Dr. Marylou Behnke (left) and Dr. Fonda Davis Eyler have found that babies exposed prenatally to cocaine are less alert and attentive than are unexposed infants.

"We now have data from longitudinal studies that have followed mothers from early in their pregnancies and their children from birth into early childhood," says Dr. Vincent Smeriglio of NIDA's Center on AIDS and Other Medical Consequences of Drug Abuse. "These studies take into account many confounding factors that are associated with cocaine use. What we see in some of these children is a pattern of subtle neurobehavioral effects associated with prenatal cocaine exposure. These include effects on a child's attention and alertness, IQ, and motor skills. The effects are not as profound as some early reports suggested, but they are very real," he says.

Effects on Attention, Alertness, and Intelligence

Studies with laboratory animals have revealed cocaine-related effects on development within regions of the brain that regulate attention, arousal, and reaction to stresses. Research involving children born to mothers who used cocaine during pregnancy has found a profile of effects related to these same brain regions. The effects are not dramatic--cocaine-exposed children were more likely than unexposed children to have scores at the low end of the normal ranges on tests that measure alertness, attention, and intelligence. However, the effects persist from birth through early childhood and suggest that cocaine-exposed children may have to work harder--or will need more help--focusing their attention, remaining alert, and processing information than do unexposed children.

NIDA-supported research conducted by Dr. Linda Mayes at the Yale University School of Medicine in New Haven, Connecticut, suggests that cocaine has an effect on regions of the brain that regulate a child's ability to pay attention, which has important implications for learning and memory. Dr. Mayes and her colleagues studied more than 600 children--either not exposed to any drug or exposed prenatally to cocaine; to cocaine and marijuana, tobacco, or alcohol; or to marijuana, tobacco, or alcohol but not to cocaine. The children were examined at ages 3, 12, 18, and 24 months. "In a variety of settings, cocaine-exposed children appear to require more stimulation to increase arousal and attention but are less able to control higher states of arousal than are unexposed children," Dr. Mayes says.

NIDA-funded research conducted at the University of Florida in Gainesville has demonstrated an association between the amount of cocaine used by a pregnant mother and her child's performance on tests used to measure alertness and attention. Dr. Fonda Davis Eyler and Dr. Marylou Behnke studied more than 300 infants, half whose mothers used cocaine during pregnancy and half whose mothers did not. "The amount of cocaine used during pregnancy was negatively related to the baby's scores on tests of orientation, attention, and alert responsiveness," says Dr. Eyler.

Unlike many other studies that have examined the effects of prenatal cocaine exposure, the research conducted by Dr. Eyler and Dr. Behnke involved women from poor rural populations rather than women from urban areas where cocaine abuse often is accompanied by abuse of a variety of other drugs. "Cocaine is pervasive in this community, but other illicit drugs--except marijuana--are not. This makes it easier for us to isolate the effects of cocaine," Dr. Behnke notes.

Although the researchers caution that it is impossible to attribute the observed effects solely to cocaine use, they note that the number of significant correlations with cocaine are far greater than would be expected by chance. "The results seem to fit into an overall pattern of effects. Twice as many cocaine-exposed infants as controls--a fourth of the sample--were unable to achieve and maintain the quiet alert state that examiners need to administer some parts of the test," observes Dr. Eyler. "In simple comparisons as well as in more complex correlations with amount of usage, it was the cocaine-exposed infants who demonstrated significant detriments, and it was always in the areas of responsiveness and regulation of attention," she says.

At the Western Psychiatric Institute and Clinic in Pittsburgh, NIDA-funded researcher Dr. Gale Richardson and her colleagues also have found an association between prenatal cocaine exposure and central nervous system deficits. "Cocaine has effects that are independent of other prenatal and postnatal factors. This has been true at each of the three age phases in our study--at birth, at age 1, and at age 3, the neurobehavioral effects are there," Dr. Richardson says.

