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Ai.coi~oi I \ M: CI I NI CAL AND EXrl KIM1 NI A I Rl - s Z~Rc l 1
Vol. 22, No. 2
April 1998
A Review of the Neurobehavioral Deficits
with Fetal Alcohol Syndrome or Prenatal
Alcohol
Sarah N. Mattson and Edward P.
Fetal alcohol syndrome is a devastating developmental disorder
caused by prenatal exposure to high amounts of alcohol. In addition
to structural abnormalities and growth deficits, fetal alcohol syn-
drome is associated with a broad spectrum of neurobehavioral
anomalies. This paper reviews the behavioral and cognitive effects of
prenatal alcohol exposure. More than 20 years of research are dis-
cussed, with a focus on 10, activity, attention, learning, memory,
language, motor, and visuospatial abilities in children prenatally ex-
posed to varying amounts of alcohol, including those with fetal alco-
hol syndrome.
Key Words: FAS, Prenatal Alcohol Exposure, Brain Function, Neu-
ropsychological Effects.
HROUGHOUT HISTORY, the negative effects of
T maternal drinking on offspring have been suspected.
Aristotle has been quoted as saying that foolish, drunken,
or hare-brain women, for the most part bring forth children
like unto themselves, morosos et Zanguidos, and in
Carthage and Sparta, laws prohibited the use of alcohol by
newlyweds presumably to prevent conception during intox-
ication. During the gin epidemic in England, in the first
half of the 18th century, physicians warned against alcohol
consumption during pregnancy, claiming this was the cause
of weak, feeble, and distempered children. Such beliefs
continued until the early 20th century. In the postprohibi-
tion medical community, however, the idea that alcohol
taken during pregnancy could be harmful to the developing
fetus was dismissed as moralism. It was thought that harm-
ful effects noted in the offspring of alcoholic women were
the result of constitutional factors that also were the cause
of the alcohol problem. It was not until the late 1960s and
early 1970s that interest in the adverse effects of alcohol
was renewed. In 1968, a group of French researchers pub-
lished the results of a study of 127 children of alcoholic
parents.2 They reported the highly distinctive appearance
From the Center for Behavioral Teratology, Department of Psychology,
San Diego State University, San Diego, California.
Presented at the 1996 Borchard Foundation Symposium on the Behavioral
Effects in Children following Prenatal Alcohol Exposure, Missillac, France,
This work was supported by the National Institute on Alcohol Abuse and
Alcoholism Grant AA10417 and AA10820.
Reprint requests: Sarah N. Mattson, Ph.D., Center for Behavioral Tera-
tolog?! 6363 Alvarado Court, Suite 209, San Diego State University, San
Diego, CA 92120.
July 28-30, 1996.
Copyright 0 1998 by The Research Society on Alcoholism.
Alcohol Clm Exp Res, Vol22, No 2, 1998: pp 279-294
of children
Riley
in Children
Exposure to
of alcoholic parents, particularly alcoholic
mothers. . . . This report went virtually unnoticed in the
United States until 1973, when Seattle dysmorphologists
documented similar findings3 and defined a specific pattern
of malformations in children born to chronic alcoholic
women as fetal alcohol syndrome (FAS).4
More than 20 years later, it is estimated that FAS affects
approximately 0.29 to 0.4SilOOO live born children. Preva-
lence estimates vary depending on socioeconomic and eth-
nic factors, and those that include Native American popu-
lations report incidences of up to 2.99/1000 births. In the
United States, at least 1200 children are born each year
with FAS, and the annual cost associated with caring for
such infants is estimated at 74.6 million dollar^.^These
estimates are strictly limited to those children who meet the
clinical criteria for FAS and do not include the spectrum of
effects caused by prenatal alcohol exposure. It is obvious,
however, that the effects of alcohol use during pregnancy
are widespread and devastating, and that these problems
are entirely preventable.
The effects of prenatal alcohol exposure fall on a con-
tinuum with FAS and perinatal death at one end and
relative normalcy on the other. Between these two end-
points are a variety of behavioral and physical features that
are termed fetal alcohol effects (FAEs) or alcohol-related
birth defects. The wide range of behavioral and cognitive
effects associated with prenatal alcohol exposure is repre-
sentative of the continuous nature of alcohols behavioral
teratogenicity. Importantly, FAS represents only one point
on the continuum, and the effects of in utero alcohol
exposure on children without FAS should also be assessed.
