Numerous studies have demonstrated the dangers of drinking alcohol during pregnancy, particularly binge and heavy patterns of drinking. However, increasing evidence indicates that moderate drinking during pregnancy may also cause problems, albeit more subtle, long-term cognitive impairments that may not become evident until adolescence and then increase in severity with maturation.
A study in the November issue of Alcoholism: Clinical & Experimental Research adds to the latter body of knowledge by providing the first report of combined physiological and behavioural deficits in adult rodent offspring of mothers that consumed alcohol during pregnancy at a blood alcohol concentration (BAC) less than half the level of legal intoxication.
"One of the continuing concerns of investigators in this field is the general public's apathy or skepticism of reports about the dangers of drinking during pregnancy," said Daniel D. Savage, Regents' Professor and Chair of Neurosciences at the University of New Mexico School of Medicine, and lead author of the study.
"Yet our findings clearly indicate that even low to moderate levels of drinking during pregnancy cause long-lasting alterations in synaptic plasticity and spatial learning in affected offspring. The lowest maternal BAC that produced these effects, 30 mg/dL, is much lower than the BACs that produce birth defects."
In general, a 120-pound woman could achieve a 30 mg/dL BAC after consuming two drinks during an hour and a half. "Most of the effects of foetal alcohol exposure reported in the literature occur primarily at BACs ranging from about 120 to 350 mg/dL," he said. "Our study's finding should have a major impact on this field of research as well as signal a warning to pregnant women and their family practitioners and obstetricians about the potential dangers of moderate drinking during pregnancy."
In their research, investigators focused on the hippocampus, a brain region that is not only important for learning and memory, but is also highly susceptible to prenatal ethanol exposure. Alcohol researchers believe that prenatal alcohol exposure diminishes hippocampal synaptic plasticity, a neurobiologic process that strengthens communication between neurons in a manner critical for new learning. One specific form of synaptic plasticity, Long-Term Potentiation (LTP), occurs when neurons are activated in a special way that leads to increased synaptic communication between neurons.
Many researchers believe that LTP is an important process for some types of learning. Normally, the synaptic strengthening that occurs with LTP can last for days to weeks. However, in rodent offspring prenatally exposed to alcohol, LTP decays away in about an hour after activation.
Glutamate, the primary excitatory neurotransmitter in the brain, plays important roles in the development and maintenance of LTP in the hippocampus and other brain regions. Evidence suggests that the LTP deficit observed in rodent offspring prenatally exposed to alcohol is due to functional changes in hippocampal glutamate neurotransmission. More specifically, glutamate receptors, the proteins that transmit the effects of glutamate as a neurotransmitter, are less functional.
For this study, three groups of pregnant rats consumed a two-per cent, three-per cent or five-per cent alcohol liquid diet throughout gestation. Three additional groups of pregnant rats were pair-fed zero-percent alcohol liquid diets that were caloric equivalents of the three alcohol diets. A seventh group consumed lab chow freely. The two-per cent, three-per cent, and five-per cent alcohol liquid diets produced average peak maternal BACs of 7, 30, and 83 mg/dL respectively.
Later, adult female offspring (roughly equivalent to humans in their mid-20s to late 30s) from each diet group were either tested for their performance in a spatial learning task (swimming related) or were sacrificed to measure activity-dependent potentiation of hippocampal neurotransmitter release, a physiological measure of synaptic plasticity.
"The key findings in this study are twofold," said Charles R. Goodlett, a professor in the department of psychology at Indiana University School of Medicine. "First, rat offspring of dams drinking the three-per cent alcohol liquid diet had impairments in spatial working memory. Although this diet produced a peak blood alcohol level of 30 mg/dL, which is also well under the legal limit for intoxication, the alcohol-exposed offspring were less able than unexposed controls to use recently acquired spatial information to perform a memory task known to require normal functioning of the hippocampus."
"The authors further show that offspring exposed to moderate amounts of alcohol during gestation also failed to generate an enhanced level of neurotransmitter release in living slices of hippocampal tissue after the slices were strongly stimulated by high-frequency electrical pulses. In summary, this correlation between deficits in spatial memory and reduced plasticity of transmitter release in the hippocampus provides new data that moderate levels of alcohol exposure can alter specific learning processes mediated by the hippocampus, and links them to a specific deficit in plasticity of neurotransmitter release," he continued.