Diurnal variations in resting-active cycles in full-term fetal heart rate changes

Early Human Development 44 (1996) 51-58

Diurnal variations in resting-active cycles in full-term fetal heart rate changes Masami Muro, Hideaki Shone*, Mayumi Kohara, Yuji Ito, Akira Uchiyama, Hajime Sugimori Department

of Obstetrics

and

Gynecology,

Saga

Medical

School,

S-I-I

Nabeshima,

Saga

849.

Japan

Received 20 July 1994; revision received 8 May 1995; accepted 31 May 1995

To elucidatethe mechanismof the resting-activecycles(RAC) of fetal heart rates(FHR), in the restingand non-restingphases(RP and NRP), 24-h FHR recordingsweremadeon 16 normalfull-term pregnantwomen.RP, NRP, RAC-1 (NRP-NRP cycle), andRAC-2 (RP-RP cycle)weredefinedbasedon the criteria of Nijhuis et al. Frequencydistributionswereplotted separatelyfor the entire 24-hperiodaswell asfor the day-time(07:00-21:OOh) andnight-time (21:OO-07:OO h), and werecomparedusingKolmogorov-Smimovtwo-sampletests.The mean durations(&S.D.) (min) of RP, NRP, RAC-I, and RAC-2 were 22.7 f 11.2,67.3 f 47.2, 90.0 * 47.6, and 89.9 f 48.6 during 24-h periods,20.1 f 7.7, 68.3 f 52.3,88.6 f 53.1,and 88.4 f 53.0 during the day-time, and 25.4 * 13.2, 66.2 f 41.2, 91.4 f 41.0, and 91.5 f 43.4 duringthe night-time.Lengthof RP wasthe only factor significantlydifferent during the day and night (P c 0.05). We proposethat there are different mechanisms controlling RP and NRP. Keywords:

Fetal heart rate; Diurnal variation; Resting-activecycle

1. Introduction Since the l%Os, diurnal variations of biological ultradian rhythms have been analyzed in attempts to elucidate the effects of environmental factors [4,10,13]. In human fetuses,periodicities of breathing movements, mouthing movements, micturi* Corresponding author. Tel.: +81 952 31 6511; fax: +81 952 31 6543. 0378-3782/96/$35,00 0 1996 Elsevier Science Ireland Ltd. All rights reserved SSDI 0378-3782(95)01691-U

52

hf. Muro

et al. /Early

Human

Development

44 (1996)

51-58

tion and eye movements have been observed using ultrasonic tomography [ 11,18,21,30]. However, little is known of the relation between fetal parameters and diurnal variation in the fetal environment because it is difficult to make ultrasonic examinations of the human fetus for longer than a few hours. Fetal heart rate (FHR) trends can be monitored for long periods of time and specitic patterns can be clearly defined relating to the different fetal behavioral states [18,29]. The criteria of the fetal behavioral states established by Nijhuis et al. have been described on the basis of eye and body movements and on FHR patterns [ 181. Additionally resting and non-resting phase (RP and NRP) in the resting-active cycle (RAC) of the FHR pattern correspond to fetal NREM and REM periods, respectively [l]. FHR patterns are thought to be the most important variable to be used when classifying the episodic fetal behavioral states over an extended period of time. While there are many reports describing the RAC of FHR [2,6,14,31,33], there is a discrepancy in the cycle length ranging from 60 to 90 min, and variation of this cycle has been given little attention. We developed a long-duration FHR recorder [25], and analyzed FHR trends in full-term normal, human pregnancies for a continuous 24-h period. Lengths of RAC and diurnal variations were analyzed. 2. Materials and methods The subjects were 16 healthy women with normal pregnancies between 37 and 39 weeks of gestation (Table 1). Subsequent deliveries and outcomes were uneventful. Table 1 Subjects Case

1 2 3 4 5 6 I 8 9 10 I1 12 13 14 15 16

Examination Gestation (weeks! days) 37x) 3112 3114 3115 38/O 38/l 3813 3814 3814 38/4 3816 39/o 3912 3915 3916 3916

‘Gravida, Para.