In the offspring, the diagnosis of FAS is based on a triad
of features: (1) pre- and/or postnatal growth deficiency; (2)
a pattern of craniofacial malformations; and (3) central
nervous system (CNS) dysfunction. Babies born with FAS
are often small for gestational age4 and continue to show
evidence of growth deficiency.6 For example, in a sample of
adolescents and adults with FAS, the mean height and
weight were 2.1 and 1.4 standard deviations below the
population mean, re~pectively.~ The pattern of craniofacial
malformations includes microcephaly, short palpebral fis-
sures, a long smooth philtrum, a thin vermilion border,
epicanthal folds, and flat mi df a~e.~ The CNS dysfunction is
279
280 MATTSON AND RILEY
Table 1. IQ Scores of Individual Cases of FAS or Alcohol-Exposed Individuals Reported in the Literature, Presented in Chronological Order Through 1996
_ _ _ _ ~ ~ ~
Authors Age n Tests IQ estimatet Comments
J ones, Smith, Ulleland, 8 Streissguth3
Palmer, Ouellette, Warner, 8 Leichtman
Root, Reiter, Andrioia, 8 Ducken
Tenbrinck 8 B~chi n~
Ko~sseff~
Char
Mulvihill Klimas, Stokes, 8 Ri~emberg~
Bierich, Majewski, Michaelis, 8 Tillner40
Majewski, Bierich, Loeser, Michaelis, Leiber, 8
Ijaiya, Schwenk, 8 Gladtke14
Bette~ken~
Van BiervlietS5
Fryns, Deroover, Parloir, Goffaux, Lebas, & Van Den
Berghe 42
Dehaene, Walbaum, Titran, Samaille-Villette,
Samaille, Crepin, Delahousse, Decocq, Delacroix,
Caquant, 8 Q~erl eu ~~
Koranyi 8 CsikyiiZ
Neidengard, Carter, 8 Smith
Ballesta 8 Cruz17
Slavney 8 Grau
Qazi, Masakawa, Milman, McGann, Chua, 8 HalleP
Qazi, Madahar, Masakawa, 8 McGann
Maller, Brandt, & Tygstr~p~~
Shaywitz, Caparulo, 8 Hodgson l 3
losub, Fuchs, Bingol, Stone, 8 Gr~mi s ch~~
Naselli. De Toni. Vianolo. Di Battista. 8 AicardP4
14m
3m
57m
46m
40m
48m
34m
3yl Om
14.5m
22m
14.5m
22m
11.7~
14.5y
11 .oy
9.9y
2y4m
3y5rn
1 l Y
6m
NfA
5Y
3y7m
6y2m
7y9m
6y6m
l Y
2y6m
15Y
1 6 ~
21Y
31-17
6m
7m
1 Om
I am
26m
13Y
4y6m
7y3m
l l m
21m
16Y
1lY
1 OY
15Y
7Y
8Y
4y6m
7Y
6Y
16m
3yl m
4y4m
4yl Om
9Y
13Y
17Y
1 OY
17Y
1 am
4Y
6~
8y6m
6v6m
1 (case 1)
1 (case 2)
1 (case 3)
1 (case 4)
1 (case 6)
1 (case 7)
1 (case 8)
1 (case 1)
1 (case 2)
1 (case 3)
1 (KC)
1 (AC)
1 (PC)
1 (RC)
1
1
1
1 (case 5)
1 (case 2)
1 (case 5)
1 (case 23)
1 (case 1)
1 (case 3)
1 (case 4)
1
1 (case 2)
1 (case 3)
I (case 4)
1 (case 7)
1 (case 10)
1 (case 11)
1 (case 12)
1 (case 13)
I (case 14)
1 (case 1)
1 (case 2)
1 (case 3)
1 (case 4)
1 (case 5)
1 (case 2)
1 (case 1)
1 (case 2)
1
1 (case 1)
1 (case 2)
1 (case 3)
1 (case 4)
1
1
1 (case 1)
1 (case 1)
1 (case 2)
1 (case 3)
1
Bayley MDI
Bayley MDI
Stanford-Binet
Stanford-Binet
Stanford-Binet
Stanford-Binet
Bayley MDI
Stanford-Binet
Bayley MDI
Bayley MDI
NfA
Cattell
NIA
NfA
Cattell
Kramer
Kramer
HAWIK
(German WISC)
Stanford-Binet
Stanford-Binet
Griffith
NfA
Brunet-Lezine
NfA
N/A
N/A
WISC-R
NIA
Merrill-Palmer
Cattell
NfA
Leiter
NIA
NIA
WAlS
N/A
WAlS
Bayley MDI
Stanford-Binet
WlSC
WlSC
WlSC
59
83
75
57
79
70
150
65
56
76
59
70
80
75
112
68
36
75
85
41
93
84
105
76
a7
54
52
65
52
35
25
37
75
58
50
60
72
59
82
54
72
73
33
70
55
66
52
70
65
74
68
50
45
68 Pa)
69 (DQ)
120
70
67
60
72
50
50
50
50
46
a0
Twins placed in foster home between
testings
Siblings; case PC had fewer
dysrnorphic features
Not identified as FAS by author$
Noonan syndrome
AEIf
Klippel-Feil malformation
Chromosomal abnormalities$
Schizophrenia
Renal anomalies
Chromosomal abnormalities$
Language disordered+
Siblings
NEUROBEHAVIORAL FINDINGS IN FAS
281
Table 1. Continued
Authors Age* n Tests IQ estimate7 Comments
Ticha, Santavy, & Matlochaz3
Aronson & OlegPrdZ4
Streissguth, Clarren, & J ones
Usowicz, Golabi, & Curry6
Marcus
Mattson, Riley, J ernigan, Ehlers, Delis, J ones, Stern,
Mattson, Riley, J ernigan, Garcia, Kaneko, Ehlers, &
Harris, MacKay. & O ~b o r n ~~
J ohnson, Hesselink, & B el l ~gi ~~
J ones45
Ernhart, Greene, Sokol, Martier, Boyd, & Ager23
3Y
3Y
4Y
<3Y
<3Y
4Y
5m
6y2m
6y4m
<l Y
1 OY
4y9m
8Y
4Y
14Y
3Y
13Y
4Y
14Y
3Y
13Y
<l Y
1 OY
4Y
14Y
17m
5yl Om
5y4m
1 Oy3m
2y2m
5yll m
12Y
14Y
1 6 ~
41-17
6.5m
12m
19m
25m
9m
13.5m
20m
7m
13m
17m
25m
1 (case 1)
1 (sib of C1)
1 (case 2)
1 (case 5)
1 (sib of C5)
1 (case 6)
1
1
1 (case 2)
1 (case 3)
1 (case 4)
1 (case 6)
1 (case 7)
1 (case 8)
1 (case 9)
1 (case 11)
1 (case 3)
1 (case 1)
1 (case 2)
1 (case 3)
1 (case 4)
1 (case 5)
1 (case 1)
1 (case 2)
2 cases
with PEA
1 (case 1)
1 (case 2)
1 (case 3;
FAE)
3y.4ylOm case 1
case 2
case 3
case 4
case 5
case 6
case 7
case 8
~
Terman-Merrill
Terman-Merrill
Brunet-Lezine
Terman-Merrill
Brunet-Lezine
Brunet-Lezine
Terman-Merrill
N/A
Bayley MDI,
Stanford-Binet,
or WPPSI*
WISC, WISC-R,
Bayley MDI
NIA
WISC-R
WISC-R
Bayley MDI
Stanford-Binet.
