Antepartum fetal heart rate variability and intervillous placental blood flow in association with smoking Ilkka Rauramo. M.D •• Matti Forss. Ph.D., Veikko Kariniemi. M.D .• and Pentti Lehtovirta. M.D. Helsinki, Finland lntervHious placental blood flow and indices of fetal heart rate variability were measured from seven healthy pregnant women in the last trimester of pregnancy, once before and twice after smoking one cigarette. A blood flow reduction was observed in seven, a rise in five, and no change in two measurements. When intervillous placental blood flow decreased both indices of variability decreased (p < 0.001), and when it increased the short-term component of fetal heart rate variability increased more significantly (p < 0.001) than did the long-term component (p < 0.01). (AM. J. OssTET. GYNECOL.
146:967, 1983.)
High fetal heart rate variability is generally considered to indicate intact nervous integrity of the human fetus. On the other hand, reduced variability in fetal heart rate is regarded as a sign of fetal hypoxemia or as an effect of drugs on the fetus. Reduced short-term component of antepartum fetal heart rate variability has been shown to predict intrapartum fetal distress in suspected intrauterine growth retardation, 1 cholestasis of pregnancy, 2 and diabetes mellitus. 3 Smoking a cigarette4 and chewing nicotine-containing gum 5 have been claimed to reduce differential index and the interval index, which describes the long-term component of fetal heart rate variability. 6 Intervillous placental blood flow has been shown to decrease in a variety of conditions: uterine contractions/ maternal physical exercise,8 diabetes mellitus, cholestasis of pregnancy, 9 and smoking. 10 Since reduced indices of antepartal fetal heart rate variability and intervillous placental blood flow seem to have some common background, the present study was undertaken to determine the possible correlation, if any, between these two parameters in association with smoking.
Patients and methods Seven healthy pregnant women gave informed consent to the study. Three of them were primiparous, and four had their second pregnancy. Six were nonsmokers, and one smoked one cigarette daily. The mean age was 27.3 years (range, 23 to 32 years), and the gestational age at the moment of the test was 3 7 or From Departments I and II of Obstetrics and Gynecology, Helsinki University Central Hospital. Supported by Avchoidon tutkimussi:Uitio, Helsinki, Finland. Received for frublication November 22, 1982. Revised February 11, 1983. Accepted March 14, 1983. Reprint requests: IlkM Rauramc, M.D., Department II of Obstetrics and Gynecology, Haartmaninkatu 2, 00290 Helsinki29, Finland.
38 weeks. The mothers were lying in fifteen degrees left lateral recumbent position during the experiment. The placenta was localized by ultrasonography. Only mothers with placentas on the anterior wall of the uterus were accepted for the study. The intervillous blood flow was measured by an intravenous Xe 1a3 method. 11 A fetal abdominal electrocardiogram was obtained with a Hewlett-Packard cardiotocograph (HP 8030A). Fetal heart rate variability analyses were performed by an on-line method described earlier. 12 A fetal abdominal electrocardiogram was used as the triggering signal. Sample time of fetal heart rate analyses was I minute. Three subsequent measurements of intervillous placental blood flow, each lasting for 10 minutes, were performed on all of the mothers. They smoked one standard cigarette comaining l mg nicotine between the first and second intervillous placental blood flow measurements to induce reduction. The test material was divided into three groups according to the change in intervillous placental blood flow: (l) blood flow increased lO% or more, (2) blood flow decreased I 0% or more, (3) blood flow change less than I Ot;!f. The indices of fetal heart rate variability in these three groups were compared by means of unpaired Student's t test.
Results In seven measurements we observed a blood flow reduction equal to or more than 10% (range, I 0% to 28%). In six cases it was induced by smoking. Intervillous placental blood flow decreased from 93 ± 11 (SD) to 74 ± 10 ml/min/100 ml intervillous blood volume. The mean differential indices decreased from 5.9 ± 2. 7 to 4.3 ± 2.0 and correspondingly the mean interval indices from 4.0 ± 2.9 to 2.2 ± 1.3 (Fig. l). In five measurements we observed an intervillous blood flow rise equal to or more than 10% (range, lO% to 71 %). In these cases intervillous placental blood flow increased
967
968
Rauramo et al.
August l 5, 1983
Am.]. Obstet. Gyneco\.
IBF
IBF
DI/I I
(ml/min/lOOmD
120
12
120
10
100
80
8
80
60
6
60
40
4
40
20
2
20
IBF
100
II
Cml lm in/ 1OOmD
DIII I 12
IBF
I DI
10
j 1
8 6 4 2
II
Fig. 1. Reduction of intervillous blood flow by I 0% or more. Changes in intervillous blood flow (IBF), differential index (DI), and interval index (II) (means ± SD). Significance of differences of means: **p < 0.00 I.
