8081 MD3 WK 3 Dis
Unique1961
AReviewoftheEffectsofPrenatalCocaineExposure.pdf
A Review of the Effects of Prenatal Cocaine Exposure Among School-Aged Children abstract
John P. Ackerman, PhD, Tracy Riggins, PhD, and Maureen M. Black, PhD Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland
Abstract CONTEXT—Studies through 6 years have shown no long-term direct effects of prenatal cocaine exposure (PCE) on children’s physical growth, developmental test scores, or language outcomes. Little is known about the effects of PCE among school-aged children aged 6 years and older.
OBJECTIVE—We reviewed articles from studies that examined the effects of PCE on growth, cognitive ability, academic functioning, and brain structure and function among school-aged children.
METHODS—Articles were obtained by searching PubMed, Medline, TOXNET, and PsycInfo databases from January 1980 to December 2008 with the terms “prenatal cocaine exposure,” “cocaine,” “drug exposure,” “substance exposure,” “maternal drug use,” “polysubstance,” “children,” “adolescent,” “in utero,” “pregnancy,” “development,” and “behavior.” Criteria for inclusion were (1) empirical research on children aged 6 years and older prenatally exposed to cocaine, (2) peer-reviewed English-language journal, (3) comparison group, (4) longitudinal follow-up or historical prospective design, (5) masked assessment, (6) exclusion of subjects with serious medical disabilities, and (7) studies that reported nonredundant findings for samples used in multiple investigations. Thirty-two unique studies met the criteria. Each article was independently abstracted by 2 authors to obtain sample composition, methods of PCE assessment, study design, comparison groups, dependent variables, covariates, and results.
RESULTS—Associations between PCE and growth, cognitive ability, academic achievement, and language functioning were small and attenuated by environmental variables. PCE had significant negative associations with sustained attention and behavioral self-regulation, even with covariate control. Although emerging evidence suggests PCE-related alterations in brain structure and function, interpretation is limited by methodologic inconsistencies.
CONCLUSIONS—Consistent with findings among preschool-aged children, environmental variables play a key role in moderating and explaining the effects of PCE on school-aged children’s functioning. After controlling for these effects, PCE-related impairments are reliably reported in sustained attention and behavioral self-regulation among school-aged children. Pediatrics 2010;125:554–565
Copyright © 2010 by the American Academy of Pediatrics Address correspondence to Maureen M. Black, PhD, University of Maryland School of Medicine, Department of Pediatrics, 737 W Lombard St, Room 161, Baltimore, MD 21201. [email protected]. FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose. All authors participated in the conceptualization, design, and preparation of the manuscript; Drs Ackerman and Riggins conducted the searches and reviewed the eligible studies; Dr Ackerman drafted the manuscript; Drs Riggins and Black conducted critical revisions; and Dr Black obtained funding.
NIH Public Access Author Manuscript Pediatrics. Author manuscript; available in PMC 2011 August 4.
Published in final edited form as: Pediatrics. 2010 March ; 125(3): 554–565. doi:10.1542/peds.2009-0637.
N IH
-P A
A uthor M
anuscript N
IH -P
A A
uthor M anuscript
N IH
-P A
A uthor M
anuscript
Keywords cocaine; maternal exposure; prenatal exposure delayed effects; attention; behavior; growth; language; adolescent development
The effects of prenatal cocaine exposure (PCE) have been examined in infants and young children across multiple developmental domains (eg, growth, intelligence, language, motor, attention, neurophysiology). A 2001 review of 36 peer-reviewed articles revealed that in most domains, the neurobiological effects of PCE play a subtle role, with effects no greater than other known teratogens or environmental factors.1 Associations between PCE and negative developmental outcomes were typically attenuated when models included conditions that commonly co-occur with PCE (eg, tobacco or alcohol exposure, malnutrition, poor quality of care).
Little is known about the long-term effects of PCE. One possibility is that PCE has direct effects on brain structure or function, which may heighten children’s vulnerability to negative developmental outcomes.2 Another possibility is that PCE is a marker for environmental risk factors and, therefore, must be considered in the context of other developmental threats, including poverty, insensitive parenting, maternal stress and depression, caregiver drug dependence, limited educational resources, unstable home environments, and high rates of domestic violence.3–5 Both perspectives highlight the need to consider the long-term effects of PCE within an environmental and developmental context that includes brain and behavioral development.
Over time, children face increasingly complex cognitive and social demands, requiring advances in aspects of executive control including sustained attention, working memory, planning, inhibitory control, and emotion regulation. Such higher-order processes are thought to underlie children’s ability to engage in behavioral self-regulation, and preclinical models have suggested that PCE may target brain regions and pathways associated with the development of these capabilities. Regions with strong dopaminergic innervation (eg, anterior cingulate cortex, prefrontal cortex, striatum) may be particularly susceptible to PCE.6 Because these regions continue to develop throughout childhood and adolescence, the effects of PCE may not be evident until many years after the initial prenatal exposure.
The effects of PCE are manifest in distinct ways at different ages. Investigations using longitudinal models with covariate controls can examine the differential effects of drug exposure over time. Studies that include parenting and environmental influences (eg, school, neighborhood, peers) are necessary to determine the amount of variance attributed to each level of influence. We reviewed studies of PCE conducted with children aged 6 years and older, focusing on outcomes associated with physical, behavioral, cognitive, and neural development.
METHODS Selection Criteria
We used the following criteria: (1) empirical research on children aged 6 years and older with PCE; (2) publication in peer-reviewed English-language journal between January 1980 and December 2008; (3) comparison group; (4) longitudinal follow-up or historical prospective design; (5) masked assessment; (6) not exclusive focus on pathology (eg, very low birth weight, HIV, brain injury, mental retardation, or other serious medical complications); and (7) production of findings that were distinct from previous reports from the same sample.
Ackerman et al. Page 2
Pediatrics. Author manuscript; available in PMC 2011 August 4.
N IH
-P A
A uthor M
anuscript N
IH -P
A A
uthor M anuscript
N IH
-P A
A uthor M
anuscript
Data Sources Articles were obtained from PubMed, Medline, TOXNET, and PsycInfo by entering key words “prenatal cocaine exposure,” “cocaine,” “drug exposure,” “substance exposure,” “maternal drug use,” “polysubstance,” “children,” “adolescent,” “in utero,” “pregnancy,” “development,” and “behavior” alone and in combinations. References of selected articles were searched to identify additional articles that met selection criteria. We identified 32 unique studies of children and adolescents with PCE; 28 (88%) were published after 2003, representing children in longitudinal cohorts who have reached school age.
Procedures Eligible articles were reviewed independently by 2 authors to determine (1) domain assessed, (2) sample composition, (3) determination of PCE, (4) design and retention, (5) outcome variables and covariates, (6) results, and (7) methodologic strengths and limitations.
RESULTS Fifteen cohorts were represented in the 32 articles reviewed. Sample sizes ranged from 26 to 1056, with a median of 188. Twenty-seven studies (84%) enrolled participants prospectively when infants were younger than 6 months. Most studies (94%) used urine toxicology and/or meconium assay in combination with maternal report to determine PCE. Six studies (19%) examined dose-response effects of PCE.
All samples comprised polysubstance-exposed children, typically with high rates of tobacco, alcohol, and marijuana exposure. Samples for which demographic data were reported were urban, most were low income (3 had no income data), and most (94%) enrolled primarily black participants. The caregiver-child relationship often differed between the PCE and comparison groups. Twenty-two studies (69%) provided nonmaternal care status, and 6 (19%) provided data on kinship status.
Physical Growth Six studies examined children’s growth (Table 1).7–12 Despite significant differences in weight, height, and head circumference at birth, there were few significant growth differences at school age.8–11 Catch-up growth generally occurs by 6 months.11 Four studies found no significant PCE-related differences in weight or weight for age. One study revealed that children with PCE who were assessed at 1, 3, 7, and 10 years grew at a slower rate than comparison children.12 Another study found that PCE dose was associated with weight-for-height standard scores.10 In both studies, children with PCE had weight for age within normal limits, which suggests that even those who were lighter than comparison children remained within normal limits.
Evidence for PCE differences in linear growth (ie, height) was mixed. Three studies showed no differences in children’s height for age. Three studies revealed that children with PCE were shorter than nonexposed children(<1 in) at school age after controlling for relevant covariates including prenatal tobacco and alcohol exposure, comorbid drug use, ethnicity, parent height, and maternal care status.7,10,12 In addition, PCE dose was associated with a small decrease in height.10 Overall, despite significant growth differences between PCE and nonexposed children at birth, height and weight differences were typically small or absent by school age.
Ackerman et al. Page 3
Pediatrics. Author manuscript; available in PMC 2011 August 4.
N IH
-P A
A uthor M
anuscript N
IH -P
A A
uthor M anuscript
N IH
-P A
A uthor M
anuscript
Global Intellectual Functioning and Academic Achievement Eight studies examined intellectual or academic functioning (Table 2).3,4,8,9,13–16 Children ranged in age from 6 to 12 years. Only 1 study showed that children with PCE had significantly lower full-scale IQ scores on standardized assessments of intellectual functioning than comparison children,8 and these differences were substantially attenuated with the inclusion of maternal and environmental covariates. One study did not reveal overall IQ differences, but it was reported that children with PCE performed worse on perceptual reasoning tasks than comparison children and that results were mediated by head circumference.16 Of the 4 studies that assessed academic achievement,3,4,14,16 it was reported for only 1 that comparison children scored higher than children with PCE.14 Most studies included in this review had low-income, urban samples with mean IQ scores between 0.5 and 1.0 SDs below the mean.
Language Functioning Five studies examined language functioning, including expressive, receptive, and global language functioning, with mixed results (Table 3).9,13,17,18,19 Three studies that examined language longitudinally17–19 found small but persistent PCE differences after controlling for relevant environmental and prenatal covariates. Language-related differences were documented early in development and persisted to the same relative degree at school age.17,19 In the only study that assessed children through the age of 9 years,18 PCE differences were not evident after controlling for environmental covariates. Evidence for dose-response effects was also inconsistent. Environmental factors such as caregiver sensitivity, vocabulary, and socioeconomic status (SES) contributed significantly to child language functioning, whereas PCE effect sizes were often small (0.07–0.20 SDs).
Behavioral Functioning Eight studies targeted behavioral functioning (Table 4).3,4,9,20–24 Most of them used parent and/or teacher report of internalizing and externalizing behaviors. Six studies revealed significant differences in behavioral functioning, all favoring nonexposed children3,20–24; however, they varied regarding the covariates and moderators in the analyses. Effect sizes for externalizing behavior problems (eg, aggression and attention) were generally small (average: 0.20 SD) and nonsignificant for internalizing behavior problems (average: 0.10 SD). Most studies, however, relied on behavioral rating scales rather than clinical interviews or other more sensitive diagnostic instruments.