WPPSl
80 Siblings of patients also were alcohol-
50
50 (DQ)
50
60-70 (DQ)
50 (DQ)
55
70
76
83
86
66
76
47
48
68
81
60
57
50
80
43
40
30
20
50
50
100
55
95
85
51
41
64, 69
exposed and had at least some
features of FAS, if not frank FAS
Laryngeal web
Agenesis of corpus callosum
89
77
<50
<50
69
<50
50
<50
81
All three cases displayed autistic
behaviors
57
63
54
95, 94
105,87
79,95
65, 79
83,87
78, 101
98, 87
50,25
Testing at earlier dates also reported*
~ _ _ _ _ ~
N/A, not applicable; sib, sibling.
* m, months: y, years.
t IQ estimates in italics are included in the mean (see text for details).
* See text for details.
9 W, developmental quotient.
#Some of these cases overlap with J ones, Smith, Ulleland, & Streissguth (1973) listed above; however, since the 1973 publication, the normative data for the
Stanford-Binet have been revised, which explains the revised 10scores for cases 3, 4, 6, and 7.
variable and can present as hyperactivity, attention deficits,
learning disabilities, or mental retardation.
Although the diagnosis of FAS does not require frank
mental retardation, intellectual capacity is very often com-
promised in these children. In fact, FAS has been called the
leading known cause of mental retardation in the Western
world. The average IQ of children with FAS falls close to
70, although the range is quite large (e.g., 20 to In
exposed children who do not meet the criteria for FAS,
some of the previously mentioned features may still be
282 MATTSON AND RILEY
Table 2. IQ Scores for Groups of Alcohol-Exposed Subjects Reported in the Literature, Presented in Chronological Order Through 1996
Authors Age n Tests Mean IQ IQ range
Streisguth & R o hs e no ~~~*~ 8m 15
4Y 13
7Y 15
Dehaene, Samaille-Villette, Samaille, Crepin, NIA 22
Walbaum, Deroubaix, & Blan~-Garin'~~'~
Streissguth, Herman, & Smith26^Rb
Streissguth, Herman, & Smith54'R"
M a j e ~s k i ~~. ~~. ' ~~f ~; Majewski &
Maj e~s ki "~~
Oleglrd, Sabel, Aronsson, Sandin,
J ohansson, Carlsson, Kyllerman, Iversen.
& HrbekZgfR
Shaywitz. Cohen, 8 S ha y~i t z ~~' ~
Streissguth, Barr, Martin, & Herman39*P
losub, Fuchs, Bingol. & Gromi ~ch~"~
Golden, Sokol, Kuhnert, &
Steinhausen, Nestler, & Spohr'
Spohr & Steinhau~en'~'~~; Steinhausen,
Aronson, Kyllerman. Sabel, Sandin, 8
O'Connor, Brill, & Sig~nan~O*~
Gobel, 8 Ne ~t l e ? ~' ~~
Oleglrd3Z*R
Coles, Smith, 8 Falek66*P
Aronson & Oleglrd'32*R
Fried & Watkir~son~'*~"
Streissguth, Barr, Sampson, Darby, &
IOffe 8 C h e mi ~k ~~' ~
M a ~t i n ~~* ~
conry71'~
Streissguth, Barr, & S a mp ~o n ~~* ~
Fried 8 Watki ns ~n~~*~~
Streissguth. Aase, Clarren. Randels, LaDue,
Carney & Chermak'Z''R
Forrest, Florey, Taylor, McPherson, 8
Streissguth, Randels. & Smith34Rc
& Smith7R
Y o ~n g ~~* ~
Coles, Brown, Smith, Platzman, Erickson, &
Falek4'*'
9m-2.5y
2.51-5y
6-1 5y
7m-21y
21 m-22y
20-21 y
5-9Y
4-25y
5
10
3
2
17
5
4
9
48 total
NIA 15
Em 10 (AAP 2 4)d
12 (AAP 2 3)
25 (AAP 2 2)
97 (AAP 2 1)
365 (AAP <1)
216 (AAP 5 0.10)
1 day-23y 63
12m 12
3-1 5y 32
6y3m (SD =34m) 32
8y7m (SD =15m) 16
1 y6m-7y 13 pairs
7-9y 8 pairs
12m 25 total
(AAP 2 1.0)
(AAP <1.0)
(AAP c 0.1)
6m 22 (cont. drinking)
11 (stopped drinking)
27 (never drank)
2.5-3oy 95
12m 10 (AA >0.85)B
116 (AA <0.14)
24m 8 (AA >0.85)
71 (AA <0.14)
4Y 421
1.5-9m
5.2-18.5~
5.2-15.8~
5.2-18.5
7.5y
3Y
4Y
12-4oy
8y6m (SD
18m
17
13 (FAS)
6 WE)
19 (controls)'
482
69 (AA/day 2 0.14)
64 (Wday <0.14)
71 (Wday 2 0.14)
59 Wday <0.14)
38 (FAS)
14 (FAE)
592
2.3y) 10
8.0~ 27 (FAS)
16.9~
9.oy 13 (FAE)
16.0~
5yl Om 25 (AA/week =11.8)
21 (Wweek =0)
Bayley MDI
Stanford-Binet
WlSC FSlQ
Brunet-Lezine
Bayley MDI
Stanford-Binet
WISCNVISC-R
WAlS
Bayley MDI, Stanford-Binet,
WISCNVISC-R, or WAlS
Kramer IQ test
NIA
WISC, WPPSI, or Stanford-
Binet
Bayley MDI
Bayley, Stanford-Binet.
