Executive Functioning in Preschool-Age Children Prenatally Exposed to Alcohol, Cocaine, and Marijuana

Executive functioning (EF) abilities allow for goal-directed behavior and resistance to competing responses (Fuster, 1989). There is no consensus on the definition of EF, but included in the abilities competing for acceptance under this rubric are working memory, planning, and inhibitory control. This study compares the performance on EF tasks of preschoolers who had prenatal exposure to cocaine, alcohol, and marijuana with that of children without such exposure. Two features of this investigation, in combination, uniquely position it to address the question of prenatal substance-exposure effects on EF. First, the large sample size, prospective design, and extensive assessment of the caregiving environment allow for control not addressed in many reports of the effects of prenatal cocaine and alcohol exposure on EF. Second, we assessed functioning much earlier in development than most investigations of the effects of prenatal substance exposure on EF. EF tasks were selected for this study on the basis of clinical evidence, which will be reviewed in more detail, that they rely on the functioning of the frontal-subcortical circuit (Diamond et al., 1997; Welsh et al., 1990). Persistent effects on the frontal-subcortical circuit of human infants have been proposed as one of the possible sequelae of prenatal exposure to cocaine (Mayes, 1999), alcohol (Kaemingk and Paquette, 1999), and marijuana (Fried and Smith, 2001). There is neurological evidence of the frontal-subcortical circuit’s vulnerability to prenatal exposure to these substances: cocaine (Frick and Dow-Edwards, 1995; Friedman et al., 1996; Spear, 1995), alcohol (Mihalick et al., 2001; Sowell et al., 2002; Wass et al., 2001), and, less directly, marijuana (Glass et al., 1997). Researchers have reported EF problems in childhood after prenatal cocaine and alcohol exposure, but many had inadequate control of potential environmental confounds. Espy et al. (1999) compared the performance of clinically recruited cocaine- and polysubstance-exposed toddlers with the performance of nonrisk toddlers on an A-not-B task, a clinically validated assessment of EF (Diamond et al., 1997). They found that the substance-exposed toddlers had lower scores. However, the sample was small, and there was inadequate investigation of potential confounds. The controls were not matched on socioeconomic status (SES) and were older than the cocaine-exposed toddlers. Noland et al. (2003) found that with a prospective design and similar SES controls, heavier cocaine exposure predicted lower performance on the A-not-B task in infants. This later study was still limited by small sample size and lack of control of caregiver psychological functioning. Studies with clinically referred samples report significant negative effects of prenatal alcohol exposure on a wide range of EF tasks, including working memory, verbal fluency, planning, set shifting, and response to feedback (Kodituwakku et al., 1995; Mattson et al., 1999). Not only have EF deficits been shown in clinically referred samples, but these alcohol-related EF deficits are independent of general intelligence (Connor et al., 2000) and seem to be associated with a distinct abnormality of corpus callosum shape (Bookstein et al., 2002). Despite these important teratogenic findings, most previous studies have several limitations, including imprecise quantification of the amount of exposure, very small sample sizes, and inadequate controls for environmental differences, such as maternal intellectual and psychosocial functioning. Three previous studies of EF after prenatal substance exposure have used prospective designs with adequate control of potential confounders. Streissguth et al. (1989) found that in 7-year-olds, prenatal alcohol exposure had a moderate relationship with EF performance. However, Richardson et al. (2002) found no independent effect of either prenatal alcohol or marijuana exposure on EF. From a large, prospective study in preschoolers, Fried et al. (1997) reported a significant marijuana effect on EF after controlling for prenatal and postnatal covariates. However, Fried and Watkinson (2002) have recently reported that in adolescence, there were no marijuana effects on EF (as measured by WCST performance) in this cohort. In summary, there have been no large prospective studies of EF in cocaine-exposed children, and there are conflicting findings from large prospective studies of prenatal alcohol and marijuana effects on EF. Where effects of prenatal alcohol and marijuana exposure have been found, the children were tested at younger ages. In this study, we assessed EF in a young (4 years old) cohort of children the majority of whose mothers had used varying combinations of cocaine, alcohol, and marijuana during pregnancy. The EF tasks assessed in this investigation [category fluency, motor planning, and tapping inhibition (TI)] are similar to tasks that have been clinically validated in adults with frontal lobe injury (Golden, 1981; Milner, 1964; and Luria, 1980, respectively). These three EF tasks are sensitive to the disruption of the dopamine/prefrontal cortical-subcortical system associated with phenylketonuria (PKU) in preschoolers (Diamond et al., 1997; Welsh et al., 1990). Children with PKU cannot metabolize an amino acid, phenylalanine (Phe), which interferes with the production of dopamine, a neurotransmitter on which the frontal-subcortical circuit selectively depends (Diamond et al., 1994). Even children treated early and continuously for PKU have increased levels of Phe. In these children, higher levels of Phe are associated with decreased performance on the EF tasks, including those chosen for this study, but not with impairment of general intellectual functioning (Diamond et al., 1997; Welsh et al., 1990). Although the category-fluency and motor-planning tasks are largely unchanged from the procedure of Welsh et al., the TI task has been modified from the version published by Diamond et al. (the modification is described in more detail in the next section). The EF tasks were administered to 316 children at the 4-year-old visit as part of an ongoing investigation of the effects of prenatal cocaine exposure. In previous studies of this cohort, prenatal cocaine exposure has been associated with decreased birth weight and head circumference (Singer et al., 2001), increased jitteriness (Singer et al., 2000), decreased receptive language (Singer et al., 1999b), disrupted global mental development (Singer et al., 2002a,b), and behavioral disturbances (Singer et al., 2002b). The postnatal environmental assessment included measures of maternal mental functioning and the home environment. With special attention to the possible confounding effects of these covariates, this study explored the direct and indirect relationships between prenatal substance exposure and EF.