In a dose-response analysis, high PCE was associated with more externalizing and total behavior problems at the age of 7 years than low or no PCE, even after covariate adjustment, including alcohol, tobacco, caregiver depression, and nonmaternal care.20 In 3 other studies,21,23,24 gender moderated behavioral outcomes; boys were at greater risk than girls for delinquency and aggression among PCE children. Three of 4 studies showed that nonmaternal care predicted externalizing problems.4,20,22
Attention Four unique studies examined sustained attention or aspects of executive control by using performance-based neuropsychological measures (Table 5)25–28 such as the Gordon Diagnostic System (GDS),29 the Test of Variables of Attention,30 and Connors’ Performance Test.31 Children with attention problems exhibited poor performance with frequent omissions, an impulsive response style, or variable reaction times.30 Poor performance has been linked to deficient frontal lobe regulatory functioning.32
In one study the GDS was used to assess attention,27 and it was reported that children with PCE were more likely to demonstrate commission errors than nonexposed comparison
Ackerman et al. Page 4
Pediatrics. Author manuscript; available in PMC 2011 August 4.
N IH
-P A
A uthor M
anuscript N
IH -P
A A
uthor M anuscript
N IH
-P A
A uthor M
anuscript
children, after covariate control. Two studies assessed children’s sustained attention by using visual continuous performance tasks at the ages of 6 and 7 years.25,26 Both studies revealed PCE differences in reaction time and omission errors but not commission errors.25 Covariates such as task complexity, nonmaternal care, and quality of caregiving environment influenced children’s attention. An additional study, in which a novel visuospatial maze learning task28 was used, showed that children with PCE made more delayed recall errors than controls and displayed slower processing speed on visuospatial learning tasks.
The mechanisms that underlie sustained attention and other aspects of executive control may be disrupted by PCE. However, the specific effects of PCE may depend on moderators, including drug type and dose, alcohol and/or tobacco exposure, child age, gender, and environmental factors (eg, SES, nonmaternal care, and caregiving quality).
Brain Structure and Function Eight studies used neuroimaging methodologies to examine brain structure and function (Table 6).33–40 Differences in both gray and white matter were reported. The PCE groups had global decreases in cortical gray matter,34 and selective volumetric decreases in the left occipital lobe, right parietal cortex38 and caudate.33,40 Volumetric increases were reported in the amygdala.40 PCE-related differences in white matter include decreased volume of the corpus callosum,38 increased diffusion in bilateral frontal projection fibers,36 and increased levels of creatine in frontal white matter36 suggesting abnormalities in energy metabolism and less mature development of frontal white matter pathways. Differences in gray and white matter varied as a function of the amount of substance exposure36,38 and number of substances to which the fetus was exposed.34 Two investigations reported correlations between gray and white matter differences and behavioral task performance were reported.36,38 These studies provide evidence that PCE disrupts frontally mediated tasks. However, small sample sizes, lack of covariate control, and sample selection limit generalizability.
Three studies that examined brain function related to PCE revealed mixed results.35,39,40 One reported reductions in global cerebral blood flow, with increases in anterior and superior regions during rest with perfusion functional MRI (fMRI).40 Another examined electrical brain responses (ie, event-related potentials) during an inhibitory control task and showed that the PCE group had slower, more prolonged event-related potential responses and a more diffuse pattern of activation than the comparison group.39 The third study revealed PCE differences in regional oxygenated blood flow by using blood oxygen level dependent contrast during a nonspatial working memory fMRI task.35
The limited data suggest subtle differences between PCE and nonexposed children on measures of brain structure and function. However, these findings await replication, because distinct methods and data-analysis techniques have been used with small samples of polysubstance-exposed children with minimal control for potentially confounding environmental factors.
DISCUSSION There are 4 major findings regarding outcomes in school-aged children with PCE. First, associations between PCE and indices of growth, intellectual functioning, academic achievement, and language functioning are modest and often explained by social risk factors such as poverty, caregiver education, placement stability, and quality of child-caregiver relationships. Children with PCE encounter more environmental risk, making it difficult to disentangle the 2 effects. For example, it is unclear whether PCE contributes to disruptive
Ackerman et al. Page 5
Pediatrics. Author manuscript; available in PMC 2011 August 4.
N IH
-P A
A uthor M
anuscript N
IH -P
A A
uthor M anuscript
N IH
-P A
A uthor M
anuscript
behaviors, which increases the possibility of out-of-home placement, or whether caregiver instability leads to negative effects on children’s behavioral self-regulation.
Most studies have shown that children with PCE perform below normative age-level expectations on global developmental measures. Children with PCE often have similar performance patterns to nonexposed children living in similar low-income, urban settings. Across groups, children’s general intellectual outcomes and language functioning tended to decline over time. It is possible that low SES, common to both the PCE and comparison groups, served to depress the children’s scores on tests of intellectual functioning and academic achievement, potentially obscuring group differences.41 PCE does not seem to confer significant risk to school-aged children’s performance on global measures of intellectual functioning, which is consistent with findings reported for younger children.1
Second, performance on tasks that assess sustained attention and behavioral self-regulation seem to be compromised by PCE. Emerging evidence indicates that PCE is likely to disrupt neuronal pathways associated with arousal regulation and areas of the brain responsible for functions such as sustained attention and behavioral self-regulation.2 Specifically, dopaminergic pathways associated with attentional networks, such as the striatal-prefrontal pathway, or other monoaminergically regulated arousal systems, such as the mesolimbic pathway, are disrupted by PCE. Impairments associated with PCE may not become evident until school age or adolescence as the prefrontal cortex and its associated networks undergo substantial developmental change.
The third finding relates to inconsistencies across research groups. Studies varied in sample composition, sample size, attrition rates, determination of exposure status, covariate control, and examination of potential moderators. Most studies (with the notable exception of neuroimaging studies) have incorporated demographic, prenatal, and postnatal environmental covariates into statistical analyses, but the specific covariates and the consistency of their use vary widely. Gender, race, birth weight, prenatal alcohol and/or tobacco exposure, nonmaternal care, continued maternal drug use, caregiver mental health, and poverty often moderate associations between PCE and developmental outcomes. Most investigators evaluate moderators and confounders before attributing observed differences to PCE, but often with low power to detect differences. Generalization is also a concern; most samples are limited to low-income, urban, black children.
Most studies involved children who were exposed to multiple substances (both legal and illegal drugs), reflecting that polysubstance use is the rule rather than an exception. Although studies of dose and timing have yielded promising findings, measurement of specific substances, dose, and timing of substance use is inconsistent because illicit substance use is unregulated, self-report varies in reliability, and biological assays are not used consistently. On the basis of a teratogenic model, increasing doses would lead to worsening outcomes. However, without evidence, negative effects may be misattributed to PCE rather than to other substances or environmental confounds. Innovative methods are needed to study specific substances, dose-effect models, and the timing and duration of exposure.
Finally, from recent studies that used neuroimaging techniques, subtle PCE effects in both brain structure and function have been reported. Although preliminary, data suggest that structural differences in brain development after PCE may be associated with specific neurocognitive deficits. However, most studies have lacked covariate control, raising concerns about potential confounds. A future aim will be to link neural differences with meaningful behavioral outcomes.
Ackerman et al. Page 6
Pediatrics. Author manuscript; available in PMC 2011 August 4.
N IH
-P A
A uthor M
anuscript N
IH -P
A A
uthor M anuscript
N IH
-P A
A uthor M
anuscript
Future Directions In future studies, researchers should strive to include both traditional cognitive-behavioral measures and assessments of executive function, decision-making, and emotion regulation in combination with measures of underlying brain structure and function. As participants in longitudinal PCE investigations approach adolescence, their health risk behaviors may increase, including adolescent drug use.21 Measures that simulate risky decision-making in a laboratory setting (eg, Balloon Analog Risk Task42) or that require emotion-regulation skills would add to the understanding of PCE effects, beyond the potential bias and unreliability of self-report measures. Findings from laboratory-based measures associated with adolescent health risk behaviors not only enhance the ecological validity of the research but also increase the relevance to public health and policy by identifying adolescents in need of intervention.
Neuroimaging technology such as fMRI represents an opportunity to link PCE to neurocognitive task performance and to the identifiable neural substrates associated with specific outcomes. A shortcoming of traditional neuropsychological tests is an inability to attribute performance to specific brain regions or pathways. Neuroimaging provides added explanatory power by demonstrating that performance is linked to specific brain activities.
Investigators should be encouraged to pool data when appropriate to enable the examination of statistical interactions. Potential moderating effects of age, gender, and caregiving stability on developmental outcomes have been noted in several studies. Others have examined severity and timing of PCE and found that PCE dose is associated with specific developmental outcomes. The evaluation of moderators will enhance our understanding of vulnerabilities associated with PCE in critical ways, but such analyses require large sample sizes to be powered adequately.
CONCLUSIONS Until recently, there have been few well-controlled longitudinal studies of PCE that assessed the physical, behavioral, cognitive, and neural development of school-aged children. Recent studies have provided evidence that PCE is associated with deficits in sustained attention and behavioral regulation, perhaps by altering brain activity in areas susceptible to the effects of toxins in utero. For global indices of development, such as physical growth and cognitive ability, PCE does not provide much additional risk beyond the multiple co- occurring environmental risk factors. However, a drug-using lifestyle increases the likelihood that children will experience multiple environmental risks, making it difficult to isolate the teratogenic effects of PCE. Progress continues to be made by including moderators and explanatory variables in statistical models to improve the interpretation of the short-and long-term effects of PCE.
From a public health perspective, prevention efforts should be aimed at not only reducing the incidence of drug use during pregnancy but also providing educational and therapeutic resources to caregivers in low-income, urban environments who face multiple environmental stressors. Developing services that promote caregiver self-care, supportiveness, and behavior-management skills may reduce the negative impact of PCE and environmental risk factors on children’s development and behavior.
Acknowledgments This study was supported by National Institute of Drug Abuse grants R01-DA07432 and R01-DA021059.
We acknowledge Maria Graciela Mujica, who contributed to reviewing data and ensuring the accuracy of details in the tables.
Ackerman et al. Page 7
Pediatrics. Author manuscript; available in PMC 2011 August 4.