Denver, Wechsler
Bayley MDI
Columbia Mental Maturity
Scale
Columbia Mental Maturity
Scale
Griffith
WISC
Bayley MDI
Bayley MDI
NIA
Bayley MDI
WPPSI
Bayley MDI
WPPSI, WISC-R, or WAIS-R
WISC-R
McCarthy GCI
WISC-WWAIS-R
WISC-R
Bayley MDI
WISC, WISC-R, Stanford-
Binet, WAIS, WAIS-R
K-ABC
79.93 (vs. 80.47)"
87.92 (vs. 95.69)
80.73 (vs. 94.90)
66
47.4
68.9
84.7
62
66
67
66 (AE Ill)
79 (AE I I )
91 (AE I)
<70n =9
70-85 n =19
98.2
98
101
109
114
116
116
NIA
86 (SD =20)
89
NIA'
92 (controls =11 1)
99 (controts =114)
95 (SD =2.99)
108 (SD =8.48)
115 (SD =7.72)
102.9
111.03
113.11
NIA
98.4
109.5
110.7
11 9.5
NIA'
67.4
60.1
86.0
87.3
NIA'
115.8
114.8
123.4
124.4
66
73
79
NIA'
66.0
66.7
79.5
82.2
83.91 (SD =12.61)
91.91 fSD =13.81)
33-1 12
15-63
47-99
60-1 05
57-67
15-99
10-96
50-95
47-1 02
61-130
82-1 13
64-150+
50-97
NIA
NIA
<70 (n =12)
70-85 (n =33)
NIA
50-89
For FASIFAE:
40-1 01
NIA
20-1 05
50-91
NIA
NEUROBEHAVIORAL FINDINGS IN FAS 283
Table 2. Continued
Authors Age n Tests Mean IQ IQ range
101.1/101.7 Russell, Czarnecki, Cowan, McPherson. & 18m
MudaP7*'
Greene, Ernhart. Ager, Sokol, Martier, 8 6rn
1Y
2Y
3Y
4yl Om
12-42~ (mean =18.4) LaDue, Streissguth, & Randels6"*R
Autt-Ramo, Korkman, Hilakivi-Clarke, 27m
Lehtonen. Halrnesmaki. & Gran~trom~~*'
Fried, O'Connell, & Watki ns~n~' *~~ 5Y
6Y
J acobson, J acobson, Sokol. Martier, Ager, 13m
OConnor. Sigrnan, & K a ~a r i ' ~~*~ 12m
Streissguth 8 Dehaer~e~~~ 17m-30~
& Kaplan-Estrin7'*'
Caruso B ten B e n~e I ' ~~' ~ N/A
Steinhausen. Willms, & Spoh?s*Rc 5y4m (SD =13m)
8y9m (SD =24m)
5y5m (SD =14m)
15ylm (SD =25m)
9y10m (SD =18m)
13y2m (SD =19m)
15y4m (SD =21.61-4 Spohr, Willms, & Stei nhau~en'~~'~~
5 (PPM >3.5)9
11 (PPAA <3.5)
97 (PPAA <1)
39 (Abstainer)
297
279
275
269
260
92 (FASIFAE)
20 (3 trimesters exp.)
20 (2 trimesters exp.)
20 (1 trimester exp.)
71 (Wday >0.14)
64 (Wday <0.14)
67 (Wday >0.14)
70 (Wday <0.14)
382
24 (Wday >0.10)
20 (Wday <0.10)
12 (FAS)
7 (FAE)
15
15
10 (PEA)h
16
31
41
WPPSI VIQ/PIQ
Bayley MDI
WAIS-WISC-R
Bayley
McCarthy GCI
Bayley MDI
Bayley MDI
Bayley, WISC-R, WAIS-R,
Stanford-Binet, Terman-
Memill, Brunet-Lezine
Columbia Mental Maturity
WISC-R
Scale, WPPSI, or WISC-R
WPPSIMIISC-R
11 1.8/99.9
107.7/101.9
107.8/100.7
N/A' N/A
70
N/A'
120.9
122.2
126.8
124.2
N/A'
12-1 08
N/A
NIA
107.79 (SD =10.7)
113.1 (SD =8.99)
69.6 56-120
93.0
91.7
69.7 NIA
NIA' NIA
8G116; n =10
71-85; n =14
51-70; n =6
36-50; n =5
C35; n =6
J anzen. Nanson, & Block68'R 52.7~1 (SD =8.82m) 10 McCarthy GCI 67.6 NIA
Larroque, Kaminski, Dehaene, Subtil, -4.5y 32 2 1.5 oz/day McCarthy GCI 89.5 (SD =2.92) NIA
Mattson, Riley, Gramling. Delis. & 8. 5~ (SD =3.8~) 34 with FAS WPPSI-WWISC-R 74.4 NIA
Delfosse, & Q u e r l e ~~~* ~ 123 <1.5 odday 103.2 (SD =1.69)
8. 5~ (SD =4.0~) 13 with PEA 83.6
N/A, not applicable; FSIQ, Full scale IQ; GCI, General Cognitive Index; K-ABC, Kaufman Assessment Battery for Children: VIQ, Verbal IQ; PIQ, Performance IQ: exp,
* Subjects are FAS: t subjects are AE 1-3; $ subjects are alcohol-exposed to varying degrees.
a Values for controls included for comparison purposes.
exposure.
