The effect of maternal consumption of alcohol on human umbilical artery blood flow

R. L. A. Erskine, M.B., and J. W. K. Ritchie, M.D.

Belfast, Northern Ireland

A Doppler ultrasound technique was used to measure the effect on human umbilical artery impedance of a

single moderate dose of alcohol consumed by mothers compared to a control solution in six normal third­trimester pregnancies. No significant difference in impedance was detected between the alcohol and the control solutions during the subsequent 90 minutes. The results suggest that the known toxicity of

maternally ingested alcohol is probably mediated by some mechanism other than a significant acute alteration in fetoplacental blood flow characteristics. (AM J OSSTET GVNECOL 1986;154:318-21.)

Key words: Alcohol, maternal consumption, umbilical artery impedance

Chronic maternal consumption of alcohol is associ­ated with well-documented detrimental effects on the fetus' although the mechanism of action is not clear. Single doses of alcohol also have been shown to have an acute effect on the fetus. McLeod et al." have shown in human studies that a single moderate dose of alcohol (0.25 gm/kg) virtually abolishes fetal breathing move­ments. Mukherjee and Hodgen" in a study of the effects of maternal administration of alcohol on the fetal mon­key used a larger dose (3.0 gm/kg of maternal weight) and noticed incidentally that the umbilical cord lost its turgidity, which suggested that a marked decrease in fetoplacental vascular impedance occurred.

Pulsed Doppler ultrasound provides a noninvasive means of measuring the impedance to flow within deeply situated blood vessels' including the human um­bilical artery.' This technique was used to investigate the acute effect on human umbilical artery impedance of drinking alcohol in the same quantity as that known to abolish fetal breathing movements. 2

Material and methods

Six pregnant women between 34 and 36 weeks of amenorrhea (mean = 35 weeks and 2 days) who gave verbal informed consent made up the study group. Each patient was asked to drink either a solution of alcohol in soda water or soda water alone in a random­ized fashion on each of two successive days. All were

From the Department of Midwifery and Gynaecology, Institute of Clinical Science and the Royal Maternity Hospital.

Supported by a Research Fellowship awarded to R. L. A. E. by the Eastern Health and Social Services Board, Belfast, Northern Ireland.

Presented at the Forty-first Annual Meeting of The Society of Obste­tricians and Gynaecologists of Canada, Jasper, Alberta, Canada,

June 10-15, 1985. Reprint requests: J. W. K. Ritchie, Department of Obstetrical Peri­

natology, Mount Sinai Hospital, 600 University Ave., Toronto, Ontario, Canada M5G lX5.

318

social drinkers who had taken alcohol during this preg­nancy at some time but consumed less than 40 gm of alcohol per week (equivalent to less than four glasses of wine). All six mothers had fetal maturity confirmed ultrasonically at 16 weeks of amenorrhea, and all were subsequently delivered normally of singleton infants of appropriate weight after 38 weeks' gestation.

No alcohol was consumed during the 24 hours pre­ceding the 2-day study period. All mothers had eaten a normal light breakfast and light lunch and had similar meals on each of the two days. The study sessions started at 4 PM each day, after the subjects had fasted from 1 PM.

A solution of ethanol (0.25 gm/kg of maternal weight) in soda water as a 15% solution was used, and the control dose was an equal volume of soda water alone. 2 To standardize maternal ingestion times, the solution was divided into three equal aliquots each to be taken by the patient over successive 5-minute periods. Thus the total time to consume the test solution was 15 minutes. The solutions were prepared and ran­domized by a third party not otherwise involved in the study.

The alcohol solution comprised 0.317 x (rnaternal weight in kilograms) ml of 100% pure dehydrated eth­anol mixed with 1.79 x (maternal weight in kilograms) ml of soda water, whereas the control solution com­prised 2.107 x (maternal weight in kilograms) ml of soda water alone. The pure alcohol had a specific grav­ity of between 0.7904 and 0.7935 with 1 ml being equiv­alent to 0.79 gm of ethyl alcohol. Thus a 70 kg patient would receive 17.5 gm of ethanol or 22.2 ml of pure alcohol solution mixed with 125 ml soda water. This is equivalent to approximately 1.75 standard measures of 40% spirit.

Seven 2 ml aliquots of maternal venous blood for estimations of serum ethanol were taken on each day of the study at the following times: zero time minus 15

Volume 154 Number 2

Maternal consumption of alcohol 319

Fig. 1. Umbilical artery sonograms obtained from a normal fetus of 36 weeks' gestation representing red blood cell velocities (vertical axis) with time.

--cardiac-­cycle

Fig. 2. Measurements required from the maximum frequency outline of umbilical artery sonograms to calculate the pulsa­tility index.

minutes, zero time plus 15,30,45,75, and 105 minutes. The test solution was consumed during the 15 minutes after zero time.