N IH
-P A
A uthor M
anuscript N
IH -P
A A
uthor M anuscript
N IH
-P A
A uthor M
anuscript
ABBREVIATIONS
PCE prenatal cocaine exposure
SES socioeconomic status
GDS Gordon Diagnostic System
fMRI functional MRI
References 1. Frank DA, Augustyn M, Knight WG, Pell T, Zuckerman B. Growth, development, and behavior in
early childhood following prenatal cocaine exposure: a systematic review. JAMA. 2001; 285(12): 1613–1625. [PubMed: 11268270]
2. Mayes LC. A behavioral teratogenic model of the impact of prenatal cocaine exposure on arousal regulatory systems. Neurotoxicol Teratol. 2002; 24(3):385–395. [PubMed: 12009493]
3. Nair P, Black M, Ackerman J, Schuler M, Keane V. Children’s cognitive-behavioral functioning at age 6 and 7: prenatal drug exposure and caregiving environment. Ambul Pediatr. 2008; 8(3):154– 162. [PubMed: 18501861]
4. Hurt H, Brodsky NL, Roth H, Malmud E, Giannetta JM. School performance of children with gestational cocaine exposure. Neurotoxicol Teratol. 2005; 27(2):203–211. [PubMed: 15734271]
5. Yumoto C, Jacobson SW, Jacobson JL. Fetal substance exposure and cumulative environmental risk in an African American cohort. Child Dev. 2008; 79(6):1761–1776. [PubMed: 19037948]
6. Harvey JA. Cocaine effects on the developing brain: current status. Neurosci Biobehav Rev. 2004; 27(8):751–764. [PubMed: 15019425]
7. Covington CY, Nordstrom-Klee B, Ager J, Sokol R, Delaney-Black V. Birth to age 7 growth of children prenatally exposed to drugs: a prospective cohort study. Neurotoxicol Teratol. 2002; 24(4): 489–496. [PubMed: 12127894]
8. Arendt R, Short E, Singer LT, et al. Children prenatally exposed to cocaine: developmental outcomes and environmental risks at seven years of age. J Dev Behav Pediatr. 2004; 25(2):83–90. [PubMed: 15083129]
9. Kilbride HW, Castor CA, Fuger KL. School-age outcome of children with prenatal cocaine exposure following early case management. J Dev Behav Pediatr. 2006; 27(3):181–187. [PubMed: 16775513]
10. Minnes S, Robin N, Alt A, et al. Dysmorphic and anthropometric outcomes in 6-year-old prenatally cocaine-exposed children. Neurotoxicol Teratol. 2006; 28(1):28–38. [PubMed: 16298510]
11. Lumeng JC, Cabral HJ, Gannon K, Heeren T, Frank DA. Prenatal exposures to cocaine and alcohol and physical growth patterns to age 8 years. Neurotoxicol Teratol. 2007; 29(4):446–457. [PubMed: 17412558]
12. Richardson, GA.; Goldschmidt, L.; Larkby, C. Effects of prenatal cocaine exposure on growth: a longitudinal analysis. Pediatrics. 2007. Available at: www.pediatrics.org/cgi/content/full/120/4/e1017
13. Delaney-Black V, Covington C, Templin T, et al. Expressive language development of children exposed to cocaine prenatally: literature review and report of a prospective cohort study. J Commun Disord. 2000; 33(6):463–481. [PubMed: 11141028]
14. Morrow CE, Culbertson JL, Accornero VH, Xue L, Anthony JC, Bandstra ES. Learning disabilities and intellectual functioning in school-aged children with prenatal cocaine exposure. Dev Neuropsychol. 2006; 30(3):905–931. [PubMed: 17083299]
15. Wasserman GA, Kline JK, Bateman DA, et al. Prenatal cocaine exposure and school-age intelligence. Drug Alcohol Depend. 1998; 50(3):203–210. [PubMed: 9649973]
16. Singer LT, Nelson S, Short E, et al. Prenatal cocaine exposure: drug and environmental effects at 9 years. J Pediatr. 2008; 153(1):105–111. [PubMed: 18571546]
Ackerman et al. Page 8
Pediatrics. Author manuscript; available in PMC 2011 August 4.
N IH
-P A
A uthor M
anuscript N
IH -P
A A
uthor M anuscript
N IH
-P A
A uthor M
anuscript
17. Bandstra ES, Vogel AL, Morrow CE, Xue L, Anthony JC. Severity of prenatal cocaine exposure and child language functioning through age seven years: a longitudinal latent growth curve analysis. Subst Use Misuse. 2004; 39(1):25–59. [PubMed: 15002943]
18. Beeghly M, Martin B, Rose-Jacobs R, et al. Prenatal cocaine exposure and children’s language functioning at 6 and 9.5 years: moderating effects of child age, birth-weight, and gender. J Pediatr Psychol. 2006; 31(1):98–115. [PubMed: 15843502]
19. Lewis, BA.; Kirchner, HL.; Short, EJ., et al. Prenatal cocaine and tobacco effects on children’s language trajectories. Pediatrics. 2007. Available at: www.pediatrics.org/cgi/content/full/120/1/e78
20. Bada HS, Das A, Bauer CR, et al. Low birth weight and preterm births: etiologic fraction attributable to prenatal drug exposure. J Perinatol. 2005; 25(10):631–637. [PubMed: 16107872]
21. Bennett D, Bendersky M, Lewis M. Preadolescent health risk behavior as a function of prenatal cocaine exposure and gender. J Dev Behav Pediatr. 2007; 28(6):467–472. [PubMed: 18091092]
22. Linares TJ, Singer LT, Kirchner HL, et al. Mental health outcomes of cocaine-exposed children at 6 years of age. J Pediatr Psychol. 2006; 31(1):85–97. [PubMed: 15802608]
23. Nordstrom Bailey B, Sood BG, Sokol RJ, et al. Gender and alcohol moderate prenatal cocaine effects on teacher-report of child behavior. Neurotoxicol Teratol. 2005; 27(2):181–189. [PubMed: 15734269]
24. Sood BG, Nordstrom Bailey B, Covington C, et al. Gender and alcohol moderate caregiver reported child behavior after prenatal cocaine. Neurotoxicol Teratol. 2005; 27(2):191–201. [PubMed: 15734270]
25. Accornero VH, Amado AJ, Morrow CE, Xue L, Anthony JC, Bandstra ES. Impact of prenatal cocaine exposure on attention and response inhibition as assessed by continuous performance tests. J Dev Behav Pediatr. 2007; 28(3):195–205. [PubMed: 17565286]
26. Ackerman JP, Llorente AM, Black MM, et al. The effect of prenatal drug exposure and caregiving context on children’s performance on a task of sustained visual attention. J Dev Behav Pediatr. 2008; 29(6):467–474. [PubMed: 19047916]
27. Savage J, Brodsky NL, Malmud E, Giannetta JM, Hurt H. Attentional functioning and impulse control in cocaine-exposed and control children at age ten years. J Dev Behav Pediatr. 2005; 26(1):42–47. [PubMed: 15718883]
28. Schroder MD, Snyder PJ, Sielski I, Mayes L. Impaired performance of children exposed in utero to cocaine on a novel test of visuospatial working memory. Brain Cogn. 2004; 55(2):409–412. [PubMed: 15177825]
29. Gordon, M.; Barkley, RA. Tests and behavioral measures. In: Barkley, RA., editor. Attention- Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment. 2. New York, NY: Guilford; 1998. p. 294-311.
30. Leark, RA.; Dupuy, TR.; Greenberg, LM.; Corman, CL.; Kindschi, CL. Test of Variables of Attention Professional Manual Version 7.0. Los Alimitos, CA: Universal Attention Disorders, Inc; 1996.
31. Conners, CK. The Conners Continuous Performance Test. Toronto, Ontario, Canada: Multi-Health Systems; 1994.
32. Barkley, RA. Attention-Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment. 2. New York, NY: Guilford; 1998.
33. Avants BB, Hurt H, Giannetta JM, et al. Effects of heavy in utero cocaine exposure on adolescent caudate morphology. Pediatr Neurol. 2007; 37(4):275–279. [PubMed: 17903672]
34. Rivkin MJ, Davis PE, Lemaster JL, et al. Volumetric MRI study of brain in children with intrauterine exposure to cocaine, alcohol, tobacco, and marijuana. Pediatrics. 2008; 121(4):741– 750. [PubMed: 18381539]
35. Hurt H, Giannetta JM, Korczykowski M, et al. Functional magnetic resonance imaging and working memory in adolescents with gestational cocaine exposure. J Pediatr. 2008; 152(3):371– 377. [PubMed: 18280843]
36. Warner TD, Behnke M, Eyler FD, et al. Diffusion tensor imaging of frontal white matter and executive functioning in cocaine-exposed children. Pediatrics. 2006; 118(5):2014–2024. [PubMed: 17079574]
Ackerman et al. Page 9
Pediatrics. Author manuscript; available in PMC 2011 August 4.
N IH
-P A
A uthor M
anuscript N
IH -P
A A
uthor M anuscript
N IH
-P A
A uthor M
anuscript
37. Smith LM, Chang L, Yonekura ML, et al. Brain proton magnetic resonance spectroscopy and imaging in children exposed to cocaine in utero. Pediatrics. 2001; 107(2):227–231. [PubMed: 11158451]
38. Singer LT, Lewin J, Minnes S, et al. Neuroimaging of 7–8 year-old children exposed prenatally to cocaine. Neurotoxicol Teratol. 2006; 28(3):386–402. [PubMed: 16832875]
39. Mayes LC, Molfese DL, Key A, Hunter NC. Event-related potentials in cocaine-exposed children during a Stroop task. Neurotoxicol Teratol. 2005; 27(6):797–813. [PubMed: 16111858]
40. Rao, H.; Wang, J.; Giannetta, J., et al. Altered resting cerebral blood flow in adolescents with in utero cocaine exposure revealed by perfusion functional MRI. Pediatrics. 2007. Available at: www.pediatrics.org/cgi/content/full/120/5/e1245
41. Engle P, Black MM. The effect of poverty on child development and educational outcomes. Ann N Y Acad Sci. 2008; 1136:243–259. [PubMed: 18579886]
42. Lejuez CW, Read JP, Kahler CW, et al. Evaluation of a behavioral measure of risk taking: the Balloon Analogue Risk Task (BART). J Exp Psychol Appl. 2002; 8(2):75–84. [PubMed: 12075692]
Ackerman et al. Page 10
Pediatrics. Author manuscript; available in PMC 2011 August 4.
