There is a traditional belief in the Aymara community of Peru and Bolivia that if a woman sees a corpse during pregnancy, her baby is likely to be sickly. The scientific understanding of prenatal exposures to toxic substances is more complicated. Depending on the specific substance and dose and the particular organ systems that are developing at the time of the exposure, impacts may vary greatly in type and severity. While exposure to alcohol has a devastating impact on some children, exposures to cocaine and other illicit drugs seem to produce much more subtle effects.

In the 1980s, observers reported a variety of possible abnormalities among some infants of mothers who used crack cocaine during pregnancy. Among them were lethargy and nonresponsiveness, frenetic movements, low pain thresholds, problems relating to caregivers, and absence of normal playfulness. These anecdotal reports amplified the existing alarm over an epidemic of drug use that had already produced extraordinary accounts of violence and familial dysfunction. Scientific research was needed to determine which of the suspected abnormalities were real, which were actually due to cocaine exposure, and what was portended for these children's future.

Since the beginning of the crack epidemic, NIDA-supported researchers have been following two important lines of investigation into the effects of prenatal exposure to cocaine. Basic researchers have been looking at cocaine's impact on fetal development in laboratory animals. At the same time, clinical researchers have been conducting longitudinal studies to track groups of cocaine-exposed babies in order to determine how prenatal exposure would influence their development from birth through adolescence.

To date, NIDA's longitudinal studies have confirmed that some children with prenatal cocaine exposure have problems with aspects of motor skills, IQ, fussiness and consolability, and attention span. Executive function-the ability to gather and use information in pursuit of one's own aims-also may be compromised. In general, these findings are consistent with results from studies with laboratory animals, which have shown that cocaine alters the development of neural systems that are crucial to behavior and response to stimuli.

There are three important points to make about what we have learned so far. First, worries that "crack babies" would never be able to function in society have turned out to be unfounded for the great majority of these children. Despite the documented deficits of some of the children in our longitudinal studies, most have passed one developmental milestone after another, albeit some more slowly than their unexposed peers. Researchers have had the gratifying experience of watching many of these children grow, walk, talk, interact with their families and social environments, and progress from grade to grade in school.

Second, even though our worst fears about prenatal cocaine exposure have not been realized, we should not be complacent. While studies have clearly established that such exposure damages few children beyond any hope of help, they have also shown that some children are affected in ways that put them in need of special help. Even when deficits are relatively slight, their potential negative consequences can be important over the long term. A child with slightly more difficulty in settling down to tasks, for example, may do poorly in school. A child who has minor difficulties in controlling emotions may develop significant family and social problems over time, especially in environments that feature drug abuse and its associated ills.

Brain function deficits that are slight on an individual basis also can have sizable impacts on society. For example, a recent analysis by researchers at Brown University in Providence, Rhode Island, of data from several studies concluded that children with fetal cocaine exposure have IQs that average 3.3 points lower than those of unexposed children from the same socioeconomic environments. For most children, a difference of such magnitude would not matter much in terms of school performance or life prospects. For some children, however, 3.3 IQ points can spell the difference between functioning in the regular classroom and needing specialized help. The Brown researchers estimated that lower IQs associated with fetal cocaine exposure increase the number of children in the Nation who need special educational services by as many as 80,550 per year. The cost of providing these services could be as high as $352 million each year.

Finally, some children who have avoided major problems so far may still hit snags in the future. The oldest children in the longitudinal studies are approaching adolescence. Will fetal cocaine exposure produce heightened vulnerability to subsequent drug abuse and addiction during this often-difficult developmental stage? Some evidence from animal studies suggests that it may. Given an unrestricted supply of cocaine, the offspring of mice injected with cocaine during preg-nancy self-administer more of the drug than do other mice. Also suggestive is a recent finding by NIDA-funded researchers that the fetal mouse brain has active dopamine receptors. The researchers speculate that cocaine stimulation during gestation could enhance the proliferation of these receptors during human fetal development. If so, the resulting extra abundance of receptors might predispose the individual to react strongly to addictive drugs.

We still have much to learn about cocaine's impact on the developing human brain. Not only are the brain alterations associated with fetal cocaine exposure various and often subtle, they also may manifest themselves in different ways as children grow. Moreover, the environments associated with prenatal cocaine exposure almost always contain other potential stumbling blocks for child development. These can range from poor maternal nutrition during pregnancy and prenatal or postnatal exposures to other drugs to parental neglect or abuse and elevated risks for a variety of other illnesses.

To isolate the specific effects of cocaine exposure from all of these confounding factors is a daunting challenge, but NIDA-supported researchers have made impressive strides in developing research protocols, interview techniques, and evaluation tools that help discriminate cocaine's effects. NIDA continues to strongly encourage researchers to explore ways to further develop these resources. As this research bears fruit, and even better tools-such as improved brain imaging, reliable biologic measures of cocaine exposure, and innovative instruments for cognitive assessment-become available, our understanding of the impact of prenatal cocaine exposure will grow.

The article "NIDA Studies Clarify Developmental Effects of Prenatal Cocaine Exposure" on page 5 of this issue of NIDA NOTES reports on some of the latest studies that are isolating the impacts of prenatal cocaine exposure from those of the environment.

The ultimate objective of NIDA's research program, of course, is to be able to design and provide effective assistance to children who need to overcome difficulties resulting from fetal cocaine exposure. In fact, there is good reason to hope that the insights into human development gained from these studies also will benefit children who were never exposed to drugs.