Maternal ethanol ingestion and the occurrence of human fetal breathing movements HAROLD













EDWARD Rochester,




The study of the development of fetal breathing movaments in human gestation may provide an increased understanding of maturation of the functional central nervous system (CM). tn seven term pregnancies low maternat blood alcohol levela suppressed fatal bre#Mng movements. No effects on fetal oxygenation OTacikbase at&us were demons&a&ad at the low bl&d aleoholhel. The suppression is therefore most corMtent with a brekt &e&of akohot on the fetal @S. This inveatiition provides further support of the the$s that fe@ moveme&reflectaeme components of fetal CNS activity. (Au. J. 06s~~~. CS~NECOL. 132:‘3!X, 1978.)

FETAL BREATHING movements have been well documented in normal gestation.’ The relationship of these movements to central nervous system (CNS) activity, especially rapid-eye-movement (REM) sleep-like states in fetal lambs and monkeys, also has been 3 It has been postulated that fetal documented?’ breathing movements may provide an indication of midbrain function throughout gestation.2 The study of patterns of fetal breathing movements may therefore provide a basis for understanding developing fetal behavior. Many ultrasound techniques, including A scan, Doppler, and real-time B scan, have been applied to

From the Departments of Obstetria and Gynecology, Electrical Engineering, and Biatkatistics, The University of Rochester Medical Center. Su@orted by Grant MC-R-360375-OZ-Ofrom the Maternal and Child Health Services, Department of Health, Educatims, and Wefare, Public He&h Sovice, and Grant 6-42 from the National Foundation March of Dimes. Presented at the Twentyjfth Annual Society for Gynecoiqic Investigation, March 15-18, 197%.

Meeting Atlanta,

of the Georgia,

Repint requests: Dr. Harold E. Fox, Department of Obstetrics and Gynecology, The Univmsib of Rochester Medical Center, Rochester, New York 14642.


the noninvasive study of human fetal breathing movements4a 3 Adequate documentation indicates that, under specific conditions, these techniques provide a reliable indication of fetal breathing activity.’ Fetal breathing movements are inhibited by maternal cigarette smoking.’ This decrease is related E~Qfetal hypoxia secondary to nicotine effects on uterine perfusion.* Fetal breathing movementsare also inhibited by the administration of Demerol to the mother.* Although this effect may be attributed to a dire&effect of Demerol on function of the fetal CNS, rectint animalstudies have indicated that administration~of Demerol to the fetus does not alter the occurrence of fetal breathing. *O The effect may be mediated by hypoxia since maternal hypoventilation and hypoxia have been demonstrated after the administration of Demerol.ll In human gestation, studies to date have not .focused on altered fetal breathing in response to an induced change in CNS activity. The depressant effects of alcohol on the CNS are well documented.**~ I3 Orally ingested alcohol quickly diffuses across the placenta and therefore, may exert adirect effect on the fetal CNS.‘B The study. reported herein served to test the hypothesis that oral alcohol consumption by pregnant women will decrease the occurrence of fetal breathing movements. 0002-9378/78/200354+05$00.50/0~

1978 The C. V. Mosbv CO.

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132 4

Maternal ethanol ingestion and fetal breathing movements

Method Seven gravid women at 37 to 39 weeks’ gestation were studied. Ages ranged from 25 to 33 years and parity ranged from 0 to 2. No patientswere at high risk as judged by standard screening criteria. All gravid women stated that they were socialdrinkers, consuming one to three cocktails per week. Participants were admitted to the study under a protocol approved by the Human Investigation Committee. Neonatal outcome was uniformly good. Sex distribution was five male and two female neonates. The mean birth weight was 3,640 & 507 (standard deviation) grams. No fetal distresswas noted. One-minute Apgar scoresranged from 5 to 9 and five-minute scores ranged from 8 to 9. Studieswere performed two hours after breakfast or lunch, with patients in a lateral recumbent position. A 30 minute baseline recording was obtained using a real-time B-scan ultrasound system.* A longitudinal thoracoabdominal orientation to the fetus was maintained. The recording technique is described elsewhere.‘” After the 30 minute baselinerecording period, the participant wasgiven 1 ounce of vodka (80 proof) in 90 ml. of diet ginger ale. Controh received 120ml. of diet ginger ale. Fetal breathing movements were then monitored continuously for an additional 60 minutes. Blood alcohol and glucose levels were measured prior to the consumption of alcohol and at 20 and 60 minutesafter consumption. A pilot seriesof frequent measurements of blood alcohol levels indicated a peak at 20 minutes and no change in blood glucoselevel throughout the test period. Videotape records were madeof the real-time B-scan images.All videotapes were reviewed subsequentlyby an experienced observer who documented fetal breathing movementson a polygraph record and on a digital magnetic tape system for analysis. Other fetal and transducer movements(producing unreadable artifact) also were documented. This technique has been described fully elsewhere.6 R0SUltS

Fig. 1 showsthe proportion of time spent in fetal breathing activity in one subject from 30 minutes before to 60 minutes after the consumption of alcohol. In all subjects,fetal breathing activity ceasedafter the ingestion of alcohol. Table I indicatesfor each subjectthe *ADR Model tem, Advanced

2130 3.5 MHz Linear Diagnostic Research,

Transducer Inc., Tempe,

Array SysArizona.