Neonate

Mother

Gestation (weeks/ days)

Weight (g) Apgar (l/5 min)

Sex

Age

G.P.”

Occupation

38/O 3813 4013 3914 3816 3816 39/O 3816 3816 3915 3912 3912 3916 3916 4011 4013

2532 2148 3018 2982 3082 2790 2610 2798 3256 3024 2622 2998 2938 2914 3332 3618

M F M M M F F F M M F M M M M M

25 31 32 31 33 34 22 34 34 25 35 29 28 28 31 32

GOP0 G4PI GOF’O G3P2 GOP0 GlPl GOP0 GIPO G3P2 GOP0 GIPO G2P1 G3P1 G2PI GOP0 G6PO

NUN? Housewife Housewife Housewife Housewife Housewife Housewife Housewife Cook Housewife Housewife Housewife Housewife Housewife Housewife Housewife

9l9 919 919 9/10 9110 919 8/9 9f9 819 9110 9110 919 919 919 919 9i9

M. Mtuo

et al. i Early

Human

Development

44 (19961

51-S

(o’clock) 17% (b.p.m.) Fig. I. An example of compressed 24-h fetal heart rate (FHR) trendgram. Hourly trendgrams of FHR are shown from the top downward.

54

M. Muro

et al. /Early

Human

Development

44 (1996)

51-58

All infants were appropriate for date and there were no anomalies. Gestational age was confirmed by ultrasonic measurements of fetal size during early pregnancy. All investigations were approved by the hospital ethics committee, and informed consent for the study was obtained from each individual mother l-9 weeks prior to the onset of the study. After admission, 24-h continuous FHR monitorings were made on all subjects who were kept in bed, in rooms exposed to normal daylight and darkness, and who slept from 2 1:OOh to 07:OO h. They all ate breakfast, lunch, and dinner at 0800, 12:00, and 18:00 h, respectively. No subjects used tobacco or other drugs. A long-duration FHR recorder was used to record the FHR, calculated by an autocorrelation method and recorded on a floppy disc [25]. The FHR data were analyzed separately on an off-line microcomputer. Trends of FHR in each case were developed from the recorded data (Fig. 1) and classified as RP and NRP, based on criteria previously established by Nijhuis et al. [18]. These criteria have been used by various groups of investigators [5,20,32] and states 1F and 2F have been confirmed to be comparable to quiet and active sleep in the newborn [23]. States 3F and 4F have often been excluded due to their low incidence [9,22] and because there is no consensus that state 4F corresponds to a particular state as ‘wakefulness’ 1191. In the present study, FHR pattern A which corresponds to state 1F was classified as RP and FHR patterns B-D which correspond to state 2F-4F were classified as NRP. We also quantified the lengths of cycles from the beginning of one NRP to the next NRP (RAC-1) and from the beginning of one RP until the start of the next RP (RAC-2) in order to decide which was regarded as RAC, RAC-1 or RAC-2. We plotted the frequency distributions of RP, NRP, RAC-1, and RAC-2 during the 24-h period, day-time (07:00-21:00 h) and night-time (21:00-07:OO h) periods. The lengths of phases and cycles were expressed as mean f SD. Comparisons between the frequency distributions were not assessed statistically using a parametric method (Student’s t-test) but rather by using a nonparametric method (Kolmogorov-Smirnov two-sample test), because shapes of frequency distributions were not known [27]. 3. Results A total of 227 cycles (227 RP and 227 NRP) obtained from 21 438 min of FHR trends from 16 subjects were analyzed, In all individuals, there was a wide range in cycle length and numbers of each cycle (Fig. 2). The range of length of the RP was narrow, with a wider variation in length during the night (Fig. 3). Mean durations (f S.D.) of RP were 22.1 f 11.2 min during the 24-h period (range, 4-75 min), 20.1 f 7.7 min during the day-time (range, 19-42 min), and 25.4 f 13.2 rnin during the night (range, 4-75 min). There was a significant difference between distributions during day-time and night-time (P < 0.01). The frequency distribution of the NRP had a generally wider range and a longer duration than the RP, but did not vary between day-time and night-time. The mean NRP length was 67.3 f 47.2 min during the 24-h period (range, 9-292 min), 68.8 f 52.3 min during day-time (range, 9-292 min), and 66.2 f 41.2 min during night-time (range, 11-212 min). There was no significant difference between NRP length during the day-time and night-time.

