A Multisite Neurobehavioral Assessment of FASD Sarah N. Mattson, Ph.D. Center for Behavioral Teratology Department of Psychology San Diego State University

Sites & Collaborators San Diego State University Sarah Mattson Edward Riley University of Minnesota Jeff Wozniak Chris Boyes Emory University Julie Kable Claire Coles University of Southern California Elizabeth Sowell

Subjects Tested Site AE Control Contrast Total 3-Year Goal % of Goal SDSU Old Young 33 12 42 23 31 18 106 53 81 131% 65% UMN 40 25 38 30 26 20 104 75 128% 93% Emory 29 17 62 100% 77% USC 19 -- 36 54 67% Subtotal Old Subtotal Young 113 175 128 73 201 86 55 141 327 190 517 297 243 540 110% 78% 96% As of 3/27/2014

Aim 1: Hierarchical Decision Tree Goal: to create a hierarchical decision tree for identifying children affected by prenatal alcohol exposure. Subjects: 437 children (8-16y) from CIFASD II Groups Alcohol-exposed (AE) Non-exposed (Non-AE) Typical controls Children with ADHD Children with IQ scores 54-88 A. Specific Aims. Aim 1: Use existing data to develop a tiered or hierarchical approach to identification of affected cases. This aim will determine the measures, from all four clinical domains of CIFASD (neurobehavior, dysmorphology, 3D facial imaging, and brain imaging) that could be used clinically to identify alcohol-affected children. Aim 2: Test the specificity and sensitivity of the model developed in Aim 1 in children ages 10-16. A battery of standardized neurobehavioral tests will be administered to subjects in three subject groups (alcohol-exposed, AE; non-exposed Controls; and non-exposed clinically-referred Contrast subjects) at four sites. Sensitivity (AE vs. Control) and specificity (AE vs. Contrast) will both be tested. Data will be combined with data from other CIFASD projects. Aim 3: Test the utility of the model in younger children, ages 5-7. A similar battery of age-appropriate standardized neuropsychological tests will be administered to young children in the same three subject groups at three of the four sites. Sensitivity and specificity will be tested as in Aim 2. Aim 4: Targeted assessment of memory function. In Phase I and II, our test batteries focused heavily on executive function, which proved to be an important domain in our preliminary neurobehavioral profile. Past studies and some preliminary data suggest that memory is another important domain and further study, including tests of both sensitivity and specificity, is warranted.  

Subjects Variable AE Non-AE N 149 288 Age 12.4 (2.4) 12.2 (2.6) IQ 83.97 (17.1) 100.2 (17.5) Sex [n (%) Female] 65 (43.6%) 109 (37.8%) Race [n (%) White] 81 (54.4%) 186 (64.6%) FAS [n (%) Dx] 42 (28.2%) -- Ethnicity [n (%) Hispanic/Latino] 19 (12.8%) 67 (23.3%) Site San Diego [n (%)] 55 (36.9%) 124 (43.1%) Atlanta [n (%)] 30 (20.1%) 52 (18.1%) Los Angeles [n (%)] 28 (18.8%) 30 (10.4%) Northern Plains [n (%)] 25 (16.8%) 34 (11.8%) New Mexico [n (%)] 11 (7.4%) 48 (16.7%)

Measures Weschler Intelligence Scale for Children-IV (WISC) Full Scale IQ Child Behavior Checklist for Ages 6-18 (CBCL) Somatic Complaints, Social Problems, Thought Problems, Rule- Breaking Behavior, Aggressive Behavior Vineland Adaptive Behavior Scales (VABS-II) Socialization, Communication, Daily Living Skills Dysmorphology Smooth Philtrum, Short Palpebral Fissures, Thin Vermillion Border, Camptodactyly, Ptosis We included measures of… IQ psychopathology, adaptive function Dysmorphology Two additional physical features were also included. Physical features would be measured by a dysmorphologist camptodactyly, referring to a child having one or more fingers being permanently bent ptosis, referring to a drooping of the eyelid. Adaptive function - the relative ability to effectively interact with society and care for one’s self

Two Entry Points Correspond with two routes of clinical identification Psychologist  Dysmorphologist Identify clinical condition before pursuing PAE Dysmorphologist Only (with psychological measures) Removed demands of child testing When alcohol-exposure suspected

Sample Decision Point N Measure 1 Scale from 1-100 Cut-off score of < 70 indicating AE Measure 1 No (% Correct) Yes (% Correct)