N IH
-P A
A uthor M
anuscript N
IH -P
A A
uthor M anuscript
N IH
-P A
A uthor M
anuscript
N IH
-P A
A uthor M
anuscript N
IH -P
A A
uthor M anuscript
N IH
-P A
A uthor M
anuscript
Ackerman et al. Page 11
TA B
LE 1
Ph ys
ic al
G ro
w th
St ud
y/ C
oh or
t Su
bj ec
ts O
ut co
m e
M ea
su re
s A
ge , y
Su bs
ta nc
e E
xp os
ur es
Se le
ct io
n/ M
at ch
in g
C on
tr ol
P C
E E
ff ec
t O
th er
E ff
ec ts
/C om
m en
ts
C ov
in gt
on e
t a l7
(2 00
2) , c
oh or
t 1 23
1 PO
L Y
, 30
9 C
O N
W ei
gh t,
he ig
ht 7
C , A
, T L
ow in
co m
e, u
rb an
, bl
ac k,
G A
> 3
8 w
k C
hi ld
: T , B
W , B
L ,
no nm
at er
na l c
ar e,
b lo
od le
ad le
ve l;
ca re
gi ve
r: ag
e, h
ei gh
t, w
ei gh
t, SE
S, s
ub st
an ce
u se
, m
ar ita
l s ta
tu s,
ps yc
ho pa
th ol
og y,
s oc
ia l
su pp
or t
W ei
gh t:
no ne
; he
ig ht
: P C
E sh
or te
r
A ss
oc ia
tio ns
s tr
on ge
r f or
ca re
gi ve
r > 3
0 y
ol d;
a lc
oh ol
ex po
su re
c on
tr ib
ut ed
to lo
w er
w ei
gh t
A re
nd t e
t a l8
(2 00
4) , c
oh or
t 2 10
1 PO
L Y
, 13
0 C
O N
W ei
gh t,
he ig
ht , H
C 7
C , A
, M , T
L ow
in co
m e,
u rb
an ,
bl ac
k, G
A >
3 7
w k
C hi
ld : A
, M , T
, r ac
e, no
nm at
er na
l c ar
e; ca
re gi
ve r:
a ge
, I Q
, S E
S, pa
ri ty
, ps
yc ho
pa th
ol og
y, h
om e
en vi
ro nm
en t
N on
e G
ro up
s di
ff er
ed o
n nu
m er
ou s
pr en
at al
a nd
e nv
ir on
m en
ta l
va ri
ab le
s
K ilb
ri de
e t a
l9 (2
00 6)
, c oh
or t 3
39 P
O L
Y ,
12 C
O N
W ei
gh t,
he ig
ht 7
C , A
, T L
ow in
co m
e, u
rb an
, bl
ac k
C hi
ld : A
, T N
on e
R C
T , e
ar ly
in te
rv en
tio n;
h ig
h at
tr iti
on ra
te ; l
im ite
d po
w er
M in
ne s
et a
l1 0
(2 00
6) , c
oh or
t 4 15
4 PO
L Y
, 13
1 C
O N
W ei
gh t,
he ig
ht ,
m or
ph ol
og y,
ne ur
om ot
or fu
nc tio
ni ng
6– 7
C , A
, M , T
L ow
in co
m e,
u rb
an ,
bl ac
k, G
A >
3 7
w k
C hi
ld : A
, M , T
, r ac
e, no
nm at
er na
l c ar
e; ca
re gi
ve r:
a ge
, I Q
, S E
S, pa
ri ty
, ps
yc ho
pa th
ol og
y, h
om e
en vi
ro nm
en t
H ei
gh t:
PC E
do se
a ss
oc ia
te d
w ith
s ho
rt er
st at
ur e;
w ei
gh t:
PC E
d os
e as
so ci
at ed
w ith
lo w
er w
ei gh
t- fo
r- h
ei gh
t sc
or es
N o
m or
ph ol
og y
or n
eu ro
m ot
or fi
nd in
gs
L um
en g
et a
l1 1
(2 00
7) , c
oh or
t 5 11
2 PO
L Y
, 9 0
C O
N
W ei
gh t,
he ig
ht , H
C 6–
7 C
, A , M
, T L
ow in
co m
e, u
rb an
, bl
ac k,
G A
> 3
6 w
k C
hi ld
: A , M
, T g
en de
r, ra
ce , G
A , n
on m
at er
na l
ca re
, b lo
od le
ad le
ve l,
an em
ia ; c
ar eg
iv er
: a ge
, he
ig ht
, w ei
gh t
N on
e N
o PC
E d
os e
as so
ci at
io ns
re po
rt ed
R ic
ha rd
so n
et al
12 (2
00 7)
, co
ho rt
6
99 P
O L
Y ,
12 5
C O
N W
ei gh
t, he
ig ht
, H C
7, 1
0 C
, A , M
, T L
ow in
co m
e, u
rb an
, 50
% b
la ck
, 5 0%
w hi
te ,
G A
> 3
4 w
k
C hi
ld : A
, M , T
g en
de r,
ra ce
, a ge
, n on
m at
er na
l ca
re ; c
ar eg
iv er
: a ge
, he
ig ht
, S E
S, e
du ca
tio n,
m ar
ita l s
ta tu
s, de
pr es
si on
, h om
e en
vi ro
nm en
t
H ei
gh t:
ch ild
re n
w ith
P C
E sh
or te
r a t 7
a nd
10 y
; w ei
gh t:
ch ild
re n
w ith
PC E
li gh
te r a
t 7 an
d 10
y ; H
C :
ch ild
re n
w ith
PC E
s m
al le
r H
C a
t 7 a
nd 1
0 y
C hi
ld re
n w
ith P
C E
w er
e 0.
75 in
s ho
rt er
, 1 0
lb li
gh te
r t ha
n C
O N
c hi
ld re
n at
a ge
1 0
y; a
ge an
d ge
nd er
m od
er at
ed e
ff ec
ts
PO L
Y in
di ca
te s
ex po
su re
to m
ul tip
le d
ru gs
; C O
N , n
on ex
po se
d co
nt ro
ls ; C
, c oc
ai ne
e xp
os ur
e; A
, a lc
oh ol
e xp
os ur
e; T
, t ob
ac co
e xp
os ur
e; G
A , g
es ta
tio na
l a ge
; B W
, b ir
th w
ei gh
t; B
L , b
ir th
le ng
th ; H
C , h
ea d
ci rc
um fe
re nc
e; M
, m ar
iju an
a ex
po su
re ; R
C T
, r an
do m
iz ed
c on
tr ol
tr ia
l.
Pediatrics. Author manuscript; available in PMC 2011 August 4.
N IH
-P A
A uthor M
anuscript N
IH -P
A A
uthor M anuscript
N IH
-P A
A uthor M
anuscript
Ackerman et al. Page 12
TA B
LE 2
G lo
ba l I
nt el
le ct
ua l F
un ct
io ni
ng a
nd A
ca de
m ic
A ch
ie ve
m en
t
St ud
y/ C
oh or
t Su
bj ec
ts O
ut co
m e
M ea
su re
s A
ge , y
Su bs
ta nc
e E
xp os
ur es
Se le
ct io
n/ M
at ch
in g
C on
tr ol
P C
E E
ff ec
t O
th er
E ff
ec ts
/C om
m en
ts
N ai
r e t a
l3 (2
00 8)
, c oh
or t 7
11 1
PO L
Y , 6
2 C
O N
St an
fo rd
-B in
et IV
6– 7
C , T
, H L
ow in
co m
e, u
rb an
, bl
ac k,
G A
> 32
w k
C hi
ld : T
, g en
de r,
ag e,
no nm
at er
na l c
ar e;
ca re
gi ve
r: S
E S,
em pl
oy m
en t,
de pr
es si
on , h
om e
en vi
ro nm
en t
N on
e G
ir ls
h ad
h ig
he r s
co re
s on
ov er
al l I
Q a
nd 4
o f 8
S ta
nf or
d- B
in et
IV s
ub te
st s
H ur
t e t a
l4 (2
00 5)
, c oh
or t 8
62 P
O L
Y ,
73 C
O N
W PP
SI -R
; S ta
nf or
d- 9
re ad
in g,
m at
h, a
nd s
ci en
ce ac
hi ev
em en
t
9– 12
C , A
, M , T
L ow
in co
m e,
u rb
an ,
bl ac
k, G
A >
34 w
k C
hi ld
: g en
de r,
ag e,
no nm
at er
na l c
ar e;
ca re
gi ve
r: s
ub st
an ce
us e,
h om
e en
vi ro
nm en
t
N on
e Sc
ho ol
o ut
co m
es w
er e
pr ed
ic te
d by
c hi
ld IQ
, h om
e en
vi ro
nm en
t, hi
st or
y of
fo st
er ca
re , a
nd c
om pu
te ri
ze d
at te
nt io
n sc
or es
A re
nd t e
t a l8
(2 00
4) , c
oh or
t 2 10
1 PO
L Y
, 13
0 C
O N
W IS
C -I
II 7
C , A
, M , T
L ow
in co
m e,
u rb
an ,
bl ac
k, G
A >
37 w
k C
hi ld
: A , M
, T , r
ac e,
no nm
at er
na l c
ar e;
ca re
gi ve
r: a
ge , I
Q ,
SE S,
p ar
ity ,
ps yc
ho pa
th ol
og y,
ho m
e en
vi ro
nm en
t
N on
e U
na dj
us te
d PC
E d
ef ic
its in
fu ll-
sc al
e an
d ve
rb al
IQ w
er e
at te
nu at
ed a
ft er
c on
tr ol
lin g
fo r
pr en
at al
a nd
e nv
ir on
m en
ta l
co va
ri at
es ; m
at er
na l I
Q a
nd ho
m e
en vi
ro nm
en t p
re di
ct ed
ch ild
IQ
K ilb
ri de
e t a
l9 (2
00 6)
, c oh
or t 3
39 P
O L
Y ,
12 C
O N
St an
fo rd
-B in
et -I
II 7
C , A
, T L
ow in
co m
e, u
rb an
, bl
ac k
C hi
ld : A
, T N
on e
R C
T , e
ar ly
in te
rv en
tio n;
h ig
h at
tr iti
on ra
te ; l
im ite
d po
w er
D el
an ey
-B la
ck et
a l1
3 (2
00 0)
, co
ho rt
1
18 6
PO L
Y ,
27 2
C O
N
W PP
SI -R
6 C
, A , M
, T L
ow in
co m
e, u
rb an
, bl
ac k,
G A
> 38
w k
C hi
ld : B
W , B
L , H
C ,
ag e,
g en
de r,
ra ce
, bl
oo d
le ad
le ve
l, no
nm at
er na
l c ar
e; ca
re gi
ve r:
a ge
, ed
uc at
io n,
m ar
ita l
st at
us , s
ub st
an ce
u se
, SE
S, h
yp er
te ns
io n,
ho m
e en
vi ro
nm en
t
N on
e N
on e
M or
ro w
e t a
l1 4
(2 00
6) , c
oh or
t 9 21
2 PO
L Y
, 19
7 C
O N
W IS
C -I
II ; W
IA T
m at
h an
d re
ad in
g su
bt es
ts 7
C , A
, M , T
L ow
in co
m e,
u rb
an ,
bl ac
k, G
A >
37 w
k C
hi ld
: A , M
, T , B
W ,
B L
, H C
, a ge
, g en
de r,
bl oo
d le
ad le
ve l,
H ea
d St
ar t a
tte nd
an ce
, no
nm at
er na
l c ar
e; ca
re gi
ve r:
a ge
, ed
uc at
io n,
m ar
ita l
st at
us , s
ub st
an ce
u se
, em
pl oy
m en
t, ho
m e
en vi
ro nm
en t
N on
e C
hi ld
re n
w ith
P C
E w
er e
3 tim
es m
or e
lik el
y th
an C
O N
ch ild
re n
to m
ee t c
ri te
ri a
fo r
le ar
ni ng
d is
ab ili
ty ; n
o PC
E do
se e
ff ec
t; bo
th g
ro up
s be
lo w
ag e-
le ve
l e xp
ec ta
tio ns
W as
se rm
an e
t al
15 (1
99 8)
, co
ho rt
1 0
98 P
O L
Y ,
10 8
C O
N W
IS C
-I II
; R av
en ’s
M at
ri ce
s 6–
9 C
, A , M
, T L
ow in
co m
e, u
rb an
, bl
ac k
C hi
ld : B
W , a
ge ,
ge nd
er , h
ei gh
t, H
C ,
bl oo
d le
ad le
ve l,
no nm
at er
na l c
ar e;
ca re
gi ve
r: a
ge , I
Q ,
ed uc
at io
n, S
E S,
N on
e So
ci al
a dv
er si
ty fa
ct or
s w
er e
st ro
ng es
t p re
di ct
or s
of c
hi ld
IQ ; b
ot h
gr ou
ps b
el ow
a ge
- le
ve l e
xp ec
ta tio
ns
Pediatrics. Author manuscript; available in PMC 2011 August 4.
