Supported by Grant AA10940 from the NIAAA and by NIH Pediatrics Initiatives (TAC).
Third Trimester Binge Ethanol Exposure Results in Fetal Hypercapnea and Acidemia but Not Hypoxemia in Pregnant Sheep
Article first published online: 11 APR 2006
Alcoholism: Clinical and Experimental Research
Volume 25, Issue 2, pages 269–276, February 2001
How to Cite
Cudd, T. A., Chen, W.-J. A., Parnell, S. E. and West, J. R. (2001), Third Trimester Binge Ethanol Exposure Results in Fetal Hypercapnea and Acidemia but Not Hypoxemia in Pregnant Sheep. Alcoholism: Clinical and Experimental Research, 25: 269–276. doi: 10.1111/j.1530-0277.2001.tb02208.x
- Issue published online: 11 APR 2006
- Article first published online: 11 APR 2006
- Received for publication July 28, 2000; accepted November 30, 2000.
- Fetal Alcohol Syndrome;
- Ovine Model System
Background: The mechanisms by which maternal ethanol abuse during pregnancy causes neurodevelopmental injury in the fetus are not well understood. The purpose of this study was to use a chronically instrumented fetal sheep model system to determine if a binge pattern of ethanol e-posure administered throughout the third trimester reduced fetal arterial partial pressure of o-ygen (PaO2); a positive finding would support the hypothesis that fetal hypoxemia may play a role in mediating ethanol-related birth defects.
Methods: Pregnant ewes received saline or 0.75, 1.25, 1.5, or 1.75 g/kg of ethanol intravenously over 1 hr beginning on day 109 of gestation (term = 145 days) for 3 consecutive days per week followed by 4 days without e-posure. The fetuses were surgically instrumented on day 113, and e-periments were performed on days 118 or 132, the 6th and the 12th ethanol e-posure, respectively.
Results: Ethanol infusions resulted in peak blood ethanol concentrations of 80.8 ± 6.5, 182.5 ± 13.5, 224.4 ± 13.9, and 260.6 ± 20.0 mg/dl ± SEM (maternal) and 70.0 ± 5.9, 149.7 ± 9.0, 216.9 ± 14.0, and 233.3 ± 19.8 mg/dl ± SEM (fetal) in response to the 0.75, 1.25, 1.5, and 1.75 g/kg doses, respectively. Maternal and fetal heart rate and maternal blood pressure increased whereas fetal blood pressure decreased in a dose-dependent manner in response to ethanol infusions. Maternal and fetal arterial pH decreased and arterial partial pressures of carbon dio-ide increased in response to ethanol infusions. Maternal PaO2 decreased whereas fetal PaO2 did not change in response to ethanol infusions.
Conclusions: A binge ethanol e-posure paradigm, three consecutive days per week throughout the third trimester at ethanol doses that created blood ethanol concentrations commonly achieved by human ethanol abusers, resulted in changes in maternal and fetal heart rate, changes in blood pressure, hypercapnea, acidemia, and maternal, but not fetal, hypo-emia. We conclude that in an ovine model system, ethanol doses that create blood ethanol concentrations as high as 260 mg/dl do not result in fetal hypo-emia. Remaining issues to address with this model system are whether neurodevelopmental injuries that are associated with maternal ethanol abuse are mediated by a reduction in fetal cerebral blood flow, fetal hypercapnea, or acidemia.