Fig. 2. Rise of intervillous placental blood flow (IBF) by IO% or more. Changes in IBF, differential index(D/), and interval index (I/) (means± SD). Significance of differences of means: *p
Table I. Individual intervillous placental blood flows (IBF) and differential and interval indices when IBF decreased 2::10%
~~.e I I IBF
Different:io.l index
78 65 105 77 89 66 IOO 82 104 93
10.1 2.6 4.3 5.I -* 3.0 2.2 2.I 10.5 5.4
6
80
4.3 3.9 4.1 6.1 5.9 4.8 2.3 1.9 I0.5 3.9
7
70 93 67
3.6 3.9 3.6
4.7 5.4
2 3 4 5
5.8 4.4 4.7 7.I 4.6 2.5 2.I 8.2 5.4 4.0 5.4 2.0
6.5 4.3 2.6 6.4 9.2 5.8 3.8 4.5 ll.8 3.9
6.4 3.7 3.6 5.4 7.3 4.7 2.3 0.7 9.3 5.5 5.0 3.4 3.9 5.5 I0.8
4.9 3.1 6.2 8.4 5.2 4.0 4.4 3.0 7.9 4.2 2.7 4.2 I2.1
Interval index
11.2 3.I 5.2 6.5 3.8 5.3 2.3 2.9 6.6 4.2 7.6 3.0 4.2
10.7 7.7 3.4 3.6 4.I 2.8 4.3 2.4 6.5 7.2 4.4 3.0 2.0 3.8 2.8 2.I I2.6 7.2 5.1 3.6
9.I 4.1 6.8 1.6 8.I 5.8 2.9 2.8
1.9 1.8 3.2 1.9 1.2 3.5 2.0 0.8 4.1 5.3 5.9 5.0 6.5 5.3 4.9 6.7 5.3 5.9 2.6
8.0 9.4 1.1 0.9 3.6 3.6 1.3 1.7 5.2 4.7 1.2 1.1 0.8 1.5 3.5 7.8 2.6 1.4 2.8. 2.I 2.6 1.4 2.8
9.1 0.6 1.6 1.7 7.4 4.4 1.2 2.0 Il.7 2.8
8.6 Il.6 1.7 0.7 3.0 4.I 1.3 1.6 9.9 7.I 1.9 2.2 1.5 1.9 1.2 2.1 3.8 7.2 2.9 3.2 1.3 1.6 1.3 2.8 2.9 3.2 1.5 2.7
2.5 0.7 4.0 2.2 3.8 1.8 0.9 1.8 8.0 2.8 1.9 0.7 2.8
5.5 3.1 1.1 1.2 2.1 1.7 3.1 2.3 2.4 3.9 1.9 5.6 1.1
1.5 3.3 1.4 1.4
15.2 0.8 3.3 1.3 6.7 4.3 1.8 1.5 0.9 1.9 Il.6 2.1 1.3 1.4 1.9 1.3 2.1
*Failure of fetal heart rate analysis. from 79 ± 23 to 98 ± 23 ml. The mean differential indices increased from 4.3 ± 2.0 to 5.9 ± 2.7, and correspondingly the mean interval indices from 2.2 ± 1.5 to 3.2 ± 1.9 (Fig. 2). No correlation was observed between the absolute values of intervillous placental blood flow and the means of fetal heart rate variability indices. The individual intervillous placental blood flows, differential indices, and interval indices are shown in Table I if intervillous placental blood flow decreased > 10% and in Table II if intervillous placental blood flow increased > 10%.
