterm and term fetuses (Fig. 1b). In the group of 18 postterm fetuses in which habituation could be determined, four fetuses were born macrosomic with a birthweight above the 95th centile GA. Three of these fetuses habituated (after 18, 11 and 4 stimuli, respectively), and one persisted in responding in the ®rst test. Fifteen women delivered vaginally without complications, seven at home and eight at the hospital. In three women, labor was induced because of GA beyond 42 weeks, they all delivered vaginally. Three women delivered by cesarean section, two because of intrapartum fetal distress and one due to a cephalopelvic disproportion. All infants did well after birth, with birth weights above the 10th centile for gestational age, a 5 min Apgar score 8 and an umbilical artery pH 7.10. Follow up after 3 months and after 1 year revealed that all infants developed normally. In the group of 32 term fetuses in which habituation could be established, seven (22%) were born by cesarean section for different reasons, but not for fetal distress. All infants did well after birth, with birth weights above the 10th centile for GA, a 5 min Apgar score 8 and an umbilical artery pH 7.10. Follow up at three months and at one year of age revealed no serious abnormalities in any infant. 4. Comment
Fig. 1. (a) Habituation rate of postterm and term fetuses in test 1 and test 2. Data are combined in a Box-Whisker plot (median, interquartile ranges, maximum and minimum). A habituation rate of 23 represents a persistent response. (b) Habituation rates of test 1 and test 2 in postterm and term fetuses. NS: not significant.
In this study, we investigated fetal habituation to repeated vibroacoustic stimulation in healthy postterm and term fetuses. The type of stimulus we used induced an immediate fetal movement response, to at least the ®rst stimulus, regardless of the fetal state. By using this stimulator and observing the immediate movement response to repeated stimulation, a clinician can easily distinguish between a response and a non-response and so determine fetal habituation. Ten percent of the postterm and 13.5% of the term
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fetuses responded irregularly to the repeated stimuli. These fetuses exhibited alternate responses and non-responses, which made determination of habituation impossible. Because the majority of the postterm and term fetuses responded consistently to each stimulus, we consider the habituation pattern of fetuses with irregular responses to be non-interpretable. To con®rm that the observed response decrement was the result of habituation rather than motor fatigue or sensory adaptation, we repeated the whole procedure within 10 min of the ®rst test. Repeated stimulation may physically exhaust the fetus so it is unable to respond or it may tire the auditory or tactile receptor which results in receptor adaptation. In real habituation, the original stimulus, when presented again, initially elicits a response but this response decreases more rapidly than when ®rst presented [22]. In our study, the habituation rate decreased signi®cantly in the second test in the postterm as well as in the term group. In fact, ®ve (28%) postterm fetuses and eight (25%) term fetuses did not respond at all to the presentation of the original stimulus within 10 min after they habituated to this stimulus. This can be explained by the fact that fetuses recognize the stimuli and habituate more rapidly to the stimuli when presented again [23]. Three postterm fetuses habituated within one stimulus in the ®rst as well as in the second test. In these fetuses an immediate startle was clearly observed within 1 s after the stimulus accompanied by an acceleration of the FHR of at least 15 bpm following the ®rst stimulus. In two fetuses FHR accelerations following consecutive stimuli were seen, whereas no movement response could be observed to these stimuli. Although FHR accelerations were observed to consecutive stimuli, we de®ned habituation only according to the movement response. But it is questionable whether this habituation after one stimulus is real habituation because there is no response decrement and no faster habituation to presentation of the original stimulus after 10 min. One of the factors that may determine the habituation rate is the degree of maturation of the fetal CNS. Groome et al. [14] examined the developmental trend in habituation of the fetal startle response to repeated vibroacoustic stimulation in normal fetuses between 28 and 40 weeks of gestation. They concluded that older fetuses habituated more rapidly than younger fetuses, with the greatest change in habituation rate between 28 and 32 weeks and 32 and 36 weeks. The ongoing maturation of the CNS in the last weeks of pregnancy, which is for example re¯ected in the change in behavioral state organization [24], appears not to be re¯ected in the fetal habituation pattern. We were unable to establish a faster habituation pattern in postterm fetuses compared with term fetuses. Leader et al. [18] used an electric toothbrush to study habituation in 112 compromised fetuses of different GA (small for GA, meconium-stained amniotic ¯uid or decreased growth velocity of the fetal biparietal diameter).
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They found that fetuses in the compromised group habituated more rapidly (<9 stimuli) or more slowly (>50 stimuli), compared with normal fetuses. Only eight of the compromised fetuses, that showed a different habituation pattern, had a 5 min Apgar score less than 6. Unfortunately, neonatal outcome, except for the Apgar scores, is not reported in their study. Leader and Baillie [20] also demonstrated that reducing the amount of oxygen inspired by the mother was associated with an impaired habituation by the fetus. Thirteen of 18 fetuses of mothers that inspired air with 12% oxygen failed to habituate within 51 stimuli. Although we followed another protocol with a different stimulator than Leader et al. used, we cannot conclude that postterm fetuses that failed to habituate or habituated within one stimulus showed fetal distress or adverse neonatal outcome. In our study, in postterm fetuses, the habituation rate varied greatly. Four fetuses persisted in responding and three habituated within one stimulus. Of the four fetuses that persisted in responding in the ®rst test, two were delivered vaginally at home, one was born after induction of labor and one was delivered by cesarean section because of intrapartum fetal compromise. Of the three fetuses that habituated within one stimulus, two were born vaginally at the hospital and one by cesarean section because of cephalopelvic disproportion. Although four postterm fetuses persisted in responding in the ®rst test and three fetuses habituated very rapidly, all these fetuses did well after birth and revealed no abnormalities at the age of three months. Apparently, there are normal postterm fetuses that fail to habituate or that habituate within one stimulus. There are even normal postterm fetuses in which habituation cannot be determined due to irregular responses. From this study we conclude that, although habituation can be clearly observed in the majority of postterm fetuses, the interfetal variability in habituation performance is such that testing of habituation is not suitable for the identi®cation of the fetus at risk for an adverse neonatal outcome. In a study in a homogenous group of healthy, full-term, minimally stressed, white neonates, normative data of the habituation rate were determined [12]. Also neonates exhibit a wide variation in the habituation performance. We attempted to ®nd normative data of fetal habituation in postterm as well as in term fetuses and also found a marked interfetal variability in habituation performance. This can be in¯uenced by many factors, although we used a homogeneous group of white, healthy, and minimally stressed fetuses. This is presumably due to the overall individual difference in fetal behavior, like there is an individual difference in neonatal behavior. This means that fetal habituation appears not to be suitable as a technique to distinguish normal from abnormal fetuses, in uncomplicated postterm and term pregnancies, due to this variability in habituation performance. Studies to investigate whether or not fetal habituation can be a tool in the evaluation of the fetal condition and functioning of the CNS in compromised fetuses are needed.
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