University of Saskatchewan Department of Psychology  An Investigation of the Long-term Neuropsychological Outcome of Prenatal Teratogenic Exposure : Fetal Alcohol Syndrome and Maternal PKU Syndrome.   Jo Nanson, Ph. D. and  Susan R. Brock, Ph. D.

Introduction Alcohol  Most commonly used human prenatal teratogen  Research to date  prospective & retrospective studies  animal models  neuroanatomical studies

Introduction Fetal Alcohol Syndrome - FAS  History of maternal alcoholism during pregnancy  Central nervous system deficits  Facial dysmorphology  Pre- and post-natal growth retardation

Introduction Phenylalanine  A large neutral amino acid in food  PKU - autosomal, recessive metabolic disorder  affected individuals unable to metabolize phenylalanine resulting in build up in the bloodstream.  Fetal-maternal plasma gradient for phenylalanine exists across the placenta

Introduction Maternal PKU Syndrome - MPKUS  History of untreated maternal PKU during pregnancy  Effects on the development of young children have been broadly described  Clinical reports have documented CNS deficits, microcephaly, intrauterine growth retardation, and congenital anomalies  Empirical data is lacking

Introduction Theoretical Questions What is the long-term neuropsychological outcome of prenatal teratogenic exposure in terms of memory and attention functioning. Are there unique patterns of prenatal teratogenic exposure that are specific to individual teratogens.

Method Design  Childhood dx of FAS  Childhood dx of MPKUS  Chronological age and IQ matched Controls

Method Participants - Prenatal Teratogen Groups  17 adults with FAS  9 male, 8 female  12 Native, 5 Caucasian  12 adults with MPKUS  5 male, 7 female  12 Caucasian

Method Participants - Control Group  84 adults administered the WAIS-R  17 CA + IQ matches for FAS participants  10 male, 7 female  4 Native, 13 Caucasian  12 CA + IQ matches for MPKUS participants  5 male, 7 female  12 Caucasian

Measures Mirsky’s four factor model of Attention  Focus  ability to select target information from an array for enhanced processing.  Sustain  ability to maintain focus and alertness over time.  Shift  ability to change attentive focus in a flexible and adaptive manner.  Encode  ability to sequentially register, recall, and mentally manipulate numeric information.

Measures Memory Battery  The WMS-R, RAVLT, and Rey Complex Figure were selected based on their ability to broadly assess the following areas:  Ability to learn  Immediate & delayed verbal memory  Recognition  Immediate & delayed visual memory

FAS Hypothesis Hypothesis I  Based on the literature to date, it was expected that adults with FAS would demonstrate poorer performance than the CA- plus IQ-matched Control group in terms of capacity to focus, sustain, shift, and encode attention as defined by Mirsky et al.'s model of attention.

Attention Results Hypothesis I  Focus  FAS more commission errors  Sustain  FAS more commission errors, less omission errors, and no differences in mean reaction time  Shift  FAS less correct responses and less perseverative responses  Encode  FAS poorer arithmetic scores

FAS Hypothesis Hypothesis II  Based on the literature to date, it was expected that adults with FAS would demonstrate poorer performance than the CA- plus IQ-matched Control group in terms of verbal memory, including the ability to learn new information, and immediate, delayed, and recognition memory ability.

Memory Results Hypothesis II  FAS  flatter learning curve  FAS  more difficulty with immediate & delayed recall of word lists, & delayed recall of paragraphs & word pairs  FAS  more intrusion errors

Exploratory Question I Attention How do adults with MPKUS differ from a CA- plus IQ-matched Control group in terms of capacity to focus, sustain, shift and encode attention as defined by Mirsky et al.'s model of attention.

Results Attention  Focus  No differences  Sustain  MPKUS more omission errors on auditory CPT test  Shift  Controls more set losses on WCST  Encode  no differences

Exploratory Question II Verbal Memory How do adults with MPKUS differ from a CA- plus IQ-matched Control group in terms of verbal memory, including ability to learn new information, immediate and delayed recall, and recognition memory ability.

Results Verbal Memory  MPKUS  poorer recognition skill

Exploratory Question III Visual Memory How do adults with FAS or MPKUS differ from a CA- plus IQ-matched Control group in terms of visual memory, including immediate and delayed recall.

Results Visual Memory  No differences

Conclusions FAS  When CA and IQ-matched Controls are employed the pattern of attention and verbal memory deficits seen in adults with FAS is similar to previous research documenting the pattern of deficits in children with FAS.  Adult individuals with FAS appear to have deficits in acquisition of new material, immediate and delayed recall of verbal material and deficits in response inhibition.

Recommendations FAS Current data suggests that the following may be helpful: ] Pharmacological interventions and cognitive strategies designed to reduce impulsivity and increase reflectivity.  Educational and vocational planning that incorporates a high degree of structure and repetition and utilizes both verbal and nonverbal instruction and cueing.  Research paradigms that attempt to further elucidate the basis of the attention and memory deficits identified in individuals with FAS, at behavioral, psychosocial, neuroanatomical and neurochemical levels.

Conclusions MPKUS  It is difficult to draw firm conclusions regarding the MPKUS data due to the small sample size, and the bimodal distribution of IQ in the sample.  Further research is needed utilizing a larger sample, and a battery of tests more sensitive to differences in ability at the low end of the IQ range.

FAS & MPKUS  Theoretical Question Are the relative effects of prenatal exposure to alcohol or phenylalanine different.

Method Participants  FAS and MPKUS participants whose Full Scale IQ were within 5 IQ points were paired resulting in 10 matches - unable to match on age  7 FAS and 1 MPKUS participant eliminated from further analyses  10 Control participants selected based on an IQ match within 5 points of one of the 10 prenatal teratogen pairs  Results - 10 triplets matched within 5 points on IQ

Exploratory Question I Attention Do adults with FAS differ significantly from adults with MPKUS in terms of capacity to focus, sustain, shift and encode attention as defined by Mirsky et al.'s model of attention.

Results Attention  Controls  more correct responses  FAS  more omission and commission errors than MPKUS & Controls  MPKUS  more omission and commission errors than Controls

Exploratory Question II Memory Do adults with FAS differ significantly from adults with MPKUS in terms of verbal and visual memory, including the ability to learn new information, immediate and delayed recall, and recognition memory ability.

Results Memory  Controls  immediate & delayed recall superior to FAS & MPKUS  FAS  more intrusion errors than MPKUS & Controls  FAS  lost information over delay

Conclusions Randomized Block Analyses  Failed to reveal some of the differences found in the FAS paired analyses  Groups differed in intrusion errors, immediate recall of visual material, omission and commission errors, and recognition ability.  MPKUS appears more similar that different from their IQ matched controls.

General Conclusions Attention & Memory  FAS appear more affected in terms of memory & attention relative to MPKUS & Controls.  Lack of consistency with previous research in terms of the pattern of attention and memory deficits identified is likely due to the use of IQ matched controls in the present study.  The large within group variance may have masked differences between the groups.

Recommendations Future Research  Replication of findings with larger samples and more sensitive measures is needed  Comparison of the attention & memory findings with measures of social and emotional development