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BNL Addiction Symposium

Abstract Details

February 16, 2007, San Francisco, CA | Symposium Home

Maternal-Fetal Drug Transfer: Implications for Drug Abuse and Therapeutics

Author: Helene Benveniste
Professor, Department of Anesthesiology, Stony Brook University and
Scientist, Medical Department, Brookhaven National Laboratory

Women of child-bearing age who suffer from diseases such as hypertension, depression, diabetes, epilepsy or chronic pain and become pregnant are most often forced to continue their medical treatment during pregnancy to survive. Nevertheless, according to pharmaceutical and medical literature, nearly all drugs used are potentially harmful to the fetus. Another untoward situation is the consumption of substances of abuse, such as nicotine (12-20% of pregnant women in the US continue to smoke during pregnancy), alcohol, cocaine, methamphetamine and narcotics (including prescription drugs), during pregnancy.

The unborn child in the womb undergoes constant developmental changes as determined by the delicate balance between maternal and paternal genetics and the surrounding maternal and external environment. The processes governing this extremely complex development are largely unknown but it is not difficult to imagine how a myriad of different ‘signals’ in the developing fetus might go astray if prematurely exposed to exogenous agents such as alcohol, nicotine, cocaine, and other pharmaceutical compounds acting in the brain because, during various stages of gestation, the fetal brain develops specific target ‘sites’ for many of these drugs. Obviously, at this early time point in development, the fetus is meant to be undisturbed and undergo development without exposure to external stimulants.

The detrimental effects of maternal alcohol abuse during pregnancy on the fetus have already been demonstrated in the unfortunate children. However, it is unsettling that we still do not understand how the fetal brain responds to most other drugs ingested by the mother. To do so would require the development of methods that would 1) allow visualization of all fetal organs; 2) follow the drug and their breakdown products when they enter the fetal circulation; 3) obtain information of the fetal effects (physiology, biochemistry, metabolism, anatomy); 4) follow the behavioral and cognitive effects of the child after delivery.

Over the last decades, researchers have developed animal models to measure the maternal-fetal exchange of drug. These studies typically provide information of the total fetal exposure to a given drug of interest because it is not possible to distinguish for example the drug exposure of the fetal liver from the fetal brain by only measuring fetal blood concentrations via the umbilical artery.

Using positron emission tomography (PET) combined with magnetic resonance imaging (MRI), we have demonstrated a new way to track the uptake and distribution of trace amounts of cocaine, nicotine, and other drugs (dopamine) in pregnant monkeys to assess the potentially damaging effects of prenatal drug exposure. We found significant differences in where and how fast drugs accumulate in maternal and fetal organs. In another series of studies we used dynamic PET to non-invasively assess the pharmacodynamic effect of clinically relevant doses of maternal cocaine use on the fetal brain, heart, and liver, as well as the placenta. Our findings have significant implications not only for prenatal exposure to drugs of abuse but also for future investigations of fetal responses to therapeutic drugs such as antidepressants, analgesics, and anti-seizure medications frequently taken during pregnancy. This talk will present these results as well as implications for the treatment of drug abuse and other maternal diseases.

Last Modified: January 31, 2008