Despite extensive adverse publicity, tobacco use continues in approximately 25% of all pregnancies in the United States, overshadowing
illicit drugs of abuse, including
cocaine. The societal cost of maternal smoking is seen most readily in underweight newborns, in high rates of perinatal morbidity, mortality and
Sudden Infant Death Syndrome and in persistent deficits in learning and behavior. We have designed animal models of
nicotine exposure to prove that
nicotine itself is a neuroteratogen, thus providing a causative link between tobacco exposure and adverse perinatal outcomes. In particular,
nicotine infusion paradigms that, like the
transdermal patch used in man, produce
drug exposure without the confounds of other components of tobacco or of episodic hypoxic-ischemic insult, have enabled a mechanistic dissection of the role played by
nicotine in fetal brain damage.
Nicotine targets specific
neurotransmitter receptors in the fetal brain, eliciting abnormalities of cell proliferation and differentiation, leading to shortfalls in the number of cells and eventually to altered synaptic activity. Because of the close regulatory association of
cholinergic and catecholaminergic systems, adverse effects of
nicotine involve multiple transmitter pathways and influence not only the immediate developmental events in fetal brain, but also the eventual programming of synaptic competence. Accordingly, defects may appear after a prolonged period of apparent normality, leading to cognitive and learning defects that appear in childhood or adolescence. Comparable alterations occur in peripheral autonomic pathways, leading to increased susceptibility to
hypoxia-induced brain damage, perinatal mortality and
Sudden Infant Death. Identifying the receptor-driven mechanisms that underlie the neurobehavioral damage caused by fetal
nicotine exposure provides a rational basis for decisions about
nicotine substitution
therapy for smoking cessation in pregnancy. In contrast to the effects of
nicotine, animal models of
crack cocaine use in pregnancy indicate a more restricted spectrum of effects, a reflection of differences both in pharmacokinetics and pharmacodynamics of the two drugs. Notably, although
cocaine, like
nicotine, also targets cell replication, its effects are short-lived, permitting recovery to occur in between doses, so that the eventual consequences are much less severe. To some extent, the effects of
cocaine on brain development resemble those of
nicotine because the two share cardiovascular actions (vasoconstriction) that, under some circumstances, elicit
fetal hypoxia-
ischemia. In light of the fact that nearly all
crack cocaine users
smoke cigarettes, the identification of specific developmental effects of
cocaine may prove difficult to detect. Although scientists and the public continue to pay far more attention to fetal
cocaine effects than to those of
nicotine or tobacco use, a change of focus to concentrate on tobacco could have a disproportionately larger impact on human health.