A pulsed Doppler Duplex ultrasonic sector scanning system (Advanced Technology Laboratories, Mark V) with a 3 MHz probe was used. This equipment pre­sents two-dimensional real-time imaging together with pulsed Doppler ultrasound in a quasi-simultaneous for­mat. The Doppler-shifted frequencies resulting from movement occurring within the sample volume (4 mm x 2 mm) are displayed visually against time as time-velocity waveforms or sonograms (Fig. 1); since the shifted frequencies resulting from blood flow are within the audible range, these signals are also passed via an amplifier to an audio output. The sample volume of the Doppler system can be moved to monitor the luminal center of the umbilical artery where maximal blood velocity occurs" by listening to the audio output in a manner akin to tuning a radio receiver. The sonograms obtained are preserved by a line scan re-

50

ETHANOL 40

mg.100ml-1 30

20

10

-15 0 +15 +30 +45 +60 +75 +105

Fig. 3. Mean maternal venous blood alcohol levels (± SE) on the alcohol-dose days (mgllOO ml).

corder. Umbilical artery impedance was estimated by calculation of the pulsatility index, which has been shown previously to be sensitive to changes in vascular resistance. 7 The measurements required (A-B/mean) to calculate the pulsatility index8

.9 are shown in Fig. 2.

The mean value for the pulsatility index of each of 10 consecutive time-velocity waveforms was obtained from the umbilical artery at zero time minus ~5 minutes and at zero time plus 30, 60, and 105 minutes. The sono­graphic printouts from the Doppler equipment were labeled with random numbers and subjected to sec­ondary waveform analysis several days later with use of the digitizing tablet of a minicomputer (Kontron, Cardio 80).

Results

No ethanol was detected in the maternal blood sam­ples taken on any of the days the control dose was given. On the days the alcohol dose was given the mean peak ethanol concentration (± SE) was 36.8 ± 6.8 mgll 00

320 Erskine and Ritchie

1.2

PI _. Ethanol .- - -. Soda

1.0 Normal range

f~~ of PI 0.8 1-- -- for

gestation

0.6

T

-150 +30 +60 +105

t MINUTES

Fig. 4. Mean values (± SE) for umbilical artery pulsatility index (PI) for each scanning session on both the alcohol-dose and control-dose days.

Mean % change

In PI (:!: S.E.)

compared with

control

+20

+10

-10

-20

ETHANOL SODA-WATER

Fig. 5. Mean percentage change (± SE) in umbilical artery pulsatility index (PI) at plus 30, 60, and 105 minutes after zero time when compared to the control value at zero time minus 15 minutes for both study days.

ml and was obtained at zero time plus 30 minutes (Fig. 3).

The mean values of the pulsatility index as calculated from 10 consecutive umbilical artery sonograms at each observation time are listed in Table I and shown graph­ically in Fig. 4. The percentage change in pulsatility index observed at each of the three postingestion ob­servation periods when compared to the control value at zero minus 15 minutes is shown in Fig. 5. There was no significant difference in the mean pulsatility index values at each observation time between the days al­cohol was given and the control days. The percentage change in pulsatility index between the first and last measurement was greater on the days alcohol was given than on the control days, but this did not reach statis­tical significance (p > 0.1; r = -0.15). Also the per­centage change in pulsatility index between the first and last scans on the alcohol days for each subject was compared to that individual's maximum serum alcohol concentration, but no consistant relationship was found (p> 0.1; r = -0.11).

All values for the pulsatility index throughout this

February, 1986 Am J Obstet Gyneco1

Table I. Mean values for umbilical artery pulsatility index obtained at each of the four examination times on each of the two study days (see also Fig. 4)

Time (min)

Alcohol day Zero - 15 Zero + 30 Zero + 60 Zero + 105

Control day Zero - 15 Zero + 30 Zero + 60 Zero + 105

Mean pulsatility index

0.84 0.86 0.87 0.81

0.78 0.82 0.86 0.85

SE

0.05 0.08 0.07 0.05

0.04 0.04 0.04 0.06

study remained within the normal range previously established in this population of normal pregnant women. IO

Comment

The mean peak ethanol concentration (± SE) was 36.8 (± 6.8) mglI 00 ml, which is comparable to that found by McLeod et al.; namely, 33 (±3.7) mgllOO ml. Peak levels in both studies occurred at zero time plus 30 minutes. Although this maternal alcohol con­centration is known to affect the fetus directly by abol­ishing fetal breathing movements, it did not signifi­cantly alter umbilical artery impedance as measured by the pulsatility index.

Brien et al." in a study of amniotic fluid levels of alcohol after maternal consumption (0.3 gm/kg of ma­ternal weight) in patients undergoing second-trimester terminations of pregnancy showed that the peak am­niotic fluid level of alcohol lagged behind peak mater­nal venous levels by some 90 minutes; although no alcohol was detectable in maternal venous blood after 3.5 hours, significant levels were still present in the amniotic fluid at this time. It is therefore possible that two to 3 hours after maternal ingestion of a dose of alcohol the fetus is still being affected by the drug, since the fetus continually swallows amniotic fluid. This hy­pothesis is somewhat supported by the fact that pla­cental resistance as measured by the mean pulsatility index tended to decrease between time zero and time zero plus 105 minutes after alcohol ingestion (Fig. 5), whereas it increased on the control days although this difference was not statistically significant. Nevertheless no acute effects were observed at a time when fetal alcohol levels might be expected to be maximal, and all pulsatility index values remained within the previously established normal range. 10

It is concluded from this study that a moderate dose of alcohol ingested by a mother during the normal third trimester does not significantly alter impedance to flow

Volume 154 Number 2

within the umbilical artery as measured by the Doppler technique. The known toxicity of drinking alcohol therefore may well be mediated by some other mech­anism and not by acute changes in fetoplacental blood flow characteristics.