N IH
-P A
A uthor M
anuscript N
IH -P
A A
uthor M anuscript
N IH
-P A
A uthor M
anuscript
Ackerman et al. Page 13
St ud
y/ C
oh or
t Su
bj ec
ts O
ut co
m e
M ea
su re
s A
ge , y
Su bs
ta nc
e E
xp os
ur es
Se le
ct io
n/ M
at ch
in g
C on
tr ol
P C
E E
ff ec
t O
th er
E ff
ec ts
/C om
m en
ts su
bs ta
nc e
us e,
h om
e en
vi ro
nm en
t
Si ng
er e
t a l1
6
(2 00
8) , c
oh or
t 11
19 2
PO L
Y ,
17 9
C O
N
W IS
C -I
V ; W
oo dc
oc k
Jo hn
so n-
II I T
es ts
o f
A ch
ie ve
m en
t
9 C
, A , M
, T L
ow in
co m
e, u
rb an
, bl
ac k,
G A
> 37
w k
C hi
ld : B
W , B
L , H
C ,
ag e,
g en
de r,
ra ce
, bl
oo d
le ad
le ve
l, no
nm at
er na
l c ar
e; ca
re gi
ve r:
a ge
, I Q
, pa
ri ty
, p re
na ta
l c ar
e, ed
uc at
io n,
m ar
ita l
st at
us , s
ub st
an ce
u se
, em
pl oy
m en
t, ho
m e
en vi
ro nm
en t
C hi
ld re
n w
ith P
C E
ha d
lo w
er pe
rc ep
tu al
re as
on in
g sc
or es
Pe rc
ep tu
al re
as on
in g
de fi
ci ts
am on
g ch
ild re
n w
ith P
C E
m ed
ia te
d by
H C
; n o
PC E
ef fe
ct s
fo r a
ca de
m ic
ac hi
ev em
en t
PO L
Y in
di ca
te s
ex po
su re
to m
ul tip
le d
ru gs
; C O
N , n
on ex
po se
d co
nt ro
ls ; C
, c oc
ai ne
e xp
os ur
e; A
, a lc
oh ol
e xp
os ur
e; T
, t ob
ac co
e xp
os ur
e; H
, h er
oi n
ex po
su re
; G A
, g es
ta tio
na l a
ge ; W
PP SI
-R , W
ec hs
le r
Pr es
ch oo
l a nd
P ri
m ar
y Sc
al e
of In
te lli
ge nc
e- R
ev is
ed e
di tio
n; M
, m ar
iju an
a ex
po su
re ; W
IS C
, W ec
hs le
r I nt
el lig
en ce
S ca
le fo
r C hi
ld re
n; W
IA T
, W ec
hs le
r I nd
iv id
ua l A
ch ie
ve m
en t T
es t;
R C
T , r
an do
m iz
ed ,
co nt
ro lle
d tr
ia l;
B W
, b ir
th w
ei gh
t; B
L , b
ir th
le ng
th ; H
C , h
ea d
ci rc
um fe
re nc
e.
Pediatrics. Author manuscript; available in PMC 2011 August 4.
N IH
-P A
A uthor M
anuscript N
IH -P
A A
uthor M anuscript
N IH
-P A
A uthor M
anuscript
Ackerman et al. Page 14
TA B
LE 3
L an
gu ag
e Fu
nc tio
ni ng
St ud
y/ C
oh or
t Su
bj ec
ts O
ut co
m e
M ea
su re
s A
ge , y
Su bs
ta nc
e E
xp os
ur es
Se le
ct io
n/ M
at ch
in g
C on
tr ol
P C
E E
ff ec
t O
th er
E ff
ec ts
/C om
m en
ts
K ilb
ri de
e t a
l9 (2
00 6)
, c oh
or t 3
39 P
O L
Y ,
12 C
O N
C E
L F-
3 7
C , A
, T L
ow in
co m
e, u
rb an
, bl
ac k
C hi
ld : A
, T N
on e
R C
T , e
ar ly
in te
rv en
tio n;
h ig
h at
tr iti
on ra
te ; l
im ite
d po
w er
B an
ds tr
a et
a l1
7
(2 00
4) , c
oh or
t 9 20
0 PO
L Y
, 17
6 C
O N
C E
L F-
P; N
E PS
Y L
an gu
ag e
C or
e; W
IS C
-I II
s ho
rt fo
rm
3, 5
, 7 C
, A , M
, T L
ow in
co m
e, u
rb an
, bl
ac k,
G A
> 37
w k
C hi
ld : A
, M , T
, B W
, B
L , H
C , a
ge , g
en de
r, bl
oo d
le ad
le ve
l, H
ea d
St ar
t a tte
nd an
ce ,
no nm
at er
na l c
ar e;
ca re
gi ve
r: a
ge ,
ed uc
at io
n, m
ar ita
l st
at us
, s ub
st an
ce u
se ,
em pl
oy m
en t,
ho m
e en
vi ro
nm en
t
C hi
ld re
n w
ith PC
E h
ad lo
w er
la ng
ua ge
fu nc
tio ni
ng a
t ea
ch ti
m e
po in
t (~
0. 2
SD )
PC E
d os
e as
so ci
at ed
w ith
s ub
tle di
ff er
en ce
s in
c hi
ld re
n’ s
la ng
ua ge
at a
ge s
3, 5
, a nd
7 y
; N o
di ff
er en
ce s
in d
ev el
op m
en ta
l tr
aj ec
to ri
es o
f P C
E a
nd C
O N
gr ou
ps
D el
an ey
-B la
ck et
a l1
3 (2
00 0)
, co
ho rt
1
18 6
PO L
Y ,
27 2
C O
N
A ri
zo na
A rt
ic ul
at io
n Pr
of ic
ie nc
y Sc
al e;
la ng
ua ge
s am
pl es
co de
d fr
om a
d ya
di c
in te
ra ct
io n
w ith
a n
ex am
in er
6 C
, A , M
, T L
ow in
co m
e, u
rb an
, bl
ac k,
G A
> 38
w k
C hi
ld : B
W , B
L , H
C ,
ag e,
g en
de r,
ra ce
, bl
oo d
le ad
le ve
l, no
nm at
er na
l c ar
e; ca
re gi
ve r:
a ge
, ed
uc at
io n,
m ar
ita l
st at
us , s
ub st
an ce
u se
, SE
S, h
yp er
te ns
io n,
ho m
e en
vi ro
nm en
t
N on
e N
o PC
E d
if fe
re nc
es in
e xp
re ss
iv e
la ng
ua ge
; c hi
ld re
n w
ith p
oo r
la ng
ua ge
w er
e 2.
4 tim
es m
or e
lik el
y to
h av
e ha
d PC
E ; q
ua lit
y of
la ng
ua ge
s am
pl es
d id
n ot
d if
fe r
be tw
ee n
PC E
a nd
C O
N c
hi ld
re n
B ee
gh ly
e t a
l1 8
(2 00
6) , c
oh or
t 5 85
P O
L Y
, 75
C O
N T
es t o
f L an
gu ag
e D
ev el
op m
en t-
3; C
E L
F- 3
6, 9
.5 C
, A , M
, T L
ow in
co m
e, u
rb an
, bl
ac k,
G A
> 36
w k
C hi
ld : A
, M , T
, g en
de r,
ra ce
, I Q
, n on
m at
er na
l ca
re , b
lo od
le ad
le ve
l, ea
rl y
in te
rv en
tio n
st at
us ; c
ar eg
iv er
: a ge
, ra
ce , e
du ca
tio n,
p ar
ity ,
ve rb
al IQ
, S E
S, ho
us eh
ol d
si ze
, su
bs ta
nc e
us e
C hi
ld re
n w
ith PC
E h
ad lo
w er
re ce
pt iv
e la
ng ua
ge sc
or es
a t 6
y o
f ag
e bu
t n ot
a t 9
y of
a ge
; n o
to ta
l l an
gu ag
e di
ff er
en ce
s af
te r
co nt
ro lli
ng fo
r co
va ri
at es
; n o
PC E
d os
e as
so ci
at io
ns
Po si
tiv e
pr ed
ic to
rs o
f l an
gu ag
e w
er e
ca re
gi ve
r v er
ba l I
Q , H
ea d
St ar
t, no
v io
le nc
e ex
po su
re ,
pl ac
em en
t i n
no nk
in fo
st er
c ar
e; ou
tc om
es m
od er
at ed
b y
B W
, a ge
, an
d ge
nd er
L ew
is e
t a l1
9
(2 00
7) , c
oh or
t 11
19 2
PO L
Y ,
17 9
C O
N
Pr es
ch oo
l L an
gu ag
e Sc
al e-
3 rd
E di
tio n
(a ge
1– 2)
; C E
L F-
P (a
ge 4
); C
A SL
(a ge
6 )
1, 2
, 4 ,
6 C
, A , M
, T L
ow in
co m
e, u
rb an
, bl
ac k
C hi
ld : A
, M , T
, B W
, B
L , H
C , a
ge , g
en de
r, ra
ce , b
lo od
le ad
le ve
l, no
nm at
er na
l c ar
e; ca
re gi
ve r:
a ge
, I Q
, re
ce pt
iv e
vo ca
bu la
ry ,
ed uc
at io
n, m
ar ita
l st
at us
, s ub
st an
ce u
se ,
pr en
at al
c ar
e, p
ar ity
, SE
S, h
om e
en vi
ro nm
en t,
ps yc
ho pa
th ol
og y
C hi
ld re
n w
ith PC
E h
ad lo
w er
la ng
ua ge
sc or
es a
t e ac
h ag
e as
se ss
ed
C hi
ld re
n w
ith P
C E
d em
on st
ra te
d la
ng ua
ge d
ef ic
its a
cr os
s al
l t im
e po
in ts
o f ~
0. 20
S D
; m al
e an
d A
A ch
ild re
n sc
or ed
~ 0.
