Preclinical studies of gestational cocaine exposure (GCE) are replete with evidence of changes in brain function at the anatomical, physiological, and behavioral levels, to include effects on developing dopaminergic systems [42,56,83,90,131]. In contrast, human studies of child outcomes have produced less consistent results, with many investigators finding only subtle impairments particularly in tasks of attention, language and memory [1,9,11,47,101,110].
Some of the variability in outcome associated with GCE in humans is undoubtedly attributable to the more complex context in which children develop, compared to the highly controlled environments in animal models. Further it is nearly impossible to control for the myriad of factors that correlate with maternal cocaine use. These factors include SES, concurrent use of other drugs, family mental health history, caregiver characteristics, child exposure to violence as witness or victim, homelessness, and parental separation and loss [19,47,86,91,96,118]. Other reasons for these varied findings may be related both to the measures chosen to assess outcomes in children and the timing of these assessments [6,37].
Studies of the effects of GCE on language development have shown mixed results. Our group found no GCE effects on language functioning assessed using the Preschool Language Scale at age 2.5 years and the Battelle Developmental Inventory Communication Subscale at ages 3 and 5 years [70,71]. Morrow et al (2004) reported differences of 2 to 3 points on language measures after controlling for important covariates, concluding that their lower standard scores put cocaine exposed children at increased need for clinical interventions . In a trajectories analysis of language performance of children assessed at ages 1, 2, 4, and 6 years, Lewis et al (2007) reported that cocaine exposed children had lower language scores at each age. Average differences between groups in Receptive, Expressive, and Total Language z-scores after controlling for confounding variables were: 0.14, 0.15, and 0.18  which corresponds to 2.1, 2.25, and 2.7 standard score points, respectively. Environmental variables including HOME scores, maternal cognitive functioning and cigarette exposure also were associated with poorer performance. Similarly, Beeghly et al (2006) found that their cohort of low-income, urban children with GCE had lower receptive language scores than unexposed children at age 6 years but not at age 9.5 years . This age difference in GCE effects on language may be due to the contrast between the increasing influence of cumulative environmental factors and the increasingly distal influence of gestational and natal factors.
Because cocaine exposure is associated with alterations in dopamine-rich prefrontal neural systems, functional processes that have been localized to these areas have been examined in exposed children. Prenatal cocaine exposure has been linked to lower levels of inhibitory control , a function localized to the anterior cingulate area of the prefrontal cortex (PFC) [5,39,106,112]. Rose-Jacobs et al (2009) identified effects on cocaine-exposed children's ability to inhibit prepotent responses as assessed using the Stroop at ages 5 and 7 years, but in this same cohort scores on a more general measure of executive function showed no cocaine effects . Noland et al (2005) reported effects of prenatal cocaine, tobacco, marijuana on selective attention indicated by higher errors of commission on a picture deletion task administered at age 4 years . Reports from another longitudinal study showed that cocaine-exposed children scored lower than controls on a summary estimate of attention assessed using three measures across ages 3, 5 and 7 years [1,9] and had slightly elevated risk for ADHD according to results of a diagnostic interview . Ackerman et al (2008) reported effects of prenatal cocaine and/or heroin exposure on sustained visual attention assessed using the Connors Continuous Performance test at age 7 years . In the cohort included in the current report, cocaine-exposed subjects made more commission errors on the Distractibility subtest of the Gordon Diagnostic System but had better Delay Task Efficiency Ratios than controls at age 10 years . No GCE effects were observed for each of the 6 remaining measures of attention and impulsivity assessed. These studies suggest that GCE is linked to poorer inhibitory control and sustained attention, yet differences reported often are for only one of many tests administered as found by Savage et al, 2005 and/or effect sizes are relatively small as reported by Morrow et al, 2009.
Imaging studies have shown differences between cocaine-exposed and control subjects in neural characteristics of brain areas that are linked to inhibitory control or attention. Cocaine exposure was related to differences in adjusted volumes in the caudate nucleus , more diffuse patterns of activation while performing a task requiring inhibitory control , and differences in activation while completing a response inhibition task . In most of these studies no performance differences were observed at the time of evaluation, suggesting that compensatory pathways were developed to ameliorate effects of cocaine exposure on these neural systems.
In studies of more general measures of functioning such as IQ and academic achievement findings are also mixed [22,68,98,118]. In 7 of the 8 studies meeting criteria for inclusion in a recent review article by Ackerman, no cocaine effects were observed but robust effects of environment were reported . The eighth study showed cocaine exposure effects in the WISC-IV composite for Perceptual Reasoning however no effects were observed for the Verbal Comprehension, Working Memory or Processing Speed Composites or for scores on the Wechsler Individual Achievement Test .
It now is well established that GCE has not produced the profound deficits anticipated in the 1980 s and 1990 s, with children described variably as joyless, microcephalic, or unmanageable [15,24,31,52,53,75,92,135]. While welcome, the fact that GCE is not as devastating as predicted in no way negates the need for evaluation for more subtle deficits such as impairments in attention, memory, and language. As is clear in the literature, “subtle deficits” may also have far reaching effects [80,98]. For example, attention deficits that are accepted among family and close friends may be more problematic in the classroom or work place. In the classroom, children with attention deficits have difficulty learning with resultant negative effects on academic performance as they approach adolescence . In the workplace, adults with attention deficits are more likely to be fired, change jobs more often, and earn lower work performance ratings . Since children prenatally exposed to cocaine may exhibit multiple subtle deficits, investigations in maturing youth are merited. Until functional outcomes (i.e., successful transition to adulthood) associated with GCE are evaluated, the clinical significance of these subtle but statistically significant effects remains unknown.
Human brain development is far from complete by late childhood and early adolescence, the oldest age at which children with GCE so far have been studied. There are robust data, to include structural and functional neuroimaging, that show the prefrontal cortex, in particular, undergoes substantial maturational change through adulthood [21,55,107,111,115,123,132]. This is a significant factor in investigations of the effects of GCE given that prefrontal cortex is one of the brain regions most likely to be affected [42,62,84,90]. As such, conclusions regarding the effects of exposure on the human brain cannot be drawn with any finality pending the investigation for such effects on the mature brain. Thus, it is possible that GCE has latent effects on NC outcome that do not manifest until adolescence or young adulthood.
Motivated by the incomplete brain maturation of the oldest subjects so far tested, the possibility of latent or “sleeper” effects as suggested by animal and human research [6,40,54,78,79,81,96,128], as well as effects reported so far by others [2,7,9,17,20,63,76,93,101,109,110,114,117], this report includes assessment of our cohort as they progress through adolescence at ages 12, 14.5 and 17 years. We elected to take a cognitive neuroscience approach to measure NC function in our cohort. Localization of NC systems has been demonstrated in cognitive neuroscience studies that show associations between task performance and activation patterns in imaging or damaged areas in patients with brain lesions. The set of tasks used in this report: 1) evaluated both frontal and nonfrontal function; 2) demonstrated sensitivity to age and IQ; 3) discriminated between middle and low SES subjects[49,99]; and 4) revealed specific relationships between aspects of early childhood experience and the development of specific NC systems. Given this we have confidence that these tasks are psychometrically sensitive for detection of potential differences that may emerge between GCE participants and Controls during later stages of maturation. Data regarding NC functioning of GCE adolescents may identify vulnerabilities in these individuals in the classroom or workplace as they transition into adulthood.