5 MINUTEINTERVALS Fig. 1. Occurrence patient. arrow.


of fetal breathing (FB) movements of alcohol administration is indicated

in one by the

1. Time from start of alcohol consumption to beginning of fetal apnea and length of apnea period for seven patients Table


Tim from start of &ohd consumption to beginning of apnea (min.)


14.8 10.1 19.6 2.9

24.3 >27.0 40.6 50.4

31.9 12.4 14.2

B32.7 >41.4 x93.5

length of time from the consumption of alcohol to the beginning of the fetal apnea period, and the actual or minimum length of time in apnea. No change in uterine activity wasnoted after alcohol consumption. Fig. 2 is the composite of fetal breathing for the seven subjects (mean per cent of time breathing + standard error of the mean [S.E.M.]) as well as the blood alcohol level achieved (mean milligrams per 100 ml. + S.E.M.). There was no significant change in blood glucose level throughout the study period. It should be noted that as the blood alcohol level decreased, the percentage of time spent breathing in-



Fox et al.

4. Composite of percentage of fetal breathing and maternal blood alcohol levels (tS.E.M.) seven subjects. Time of alcohol administration is indicated by the arrow. Fig.

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creased. No changes were seen in the control group (Fig. 3). Patterns of fetal breathing movements were- examined. In all cases, each fetus had periods of apparently regular breathing prior to the consumption of alcohol, and regular breathing resumed in all cases where recording was continued for a sufficient time. Breathing rate, as an indicator of pattern change, was sampled for two one-minute intervals prior to the ingestion of alcohol. The sampled rates ranged from-42 to 60 breaths per minute. In the contro1 patients, the rates ranged from 39 to 55 breaths per one-minute interval. The breathing rate was sampled twice after the ingestion of alcohol and when possible after the resumption of breathing. There was no clear change in breathing rate at any of these sample points. Fig. 4 shows the occurrence of other fetal movements (OFM) during the recording session. There was no apparent pattern change in these movements in association with alcohol consumption.


s ti

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Am. J. Obstet. Gynecrtt.








TIF~E (MINUTES) Fig. 3. Composite of percentage (2S.E.M.) of fetal breathing (FB) in five control patients. Diet ginger ale was administered at time 0.

The rapid movement of alcohol across then placenta has been well documented for near-term gestations.r8 Because alcohol reaches the fetus rapidly and eventually reaches the same concentration as in meternal blood,‘r an effect on the fetus even at low lebds of consumption is not surprising.

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Maternal ethanol ingestion and fetal breathing movements

132 4


Fig. 4. Composite of percentage of other fetal movement and maternal blood alcohol levels (+S.E.M.) for seven subjects. Time of alcohol administration is indicated by the arrow.

As a result of the widespread use of alcohol infusions in attempts to control premature labor, a number of studies have been carried out to define the effects of alcohol on the metabolic environment of the fetus. In a series of studies, P. V. Dilt@ Is* rg examined the effect of alcohol infusions to the pregnant ewe on fetal lamb pH and blood gases. He found that for blood alcohol concentrations ranging from 42 to 201 mg. per 100 ml. of ethanol in non-barbiturate-treated lambs, no fetal acidosis or hypoxia could be detected. Subsequent studies by Horiguchi and associatesZo and Mann and colleagues2’ demonstrated that after prolonged alcohol infusions in monkeys and sheep a significant acidosis could occur. The alcohol level achieved in the current experiments after an oral load of 1 ounce of 80 proof vodka was considerably less than any alcohol level associated with fetal blood gas changes in animal models. The depressant effect of alcohol on the CNS is well documented, Mann and co-workers2’ demonstrated that the fetal electrocorticogram shows a decrease in amplitude and a slowing of the dominant rhythm as blood alcohol concentrations increase. In both adult REFERENCES 1. Dawes, G. S., Fox, H. E., LeDuc, B. M., Liggins, G. C., and Richards, R. T.: Respiratory movements and rapid eye movement sleep in the fetal lamb, J. Physiol. 220: 119, 1972.

human and animal models, there is a shift toward lower-frequency components of the electroencephalogram. r2, r3, 21 In fetal lambs and monkeys, breathing movements occur during periods of activity similar to REM sleep. Low doses of alcohol have been shown to disrupt REM sleep activity.z2

Summary In this series of experiments a decrease in the occurrence of fetal breathing movements has been associated with low levels of maternal blood alcohol. Within 31 minutes of maternal consumption of 1 ounce of 40 per cent alcohol, fetal breathing movements were suppressed. The blood alcohol level was very low, well below any level associated with fetal acidosis or hypoxia. No changes in blood glucose levels were seen. The decreased breathing probably was caused by a direct pharmacologic effect on the fetal CNS. From the data recorded the hypothesis that maternal alcohol consumption suppresses fetal breathing activity is accepted. This observation provides further evidence of the relationship between fetal CNS activity and fetal breathing.