33 S
D b
el ow
sa m
pl e
m ea
n; n
o PC
E d
os e
as so
ci at
io n;
h om
e en
vi ro
nm en
t an
d ca
re gi
ve r l
an gu
ag e
fu nc
tio ni
ng w
er e
co rr
el at
ed to
ch ild
la ng
ua ge
o ut
co m
es
Pediatrics. Author manuscript; available in PMC 2011 August 4.
N IH
-P A
A uthor M
anuscript N
IH -P
A A
uthor M anuscript
N IH
-P A
A uthor M
anuscript
Ackerman et al. Page 15 PO
L Y
in di
ca te
s ex
po su
re to
m ul
tip le
d ru
gs ; C
O N
, n on
ex po
se d
co nt
ro ls
; C E
L F,
C hi
ld re
n’ s
E va
lu at
io n
of L
an gu
ag e
Fu nd
am en
ta ls
; C , c
oc ai
ne e
xp os
ur e;
A , a
lc oh
ol e
xp os
ur e;
T , t
ob ac
co e
xp os
ur e;
R C
T ,
ra nd
om iz
ed , c
on tr
ol le
d tr
ia l;
N E
PS Y
, D ev
el op
m en
ta l N
eu ro
ps yc
ho lo
gi ca
l A ss
es sm
en t;
W IS
C , W
ec hs
le r I
nt el
lig en
ce S
ca le
fo r C
hi ld
re n;
G A
, g es
ta tio
na l a
ge ; M
, m ar
iju an
a ex
po su
re ; B
W , b
ir th
w ei
gh t;
B L
, bi
rt h
le ng
th ; H
C , h
ea d
ci rc
um fe
re nc
e; W
PP SI
-R , W
ec hs
le r P
re sc
ho ol
a nd
P ri
m ar
y Sc
al e
of In
te lli
ge nc
e- R
ev is
ed e
di tio
n; C
A SL
, C om
pr eh
en si
ve A
ss es
sm en
t o f S
po ke
n L
an gu
ag e.
Pediatrics. Author manuscript; available in PMC 2011 August 4.
N IH
-P A
A uthor M
anuscript N
IH -P
A A
uthor M anuscript
N IH
-P A
A uthor M
anuscript
Ackerman et al. Page 16
TA B
LE 4
B eh
av io
ra l F
un ct
io ni
ng
St ud
y/ C
oh or
t Su
bj ec
ts O
ut co
m e
M ea
su re
s A
ge , y
Su bs
ta nc
e E
xp os
ur es
Se le
ct io
n/ M
at ch
in g
C on
tr ol
P C
E E
ff ec
t O
th er
E ff
ec ts
/C om
m en
ts
N ai
r e t a
l3 (2
00 8)
, c oh
or t 7
11 1
PO L
Y , 6
2 C
O N
C B
C L
6– 7
C , T
, H L
ow in
co m
e, u
rb an
, bl
ac k,
G A
> 32
w k
C hi
ld : T
, g en
de r,
ag e,
no nm
at er
na l c
ar e;
ca re
gi ve
r: S
E S,
em pl
oy m
en t,
de pr
es si
on , h
om e
en vi
ro nm
en t
N on
e B
eh av
io r d
if fe
re nc
es a
tte nu
at ed
af te
r c on
tr ol
lin g
fo r e
nv ir
on m
en ta
l co
va ri
at es
; b oy
s di
sp la
ye d
hi gh
er le
ve ls
o f a
tte nt
io n
pr ob
le m
s an
d ag
gr es
si on
th an
g ir
ls
H ur
t e t a
l4 (2
00 5)
, c oh
or t 8
62 P
O L
Y ,
73 C
O N
C B
C L
; T R
F 9–
12 C
, A , M
, T L
ow in
co m
e, u
rb an
, bl
ac k,
G A
> 34
w k
C hi
ld : g
en de
r, ag
e, no
nm at
er na
l c ar
e; ca
re gi
ve r:
s ub
st an
ce us
e, h
om e
en vi
ro nm
en t
N on
e D
es pi
te n
um er
ou s
pr en
at al
a nd
en vi
ro nm
en ta
l d if
fe re
nc es
, n o
PC E
ef fe
ct s
w er
e re
po rt
ed ; h
ig h
at tr
iti on
m ay
h av
e co
nt ri
bu te
d to
lim ite
d po
w er
K ilb
ri de
e t a
l9 (2
00 6)
, c oh
or t 3
39 P
O L
Y ,
12 C
O N
C B
C L
, c od
ed p
ar en
t- ch
ild p
la y
in te
ra ct
io ns
7 C
, A , T
L ow
in co
m e,
u rb
an ,
bl ac
k C
hi ld
: A , T
N on
e R
C T
, e ar
ly in
te rv
en tio
n; h
ig h
at tr
iti on
ra te
; l im
ite d
po w
er ; C
as e-
m an
ag ed
P C
E g
ro up
s ho
w ed
m or
e po
si tiv
e in
te ra
ct io
ns th
an P
C E
ro ut
in e
ca re
g ro
up in
p la
y pa
ra di
gm
B ad
a et
a l2
0
(2 00
7) , c
oh or
t 2 65
8 PO
L Y
, 73
0 C
O N
C B
C L
3, 5
, 7 C
, A , H
, M , T
L ow
in co
m e,
u rb
an ,
bl ac
k, G
A >
32 w
k C
hi ld
: A , H
, M , T
, H C
, ge
nd er
, r ac
e, v
io le
nc e
ex po
su re
, n on
m at
er na
l ca
re ; c
ar eg
iv er
: a ge
, su
bs ta
nc e
us e,
h om
e en
vi ro
nm en
t, ps
yc ho
pa th
ol og
y
C hi
ld re
n w
ith PC
E h
ad m
or e
ne ga
tiv e
be ha
vi or
al fu
nc tio
ni ng
; in
cr ea
se d
PC E
do se
w as
as so
ci at
ed w
ith ne
ga tiv
e tr
aj ec
to ri
es o
f in
te rn
al iz
in g,
ex te
rn al
iz in
g, an
d to
ta l
be ha
vi or
pr ob
le m
s
A dd
iti on
al n
eg at
iv e
ef fe
ct s
on be
ha vi
or o
ut co
m es
a re
o bs
er ve
d w
he n
PC E
c o-
oc cu
rr ed
w ith
pr en
at al
a nd
p os
tn at
al to
ba cc
o an
d al
co ho
l e xp
os ur
e; v
io le
nc e
ex po
su re
a nd
c ar
eg iv
er d
ep re
ss io
n ha
ve a
n eg
at iv
e in
fl ue
nc e
on a
ll be
ha vi
or al
o ut
co m
es
B en
ne tt
et a
l2 1
(2 00
7) , c
oh or
t 12
60 P
O L
Y ,
94 C
O N
Se lf
-r ep
or te
d su
bs ta
nc e
us e,
ag gr
es si
on , a
nd di
sr eg
ar d
fo r s
af et
y on
Y ou
th R
is k
B eh
av io
r S ur
ve y
10 C
, A , M
, T L
ow in
co m
e, u
rb an
, bl
ac k,
G A
> 32
w k
C hi
ld : A
, M , T
, a ge
, ge
nd er
, r ac
e, b
lo od
le ad
le ve
l, ne
on at
al m
ed ic
al p
ro bl
em s,
no nm
at er
na l c
ar e;
ca re
gi ve
r: S
E S,
su bs
ta nc
e us
e, en
vi ro
nm en
ta l r
is k
N o
di re
ct P
C E
ef fe
ct s
G en
de r m
od er
at ed
P C
E e
ff ec
ts su
ch th
at b
oy s
w ith
P C
E re
po rt
ed m
or e
hi gh
ri sk
b eh
av io
r t ha
n gi
rl s
w ith
P C
E a
s m
ea su
re d
by a
co m
po si
te h
ea lth
ri sk
b eh
av io
r sc
or e
an d
m or
e cu
rr en
t t ob
ac co
us e
L in
ar es
e t a
l2 2
(2 00
6) , c
oh or
t 11
16 9
PO L
Y ,
15 3
C O
N
C B
C L
; D om
in ic
In te
ra ct
iv e
(c hi
ld se
lf -r
ep or
t)
9 C
, A , M
, T L
ow in
co m
e, u
rb an
, bl
ac k,
G A
> 37
w k
C hi
ld : A
, M , T
, B W
, B
L , H
C , a
ge , g
en de
r, ra
ce , b
lo od
le ad
le ve
l, no
nm at
er na
l c ar
e; ca
re gi
ve r:
a ge
, I Q
, pr
en at
al c
ar e,
C hi
ld re
n w
ith PC
E s
el f-
re po
rt ed
h ig
he r
av er
ag e
nu m
be r
of o
pp os
iti on
al -
de fi
an t a
nd
O nl
y ch
ild s
el f-
re po
rt ed
P C
E di
ff er
en ce
s; N
on m
at er
na l
ca re
gi ve
rs o
f c hi
ld re
n w
ith P
C E
re po
rt ed
a h
ig he
r n um
be r o
f ex
te rn
al iz
in g
be ha
vi or
p ro
bl em
s
Pediatrics. Author manuscript; available in PMC 2011 August 4.