M. Muro

Case 0

9 60

CaeelO

er al. /Early

Case11

Human

Case12

Development

44 /@%J

Cam13

Case14

51-58

C&w15

Case16

0

AM

7 12

PM Q

11 to’ckxk)

Fig. 2. Classification of fetal heart rate changes as each phase during 24 h. Horizontal bars indicate restine phases and arrows indicate the start of recordings. 24hour period lool

.. . .

Day( 7:00-21 :OO)

Night ( 21:00-7:oOI

1 . .

P .

A

i

I .

. . . . . km”,

Fig. 3. Comparison of frequency distributions of lengths of resting (A) and non-resting phases (B) in each time period. *Statistically significant difference by Kolmogorov-Smimov two-sample test; N.S., not significant.

56

M. Muro

et al. /Early

24hour period

N:S.

Human

..

Development

Day (7:00-21:OO)

.

Nk

-. .. ..

m

I

4

44 (19%)

51-58

Night (21 :UO-730 )

N:S.

m

Fig. 4. Comparison of the frequency distributions of the lengths of RAC-I, from the beginning of nonresting phase until the beginning of the next non-resting phase (A), and RAC-2, from the beginning of resting phase until the beginning of the next resting phase(B), in each of time period; N.S., not significant.

The mean duration (*S.D.) of the RAG1 was 89.9 f 48.6 min during the 24-h period (range, 14-315 min), 88.4 f 53.0 min during the day-time (range, 14-315 min), and 91.5 f 43.4 min during the night-time (range, 28-237 min), while the RAC-2 was 90.9 f 47.6 min (range, 16-299 min), 88.6 * 53.1 min (range, 16-299 min), and 91.4 f 43.4 min (range, 27-228 min), respectively. Statistically, there were no significant differences between the frequency distributions of RAG1 and RAC-2 in each time period, or between day-time and night-time (Fig. 4). In the present study, we considered these two RACs, namely RAC-1 and RAC-2 as RAC. 4. Discussion While RAC has been extensively examined [7,14,33], observations for 60 min suggested a cycle length of approximately 60 min [6,29] while observations for 24 h revealed a 90-min cycle [2,31]. Our results indicate that an observation period of 60 min is too short for analysis of the NRP and RAC because individual cycle lengths vary. We analyzed data obtained from 24-h continuous FHR recordings, and found the mean length of the various cycles and phases to be consistent with the data obtained by Arduini et al. [2] and Visser et al. [31] who also made 24-h FHR recordings.

