Third Trimester Binge Ethanol Exposure Results in Fetal Hypercapnea and Acidemia but Not Hypoxemia in Pregnant Sheep

Abstract

A binge ethanol exposure 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, hypoxemia. 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 hypoxemia. 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.

All Three Trimester Binge Alcohol Exposure Causes Fetal Cerebellar Purkinje Cell Loss in the Presence of Maternal Hypercapnea, Acidemia, and Normoxemia: Ovine Model

“…Tissue hypoxia has been proposed as a mechanism involved in prenatal alcoholmediated injury. This hypothesis is supported by the observation that both hypoxia and fetal alcohol exposure induce similar craniofacial defects and neuronal deficits (Bronsky et al, 1986;Cudd et al, 2001). The hippocampal CA1 pyramidal cells and the cerebellar Purkinje cells are both vulnerable to hypoxia (Aitken and Schiff, 1986;Auer et al, 1989;Rees et al, 1999) as well as to alcohol.…”

“…Therefore, a secondary goal in this study was to assess the changes in maternal blood gases and pH following a binge-like alcohol exposure throughout gestation. We used a weekend binge pattern, a drinking pattern common in women who use alcohol during pregnancy (Caetano et al, 2006;Cudd et al, 2001;Ebrahim et al, 1999;Gladstone et al, 1996;Maier and West, 2001a) and who are more likely to refrain compared with everyday drinkers if convinced that drinking poses a hazard to their baby.…”

Alcohol‐Mediated Purkinje Cell Loss in the Absence of Hypoxemia During the Third Trimester in an Ovine Model System

“…Many of the physiologic dependent variables from this exposure paradigm have been reported previously (Cudd et al, 2001).…”

“…However, Smith et al (1989b) found no evidence of hypoxemia in a chronic fetal sheep subjected to acute alcohol exposure. Recently, our report showed that 1.75 g/kg alcohol delivered through the femoral vein of the mother produced maternal, but not fetal, hypoxemia (Cudd et al, 2001). Taken together, it remains unclear at present whether alcohol would produce fetal hypoxia to an extent in utero that will induce neuronal damage or whether neuronal damage can occur in the absence of hypoxic or hypoxemic conditions in the mother or fetus.…”

“…After detailed analysis of maternal and fetal arterial blood gases, in which fetal hypoxemia was not detected (Cudd et al, 2001), we hypothesized that neuronal loss could occur in the absence of hypoxemia or hypoxia. Should this be true, it will be the most convincing evidence to date that hypoxia or hypoxemia is not the major mechanism that mediates alcohol-induced neuronal loss during brain development.…”