N IH
-P A
A uthor M
anuscript N
IH -P
A A
uthor M anuscript
N IH
-P A
A uthor M
anuscript
Ackerman et al. Page 17
St ud
y/ C
oh or
t Su
bj ec
ts O
ut co
m e
M ea
su re
s A
ge , y
Su bs
ta nc
e E
xp os
ur es
Se le
ct io
n/ M
at ch
in g
C on
tr ol
P C
E E
ff ec
t O
th er
E ff
ec ts
/C om
m en
ts ed
uc at
io n,
m ar
ita l
st at
us , s
ub st
an ce
u se
, ho
m e
en vi
ro nm
en t,
ps yc
ho pa
th ol
og y
A D
H D
sy m
pt om
s th
an C
O N
c hi
ld re
n; no
C B
C L
di ff
er en
ce s
N or
ds tr
om B
ai le
y et
a l2
3
(2 00
5) , c
oh or
t 1
21 4
PO L
Y ,
28 5
C O
N
T R
F 6–
7 C
, A , M
, T L
ow in
co m
e, u
rb an
, bl
ac k,
G A
> 38
w k
C hi
ld : A
, T , B
W , a
ge ,
IQ , g
en de
r, ra
ce , b
lo od
le ad
le ve
l, vi
ol en
ce ex
po su
re , n
on m
at er
na l
ca re
; c ar
eg iv
er : a
ge ,
IQ , e
du ca
tio n,
m ar
ita l
st at
us , s
ub st
an ce
u se
, SE
S, s
oc ia
l s up
po rt
, ho
m e
en vi
ro nm
en t
N o
PC E
d ir
ec t
ef fe
ct s
D es
pi te
a n
ab se
nc e
of d
ir ec
t P C
E ef
fe ct
s, b
oy s
w ith
P C
E a
nd a
lc oh
ol ex
po su
re a
nd g
ir ls
w ith
P C
E a
nd no
a lc
oh ol
e xp
os ur
e ha
d el
ev at
ed ex
te rn
al iz
in g
be ha
vi or
s co
re s
So od
e t a
l2 4
(2 00
5) , c
oh or
t 1 21
4 PO
L Y
, 28
5 C
O N
C B
C L
6– 7
C , A
, M , T
L ow
in co
m e,
u rb
an ,
bl ac
k, G
A >
38 w
k C
hi ld
: A , T
, B W
, a ge
, IQ
, g en
de r,
ra ce
, b lo
od le
ad le
ve l,
vi ol
en ce
ex po
su re
, n on
m at
er na
l ca
re ; c
ar eg
iv er
: a ge
, IQ
, e du
ca tio
n, m
ar ita
l st
at us
, s ub
st an
ce u
se ,
SE S,
s oc
ia l s
up po
rt ,
ho m
e en
vi ro
nm en
t, ps
yc ho
pa th
ol og
y
N o
PC E
d ir
ec t
ef fe
ct s
Fi nd
in gs
e xt
en d
te ac
he r-
re po
rt da
ta fr
om N
or ds
tr om
B ai
le y
et a
l2 3
an d
su gg
es t t
ha t g
en de
r a nd
al co
ho l e
xp os
ur e
m od
er at
e as
so ci
at io
ns b
et w
ee n
PC E
a nd
ca re
gi ve
r r ep
or t o
f c hi
ld ag
gr es
si on
a nd
d el
in qu
en cy
PO L
Y in
di ca
te s
ex po
su re
to m
ul tip
le d
ru gs
; C O
N , n
on ex
po se
d co
nt ro
ls ; C
B C
L , C
hi ld
B eh
av io
r C he
ck lis
t ( pa
re nt
fo rm
); C
, c oc
ai ne
e xp
os ur
e; T
, t ob
ac co
e xp
os ur
e; H
, h er
oi n
ex po
su re
; A A
, A fr
ic an
A m
er ic
an /b
la ck
; G A
, g es
ta tio
na l a
ge ; T
R F,
A ch
en ba
ch T
ea ch
er R
ep or
t F or
m ; A
, a lc
oh ol
e xp
os ur
e; M
, m ar
iju an
a ex
po su
re ; A
D H
D , a
tte nt
io n-
de fi
ci t/h
yp er
ac tiv
ity d
is or
de r;
R C
T , r
an do
m iz
ed , c
on tr
ol le
d tr
ia l;
H C
, h ea
d ci
rc um
fe re
nc e;
B W
, b ir
th w
ei gh
t; B
L , b
ir th
le ng
th .
Pediatrics. Author manuscript; available in PMC 2011 August 4.
N IH
-P A
A uthor M
anuscript N
IH -P
A A
uthor M anuscript
N IH
-P A
A uthor M
anuscript
Ackerman et al. Page 18
TA B
LE 5
A tte
nt io
n
St ud
y/ C
oh or
t Su
bj ec
ts O
ut co
m e
M ea
su re
s A
ge , y
Su bs
ta nc
e E
xp os
ur es
Se le
ct io
n/ M
at ch
in g
C on
tr ol
P C
E E
ff ec
t O
th er
E ff
ec ts
/C om
m en
ts
A cc
or ne
ro e
t al
25 (2
00 7)
, co
ho rt
9
21 9
PO L
Y ,
19 6
C O
N
T O
V A
; C PT
; C B
C L
at te
nt io
n sc
al e;
N E
PS Y
a tte
nt io
n/ ex
ec ut
iv e
fu nc
tio n
do m
ai n
5, 7
C , A
, M , T
L ow
in co
m e,
u rb
an ,
bl ac
k, G
A >
37 w
k C
hi ld
: A , M
, T , B
W ,
B L
, H C
, a ge
, I Q
, ge
nd er
, b lo
od le
ad le
ve l,
sp ec
ia l
se rv
ic es
, no
nm at
er na
l c ar
e; ca
re gi
ve r:
a ge
, ed
uc at
io n,
m ar
ita l
st at
us , s
ub st
an ce
u se
, em
pl oy
m en
t, ho
m e
en vi
ro nm
en t
C hi
ld re
n w
ith PC
E m
ad e
m or
e om
is si
on e
rr or
s, ha
d sl
ow er
re sp
on se
ti m
e, a
nd m
or e
re sp
on se
- tim
e va
ri ab
ili ty
o n
co m
pu te
ri ze
d su
st ai
ne d
at te
nt io
n ta
sk s
C hi
ld re
n w
ith P
C E
p er
fo rm
ed 0.
25 –
0. 32
S D
b el
ow C
O N
ch ild
re n
on s
us ta
in ed
a tte
nt io
n m
ea su
re s
fr om
3 –7
y o
f a ge
; ch
ild re
n w
ith P
C E
d is
pl ay
ed sl
ow er
re sp
on se
ti m
e an
d gr
ea te
r va
ri ab
ili ty
a t 7
y o
f a ge
a nd
m or
e om
is si
on e
rr or
s 5
an d
7 y
of a
ge
A ck
er m
an e
t al
26 (2
00 8)
, co
ho rt
7
88 P
O L
Y ,
56 C
O N
C PT
7 C
, A , T
, H L
ow in
co m
e, u
rb an
, bl
ac k,
G A
> 32
w k
C hi
ld : B
W , a
ge , I
Q ,
ge nd
er , n
on m
at er
na l
ca re
; c ar
eg iv
er : a
ge ,
IQ , e
du ca
tio n,
m ar
ita l s
ta tu
s, su
bs ta
nc e
us e,
S E
S, em
pl oy
m en
t, ea
rl y-
in te
rv en
tio n
st at
us ,
ps yc
ho pa
th ol
og y
C hi
ld re
n w
ith PC
E in
m at
er na
l ca
re d
is pl
ay ed
m or
e om
is si
on er
ro rs
o n
co m
pu te
ri ze
d su
st ai
ne d
at te
nt io
n ta
sk
Fi nd
in gs
in di
ca te
d th
at c
hi ld
re n
w ith
P C
E ra
is ed
in a
d ru
g- u
si ng
co nt
ex t m
ay b
e vu
ln er
ab le
to at
te nt
io n
pr ob
le m
s
Sa va
ge e
t a l2
7
(2 00
5) , c
oh or
t 8 40
P O
L Y
, 40
C O
N G
D S;
T ra
il M
ak in
g T
es t;
Se as
ho re
R hy
th m
T es
t
10 C
, A , T
, M L
ow in
co m
e, u
rb an
, bl
ac k,
G A
> 32
w k
C hi
ld : I
Q , g
en de
r, no
nm at
er na
l c ar
e; ca
re gi
ve r:
s ub
st an
ce us
e
C hi
ld re
n w
ith PC
E m
ad e
m or
e co
m m
is si
on e
rr or
s on
th e
m os
t di
ff ic
ul t
di st
ra ct
ib ili
ty ta
sk on
th e
G D
S
N o
di ff
er en
ce s
be tw
ee n
PC E
a nd
C O
N c
hi ld
re n
on a
tte nt
io n
or im
pu ls
iv ity
e xc
ep t w
he n
co gn
iti ve
de m
an ds
w er
e hi
gh ; l
im ite
d po
w er
, h ig
h at
tr iti
on re
po rt
ed
Sc hr
od er
e t a
l2 8
(2 00
4) , c
oh or
t 13
40 P
O L
Y ,
11 C
O N
G ro
to n
M az
e L
ea rn
in g
T es
t 8
N ot
re po
rt ed
L ow
in co
m e,
b la
ck ,
G A
n ot
re po
rt ed
C hi
ld : I
Q C
hi ld
re n
w ith
PC E
d is
pl ay
ed sl
ow er
v is
ua l-
m ot
or s
pe ed
a nd
m ad
e m
or e
er ro
rs on
a d
el ay
ed pr
oc ed
ur al
le ar
ni ng
ta sk
C hi
ld re
n w
ith P
C E
w er
e le
ss ef
fi ci
en t a
t c om
pl et
in g
vi su
al m
az es
, p ar
tic ul
ar ly
a ft
er a
d el
ay ;
lim ite
d sa
m pl
e si
ze a
nd c
ov ar
ia te
co nt
ro l
PO L
Y in
di ca
te s
ex po
su re
to m
ul tip
le d
ru gs
; C O
N , n
on ex
po se
d co
nt ro
ls ; T
O V
A , T
es t o
f V ar
ia bl
es o
f A tte
nt io
n; C
B C
L , C
hi ld
B eh
av io
r C he
ck lis
t ( pa
re nt
fo rm
); C
PT , C
on ne
rs ’ C
on tin
uo us
P er
fo rm
an ce
T es
t; N
E PS
Y , D
ev el
op m
en ta
l N eu
ro ps
yc ho
lo gi
ca l A
ss es
sm en
t; C
, c oc
ai ne
e xp
os ur
e; A
, a lc
oh ol
e xp
os ur
e; M
, m ar
iju an
a ex
po su
re ; T
, t ob
ac co
e xp
os ur
e; G
A , g
es ta
tio na
l a ge
; B W
, b ir
th w
ei gh
t; B
L , b
ir th
le ng
th ; H
C , h
ea d
ci rc
um fe
re nc
e; H
, h er
oi n
ex po
su re
.
Pediatrics. Author manuscript; available in PMC 2011 August 4.