Retrospective study: prospective study.
This sample includes patients reported earlier in J ones, Smith, Ulleland. and Streissguth (1973).
Retest.
AAP =oz of absolute alcohol consumed/day in the month prior to pregnancy recognition; I AA =1-2 drinks of beer, 2 drinks of wine, or 2 drinks of liquor.
AA =oz of absolute alcohol/day during pregnancy.
PPAA =oz of absolute alcohol consumed prior to pregnancy recognition.
This study involves 16 sets of twins; PEA =prenatally exposed to alcohol, no diagnosis.
'See text for details.
present. Importantly, in the absence of the specific facial
malformations, and thus the diagnosis of FAS, cognitive
deficits, even mental retardation can still be present.
The intent of this paper is to review the behavioral and
cognitive effects of prenatal alcohol exposure. More than
20 years of research are discussed, with a focus on IQ,
activity, attention, learning, memory, language, motor, and
visuospatial abilities in children prenatally exposed to vary-
ing amounts of alcohol, including those with FAS. Animal
studies will only be briefly discussed in support of human
studies.
INTELLIGENCE
In the more than 20 years since FAS was first described,
an array of cognitive and behavioral characteristics have
been identified in children and animals exposed to alcohol
Various authors have addressed the effect of
prenatal alcohol exposure on IQ, and in general, such
exposure leads to a decreased IQ score. Both individual
cases and group means have been reported in the litera-
ture. Although some comparability between reports is pos-
sible, there are differences in the measures that have been
284 MATrSON AND RILEY
used to evaluate intellectual functioning. The predominant
tests that have been used are the Bayley Scales of Infant
Mental and Motor Development (subsequently called the
Bayley), which provides a Mental Development Index
(MDI); the Stanford-Binet Intelligence Scale; and the
Wechsler scales that include the Wechsler Preschool and
Primary Scale of Intelligence, original and revised versions
(WPPSI and WPPSI-R); Wechsler Intelligence Scale for
Children, original and revised versions (WISC and WISC-
R); and the Wechsler Adult Intelligence Scale, original and
revised versions (WAIS and WAIS-R). The Stanford-Binet
and the Wechsler scales provide Intelligence Quotients or
IQ scores based on comparison with large standardization
groups. In the following discussion of IQ in FAS, the
specific tests used will be mentioned if this information is
available. Individual case reports that include I Q estimates
are listed in Table 1 and IQ reports of alcohol-exposed
groups are listed in Table 2. Although general information
about intelligence in FAS will be reviewed, only cases that
require more detailed description will be discussed here,
and the reader is referred to the tables for a complete list
of reports that include measures of IQ.
Reports of Individual Cases of Children with FAS
Early reports of children with FAS were often descriptive
studies of very small groups of children or individuals.
Measurements of intelligence were not always included or
were described qualitatively (i.e., borderline or mentally
retarded) rather than quantitatively. A review of the avail-
able reports, detailed in Table 1, reveals a mean I Q of FAS
cases is 65.73 (SD =20.2), with a range of 20 to 120. This
mean encompasses all cases that are clearly FAS and had
an exact I Q estimate (n =79). When more than one testing
was reported for the same individual, only the most recent
score was included in the mean. Several of these cases
deserve a more detailed discussion. The earliest reports of
J ones and his colleagues3 on eight infants and young chil-
dren with FAS documented MDIs and IQ scores for seven
patients in the range of 50 to 83 (mean =67.6) using the
Bayley and the Stanford-Binet. In a 10-year follow-up,
these cases were rereported according to the revised Stan-
ford-Binet normative data. The new range of the original
IQ scores for six of the seven children was rereported as 47
to 83 (mean =62.3). Two additional cases were also re-
ported with IQ scores of 30 and 43 at the ages of 7 months
and 4 years, respectively. At the 10-year follow-up, the I Q
scores of these eight patients were 20 to 86 (mean =61)
using the Stanford-Binet and WI SC6 The issue of the
stability of I Q over time in individuals exposed to alcohol
prenatally is addressed later in this paper.
In 1974, the cases of three siblings (one singleton and
monozygotic twins) born to an alcoholic mother were de-
scribed by Palmer et al. These three children met the
existing criteria for FAS and had MDI/IQ scores of 65
(Stanford-Binet), 56, and 59 (Bayley) at their first assess-
ment at the ages of 3 years 10 months, 14.5 months, and
14.5 months of age, respectively. After the twins were
placed in a good foster home, they were reassessed and
earned MDI values of 76 and 70. Four new cases, who were
all children of one alcoholic woman, were described by
Root et a1.12 All were diagnosed as having FAS, although
one (PC, the third child) had fewer dysmorphic features.
The IQ scores of these children were 80,75,112, and 68. It
is notable that PC, the third child, had fewer dysmorphic
features and the highest I Q of the group. In a report
proposing a new syndrome, a child was described who
seemed to meet the criteria for FAS and had an alcoholic
mother. Although the author did not recognize the case as
FAS, an editorial note identified the similarity between the
case and the recent description of FAS by J ones and col-
leagues. This child had an IQ of 75.13
Majewski et al. l4 reported three examples of alcohol
embryopathy (AE), including one boy with AE I who had
an IQ of 105, using Kramers method of assessment. The
term alcohol embryopathy is used in place of fetal alcohol
syndrome by German researchers who considered it more
appropriate because the associated dysmorphology occurs
during the embryonic period of development. In addition,
the use of AE terminology includes a gradation of effects
that is not traditionally associated with the FAS terminol-
ogy. Three degrees (I, 11, and 111) are used to describe
alcohol-exposed children with mild (I) to severe (111) alco-
hol-related effe~ts. ~
Intellectual functioning has been reported for children
with FAS who also have other disorders or malformations.
