FETUS, PLACENTA, AND NEWBORN
Human fetal breathing movements after carbohydrate ingestion in fasting and nonfasting subjects HAROLD
E. FOX,
CHARLES
W.
MARGARET Rochester
M.D.
HOHLER,
M.D.
STEINBRECHER,
and New
York,
New
York,
B.S. and
Miami,
Florida
Human fetal breathing movements were observed by means of the linear array real-time B-scan technique in 40 study sessions at 35 to 36 weeks’ gestation. Fasting and nonfasting subjects received water or 75 gm of glucose orally. Fetal breathing activity, observed as movement of the chest wall, was analyzed. The data support conclusions that fetal breathing increased after maternal ingestion of glucose in both fasting and nonfasting subjects, that the absolute increases in fetal breathing were similar for fasting and nonfasting subjects, and that fetal breathing occurred more frequently in nonfasting control subjects than in fasting control subjects in the setting of the study. (AM. J. OBSTET. GYNECOL. 144:213, 1982.)
ULTRASOUND was first used by Boddy and Robinson,’ in 1971, to document the presence of fetal breathing movements. Since then, considerable effort has been expended in order to understand the control of fetal breathing movements and their potential significance as an indicator of fetal well-being. The develA-MODE
From the University of Rochester Strong Memorial Hospital and the College of Physicians and Surgeons, Columbia University. Supported in part by March of Dimes-Birth Defects Foundation Clinical Research Grant 6-42, Department of Health, Education and Welfare, United States Public Health Seruice, Bureau of Community Health Services, Maternal and Child Health Services Research Grant MC-R-35037503, and National Institute of Child Health and Human Development Grant No. HD-13063. Received for publication Revised
May
Accepted May
April
20, 1981.
18, 1982. 25, 1982.
Reprint requests: Harold E. Fox, M.D., Defiartment of ObstetricslGynecology, Regional Center for ‘Tertiary ” Perinatal Care. Presbyterian Hospital in the City of New York, College of Phys&ans and surgeons, Columbti University, 630 West 168th St., New York, New York 10032. 0002-9378/821180213+05$00.50/0~
1982
The
C. V. Mosby
Co.
opment of B-mode real-time ultrasound scanning has facilitated the investigation of fetal breathing movements in the human.2 The presence of fetal breathing during the latter half of the third trimester of pregnancy has been associated with fetal well-being and good neonatal outcome. 3--j Factors which control fetal breathing remain poorly understood.6* 7 A relationship has been demonstrated between maternal blood glucose concentration and the percentage of time during which the fetus makes breathing movements. Boddy and associates7 showed that the incidence of fetal breathing movements increases after the intravenous infusion of glucose to the fasting mother. We demonstrated a similar effect with a 75 gm oral glucose 1oad.s Patrick and associates9 demonstrated an increase after maternal ingestion of an 800 calorie meal. Recently, Natale and associateslO showed that, 1 hour after 50 gm of glucose had been consumed by fasting gravid women, there was a significant increase in fetal breathing activity. The amount of time spent breathing, expressed by 15-minute intervals, was observed to peak 1 hour after the maximum maternal blood glucose level. The increased fetal breathing did not return to control levels until after the third hour of observation. 213
214
Fox,
Hohler,
and Steinbrecher
September Am. J. Obstet.
NG NN FG FN
15, 1982 Gynecol.
0 0 A A
, -30
-15
0
15
30
45
60
Time
75
go
105
120
135
I50
165
160
in Minutes
Fig. 1. Plasma glucose and fetal breathing activity before and after drinks for nonfasting (fed) group which received glucose (NC), nonfasting (fed) group which received water (NN), fasting group which received glucose (FG), and fasting group which received water but no glucose (FN). (Mean % SEM). Glucose or water was given at the vertical line (time).
