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 QuestionsWhat 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

AttentionHow 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 MemoryHow 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

FASCurrent 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 QuestionAre 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

AttentionDo 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

MemoryDo 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