I n 1976, a child with FAS and Noonan phenotype was
reported to have an I Q of 85.16 Chromosomal abnormali-
ties in children with FAS have been reported in three cases.
The first report described two children with I Q scores of 66
and 55 and had the following chromosomal abnormalities:
46, XY, inv. (3) (p13q27) and 45, XY, -14, -15, +t
(14q15q). It is unclear what role these abnormalities had in
the etiology of the dysmorphic and cognitive anomalies
observed in these two children. It is notable that other
family members, including one mother, had similar dysmor-
phic feature^.'^The second report was of a girl with an I Q
of 50 and 47 chromosomes in all cells. In addition, a
15-year-old girl with FAS and schizophrenia was de-
scribed. Her IQ was estimated to be 52, although psy-
chotic symptomatology may have interfered with valid as-
sessment. I Q scores of additional cases of FAS with
Klippel-Feil malformation2 and renal anomalies21 have
also been noted.
I n the 1980s, fewer case reports included a measure of
IQ, although a similar number of cases were reported.
According to Abe1,22 245 cases of FAS were documented
between 1973 and 1979, with 45 reports of I Q (18.4%).
Alternatively, in the 205 cases reported between 1980 and
1988, only 13 included IQ scores (6.3%). A review of the
literature uncovered four more I Q reports. Two come from
a study included by Abel but not included in his listingz3
NEUROBEHAVIORAL FINDINGS IN FAS 285
and two from a review article by Aronson & OlegHrd.24
Since Abels comprehensive summary of FAS reports, very
few reports have included I Q scores or even individual case
descriptions. This decrease in case reports reflects the
growing recognition of FAS and the increase in retrospec-
tive and prospective group studies.
Reports of Groups of FAS or Alcohol-Exposed Children:
Retrospective and Prospective Studies
As the study of the effects of prenatal alcohol exposure
progressed, larger retrospective and prospective studies
were initiated. Retrospective studies have evaluated groups
of children with FAS or varying degrees of alcohol-related
effects and have reported results as a function of group
means for FAS/alcohol-exposed and nonexposed controls.
Benefits of this type of study include the value of larger
groups of subjects and the inclusion of control groups.
Alternatively, confounding factors, such as cultural or so-
cioeconomic effects, as well as the possibility of an ascer-
tainment bias, sometimes confuse the results. Additional
difficulties arise in these and other studies in terms of
potential confounding variables, such as maternal IQ, pa-
ternal effects, medication usage, and other comorbidity
factors. These factors are often not addressed in retrospec-
tive studies, but their relevance cannot be ignored. Well-
controlled studies, including well-matched control groups,
help reduce the problem of confounds but ascertainment
remains a difficulty with this type of sample. In addition,
because the children in retrospective studies are identified
after birth and frequently medical records and/or contact
with the biological mother is unavailable, there is often
little reliable information about the degree of alcohol ex-
posure. When only children with FAS are evaluated, less of
a problem exists because alcohol exposure is typically in-
cluded in the diagnostic criteria and the relationship be-
tween such exposure and the resulting physical features is
clear. In other words, because alcohol exposure is part of
the traditional diagnostic criteria, children with unknown
prenatal histories are excluded by definition. When less
affected non-FAS children are evaluated, there is more
reliance on prenatal alcohol history for study inclusion.
Retrospective studies (see Table 2 for complete list),
such as the early Seattle st~di es ~~ ~ or studies out of Ger-
man~, ~- ~ reported an overall mean IQ of 72.26 (range of
means =47.4-98.2). This weighted mean (the mean was
adjusted for sample size differences) encompasses all ret-
rospective group studies (17 studies) of children with FAS
or AE (total n =269) as detailed in Table 2.
A few retrospective studies require more detailed discus-
sion. Although traditional studies of intellectual function-
ing in FAS began with children of alcohotic mothers, Shay-
witz et al.30 started with a large group of learning disabled
children and discovered 15 who were born to alcoholic
Women. This group had a mean I Q of 98.2 (range =
80-113) using the WISC, WPPSI, or Stanford-Binet. The
authors, however, were interested in learning difficulties in
children of normal intelligence who were born to alco-
holic mothers, and these children may not truly be repre-
sentative of FAS. In a different group of 63 children with
FAS, I Q information was available for the 30 that were
over the age of 3 years. The I Q scores ranged from 50 to 97,
with most patients having I Q scores between 65 and 70, and
mental retardation was found in 14 of the 30 (46%).31 A
group of 21 alcohol-exposed subjects and a well-matched
control group were assessed by Aronson and colleagues32
using Griffiths Mental Developmental Scales and the
WISC. The mean performances of the alcohol-exposed
group were 19 and 15 I Q points below the control group on
the Griffiths and WISC, respectively. Only 10 of the 21
alcohol-exposed individuals met criteria for FAS, reiterat-
ing that the effects of alcohol are important even in the
nondysmorphic individual. Finally, in a long-term follow-up
of adolescents and adults with FAS (n =38) or FAE (n =
14), mean IQ was determined to be 68 (range =20-105).