CIFASD II: 81.8% Overall PPV: 78.8% NPV: 83.2% Sensitivity: 73.2% Specificity: 86.2% N=437 AE=149 Non-AE=288 Admin CBCL (CBCL > 1) OR = 30.469; p <.001 Yes (N=207) 186 Correct 89.9% No (N=222) 172 Correct Admin WISC FSIQ < 91 OR = 5.871; p<.001 (N=65) 30 Correct 46.2% (N=157) 137 Correct 87.3% “Yes” in Part 1 (N=272) FAS? Yes (N=33) 33 Correct 100% No (N=239) Dysmorphology (Physical > 1) OR = 2.130; p=.017 Yes (N=59) 34 Correct Admin VABS > 2 OR = 11.310; p<.001 Yes (N=31) 25 Correct 80.6% No (N=26) 19 Correct 73.1% No (N=136) (83 Correct) OR = 4.66; p<.001 Yes (N=38) No (N=89) 63 Correct Admin Phys2 > 1 OR=5.937; p=.002 Yes (N=16) 10 Correct 62.5% No (N=73) 57 Correct 78.1% Physical: PFL less than 10 percentile, Smooth Philtrum, Thin Vermillion Border Phys2: Camptodactyly, Ptosis CBCL: Somatic Complaints, Social Problems, Thought Problems, Attention Problems, Rule Breaking Behavior, Aggressive Behavior, Internalizing Problems, Externalizing Problems (T>65) VABS: Socialization, Communication, Daily Living Skills (SS<85) IQ: WISC FSIQ 3/16/2015

N=437 CBCL FAS? WISC VABS VABS Yes in Part 1 Dysmorph 2 Dysmorph 1 CIFASD II - Entry Point 1 N=437 Yes in Part 1 CBCL FAS? WISC Proposed Clinical 89.9% Dysmorph 1 Proposed AE 100% Proposed Non-AE 87.3% Proposed Clinical 46.2% VABS VABS Entry point 1 First examined for clin CBCL-psychopathology Criteria for clinical problems; given wisc || Those with clinical problems as proposed by our model || are then referred to a specialist to test for alcohol exposure Dysm1: PFL less than 10 percentile, Smooth Philtrum, Thin Vermillion Border Dysm2: Camptodactyly, Ptosis CBCL: Somatic Complaints, Social Problems, Thought Problems, Attention Problems, Rule Breaking Behavior, Aggressive Behavior, Internalizing Problems, Externalizing Problems (T>65) VABS: Socialization, Communication, Daily Living Skills (SS<85) IQ: WISC FSIQ Dysmorph 2 Proposed AE 65.8% Proposed Non-AE 73.1% Proposed AE 80.6% Proposed Non-AE 78.1% Proposed AE 62.5%

N=437 CBCL FAS? WISC VABS VABS Yes in Part 1 Dysmorph 2 Dysmorph 1 CIFASD II - Entry Point 1 N=437 Yes in Part 1 CBCL FAS? WISC Proposed Clinical 89.9% Dysmorph 1 Proposed AE 100% Proposed Non-AE 87.3% Proposed Clinical 46.2% VABS VABS These children are they run through the rest of the model until they reach the stopping points || Created when our samples became too small or no measure could be found Dysmorph 2 Proposed AE 65.8% Proposed Non-AE 73.1% Proposed AE 80.6% Proposed Non-AE 78.1% Proposed AE 62.5%

Overall Accuracy 81.8% Proposed AE 100% Proposed Non-AE 87.3% CIFASD II Model Dev. Entry Point 1 Overall Accuracy 81.8% Proposed AE 100% Proposed Non-AE 87.3% When analyzing || accuracy rates at these stopping points we obtain an || accuracy rate of 81.8% when entering at point 1. Misclassified subjects: Entry Point 1.  There were 34 subjects in the AE group that were misclassified as Non-AE. In comparison to the subjects in the AE group that were correctly classified, (N=93), these subjects differed significantly (p<.05) on age (younger), IQ (higher), and rate of ADHD diagnosis (lower). They did not differ on sex, handedness, ethnicity, or race. There were 25 subjects in the Non-AE group that were misclassified as AE. In comparison to the subjects in the Non-AE group that were correctly classified (N=222), these subjects differed significantly (p<.05) on IQ (lower) and rate of ADHD diagnosis (higher). They did not differ on sex, handedness, ethnicity, and race Proposed AE 65.8% Proposed Non-AE 73.1% Proposed AE 80.6% Proposed Non-AE 78.1% Proposed AE 62.5%