Comment The main finding of the present study was that differential index and interval index correlated significantly with both decreasing and increasing intervillous placental blood flow. Earlier studies have revealed that tobacco smoking decreases intervillous placental blood flow 10 and both differential index and interval index in late pregnancy. 4 Thus it is obvious that whatever the basal indices are they react similarly to tobacco smoking. In the group in which intervillous placental blood flow increased, both blood flow measurements
FHR variability and placental blood flow with smoking 969
Volume 146 Number 8
Table II. Individual intervillous placental blood flows (IBF) and differential and interval indices when IBF increased ~10%
~~~I 2 3 4 5
IBF 65 Ill 77 85 ll9 131 66 74 70 88
I
3.9 4.4 6.1 3.1 1.9 3.8 4.8 2.8 3.6
Interval index
Differential index 2.6 3.8 5.1 6.5 3.0 4.8 3.0 5.6 4.7
4.4 4.5 7.1 3.7 2.8 6.6 4.6 5.1 4.0
4.3 4.8 6.4 3.7 3.2 3.8 5.8 3.5
3.7 4.3 5.4 8.1 3.7 4.8 4.7 2.3 3.4 5.7
3.1 6.9 8.1 7.6 4.3 4.7 4.0 1.9 2.7 7.9
3.1 7.0 6.5 8.0 3.1 4.4 5.3 5.4 3.0
3.4 6.0 4.3 3.8 4.2 4.2 4.4 7.5 3.6
3.6 4.3 2.4 6.3 2.4 4.7 3.0 7.7 5.3
4.1 5.1 1.6 7.5 4.1
-*
5.8 6.1 4.9 12.4
1.8 l.l 1.9 2.5 5.7 3.0 3.5 5.4 6.7
1.1 1.1 1.3 3.1 2.2 2.0 5.2 8.2 2.8
0.9 1.7 1.7 6.9 2.1 2.8 4.7 2.9 2.1
0.6 2.1 1.7 1.4 2.5 1.8 4.4 3.6
1.7 2.7 1.3 5.8 4.5 2.0 1.9 3.4 1.6 1.4
0.7 1.9 1.6 2.5 2.9 2.4 2.2 1.2 1.3
2.1
0.7 2.1 2.2 2.7 l.9 4.2 1.8 6.9 0.7
l.l 6.1 3.1 5.3 1.4 3.6 1.9 2.3 1.4
1.2 8.0 2.3 3.1 0.8 2.3 5.6 2.8 1.9
0.8 9.3 1.3 3.6 1.0 4.3 1.9 1.3 2.1
*Failure of fetal heart rate analysis.
were made after smoking. In this situation differential index seems to follow intervillous placental blood flow more closely than does interval index. Placental blood flow has been found to be lowered in hypertensive and preeclamptic pregnancies with different isotope methods. Browne and VealP 3 found a 60% decrease with a 24 Na method. Significant reductions have also been found with 113ln 14 and 133Xe methods.9· 15 In diabetic pregnancies,.20% to 45% decreases of intervillous placental blood flow have been detected depending on the severity of diabetes. 9 • 16 Cholestasis of pregnancy and suspected intrauterine growth retardation are also associated with lowered intervillous placental blood flow. 9 In these groups of pregnancy complications, fetal distress and asphyxia are more common than they are in uncomplicated pregnancies. On the other hand low antepartal differential indices have been shown to predict intrapartal fetal distress in the same risk groups. !-3. 17 Thus, this study gives some support to our hypothesis that the decrease of differential index is due to fetal hypoxia, possibly mediated by intervillous placental blood flow decrease, and that the decrease of interval index is due to a direct narcotic effect. 1 We did not lind any correlation between the absolute values of intervillous placental blood flow and the indices of fetal heart rate variability. The lack of this correlation may be due to various factors: The total intervillous placental blood flow may fluctuate and have individual and local variations. However, the consistent changes of intervillous placental blood flow and indices of variability in the present study suggest that the 133 Xe method can be used in successive measurements of the same individual.
3.
4. 5. 6. 7. 8.
9.
10. II.
12. 13. 14.
15.
16.
REFERENCES I. Kariniemi, V., and Ammiilii, P.: Short-term variability of fetal heart rate during pregnancies with normal and insufficient placental function, AM. J. OBSTET. GYNECOL. 139:33, 1981. 2. Ammlilii, P., and Kariniemi, V.: Short-term variability of
17.
fetal heart rate in cholestasis of pregnancy, AM. J. 0BSTET. GYNECOL. 141:217, 1981. A.mmala, P., and Kariniemi, V.: Short-term variability of fetal heart rate variability in insulin-dependent diabetic pregnancies, J. Perinatal. Med. 11:97, 1983. Lehtovirta, P., Forss, M., Kariniemi, V., and Rauramo, I.: The acute effects of smoking on fetal heart rate variability, Br. J. Obstet. Gynaecol. 90:3, 1983. Lehtovirta, P., Forss, M., Kariniemi, V., and Rauramo, 1.: The acute effects of nicotine on foetal heart rate variability, Br. J. Obstet. Gynaecol. In press. Yeh, S.-Y., Forsythe, A., and Hon, E. H.: Quantification of fetal heart beat-to-beat interval differences, Obstet. Gynecol. 41:355, 1973. Brotanek, V ., Hendricks, C. H., and Yoshida, T.: Changes in uterine blood flow during uterine contractions, AM. J. 0BSTET. GYN};COL. 103:1108, 1969. Morris, N., Osborn, S. B., Wright, H. P., and Hart, A.: Effective uterine bi