In order to assure normal fetal development, mother and fetus must both - at different times during gestation - contribute appropriate levels of thyroid hormone. If not, brain defects can result, some of which resemble those found in children suffering from fetal alcohol syndrome (FAS). Due to these commonalities, some researchers speculate that alcohol may mediate alcohol-related birth defects (ARBDs) by inducing hypothyroid conditions in utero. A study in the January issue of Alcoholism: Clinical & Experimental Research investigates if alcohol consumption during the equivalent of the third trimester in sheep results in an alteration of fetal or maternal thyroid function.
"The thyroid hormone system plays important roles in growth, development and in the function of other hormone and organ systems," explained Timothy A. Cudd, associate professor of physiology at Texas A&M University and lead author of the study. "Both mother and fetus must contribute thyroid hormone for normal fetal development. Early in development, before the fetus is capable of producing thyroid hormone, maternal thyroid hormone crosses the placenta to influence fetal development. Later in development, when higher concentrations are required for normal fetal development, a fetal contribution is required to create sufficient concentrations."
Cudd and his co-authors knew that brain abnormalities found in children who were exposed to abnormally low concentrations of thyroid hormone during fetal development are similar to brain abnormalities found in children exposed to alcohol in utero. "From a behavioral standpoint," said Cudd, "children born to hypothyroid mothers score less well on intelligence, attention, language, reading ability and school performance measures compared to children born to mothers with normal thyroid function. These deficiencies are similar to those in children with ARBDs. From an anatomical perspective, hypothyroidism and fetal alcohol exposure both affect the development of the hippocampus and the cerebellum." Knowing these similarities, the study authors investigated if ARBDs are, in part, a result of alcohol-mediated thyroid hormone system dysfunction.
Researchers gave pregnant ewes alcohol doses of 0.75, 1.25, 1.5 or 1.75 g/kg or saline through catheters beginning on day 109 of gestation (a full term for sheep is 145 days). The ewes received alcohol or saline on three consecutive days, followed by four days without exposure, thereby mimicking a pattern of binge drinking. Fetal and maternal blood samples were collected on days 118 or 132.
"The administration of alcohol to sheep during the equivalent of the third trimester of pregnancy resulted in altered thyroid function in both the mother and fetus," said Cudd.
"This is an important study because even today so little is known regarding the mechanisms through which alcohol intake by pregnant mothers is bad for their fetuses," said Catherine Rivier, a professor of neuroendocrinology/neurosciences at The Salk Institute. "In addition, the sheep is a good model for the human because the thyroid system of both species develops similarly during gestation. Prior to this study, we knew that, in general, fetal brain development requires thyroid hormones to grow normally and build all the right connections. We knew that children born to mothers who have low thyroid hormone levels are often retarded. These results show us that alcohol given to a pregnant mother lowers thyroid hormones in both the fetus and the mother. This finding gives investigators the rationale for doing additional experiments to see if these changes in thyroid hormones participate in defects due to alcohol during gestation."
Cudd believes that the study’s findings do indeed support the hypothesis that alcohol might mediate ARBDs by altering thyroid function in the fetus and/or in the mother. "Nonetheless," he said, "further studies are necessary to conclude that this is the case in humans. Clearly, abstaining from alcohol use during pregnancy is the safest course. However, if our findings are proven to hold in humans, then it may be possible to monitor thyroid function and even correct abnormal thyroid function in mothers to potentially mitigate the actions of alcohol on the fetal brain."
Funding for this Addiction Science Made Easy project is provided by the Addiction Technology Transfer Center National Office, under the cooperative agreement from the Center for Substance Abuse Treatment of SAMHSA.
Articles were written based on the following published research:
Cudd, T.A., Chen, W-J.A., & West, J.R. (2002, January). Fetal and maternal thyroid hormone responses to ethanol exposure during the third trimester equivalent of gestation in sheep. Alcoholism: Clinical and Experimental Research, 26(1), 53-58.