N=437 CBCL FAS? WISC VABS VABS Yes in Part 1 Dysmorph 2 Dysmorph 1 Enter Point 1 CIFASD II - Entry Point 2 N=437 Yes in Part 1 CBCL FAS? WISC Proposed Clinical 89.9% Dysmorph 1 Proposed AE 100% Proposed Non-AE 87.3% Proposed Clinical 46.2% VABS VABS For entry point 2, we used the same overall model, but the section where clinical problems were diagnosed is removed. Dysmorph 2 Proposed AE 64.1% Proposed Non-AE 83.3% Proposed AE 80.6% Proposed Non-AE 88.0% Proposed AE 32.3%

N=437 CBCL FAS? WISC VABS VABS Yes in Part 1 Dysmorph 2 Dysmorph 1 Enter Point 1 CIFASD II - Entry Part 2 N=437 Yes in Part 1 CBCL FAS? WISC Proposed Clinical 89.9% Dysmorph 1 Proposed AE 100% Proposed Non-AE 87.3% Proposed Clinical 46.2% VABS VABS and again we want to focus on these final stopping points Dysmorph 2 Proposed AE 64.1% Proposed Non-AE 83.3% Proposed AE 80.6% Proposed Non-AE 88.0% Proposed AE 32.3%

Overall Accuracy 80.2% Proposed AE 100% Proposed AE 64.1% CIFASD II Model Dev. Entry Point 2 Overall Accuracy 80.2% Proposed AE 100% Misclassified subjects: Entry Point 2.  There were 26 subjects in the AE group that were misclassified as Non-AE. In comparison to the subjects in the AE group that were correctly classified, (N=102), these subjects differed significantly (p < .05) on ethnicity (fewer Hispanics), IQ (higher), and rate of ADHD diagnosis (lower). They did not differ on handedness, race, sex, or age. There were 41 subjects in the Non-AE group that were misclassified as AE. In comparison to the subjects in the Non-AE group that were correctly classified, there subjects differed significantly (p < .05) on IQ (lower) and rate of ADHD diagnosis (higher). They did not differ on handedness, ethnicity, race, sex, or age. Proposed AE 64.1% Proposed Non-AE 83.3% Proposed AE 80.6% Proposed Non-AE 88.0% Proposed AE 32.3%

Refer to Dysmorphology CIFASD II - Entry Point 1 N=1 Refer to Dysmorphology CBCL>65 (1) FAS? Proposed Clinical 89.9% PFL, Phil, Verm (1) VABS <86 (2) Dysm1: PFL less than 10 percentile, Smooth Philtrum, Thin Vermillion Border Dysm2: Camptodactyly, Ptosis CBCL: Somatic Complaints, Social Problems, Thought Problems, Attention Problems, Rule Breaking Behavior, Aggressive Behavior, Internalizing Problems, Externalizing Problems (T>65) VABS: Socialization, Communication, Daily Living Skills (SS<85) IQ: WISC FSIQ Proposed AE 80.6%

Aim 2 & 3: Validate Decision Tree in CIFASD III Aim 2: Validate tree in older sample (10-16) Subjects: 289 children (10-16y) from CIFASD III Aim 3: Validate tree in younger sample (5-7) Subjects: 165 children (5-7y) from CIFASD III Groups Alcohol-exposed (AE) Non-exposed (Non-AE) Typical controls Children with parent-reported behavioral concerns Aim 2: Test the specificity and sensitivity of the model developed in Aim 1 in children ages 10-16. A battery of standardized neurobehavioral tests will be administered to subjects in three subject groups (alcohol-exposed, AE; non-exposed Controls; and non-exposed clinically-referred Contrast subjects) at four sites. Sensitivity (AE vs. Control) and specificity (AE vs. Contrast) will both be tested. Data will be combined with data from other CIFASD projects. Aim 3: Test the utility of the model in younger children, ages 5-7. A similar battery of age-appropriate standardized neuropsychological tests will be administered to young children in the same three subject groups at three of the four sites. Sensitivity and specificity will be tested as in Aim 2. Aim 4: Targeted assessment of memory function. In Phase I and II, our test batteries focused heavily on executive function, which proved to be an important domain in our preliminary neurobehavioral profile. Past studies and some preliminary data suggest that memory is another important domain and further study, including tests of both sensitivity and specificity, is warranted.  

