The exaggerated blood acetaldehyde response that has been reported after ethanol administration to pregnant rats was found to be the beginning of a much larger alteration occurring during lactation. Indeed, at the end of pregnancy, we confirmed a 4-fold increase in the acetaldehyde values above nonpregnant values after an intragastric dose of 3 g/kg ethanol. During gestational days 1 to 17, the levels did not differ. After delivery, the exaggerated acetaldehyde response to ethanol was increased, producing acetaldehyde concentrations 15-fold greater than in nonlactating controls. This response returned to nonpregnant levels with weaning and could be abolished by removing the pups at birth. The intensified response was associated with both an enhanced rate of ethanol oxidation and a decreased low Km aldehyde dehydrogenase activity in liver mitochondria. At the end of pregnancy, measurable concentrations of acetaldehyde were found in umbilical venous blood and fetal blood. However, they amounted to only one-quarter of maternal values whereas ethanol levels were similar. Thus, during late pregnancy and lactation, there is a marked increase in maternal blood acetaldehyde after ethanol intake. In the presence of a normal placenta, however, an acetaldehyde concentration gradient exists between the mother and the fetus.

Fetal injury associated with maternal ethanol ingestion is a major cause of congenital anomalies and mental retardation. Studies with animals suggest that acetaldehyde, the primary hepatic oxidative metabolite of ethanol, may contribute to fetal damage. It is not known, however, whether acetaldehyde reaches the human fetus, either by placental production or transfer. Studies utilizing the perfused human placental cotyledon show that the human placenta oxidizes ethanol to acetaldehyde, releasing it into the fetal perfusate. Moreover, when acetaldehyde is present in the maternal perfusate, it is transferred to the fetal side, reaching approximately 50 percent of the maternal level. These findings suggest that the human placenta may play a pivotal role in the pathophysiology of ethanol-associated fetal injury.

On day 20 of gestation, after ethanol feeding (27% ethanol calories, 25% protein), placental weights, DNA, RNA and water content were greater than in controls pair-fed an isocaloric diet without ethanol or those ad lib fed a pellet diet of similar composition. Rat litter size and fetal body, liver and brain weights were similar in all groups. In vivo fetal amino acid accumulation was significantly lower after alcohol exposure despite similar placental uptake. These results indicate that both placental hyperplasia and abnormal fetal amino acid uptake occur at a low alcohol dose when fetal body weight is unaffected.

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