The mean I Q of the FAS group, at 66, was lower than that
of the FAE group that was 73.7
Recently, the IQ performances of children with FAS were
compared with alcohol-exposed children with few if any fea-
tures of FAS.33 All chddren in this study were exposed pre-
natally to high amounts of alcohol; however, only the FAS
group displayed the craniofacial anomalies and growth deficits
associated with the diagnosis. The other group was designated
as having prenatal exposure to alcohol (PEA) and had docu-
mented exposure to high levels of alcohol, but were not dys-
morphic, microcephalic, or growth retarded. In comparison
with normal controls, both groups of alcohol-exposed children
displayed significant deficits in overall IQ measures, as well as
deficits on most of the subtest scores. Importantly, these
deficits in IQ were found in both alcohol-exposed groups.
Whereas the PEA subjects usually obtained marginally higher
IQ scores than those with FAS, few significant differences
were found between the two alcohol-exposed groups. These
results indicate that high levels of prenatal alcohol exposure
are related to an increased risk for deficits in intellectual
functioning and that these deficits can OCCUT in children with-
out all of the physical features required for a diagnosis of FAS.
Similarly, individuals with the partial phenotype of FAS, or
FAE, display IQ def i ~i ts.~,~ Our PEA subjects may be some-
what similar to individuals identified by other groups as having
FAE; however, individuals withPEA display few if any of the
facial features of FAS, and are not growth retarded or micro-
cephalic.
Prospective studies of the effects of prenatal alcohol
exposure have evaluated pregnant women using a variety of
prenatal measurements, including alcohol consumption.
The resulting offspring have been followed longitudinally,
up to 14 years in the case of Streissguth et al.35 The
strengths of such studies are obvious. They allow for a
better understanding of the exposure patterns and can
include measurement of other, possibly confounding, fac-
tors (e.g., smoking, other drug use). Although very often
MATSON AND RILEY
286
the children in these prospectively identified groups do not
have FAS and the level of alcohol exposure is relatively low,
the use of large groups of mothers allows for an assessment
of the relationship between alcohol exposure and offspring
behavior. As a consequence of the design of these large
prospective studies, relationships between the variables are
described, and group means are often not reported. How-
ever, some prospective studies still include IQ values pre-
sented as a function of alcohol exposure level.
Similar to the retrospective studies, prospective studies
have found decrements in IQ related to alcohol exposure.
Golden et al.36 assessed twelve 1-year-old children who
were identified as having FAS, based on prospectively gath-
ered information on alcohol exposure and neonatal exam-
ination. Using the Bayley, the mean MDI for this group was
estimated as 86. In 1990, Ioffe and Cherni ~k~~ reported a
mean MDI of 67.4 in a group of 17 alcohol-exposed infants
(1.5 to 9 months of age) identified prospectively. Addition-
ally, a group of 20 prospectively identified, alcohol-exposed
children (only six with FAS) whose mothers continued to
drink throughout pregnancy had significantly lower scores
on the Bayley than children whose mothers drank during
the first trimester only.38
With the use of prospective investigation of alcohol use
during pregnancy, more information has become available
about the effects of different levels of alcohol exposure.
Streissguth and her colleagues have followed the children
of nearly 500 mothers from the prenatal period through the
age of 14 years. In 1980, she reported a relationship be-
tween the amount of alcohol consumed and performance
on the Bayley at 8 months of age.39 The mean MDIs ranged
from 116 for infants of mothers who drank <0.10 AAP
(ounce of absolute alcohol per day prior to pregnancy
recognition) to 98 for infants whose mothers consumed >4
AAP. O'Connor et a1.4' reported a similar result. In twenty-
five 12-month-old infants, mean Bayley MDI decreased
from 115 with <0.1 AAP to 95 with >1 AAP.
Similarly, other groups have reported decreases in
MDI/IQ in relation to alcohol exposure. Moderate alcohol
use during pregnancy [mean consumption =0.31 oz abso-
lute alcohol per day (Mday)] was related to decreased
performance on the Bayley in 24-month-old ~f f spri ng.~~
Furthermore, Coles et a1?* reported a decrease in overall
mental processing on the Kaufman Assessment Battery for
Children in a group of children (mean age =5 years, 10
months) whose mothers drank throughout pregnancy
(mean consumption =11.8 Mweek). Importantly, Stre-
issguth has continued to find decreases in I Q in relation to
alcohol exposure as the study population matured. Specif-
ically, at 4 years of age, exposure to M day was related to
a decrease in full-scale IQ of nearly 5 points43 and exposure
to 1 M day was associated with a 6-point decrement in
full-scale I Q at age 7.44 I Q was not assessed at the 14-year
follow-up (Streissguth, personal communication, October
1994).
Importantly, one benefit of prospective studies over ret-
rospective studies is that they allow greater understanding
of the effects of pregnancy drinking dose and pattern.
Although animal studies (e.g., Refs. 45 to 47) clearly indi-
cate the importance of pattern and timing of alcohol expo-
sure and binge-drinking has been identified as a significant
risk factor for negative neurobehavioral outcome (e.g., Ref.
44), more information is needed. For example, beyond
trimester of exposure (e.g., Ref. 48), little is known about
the relationship between timing of alcohol exposure and
later neurobehavioral outcome in humans. Future studies
should emphasize more detailed analyses of factors such as
timing and dose of in-pregnancy drinking.