M. Muro et al. /E&y

Human Devdopmenr 44 (1996) 51-58

There has been no documentation concerning the diurnal variation in lengths of RP, NRP, and RAC, although both Arduini et al. [2] and V&r et al. (311 reported diurnal variations in the baseline FHR and the variability of FHR changes. With regard to the difference in frequency distribution between day-time and night-time, we found no differences in the length of NRP, but significant differences in length of RP. Diurnal variations of extra maternal stimuli or maternal hormonal factors are considered to influence changes in the length of RP between day-time and nighttime. Vibroacoustic stimuli are well recognized to induce accelerations in FHR I&9,26], and Arduini et al. suggested that maternal plasma cortisol levels that have a circadian rhythm 1221 were associated with diurnal variations in fetal activity and variability in FHR [2,3]. The diurnal variation in RP might occur because RP is more sensitive to the diurnal variations of these stimuli. Thus, there seem to be different mechanisms related to RP and NRP. Nijhuis et al. [18], Koyanagi et al. [17] and de Vries et al. [7J studied &relation between fetal eye movement and other fetal behavior and found that RP and NRP in FHR changes correspond to NREM and REM periods, respectively [l]. Studies of fetal eye movement show that NREM and REM periods in the fetus depend on different regulatory mechanisms since, ontogenetically, the NREM period appears later than the REM period (161. In addition the hypothalamus, which is considered to be the center of RP and NREM [15,28] is affected by hormonal transpkcental substances such as sleep substances 1131 because of the absence of the blood brain barrier [24]. Our conclusion supports these postulations. In the period since 1970, deceleration, acceleration and variability in FHR have been considered valuable indicators of fetal well-being and much less attention was directed to diurnal variation. It is our view that assessments of diurnal variations in FHR patterns and RAC will greatly add to estimations of fetal maturity and well-being. References [I] Arduini, D., Rizzo, G., Giorlandino, C., Vizzone, A., Nava, S., Dell’Acqua, S., Valensise, H. and Romanini, C. (1985): The fetal behavioural state: An ultrasonic study. Prenatal Diagn., $269-276. [2] Arduini, D., Rizzo, G., Parlati, E., Giorlandino, C., Valensise, H., Dell’Aqua, S. and Romanini, C. (1986): Modifications of ultradian and circadian rhythms of fetal heart rate after fetal-maternal adrenal gland suppression: a double blind study. Perinatal Diagn., 6, 409-417. [31 Arduini, D., R&o, G., Parlati, E., Dell’Aqua, S., Romanini, C. and Mancuso, S. (1986): Loss of circadian rhythms of fetal behaviour in a totally adrenalectomised pregnant women. Gynecol, Obstet. Invest., 23, 226-229. [4] Borbely, A.A. (1982): A two process model of sleep regulation. Hum. Neurobiol., 1, 19.5-204. [S] Conners, G., Gillis, S., Hunse, C., Gagnon, R. and Richardson, B. (1991): The interaction ofbehavioural state, heart rate and resistanceindex in the human fetus.J. Dev. Physiol., 15, 33 1-336. [6] Dawes, G.S., Houghton, C.R.S., Redman, C.W.G. and Visser, G.H.A. (1982): Pattern of the normal human fetal heart rate. Br. J. Obstet. Gynaecol., 89, 276-284. [7] De Vries, J.I.P., Visser, G.H.A., Mulder, E.J.H. and Prechtl, H.F.R. (1987): Diurnal and other vrriations in fetal movement and heart rate patterns at 20-22 weeks. Early Hum. Dev., 15, 333-348 (81 Gagnon, R., Hunse, C., Carmichael, L., Fellows, F. and Patrick, J. (1987): Human fetal response to vibratory acoustic stimulation from twenty-six weeks to term. Am. J. Obstet. Gynecol., 157. 1357-1381.

58

M. Muro

et al. /Early

Human

Development

44 (1996)