N IH
-P A
A uthor M
anuscript N
IH -P
A A
uthor M anuscript
N IH
-P A
A uthor M
anuscript
Ackerman et al. Page 19
TA B
LE 6
B ra
in S
tr uc
tu re
a nd
F un
ct io
n
St ud
y/ C
oh or
t Su
bj ec
ts O
ut co
m e
M ea
su re
s A
ge , y
Su bs
ta nc
e E
xp os
ur es
Se le
ct io
n/ M
at ch
in g
C on
tr ol
P C
E E
ff ec
t O
th er
E ff
ec ts
/C om
m en
ts
A va
nt s
et a
l3 3
(2 00
7) , c
oh or
t 8
25 PO L
Y ,
24 C
O N
B ila
te ra
l c au
da te
v ol
um e
14 C
, A , T
, M L
ow in
co m
e, b
la ck
, G
A >
34 w
k N
on e
re po
rt ed
C hi
ld re
n w
ith PC
E h
ad s
m al
le r
ca ud
at e
PC E
is a
ss oc
ia te
d w
ith re
du ce
d ca
ud at
e vo
lu m
e; c
au da
te is
a n
ar ea
o f d
op am
in er
gi c
in ne
rv at
io n
an d
im pl
ic at
ed in
at te
nt io
n; li
m ite
d sa
m pl
e si
ze an
d co
va ri
at e
co nt
ro l
R iv
ki n
et a
l3 4
(2 00
8) , c
oh or
t 5
14 PO L
Y ,
21 C
O N
V ol
um es
o f c
or tic
al g
ra y
an d
w hi
te m
at te
r, su
bc or
tic al
g ra
y m
at te
r, ce
re br
al s
pi na
l f lu
id , a
nd to
ta l p
ar en
ch ym
a, H
C
12 C
, A , T
, M L
ow in
co m
e, b
la ck
, G
A >
36 w
k C
hi ld
: A , M
, T ,
ag e,
g en
de r,
to ta
l in
tr ac
ra ni
al v
ol um
e
C hi
ld re
n w
ith PC
E h
ad re
du ce
d co
rt ic
al g
ra y,
to ta
l pa
re nc
hy m
al vo
lu m
es , a
nd H
C
A s
nu m
be r o
f p re
na ta
l s ub
st an
ce ex
po su
re s
in cr
ea se
d, c
or tic
al gr
ay a
nd to
ta l p
ar en
ch ym
al vo
lu m
e de
cr ea
se d;
s m
al le
st vo
lu m
es fo
un d
in c
hi ld
re n
w ith
PC E
e xp
os ed
to m
ul tip
le su
bs ta
nc es
; l im
ite d
sa m
pl e
si ze
an d
co va
ri at
e co
nt ro
l
H ur
t e t a
l3 5
(2 00
8) , c
oh or
t 8
17 PO L
Y ,
17 C
O N
B eh
av io
ra l a
cc ur
ac y
to no
ns pa
tia l w
or ki
ng m
em or
y ta
sk a
nd m
ea n
B O
L D
s ig
na l f
ro m
fM R
I
14 C
, A , T
, M L
ow in
co m
e, u
rb an
, bl
ac k,
G A
> 34
w k
D is
cr im
in at
io n
sc or
es fr
om be
ha vi
or al
ta sk
; n o
co va
ri at
es b
ut m
at ch
ed b
y ge
nd er
an d
IQ
N on
e N
o PC
E e
ff ec
ts d
et ec
te d
in be
ha vi
or al
o r i
m ag
in g
da ta
; lim
ite d
sa m
pl e
si ze
a nd
co va
ri at
e co
nt ro
l
W ar
ne r e
t a l3
6
(2 00
6) , c
oh or
t 14
28 PO L
Y ,
25 C
O N
Fr on
ta l w
hi te
m at
te r
in te
gr ity
u si
ng D
T I d
ur in
g St
ro op
a nd
T ra
il M
ak in
g T
es t
10 C
, A , T
, M B
la ck
, G A
> 36
w k
C hi
ld : A
, M , T
, I Q
, ge
nd er
D T
I: c
hi ld
re n
w ith
P C
E h
ad hi
gh er
a ve
ra ge
di ff
us io
n co
ef fi
ci en
ts in
fr on
ta l f
ib er
s; B
eh av
io r:
ch ild
re n
w ith
PC E
h ad
lo ng
er co
m pl
et io
ns tim
es o
n pa
rt B
of th
e T
ra il
M ak
in g
T es
t
PC E
w as
re la
te d
to h
ig he
r di
ff us
io n
va lu
es in
fr on
ta l w
hi te
m at
te r,
w hi
ch s
ug ge
st s
le ss
in te
gr ity
a nd
/o r s
lo w
er m
at ur
at io
n of
fr on
ta l a
re as
; di
ff er
en ce
s w
er e
re la
te d
to po
or er
p er
fo rm
an ce
o n
T ra
il M
ak in
g T
es t b
y PC
E g
ro up
Sm ith
e t a
l3 7
(2 00
1) , c
oh or
t 15
14 PO L
Y ,
12 C
O N
W ho
le a
nd re
gi on
al b
ra in
vo lu
m es
; m et
ab ol
ite co
nc en
tr at
io ns
u si
ng 1
H -
M R
S in
ri gh
t f ro
nt al
w hi
te m
at te
r a nd
ri gh
t s tr
ia tu
m
8– 9
N ot
re po
rt ed
V ar
ia bl
e SE
S, u
rb an
, 40
% b
la ck
, 4 0%
w hi
te , G
A >
36 w
k
C hi
ld : a
ge , g
en de
r V
ol um
e: n
on e;
M et
ab ol
ite s:
ch ild
re n
w ith
PC E
h ad
a 1
3% in
cr ea
se in
ri gh
t fr
on ta
l w hi
te m
at te
r l ev
el s
of cr
ea tin
e
In cr
ea se
d cr
ea tin
e fo
un d
in ri
gh t
fr on
ta l w
hi te
m at
te r s
ug ge
st s
th at
b io
ch em
ic al
c ha
ng es
c au
se d
by P
C E
m ay
o cc
ur a
t c el
lu la
r le
ve l;
no e
vi de
nc e
fo r P
C E
- re
la te
d st
ru ct
ur al
o r v
ol um
et ri
c da
m ag
e; li
m ite
d sa
m pl
e si
ze a
nd co
va ri
at e
co nt
ro l
Si ng
er e
t a l3
8
(2 00
6) , c
oh or
t 11
21 PO L
Y ,
14 C
O N
G ra
y an
d w
hi te
m at
te r
vo lu
m es
; N E
PS Y
s ub
te st
s; C
A SL
8 C
, A , T
, M L
ow in
co m
e, u
rb an
, bl
ac k,
G A
> 37
w k
N ot
re po
rt ed
V ol
um e:
ch ild
re n
w ith
PC E
h ad
g ra
y m
at te
r r ed
uc tio
ns in
o cc
ip ita
l a nd
PC E
a ss
oc ia
te d
w ith
lo ng
-t er
m ch
an ge
s in
b ra
in c
om po
si tio
n, w
hi ch
w er
e re
la te
d to
pe rf
or m
an ce
o n
ne ur
op sy
ch ol
og ic
al te
st s;
Pediatrics. Author manuscript; available in PMC 2011 August 4.
N IH
-P A
A uthor M
anuscript N
IH -P
A A
uthor M anuscript
N IH
-P A
A uthor M
anuscript
Ackerman et al. Page 20
St ud
y/ C
oh or
t Su
bj ec
ts O
ut co
m e
M ea
su re
s A
ge , y
Su bs
ta nc
e E
xp os
ur es
Se le
ct io
n/ M
at ch
in g
C on
tr ol
P C
E E
ff ec
t O
th er
E ff
ec ts
/C om
m en
ts pa
ri et
al lo
be s;
W hi
te m
at te
r re
du ct
io ns
in co
rp us
c al
lo su
m ;
PC E
d os
e ef
fe ct
s fo
r g ra
y an
d w
hi te
m at
te r
vo lu
m e
lim ite
d sa
m pl
e si
ze a
nd co
va ri
at e
co nt
ro l
M ay
es e
t a l3
9
(2 00
5) , c
oh or
t 13
15 PO L
Y ,
14 C
O N
R ea
ct io
n tim
e, a
cc ur
ac y,
la te
nc y
an d
am pl
itu de
o f
E R
P si
gn al
s du
ri ng
a St
ro op
p ar
ad ig
m
8 C
, A , T
, M U
rb an
, b la
ck , G
A n
ot re
po rt
ed E
xp er
im en
ta l a
nd co
nt ro
l g ro
up s
w er
e m
at ch
ed o
n th
e ba
si s
of a
ge , r
ac e,
an d
SE S;
n o
co va
ri at
e co
nt ro
l
C hi
ld re
n w
ith PC
E h
ad s
lo w
er an
d pr
ol on
ge d
E R
P si
gn al
s ac
ro ss
a w
id er
ra ng
e of
el ec
tr od
e si
te s
B ra
in re
sp on
se s
in P
C E
g ro
up w
er e
sl ow
er a
nd m
or e
di st
ri bu
te d
su gg
es tin
g PC
E in
hi bi
ts re
gi on
al s
pe ci
al iz
at io
n; lim
ite d
sa m
pl e
si ze
a nd
co va
ri at
e co
nt ro
l
R ao
e t a
l4 0
(2 00
7) , c
oh or
t 8
25 PO L
Y ,
24 C
O N
A bs
ol ut
e an
d re
la tiv
e C
B F
us in
g pe
rf us
io n
fM R
I, ov
er al
l a nd
re gi
on al
g ra
y m
at te
r v ol
um e
in fr
on ta
l lo
be , l
im bi
c st
ru ct
ur es
, oc
ci pi
ta l l
ob e,
a nd
th al
am us
14 C
, A , T
, M L
ow in
co m
e, u
rb an
, bl
ac k,
G A
> 34
w k
C hi
ld : a
ge , g
en de
r, gl
ob al
C B
F an
d gr
ay m
at te
r v ol
um e
C B
F: c
hi ld
re n
w ith
P C
E h
ad re
du ce
d gl
ob al
C B
F in
te ns
iti es
in p
os te
ri or
a nd
in fe
ri or
b ra
in re
gi on
s an
d re
la tiv
e in
cr ea
se s
in a
dj us
te d-
C B
F in
a nt
er io
r a nd
su pe
ri or
b ra
in re
gi on
s; V
ol um
e: ch
ild re
n w
ith PC
E h
ad re
gi on
al de
cr ea
se s
in g
ra y
m at
te r i
n ca
ud at
e an
d in
cr ea
se d
gr ay
m at
te r i
n am
yg da
la
PC E
w as
re la
te d
to re
du ct
io ns
in gl
ob al
C B
F du
ri ng
a do
le sc
en ce
an d
sp ec
if ic
g ra
y m
at te
r al
te ra
tio ns
, w hi
ch s
ug ge
st s
th at
co m
pe ns
at or
y m
ec ha
ni sm
s m
ay de
ve lo
p du
ri ng
n eu
ra l o
nt og
en y;
lim ite
d co
va ri
at e
co nt
ro l
PO L
Y in
di ca
te s
ex po
su re
to m
ul tip
le d
ru gs
; C O
N , n
on ex
po se
d co
nt ro
ls ; C
, c oc
ai ne
e xp
os ur
e; A
, a lc
oh ol
e xp
os ur
e; T
, t ob
ac co
e xp
os ur
e; M
, m ar
iju an
a ex
po su
re ; G
A , g
es ta
tio na
l a ge
; H C
, h ea
d
ci rc
um fe
re nc
e; B
O L
D , b
lo od
o xy
ge n
le ve
l d ep
en de
nt ; D
T I,
di ff
us io
n te
ns or
im ag
in g;
1 H
-M R
S, p
ro to
n m
ag ne
tic re
so na
nc e
sp ec
tr os
co py
; N E
PS Y
, D ev
el op
m en
ta l N
eu ro
ps yc
ho lo
gi ca
l A ss
es sm
en t;
C A
SL ,
C om
pr eh
en si
ve A
ss es
sm en
t o f S
po ke
n L
an gu
ag e;
E R
P, e
ve nt
-r el
at ed
p ot
en tia
l; C
B F,
c er
eb ra
l b lo
od fl
ow .
Pediatrics. Author manuscript; available in PMC 2011 August 4.