N=289 CBCL FAS? DAS-II VABS VABS Yes in Part 1 Dysmorph 1 Proposed AE CIFASD III - Entry Point 1 - Older N=289 Yes in Part 1 CBCL FAS? DAS-II Proposed Clinical 91.7% Dysmorph 1 Proposed AE 100% Proposed Non-AE 77.5% Proposed Clinical 39.3% VABS VABS Entry Point 1. There were 19 subjects in the AE group that were misclassified as Non-AE. In comparison to the subjects in the AE group that were correctly classified, (N=65), these subjects did not differ significantly on any of the tested variables (p ≥ .121). There were 19 subjects in the Non-AE group that were misclassified as AE. In comparison to the subjects in the Non-AE group that were correctly classified (N=113), these subjects differed significantly (p<.05) on Age (younger) and rate of ADHD diagnosis (lower). Groups did not differ on handedness, ethnicity, race, sex, or GCA. There were 26 subjects in the Non-AE group that were misclassified as AE. In comparison to the subjects in the Non-AE group that were correctly classified (N=94), these subjects differed significantly (p<.05) on race (fewer White subjects), and GCA (lower). Groups did not differ on handedness, ethnicity, sex, age, or rate of ADHD diagnosis. Proposed Non-AE 75% CBCL Proposed Non-AE 63.6% Proposed AE 88.2% Proposed Non-AE 57.1% Proposed AE 78.9%

N=437 CBCL FAS? DAS-II VABS VABS Yes in Part 1 Proposed Non-AE 94% Enter Point 1 CIFASD III Entry Point 2 Older N=437 Yes in Part 1 CBCL FAS? DAS-II Proposed Clinical 91.7% Dysmorph 1 Proposed AE 100% Proposed Non-AE 77.5% Proposed Clinical 39.3% VABS VABS Proposed Non-AE 94% For entry point 2, we used the same overall model, but the section where clinical problems were diagnosed is removed. CBCL Proposed Non-AE 73.8% Proposed AE 83.3% Proposed Non-AE 64% Proposed AE 78.9%

N=165 CBCL FAS? DAS-II VABS Yes in Part 1 Dysmorph 1 Proposed AE 100% CIFASD III - Entry Point 1- Younger N=165 Yes in Part 1 CBCL FAS? DAS-II Proposed Clinical 93.9% Dysmorph 1 Proposed AE 100% Proposed Non-AE 72.7% Proposed Clinical 50% Proposed Non-AE 75% VABS Entry Point 1. There were 12 subjects in the AE group that were misclassified as Non-AE. In comparison to the subjects in the AE group that were correctly classified, (N=29), these subjects did not differ significantly on any of the tested variables (p ≥ .170). There were 4 subjects in the Non-AE group that were misclassified as AE. In comparison to the subjects in the Non-AE group that were correctly classified (N=50), these subjects differed significantly (p<.05) on GCA (lower), handedness (more non-left), and rate of ADHD diagnosis (higher). They did not differ on ethnicity, race, sex, or age. Proposed Non-AE 63.6% Proposed AE 88.2%

N=437 CBCL FAS? DAS-II VABS Yes in Part 1 Dysmorph 1 Proposed AE 100% Enter Point 1 CIFASD III Entry Point 2 Younger N=437 Yes in Part 1 CBCL FAS? DAS-II Proposed Clinical 93.9% Dysmorph 1 Proposed AE 100% Proposed Non-AE 72.7% Proposed Clinical 50% Proposed Non-AE 88.5% VABS For entry point 2, we used the same overall model, but the section where clinical problems were diagnosed is removed. Entry Point 2. There were 17 subjects in the AE group that were misclassified as Non-AE. In comparison to the subjects in the AE group that were correctly classified, (N=30), these subjects differed on age (younger). They did not differ on ethnicity, race, sex, GCA, or rate of ADHD diagnosis. There were 5 subjects in the Non-AE group that were misclassified as AE. In comparison to the subjects in the Non-AE group that were correctly classified (N = 71), these subjects differed on handedness (more non-left), age (older), GCA (lower), and rate of ADHD diagnosis (higher). Groups did not differ on sex or race. Proposed Non-AE 69.4% Proposed AE 82.1%

Overall Accuracies & Summary CIFASD II: Model Development Entry Point 1: 81.8% Entry Point 2: 80.2% CIFASD III: Model Validation Younger (n=165) Entry Point 1: 76.7% Entry Point 2: 82.1% Older (n=289) Entry Point 1: 76.9% Entry Point 2: 83.00% Summary We used 4 measures (1 child measure, 2 parent questionnaires, dysmorphology exam) We accurately classified ~80% of children We validated our model on an independent sample* and in 2 age groups There is still room for improvement Missclassified subjects for CIFASD II were:

Aim 2 & 3: Examine Effects of Age Goal: to examine the role of age in the effects of prenatal alcohol exposure Are the same behavioral features as important in our younger age group (5-7y)? Groups Three subject groups Alcohol-exposed (AE, n = 156) Non-exposed Typical Controls (Control, n = 182) Children with parent-reported behavioral concerns (Contrast, n = 114) Two age groups 5-7y & 10-16y Aim 2: Test the specificity and sensitivity of the model developed in Aim 1 in children ages 10-16. A battery of standardized neurobehavioral tests will be administered to subjects in three subject groups (alcohol-exposed, AE; non-exposed Controls; and non-exposed clinically-referred Contrast subjects) at four sites. Sensitivity (AE vs. Control) and specificity (AE vs. Contrast) will both be tested. Data will be combined with data from other CIFASD projects. Aim 3: Test the utility of the model in younger children, ages 5-7. A similar battery of age-appropriate standardized neuropsychological tests will be administered to young children in the same three subject groups at three of the four sites. Sensitivity and specificity will be tested as in Aim 2. Aim 4: Targeted assessment of memory function. In Phase I and II, our test batteries focused heavily on executive function, which proved to be an important domain in our preliminary neurobehavioral profile. Past studies and some preliminary data suggest that memory is another important domain and further study, including tests of both sensitivity and specificity, is warranted.  

Relation of Age & Exposure to Problem Behaviors Internalizing Bx Externalizing Bx ns ns * ns Also in keeping with Aims 2 & 3, we have completed a study of the relation between age and problem behaviors in children with prenatal alcohol exposure. For this study, we were interested in analyzing the developmental course of internalizing and externalizing problem behaviors in children with prenatal alcohol exposure and secondarily to compare the course to that seen in children with other clinical disorders. Subjects were 452 children from CIFASD III, comprising 3 groups: alcohol exposed (AE, n = 156), non-exposed with other clinical diagnoses (CONT, n = 114), and typically developing controls (CON, n = 182). 2 age ranges were analyzed: 5-7y (Y, n = 167) and 10-16y (O, n = 285). We included the following parent ratings: CBCL internalizing and externalizing T-scores, VABS internalizing and externalizing V-scores, and Conners3 ODD and CD T-scores. Scores were combined into Internalizing and Externalizing latent variables using confirmatory factor analysis. These two latent variables were then analyzed using a 3 (Group) x 2 (Age) MANOVA. These analyses revealed significant main effects of Group and Age, while a significant Group x Age interaction was discovered for both internalizing and externalizing latent variables (ps < .047). Follow-up analyses revealed that clinical groups displayed significantly higher levels of problem behaviors compared to the CON group in both age ranges. However, while internalizing and externalizing behaviors in the AE group remained high and constant throughout development, these behaviors significantly decreased with age in the CONT group. Problem behaviors in the CON group did not fluctuate with age. These results suggest that both children with prenatal alcohol exposure and non-exposed children with other diagnoses show impairments in social functioning relative to controls, but the pattern of development differs significantly between the two clinical groups. Problem behaviors remain elevated and do not change with age in children with prenatal alcohol exposure, while they decrease with age in children with other diagnoses, albeit not to the level of control children. Further research focused on exploring the pattern of deficits present in children with prenatal alcohol exposure will lead to improved differential diagnosis and effective intervention. Data have been analyzed and we are preparing a paper for review by co-authors. Group: p < .001 AgeRange: p = .773 Group x AgeRange : p = .278 Group: p < .001 AgeRange: p = .223 Group x AgeRange : p = .023