REFERENCES

1. Jones KL, Smith DW. The fetal alcohol syndrome. Te­trology 1975;12:1-5.

2. McLeod W, BrienJ, Loomis C, Carmichael L, Probert C, Patrick J. Effect of maternal ethanol ingestion on fetal breathing movements, gross body movements, and heart rate at 37 to 40 weeks' gestational age. AM J OBSTET Gy­NECOL 1983;145:251-7.

3. Mukherjee AB, Hodgen GD. Maternal ethanol exposure induces transient impairment of umbilical circulation and fetal hypoxia in monkeys. Science 1982;218:700-2.

4. Woodcock JP, Skidmore R. Principles and applications of Doppler ultrasound. In: Wells PNT, Ziskin MC, eds. New

Maternal consumption of alcohol

techniques and instrumentation in ultrasonography. New York: Churchill Livingstone, 1980.

5. Griffin D, Cohen-Overbeek T, Campbell S. Fetal and uteroplacental blood flow. Clin Obstet Gynaecol 1983; 10:565-602.

6. McDonald DA. Blood flow in arteries. 2nd ed. London: Edward Arnold, 1974.

7. Atkinson P, WoodcockJP. Doppler ultrasound and its use in clinical measurement. London: Academic Press, 1982.

8. Gosling RG, King DH. Ultrasonic angiography. In: Has­cus AW, Adamson L, eds. Arteries and veins. Edinburgh: Churchill Livingstone, 1975:61-98.

9. Gosling RG, King DH. Processing arterial Doppler signals for clinical data. In: de Vlieger M, et aI., eds. Handbook of clinical ultrasound. New York: John Wiley & Sons, 1978:613-46.

10. Erskine RLA, Ritchie JWK. Umbilical artery blood flow characteristics in normal and growth-retarded fetuses. Br J Obstet Gynaecol 1985;92:605-10.

11. Brien JF, Loomis CW, Tranmer J, McGrath M. Disposi­tion of ethanol in human maternal venous blood and am­niotic fluid. AM J OBSTET GYNECOL 1983; 146: 181-6.

The effect of electrical stimulation on behavioral states in the fetal lamb

Renato Natale, M.D., and Constance Nasello-Paterson, B.Sc.

London, Ontario, Caruula

Brachial nerve stimulation at two frequencies (0.01 and 0.05 pulse per second, pps) with the fetus in either

low-voltage electrocortical activity with eye movements or high-voltage electrocortical activity without eye movements was studied in five chronically catheterized fetal lambs at 130 to 140 days' gestation. During low-voltage electrocortical activity with eye movements, there were slight alterations in electrocortical state

and electromyographic activity at 0.01 pps. At 0.05 pps these electromyographic changes were enhanced above those expected as a result of state changes but returned to control values during the recovery period. During high-voltage electrocortical activity without eye movements, the state changes were much more dramatic, while electromyographic activity increased significantly only at 0.05 pps. It was of note that in both high- and low-voltage electrocortical activity the fetal heart rate changed only during the recovery period at 0.05 pps. It is concluded that fetal behavioral state influences the interpretation of biophysical measurements in the fetus and that the effect of stimulation is more pronounced if applied when the fetus is in high-voltage electrocortical activity without eye movements. (AM J OBSTET GVNECOL 1986;154:321-8.)

Key words: Stimulation, behavioral states, electrocortical activity

In clinical obstetrics, behavioral states in the fetus, as defined by fetal heart rate and its variations, I. 2 fetal breathing, and gross fetal body movements," 4 provide

From the Department of Obstetrics and Gynecology, University of Western Ontario.

Funded by a grant from the Medical Research Council of Canada and in part by the Physicians' Services Incorporated Foundation.

the physiologic basis of the nonstress test as an impor­tant evaluator of fetal health in the antenatal period.5

However, since periods of rest are separated by periods of activity under normal conditions, various investi­gators have undertaken to stimulate the fetus during periods of flat fetal heart rate tracings in an attempt to identify the sick fetus.6-9

Presented at the Forty-first Annual Meeting of The Society of Obste­tricians and Gynaecologists of Canada, jasper, Alberta, Canada, june 10-15, 1985.

Reprint requests: Dr. Renato Natale, Department of Obstetrics and Gynecology, University of Western Ontario, St. joseph's Hospital, 268 Grosvenor St., London, Ontario, Canada N6A 4V2.

Few attempts, however, have been made to try to clarify the physiologic characteristics underlying such stimulation maneuvers. IO

.12

The purpose of the present set of experiments was to test the hypothesis that clinically measurable param-

321