Disposition of ethanol in maternal blood, fetal blood, and amniotic fluid of third-trimester pregnant ewes

doi:10.1016/0002-9378(85)90632-5

American Journal of Obstetrics and Gynecology

Volume 152, Issue 5, 1 July 1985, Pages 583-590

https://doi.org/10.1016/0002-9378(85)90632-5 Get rights and content

Abstract

The disposition of ethanol in maternal arterial blood, fetal arterial blood, and amniotic fluid of nine conscious, cannulated pregnant ewes (128 to 137 days' gestation) was determined for 1-hour maternal intravenous infusion of ethanol, 1 gm/kg maternal body weight. The maternal arterial blood and fetal arterial blood ethanol concentration-time curves were virtually superimposable up to 14 hours. The apparent zero-order ethanol elimination rates for maternal arterial blood and fetal arterial blood were similar. There was a time lag in the transfer of ethanol into amniotic fluid relative to fetal arterial blood, and the peak ethanol concentration in amniotic fluid was significantly lower than the concentrations in maternal arterial blood and fetal arterial blood. The apparent zero-order ethanol elimination rate for amniotic fluid was slower, but not significantly so, compared with the ethanol elimination rates for maternal arterial blood and fetal arterial blood. Ethanol-derived acetaldehyde was found in maternal arterial blood, fetal arterial blood, and amniotic fluid at concentrations at least 1000-fold lower than the respective ethanol concentrations. The data indicate that, for administration of this ethanol dosage regimen to the third-trimester pregnant ewe, there is rapid, bidirectional placental transfer of ethanol; elimination of ethanol from the fetus is regulated primarily by maternal elimination of ethanol; the amniotic fluid may serve as a reservoir for ethanol in utero; and there is appreciable acetaldehyde-metabolizing capacity.