Previous studies have repeatedly documented the effect of a glucose load in fasting subjects. The objective of the current study was to determine the response of fetal breathing to maternal ingestion of glucose in nonfasting subjects. The hypothesis to be tested was that fetal breathing movements increase in nonfasting as well as in fasting subjects after maternal ingestion of glucose. Method A sample of 25 pregnant volunteers was studied. Their average age was 28.8 years (SD 2 3.8 years), and the gestational age was 35 to 36 weeks. Twelve women participated in one study session, 11 women were studied at two sessions, and two women were observed on three separate occasions for a total of 40 sessions. None of the subjects demonstrated abnormal carbohydrate tolerance or was high risk according to the criteria of Goodwin and associates.” The study sample was divided into two groups, one of which fasted overnight and the other ate a standard meal prior to the study (nonfasting). In all subjects, a heparin lock was placed for the sampling of venous blood, after informed consent had been obtained. Real-time B-mode ultrasound scanning (Advanced Diagnostic Research, Inc., Tempe, Arizona) was used
to visualize
including
the chest and abdominal
a longitudinal
image
of the
fetus,
wall. A video system
was used to record the image for analysis.’ Baseline maternal blood glucose levels were obtained, and a period of 40 minutes was allowed for a baseline recording of fetal breathing movements. Twenty subjects were asked to arrive at the laboratory at 9 AM after an overnight fast. Ten subjects received a drink that contained the equivalent of 75 gm of glucose (Glucola). Ten subjects were given a control drink of water that contained no glucose. Videotape recording was continued for an additional 3 to 4 hours. during which time four additional samples of maternal blood were drawn (at 30, 60, 90, and 190 minutes) to document maternal blood glucose levels. A second group of 20 studies was carried out with subjects who were not asked to fast overnight and who had eaten at 8:00 AM. In this instance, at 10 study sessions, the women received the drink that contained 75 gm of glucose. At 10 sessions, the control drink of water was administered. All studies were carried out with patients in a lateral recumbent or semi-Fowler position. The videotapes were evaluated by an experienced observer, and fetal breathing activity was scored for computer analysis as described previously.’ The data were processed by 15minute
intervals
according
to
the
percentage
of
time spent in apnea. (Apnea was defined as intervals of 6 seconds or more without fetal breathing movements.) Apnea time was converted to the percentage of time
Volume Number
Fetal
144 2
I
I 0
I
15
I
I
1
/
I
30
45
60
75
90
Time
after
ingestion
215
/
,
120
carbohydrate
135
150
in Minutes A A a o
Fig.
I
105
breathing
FN FG NN NG
(Fasting No Glucose) (Fasting Glucose) (Non Fasting (Fed) (Non Fasting (Fed)
No Glucose) Glucose)
2. Fetal breathing activity after drink (vertical line) as a percentage of baseline activity by group.
spent in fetal breathing (%FB = 100% - % time apnea) and was compared over time with maternal plasma glucose levels in each group. Results Review of recordings of maternal blood pressure revealed no hypertension or hypotension at or during the study sessions. Neonatal outcome was uniformly good. At the time of delivery, gestational ages ranged from 38 to 42 weeks, and birth weights were observed over the range of 2.68 to 4.15 kg. Apgar scores at 1 minute were 7 or greater, and at 3 minutes, 8 or greater. Fig. 1 depicts the change in plasma glucose concentration in each study group over the study period. The lowest fasting plasma glucose values were in the fasting groups, with higher control period values in the nonfasting groups. The peak plasma glucose concentration was seen from 30 to 60 minutes after ingestion of the glucose-containing solutions. No change was seen in the plasma glucose concentration of the groups given water, until 150 minutes, when the plasma glucose of the nonfasting subjects began to decrease. Fig. 1, b depicts the percentage of time spent in fetal breathing activity per 15-minute interval for each of the study groups. The percentage of time occupied by fetal breathing activity was lowest in the fasting group that was given water. A larger percentage of the time was spent in fetal breathing activity per 15-minute interval in each of the other study groups. The fasting subjects who received glucose showed considerably more fetal breathing activity than the fasting subjects who received water, and approximately the same amount of
breathing activity as the nonfasting group that received water. The nonfasting group that received glucose demonstrated the highest percentage of time spent in fetal breathing activity. Statistical comparison of fetal breathing activity from 45 to 120 minutes of the study session revealed significantly greater breathing activity in both the fasting and nonfasting groups after the administration of glucose than in the fasting group given no glucose (p < 0.01). No significant difference in fetal breathing activity was seen between the groups that received glucose and the nonfasting group that was given water, although a strong trend was appreciated, with more fetal breathing consistently seen in the group that received glucose (p < 0.12). Fig. 2 shows, for each group, the change in fetal breathing activity for each 15-minute interval in the study period compared to the mean baseline percentage of time spent in fetal breathing activity. Both the nonfasting group given glucose and the fasting group given glucose showed an increase by more than 30% of the time in fetal breathing activity. The peak values occurred by 105 minutes in both the nonfasting and fasting groups given glucose and showed a maximum percentage increase of 148% above the mean baseline in the nonfasting group and 159% above mean baseline in the fasting group given glucose. Comment The results indicate that the percentage of time spent in fetal breathing activity increases after ingestion of glucose in both fasting and nonfasting subjects.