2. Fox, H. E.: Fetal breathing movements and ultrasound, Am. J. Dis. Child. 130: 127, 1976. 3. Martin, C. B., Murata, Y., Petrie, R. H., et al.: Respiratory movements in fetal rhesus monkeys, AM. J. OBSTET. GYNECOL. 119: 939, 1974.


Fox et al.

4. Boddy, K., and Robinson, J. S.: External method for detection of fetal breathing in utero, Lancet 2: 1231, 1971. 5 Hohler, C. W.; and Fox, H. E.: Real-time grey scale B-scan ultrasound recording of human fetal breathing movements in utero, in White, D., editor: Ultrasound in Medicine, New York, 1976, Plenum Publishing Company. 6. Fox. H. E., and Hohler, C. W.: Fetal evaluation by realtime imaging, Clin. Obstet. Gynecol. 20: 339, 1977. 7. Manning, F., Wyn Pugh, E., and Boddy, K.: Effect of cigarette smoking on fetal breathing movements in nor&l pregnancies,Br. Med. J. 1: 55% 1975. 8. Manning, F. A., and Feyerbead, C.: Cigarette smoking and fetal breathing movements, Br. J. Gbstet. Gynecoc 83: 262, 1976. Y. Gennser, G., Marsal, K., and Linstrom, K.: The influence of external factors on breathing movements in the human fetus, in Rooth, G., and Bratteby, L. E., editors: Perinatal Medicine, Sweden, 1976, Almquist and Wiksell, pp. 181186. 10. Boddy, K., Dawes, G. S., Fisher, R., Pinter, S., and Robinson, J. S.: The effects of pentobarbitone and pethidine on fetal breathing movements in sheep, Br. J. Pharmacol. 57: 311, 1976. 11. Huch, A., Huch, R., Lindmark, G., and Rooth, G.: Maternal hypoxaemia after pethidine, Br. J. Obstet. Cynaecol. 81: 608, 1974. 12. O’Hara, K., and Homma, H.: Ethanol and central nervous system, Int. J. Neural. 9: 168, 1974. H.: Direct effects of ethanol on the central ner13. Holant, vous system. Fed. Proc. 34: 1930, 1975.

14. Waltman, R., and Iniquez, E. S.: Placental transfer01 ethanol and its elimination at term, Obstet. Gynecrrl. 40: 180, 1972. 15. Fox, H. E., and Hohler, C. W.: Fetal breathing and ultrasound, in Sanders, R. C., and James. A. E.: 1.‘1trasonography in obstetrics and gynecology. New York, 1977, Appleton-Century-Crofts, Inc. 16. Dilts, P. V., Jr.: Placental transfer of ethanol. A&%. J. OBSTET. GYNECOL. 107: 1185, 1970. 17. Idknplan-Heikkil;i, J. E., Fritchie, G. E., Ho, B. T., et al.: Placental transfer of C”-ethanol, AM. J. OBSTET. GYNECOL. 110: 426, 1971. 18. Dilts, P. V., Jr.: Effect of ethanol on maternal and fetal acid-base balance, AX J, OB~T~TET. GYNECOI.. 10% 1018, 1970. 19. Dilts, P. V., lr.: Effect of ethanol on uterine and u’mbilical hemodyna&cs and oxygen transfer, AM. J. OBSTEI.. GYNECOL. 10% 221. 1970. T., Suzuki, K., Comas-Urrutia, A. C.. et al.: 20. Horiguchi, Effect of ethanol upon uterine activity and fetal acid-base state of the rhesus monkey, AM. J. OBSTET. GYNECOL. 109: 910, 1971. A., Liu, IM., et al.: Effect 21. Mann, L. I., Bhakthavathsalan, of alcohol on fetal cerebral function and metabolism, AM. J. OBSTET. GYNECOL. 122: 845, 1975. on offspring including 22. Rosett, H. L.: Effects of alcohol the fetal alcohol syndrome, in:Report to Congress: Alcohol and Health, 1977.

Maternal ethanol ingestion and the occurrence of human fetal breathing movements.

Maternal ethanol ingestion and the occurrence of human fetal breathing movements HAROLD E. FOX, MARGARET M.D. STEINBRECHER DAVID PESSEL, PH.D...
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