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Citation Excerpt :
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The objectives of this study were to elucidate the ontogeny of the activity of alcohol dehydrogenase (ADH), low K_m aldehyde dehydrogenase (ALDH) and high K_m ALD in the liver and placenta of the guinea pig, and to determine the relationship between the relative activity of each enzyme in the guinea pig maternal-placental-fetal unit and the disposition of ethanol and its proximate metabolite, acetaldehyde. The enzyme activities were determined in maternal liver, fetal liver, and placenta of the guinea pig at 34, 50, 60 and 65 days of gestation (term, about 66 days), in the liver of the 2-day-old neonate, and in adult liver. There was low ADH activity in fetal liver and placenta throughout gestation and in neonatal liver. The fetal liver low K_m ALDH activity increased progressively and, at 60 days of gestation, was similar to adult liver activity, as was also the case for neonatal liver enzyme activity. Placental low K_m ALDH activity was less than adult liver activity throughout gestation. Fetal hepatic high K_m ALDH activity increased during gestation, but was less than adult liver activity, as was also the case for neonatal liver enzyme activity. Placental high K_m ALDH activity was low throughout gestation. For oral administration of 0.5 g ethanol/kg maternal body weight to pregnant guinea pigs at mid-gestation (34 days), the maternal blood and fetal body ethanol concentration-time curves were similar. Acetaldehyde was measurable in maternal blood and fetal body at similar concentrations, which were 100- to 1000-fold less than the respective ethanol concentrations. The major difference in the disposition of ethanol and acetaldehyde at near-term pregnancy, compared with mid-gestation, was the lack of measurable acetaldehyde in fetal blood. These results indicate that the guinea pig fetus throughout gestation has virtually no capacity to oxidize ethanol, and its duration of exposure to ethanol is regulated by maternal hepatic ADH-catalyzed biotransformation of ethanol. The fetus, however, appears to have increasing low K_m ALDH-dependent capacity to oxidize ethanol-derived acetaldehyde during development, and would appear to be increasingly protected from exposure to acetaldehyde as gestation progresses.
Effects of multiple-dose maternal ethanol infusion on fetal cardiovascular and brain activity in lambs
1988, American Journal of Obstetrics and Gynecology
Ethanol (2 gm/kg of maternal body weight administered in four equal doses of 0.5 gm/kg over 5 hours) was infused intravenously into nine chronically prepared pregnant ewes between 124 and 137 days' gestation. The data demonstrated a dose-response relationship between fetal arterial ethanol concentrations and the incidence of fetal breathing movements. Suppression of normal fetal electrocortical activity occurred at a low ethanol concentration and returned to control values at a time of very high arterial artanol concentrations. This experimental model of a binge drinking episode further supports the hypothesis that ethanol suppresses fetal breathing movements by a direct central mechanism rather than indirectly by alteration of electrocortical activity.
Metabolic response to starvation at late gestation in chronically ethanol-treated and pair-fed undernourished rats
1988, Metabolism
To study the role of undernourishment in the negative effects of ethanol during pregnancy and to determine whether maternal ethanol intake modifies metabolic response to starvation at late gestation, female rats receiving ethanol in their drinking water before and during pregnancy (ethanol group) were compared with animals that received the same amount of solid diet as the ethanol group rats (pair-fed group) and with normal rats fed ad libitum (control group). All animals were killed on the 21st day of gestation, either in the fed state or after 24-hours fasting. The body weight of ethanol rats was lower than that of controls but higher than that of pair-fed rats. When compared with controls, ethanol and pair-fed rats had reduced fetal body weights, whereas fetal body length was reduced only in the former. In the fed state, blood glucose concentration was lower in the ethanol and pair-fed rats and fetuses than in controls. Twenty-four-hour starvation caused a reduction in this parameter only in control and ethanol mothers. In the fed state, maternal liver glycogen concentration was lower in ethanol and higher in pair-fed mothers than in controls. Blood β-hydroxybutyrate levels were higher in ethanol-treated mothers than in the others, and 24-hour starvation increased this parameter in ethanol and control rats to a greater extent than in the pair-fed ones. Liver triacylglyceride concentration was higher in ethanol-treated mothers than in the other two groups, and starvation caused this concentration to increase in ethanol and control groups but not in the pair-fed group. Maternal liver lipoprotein lipase activity did not differ among the groups when fed, but increased significantly with starvation in controls and ethanol-treated rats. Individual values of lipoprotein lipase activity in all the starved groups correlated with liver triacylglyceride concentrations. Results indicate that maternal undernourishment in ethanol-treated rats contributes to the negative effects of ethanol on fetal development in addition to certain other changes, such as the increase in maternal redox state and in circulating and liver triglycerides, directly related to ethanol oxidation. The intense maternal hypoglycemia observed in rats from the ethanol group could impair glucose availability to the fetus, and this situation would worsen with starvation. The higher hepatic glycogen levels in pair-fed mothers and their fetuses in the fed state as compared with the ethanol group, in spite of their similar hypoglycemia, seems to indicate a different metabolic adaptation in the two groups. A relationship is proposed in the starved condition between maternal liver lipoprotein lipase activity and changes in liver triacylglyceride and circulating ketone bodies in the three groups studied. The findings seem to indicate that, in spite of the metabolic disturbances produced by ethanol intake in the mother, the response to starvation in ethanol rats was similar to the one observed in controls, and different from the one in the pair-fed animals.

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^☆: Supported by grants from the Medical Research Council of Canada, The Hospital for Sick Children Foundation, The Physicians' Services Incorporated Foundation, the Faculty of Medicine Trust Fund, Queen's University, and the Richard and Jean Ivey Foundation.

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Disposition of ethanol in maternal blood, fetal blood, and amniotic fluid of third-trimester pregnant ewes☆

Abstract

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

J Pharmacol Methods

Prog Neuropsychopharmacol Biol Psychiat

Am J Obstet Gynecol

Toxicol Appl Pharmacol

Biochim Biophys Acta

Teratogenic effects of alcohol in humans and laboratory animals

Science