At birth, the children exposed prenatally to cocaine showed more abnormal reflexes, less motor maturity, and poorer ability to regulate their state of attentiveness than did unexposed children. At 1 year and at 3 years, those children were less adaptable and more likely to be fussy and overly persistent than were unexposed children.

At 3 years, the exposed children scored lower on an intelligence test than did unexposed children, were more restless, had shorter attention spans and less focused attention, and made more attempts to distract the examiner than did children who were not exposed to cocaine before birth, Dr. Richardson notes.

The study will follow children through 10 years of age and will allow researchers to control for many of the circumstances, such as multiple drug exposure and pre- and postnatal environment, that might mask or confound cocaine-related effects. "We have a large sample of women who were enrolled early in their pregnancies from a prenatal care clinic, not a drug treatment program. We have continued to interview the mothers extensively to collect as much information as possible about the postnatal environment," Dr. Richardson says.

Effects on Motor Development

During their first few years of life, children develop the fine motor skills that help them learn to write and draw. NIDA-supported research suggests that prenatal exposure to cocaine has a damaging effect on the development of these skills and on a child's ability to remain alert and attentive.

NIDA-funded research conducted by Dr. Robert Arendt and Dr. Lynn Singer at Case Western Reserve University in Cleveland has shown an association between prenatal cocaine exposure and decreased motor development in children at age 2. Their study involved nearly 200 cocaine-exposed and unexposed infants recruited from an urban hospital newborn nursery and pediatric clinic.

"The cocaine-exposed children performed significantly less well on both the fine and the gross motor development indices. These findings indicate that the lag in development extends beyond the neonatal period in exposed children," Dr. Arendt says.

"Motor functions are more 'hard-wired' than behavior, and are less likely to be influenced by environment as a child grows up. The effects of cocaine exposure on motor development that show up early should still be there as the child grows older," Dr. Singer says. "We previously found motor development effects in the cocaine-exposed group when we looked at them at 4 months and again at 12 months. Now we know that these effects persist through age 2," she adds.

Preliminary data from examination of the same children at age 4 suggest that cocaine-related deficits in fine motor development last into early childhood, although the motor skill problems associated with prenatal cocaine exposure are not more severe than those seen in some unexposed children in the course of normal clinical practice, Dr. Arendt notes. "These kids can be helped with physical therapy and other interventions just as successfully as any other child with similar motor problems. It's important to know that they will need some help, and it's important to see to it that they get this help. Without properly developed motor skills, it is difficult for a child to control a pencil to draw a picture or write their ABCs," Dr. Arendt says.

"No study involving mothers and children in an environment of drug abuse can perfectly isolate the effects of cocaine or any other drug from the combined effects of that environment, but we can use statistical methods and study design to control for many of the confounding variables. What we see is that cocaine does have an effect that is independent of other variables," Dr. Arendt says.

Sources

Arendt, R.; Angelopoulos, J.; Salvator, A.; and Singer, L. Motor development of cocaine-exposed children at age two years. Pediatrics 103:86-92, 1999.

Arendt, R., et al. Sensorimotor development in cocaine-exposed infants. Infant Behavior and Development 21:627-640, 1998.

Eyler, F.D.; Behnke, M.; Conlon, M.; Woos, N.S.; and Wobie, K. Birth outcome from a prospective, matched study of prenatal crack/cocaine use; II. Interactive and dose effects on neurobehavioral assessment. Pediatrics 101:237-241, 1998.

Mayes, L.; Grillon, C.; Granger, R.; and Schottenfeld, R. Regulation of arousal and attention in preschool children exposed to cocaine prenatally. Annals of the New York Academy of Sciences 846:126-143, 1998.

Richardson, G.A. Prenatal cocaine exposure: A longitudinal study of development. Annals of the New York Academy of Sciences 846:144-152, 1998.

Smeriglio, V.L., and Wilcox, H.C. Prenatal drug exposure and child outcome. Clinics in Perinatology 26(1):1-16, 1999.