216
Fox, Hohler, and Steinbrecher
Because of the large magnitude of variance in the percentage of time spent in fetal breathing activity, one should carefully interpret statistically significant differences between any two points in the study. Our observations do support the recent observations by others of increased fetal breathing after meals or the administration of glucose. $3g As seen in Fig. 1, it is evident in both experimental groups that the maternal plasma glucose levels rose above the preingestion value and higher than any glucose levels measured in the control subjects. The elevation of maternal plasma glucose was associated with a rise in the percentage of time occupied by fetal breathing movements, which reached levels significantly higher than baseline (p < 0.001) at 50 to 70 minutes after the administration of the glucose. Because of the variance in the percentage of time occupied by fetal breathing at each data point, it was not possible to identify precisely the occurrence of a statistically significant peak of fetal breathing activity related to baseline measures. The mean incidence of fetal breathing activity from 45 to 120 minutes after the ingestion of 75 gm of glucose demonstrated the significant differences between the study groups. The fact that there was no statistically significant difference between the fasting group given glucose and the nonfasting group given water may have been due to the fact that these groups experienced ingestion of carbohydrate with a time phase shift, since the nonfasting group had eaten a standard meal 1 to 2 hours before the recording session. Fig. 2 demonstrates that the absolute increases in the percentage of time spent breathing were nearly identical for both the fasting and the nonfasting subjects given glucose. The trend toward an increase in fetal breathing activity for the nonfasting patients given water may have resulted from the effects of the meal consumed approximately 1 hour prior to the initiation of the study. The glucose values in the nonfasting group given water were greater than the values in the fasting group given water and consistent with the consumption of the meal. Both the fasting and the nonfasting groups given glucose showed approximately a 150% sustained increase in the occurrence of fetal breathing activity.
REFERENCES
1. Boddy, K., and Robinson, J. D.: External method of detection of fetal breathing in utero, Lancet 2: 123 1, 197 1. 2. Fox, H. E., and Hohler, C. W.: Fetal evaluation by realtime imaging, Clin. Obstet. Gynecol. 20:339, 1977. 3. Boddy, K.:Zn Beard, RW, and Nathanielsz, P. W., editors: Fetal Physiology and Medicine, London, 1976, W. B. Saunders Co., Ltd., p. 302.
September Am. J. Obstet.
15, 1982 Gynecol.
A number of factors such as hypoxia, nicotine, and drugs have been associated with changes in fetal breathing.‘, s, 6 The physiologic mechanisms involved in the control of fetal breathing movements have not been elucidated. Variables that affect the occurrence of fetal breathing movements must be defined in order to begin to approach the question of physiologic control mechanisms. On the basis of recent studies, including the current study, it is apparent that the maternal ingestion of carbohydrates will affect the amount of time occupied by fetal breathing movements. The current study showed that the fetuses of both fasting and nonfasting groups demonstrated increased fetal breathing activity after maternal consumption of glucose. The percentage of time spent in fetal breathing activity was greatest in the fed subjects. The data indicated that carbohydrate load had an additive effect on the incidence of fetal breathing movements. If the monitoring of fetal breathing activity is to be used as an indication of fetal well-being, it would be desirable to make such observations during a period of time in which fetal breathing movements are likely to be observed and in which long periods of apnea are not normally observed. The data presented here suggest that an oral glucose load given to a nonfasting gravid woman approximately 1 hour prior to a monitoring session will maximize the occurrence of fetal breathing activity. From the data presented, we conclude that our initial hypothesis is correct: Fetal breathing movements increase in nonfasting as well as in fasting subjects after maternal ingestion of glucose. In addition, we concluded that: (1) the absolute increase in the percentages of time occupied by fetal breathing activity were similar in fasting and nonfasting subjects; (2) in the setting of our study, the percentage of time occupied by fetal breathing activity was increased in nonfasting subjects as compared to fasting subjects; and (3) the occurrence of fetal breathing activity was greatest in nonfasting subjects who had received an oral glucose load approximately 1 hour prior to the recording session.
4. Boddy, K.: In Beard, R. W., and Nathaniel=, P. W., editors: Fetal Physiology and Medicine, London, 1976, W. B. Saunders Co., Ltd., p. 302. 5. Platt, L. D., Manning, F. A., Lemay, M., and Sipos, L.: Human fetal breathing: Relationship to fetal condition, AM. J. OBSTET. GYNECOL. 132:514, 1978. 6. Fox, H. E., Inglis, J., and Steinbrecher, M.: Fetal breathing movements in uncomplicated pregnancies. I. Rela-
Volume Number
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tionship to gestational age, AM. J. OBSTET. GYNECOL. 134:544, 1979. 7. Boddy, K., Dawes, G. 8, and Robinson, J. S.: In Gluck, L., editor: Modern Perinatal Medicine, Chicago, 1975, Year Book Medical Publishers, p. 381. 8. Hohler, C. W., Fox, H. E., Jaeger, H., lnglis, J., and Steinbrecher, M.: Realtime B-scan observations: Effect of maternal glucose load on human fetal breathing, in White, D. N., editor: Ultrasound in Medicine, New York, 1977, Plenum, vol. 19, pp. 721-725.
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9. Patrick, J., Natale, R., and Richardson, R.: Patterns of human fetal breathing activity at 34 to 35 weeks’ gestational age, AM. J. OBSTET. GYNECOL. 132:507, 1978. 10. Natale, R., Patrick, J., and Richardson, B.: Effects of human maternal venous plasma glucose concentrations on fetal breathing movements, AM. J. OBSTET. GYNECOL. 132:36, 1978. 11. Goodwin, J. W., Dunne, J. T., and Thomas, B. W.: Antepartum identification of the fetus at risk, Can. Med. Assoc. J. 101:458, 1969.