51-58

(91 Gagnon, R., Hunse, C. and Foreman, J. (1989): Human fetal behavioral states after vibratory stimulation. Am. J. Obstet. Gynecol., 161, 1470-1476. [IO] Harker, J.E. (1960): Endocrine and nervous factors in insect circadian rhythms. Cold Spring Harbor Symp. Quant. Biol., 25. 279-287. [I I] Horimoto, N., Koyanagi, T., Nagata, S., Nakahara, H. and Nakano, H. (1989): Concurrence of mouthing movement and rapid eye movement/non-rapid eye movement phases with advance in gestation of the human fetus. Am. J. Obstet. Gynecol., 161, 344-351. 1121 Horimoto, N., Koyanagi, T., Satoh, S., Yoshizato, T. and Nakano, H. (1990): Fetal eye movement assessed with real-time ultrasonography: Are there rapid and slow eye movements? Am. J. Obstet. Gynecol., 163, 1430-1434. [13] Inoue, S. (1989): Biology of Sleep Substances. CRC Press, Boca Raton, FL. [14] Junge, H.D. (1979): Behavioral states and state related heart rate and motor activity patterns in the newborn infant and the fetus antepartum - A comparative study. 1. Technique, illustration of recordings, and general results. J. Perinat. Med., 7, 85-107. [IS] Kawamura, H. (1986): Back to the hypothalamus: a crucial road for sleep research. Behav. Brain Sci., 9, 41 l-413. [16] Koffwarg, H.P., Muzio, T.N. and Dement, W.C. (1966): Ontogenetic development of human sleepdreaming cycle. Science, 152, 604-605. 1171 Koyanagi, T., Horimoto, N., Hirose, K. and Nakano, H. (1987): A multiple and comprehensive study of fetal behavior. In: The fetus as a patient ‘87, pp. 71-82. Editor: K. Maeda. Elsevier, Amsterdam. [18) Nijhuis, J.G., Prechtl, H.F.R., Martin, C.B. Jr. and Brats, R.S.G.M. (1982): Are there behavioural states in the human fetus? Early Hum. Dev., 6, 177-195. 1191 Nijhuis, J.G., Marlin, C.B. Jr. and Prechtl, H.F.R. (1984): Behavioural states of the human fetus. In: Continuity of Neural Functions from Prenatal to Postnatal Life. Editor: H.F.R. Prechtl. Clin. Dew. Med., 94: 65-79. [ZO] Oosterhof, H., Lander, M. and Aarnoudse, J.A. (1993): Bchavioural states and Doppler velocimetry of the renal artery in the near term human fetus. Early Hum. Dev., 33, 183-189. (211 Patrick, J., Natale, R. and Richardson, B. (1978): Patterns of human fetal breathing activity at 34 to 35 weeks gestational age. Am. J. Obstet. Gynecol., 13, 507-513. (22) Patrick, J., Challis, J., Natale, R. and Richardson, B. (1979): Circadian rhythms in maternal plasma cortisol, estrone, estradiol and estriol at 34-35 weeks gestation. Am. J. Obstet. Gynecol., 135, 791-798. [23] Pillai, M. and James, D. (1990): Are the behavioural states of the newborn comparable to those of the fetus? Early Hum. Dev., 22, 39-49. [24] Reppert, S.M., Coleman, R.J., Heath, H.W. and Swedlow, J.R. (1984): Pineal N-acetyltransferase activity in IO-day-old rats: a paradigm for studying the developing circadian system. Endocrinology, 115, 918-925. [25] Shone, H., Muro, M., Kohara, M., Ito, Y., Nagasawa, T. and Sugimori, H. (1994): Fetal heart rate recorder for long-duration use in active full-term pregnant women. Obstet. Gynecol., 83, 301-306. (26) Smith, C.V., Phealan, J.P. and Paul, R.H. (1985): Broussard P. Fetal acoustic stimulation test. Am. J. Obstet. Gynecol., 153, 567-568. 1271 SPSS (1981): Update 7-9, pp. 232-234. Editors: C.H. Hull and N.H. Nie. McGraw-Hill, New York. [28] Terao, T., Kawashima, Y ., Noto, H., Inamoto, Y ., Lin, T.Y ., Sumimoto, K. and Maeda, K. (1984): Neurological control of fetal heart rate in 20 cases in anencephalic fetus. Am. J. Obstet. Gynecol., 149, 201-208. [29] Timor-Trirsch, I.E., Dierker, L.J., Hertz, R.H., Deagan, N.C. and Rosen, M.G. (1978): Studies of antepartum behavioral state in the human fetus at term. Am. J. Obstet. Gynecol., 132, 524-528. [JO] Visser, G.H.A., Goodman, J.D.S., Levine, D.H. and Dawes, G.S. (1981): Micturition and the heart rate period cycle in the human fetus. Br. J. Obstet. Gynaecol., 88, 803-805. 1311 Visser, G.H.A., Goodman, J.D.S., Levine, D.H. and Dawes, G.S. (1982): Diurnal and other cyclic variations in human fetal heart rate near term. Am. J. Obstet. Gynecol., 142, 535-544. I321 Visser, G.H.A., Mulder, E.J.H., Stevens, H. and Verweij, R. (1993): Heart rate variation during fetal behavioural states 1 and 2. Early Hum. Dev., 34, 21-28. I331 Wheeler, T. and Murrills, A. (1978): Patterns of fetal heart rate during normal pregnancy. Br. J. Obstet. Gynaecol., 85, 18-27.