Aim 2 & 3: Examine Effects of Age Goal: to examine the role of age in the effects of prenatal alcohol exposure Are the same neuropsychological and psychopathological features as important in our younger age group (5-7y)? Groups Two exposure groups Alcohol-exposed (AE, n = 151) Non-exposed Typical Controls (Control, n = 175) Two age groups: 5-7y and 10-16 Results We examined 15 measures of neuropsychological function and 11 measures of behavior and psychopathology All variables tested showed significant effects of exposure group Only 5 variables showed significant effects of age (0 showed effects of sex) In keeping with Aims 2 & 3, we have also examined CIFASD III data for differences based on age. In particular, we were interested in age differences in neuropsychological functioning, psychopathology, and adaptive behavior. Subjects were 326 children with (AE; n=151) and without (CON; n=175) prenatal alcohol exposure. Two age groups were considered, as proposed: 5-7 (child) and 10-16 (adolescent). Data were analyzed using 3 MANCOVAs with a 2 (Exposure history) x 2 (Sex) x 2 (Age) design for neuropsychological functioning, psychopathology, and adaptive behavior, respectively. Covariates were included when appropriate. Analyses indicated a significant omnibus effect of exposure for all analyses. Follow-up tests revealed significant main effects of exposure (AE<CON) on all variables. A significant main effect of age was found in the neuropsychological performance and adaptive functioning analyses, but not for psychopathology. Follow-up tests revealed that older children had significantly poorer scores than younger children on two language tasks, and one measure of visuospatial ability. Older children also had significantly poorer communication and socialization scores than younger children. There were no significant main effects of sex for any analysis, and there were no significant interactions in any of the omnibus analyses. As previously reported, a history of prenatal alcohol exposure resulted in impaired neuropsychological and behavioral functioning. Clinically, the lack of interactions in these findings suggests consistent performance patterns across age and sex, regardless of exposure history. These cross-sectional data suggest that the same diagnostic tool may be effective across sexes and across development from childhood to adolescence. These data were presented at the 2014 RSA meeting and a complete draft of the paper has been completed.

Aim 4: Targeted Assessment of Memory Goal: to conduct a detailed assessment of memory function in children with prenatal alcohol exposure Groups Two subject groups: AE, Controls, Contrast Two age groups: 5-7y and 10-16y Measures: CVLT-C Analyses: Group x Age Aim 4: Targeted assessment of memory function. In Phase I and II, our test batteries focused heavily on executive function, which proved to be an important domain in our preliminary neurobehavioral profile. Past studies and some preliminary data suggest that memory is another important domain and further study, including tests of both sensitivity and specificity, is warranted.  

Plans Immediate Longer term Continue to collect data Prepare and submit 5 papers Age (internalizing/externalizing) Decision tree Age (neuropsych/bx) Memory (age) Memory (brain) Longer term Calculator/App for decision tree Recruit additional samples/datasets to test decision tree Continue discussion on how to (or whether?) to include facial imagin into decision tree During the next funding year we plan to continue data collection at all 4 sites, and analyze new and existing data to meet our aims. We are preparing 5 manuscripts, as listed below.   1. Goh, Mattson, et al., and the CIFASD. Relation Between Age and Internalizing and Externalizing Behaviors in Children with Prenatal Alcohol Exposure. (Aims 2 & 3). Manuscript in preparation (data being analyzed), CIFASD concept proposal form submitted in January 2015. This project was described in the progress section, above. 2. Mattson, Jones, Goh, Doyle, et al., and the CIFASD. Developing a decision tree for clinical identification of children affected by prenatal alcohol exposure. (Aim 1) Manuscript in preparation (paper being written), CIFASD concept proposal form submitted in January 2015. 3. Panczakiewicz, Mattson et al., and the CIFASD. Neuropsychological and behavioral functioning do not vary by age & sex in FASD (Aims 2 & 3). Manuscript in preparation (paper being written), CIFASD concept proposal form submitted in January 2015. 4. Panczakiewicz, Gross, Mattson, et al., and the CIFASD. Targeted assessment of memory function in FASD (Aim 4). Manuscript in preparation (data being analyzed), CIFASD concept proposal form submitted in January 2015. For this study, we are examining memory variables collected during CIFASD III. We are specifically interested in the memory profiles of children and adolescents with FASD, and how they vary by age (5-7y and 10-16y). The specific questions we are asking are: (1) Are types of memory differentially affected by PAE? (2) What are the relative memory strengths and weakness of children with FASD? And (3) Does the memory profile of children with PAE differ from children in the contrast group? Our hypotheses are that, as in previous studies, children with FASD will perform more poorly than controls and that these deficits will be consistent across age group. We will also examine the relation between memory function and other important variables, like adaptive behavior. Given the inclusion of our contrast group, we think this last comparison will be especially interesting. This study is directly related to Aim 4 (memory) and Aim 3 (age) 5. Mattson, et al., and the CIFASD. Brain-behavior relations in FASD: Focusing on memory function. (Aim 4) Manuscript in preparation (data base under construction), CIFASD concept proposal form submitted in January 2015. For this study, we are collaborating with the brain imaging group. Data from both brain imaging and neuropsychological assessments will be analyzed to examine the neural correlates of memory function. This study is directly related to Aim 4.