Studies Finding No Effect of Prenatal Alcohol Exposure do
Exist
Not all studies report decreases in intellectual perfor-
mance, however. A 1991 report from Scotland used the
Bayley to assess five hundred ninety-two 18-month-olds
and found an increase in performance related to pre- and
postpregnancy alcohol con~umpti on.~~ Furthermore, alco-
hol exposure was unrelated to cognitive outcomes on the
McCarthy in children 3 through 6 years of age.50751 As the
authors point out, however, the exposure levels in this study
were very low (mean =0.43 to 0.45 Mday) in the higher
exposure group. Another study of children exposed to low
amounts of alcohol (mean =0.07 Mday) found no effect
of alcohol exposure on the Bayley at ages 6 months and 1,
2, and 3 years, and the WPPSI at age 4 years, 10 monthss2
Concordance of IQ in Twins Exposed to Alcohol Prenatally
Additional information on IQ as a function of in utero
alcohol exposure is also available in studies examining twi n
pairs. In an interesting report of the concordance of diagnosis
and IQ in twin children of alcoholic mothers, Streissguth and
DehaeneS3 described 16 pairs of twins, both monozygotic and
dizygotic. For the most part, the twin pairs were concordant
for diagnosis (i.e., FAS, FAE, or none). Monozygotic twins
were exclusively concordant for diagnosis; and, as would be
expected, there was more variability in the dizygotic twins. In
no case, however, did one twin receive the diagnosis of FAS,
whereas the other received no diagnosis. In terms of mental
development, the IQ scores for diagnosis-concordant pairs
differed by an average of 8.1 points, whereas the discordant
pairs differed by 12.5 points. In the three pairs of monozygotic
twins tested, the mean difference was 4.3 IQ points, and the
dizygotic twins differed by an average of 11 points. For this
sample, the mean IQ for the FAS, FAE, and no diagnosis (but
alcohol-exposed) groups were 69.6, 93.0, and 91.7, respec-
tively.
Stability of I Q in Children Exposed to Alcohol Prenatally
The stability of IQ over time in patients with FAS was
evaluated in a report by Streissguth et al.54 Retest of 17
patients 1 to 4 years (median interval =1.75 years) after
NEUROBEHAVIORAL FINDINGS IN FAS 2x7
initial evaluation revealed a high correlation between test
and retest IQ scores, although four of these patients
(23.5%) achieved scores >1 SD from their original evalu-
ation (two improved). The mean IQ from the first testing
was 66 (range =15-99), and the second testing was 67
(range =10-96). I n the 10-year follow-up mentioned pre-
viously,6 the mean improvement was 9.1 I Q points (range =
1-30), with only one patient (12.5%) improving >1 SD. In
an extension of these earlier studies, Streissguth reported
additional test-retest data of adolescents and adult^.'^Over
an average test-retest interval of 8.3 years, the correlation
of I Q between testings was 0.78 for FAS patients (n =27)
and 0.88 for FAE patients (n =13). The mean IQ scores
were 66.0 (range =29-105) at initial test and 66.7 (range =
20-91) at retest for the FAS group and 79.5 (range =
56-101) and 82.2 (range =65-114) for the FAE group. In
all, only 7 of 40 patients (17.5%) were >1 SD from their
previous test performance (five improved). Other reports
of repeated indicate relatively good stability
of I Q over time, with the most variability in younger pa-
tients (see Table 1 for summary). One study indicated
improvement in intellectual functioning over a 3-year peri-
~ d , ~ ~ although this may have been due to a few children
who moved from the below average range (70-85) to av-
erage range (86-115) of i ntel l i gen~e.~~ I n the children with
I Q scores in the mentally retarded (<70) and above aver-
age ranges (>115), there was no significant change in
performance. Later reports by the same authors suggest
greater stability over longer periods of time.59
WQ vs. PZQ in Individuals with FAS
It has been suggested that FAS is associated with greater
decrements in Verbal I Q (VIQ) than in Performance I Q
(PIQ).60,61 However, a review of the studies where this
information is actually available suggests that the results
are equivocal. In eight case reports of individuals with FAS,
four cases16,19,62,63 displayed PIQ >VIQ, with a mean
difference of 8.5 IQ points (range =3-22). However, six
cases11,56,64,65 demonstrated VIQ > PIQ, and the mean
difference was 17 IQ points (range =11-26). In two cas-
e ~ , ~ ~ , ~ ~ there was no difference between the two subscales.
The average VIQ and PI Q scores from these case reports
are 61.00 (SD =12.82) and 55.33 (SD =13.45), respec-
tively. In the 17 group studies of individuals with FAS
where the relevant data were available, 10 stud-
ies25,32,33,44,49,50,66-69 indicated no differential effect of pre-
natal alcohol exposure on verbal versus nonverbal abilities.
In one of these although the scores for VI Q and
PIQ were equal, PIQ was more affected than VIQ. How-
ever, in another the opposite was true. PIQ (or
PDI) was greater than VI Q (or MDI) in five group stud-
ies,7341,61270,71 whereas VIQ was greater than PIQ in two
s t ~di es . ~~, ~~ In one of these studies,71 which has been cited
as evidence for the PIQ-VIQ differential, the FAS and
FAE subjects did in fact display greater PI Q than VIQ
scores. However, the greatest difference between these two
subscales was in the control group; in fact, PIQ appeared to
be more affected than VI Q when the alcohol-exposed sub-
jects were compared with these controls. It is therefore
unclear whether VIQ is consistently affected to a greater
degree than PIQ in individuals with FAS. It is clear, how-
ever, that FAS is related to decreased intellectual function-
ing with an average I Q between 65 and 75, and that this
level of performance is stable across time. Furthermore this
decrease in performance is also seen in children with pre-
natal alcohol exposure in the absence of FAS.
OTHER NEUROBEHAVIORAL DOMAINS
The following sections detail the ability levels of children
with FAS in five neurobehavioral domains: activity and
attention, learning and memory, language, motor, and
visuospatial functioning. Studies involving children with
FAS or prenatal alcohol exposure are included, and brief
discussions of animal studies are included when appropri-
ate. The results of neuropsychological studies of children
with FAS are summarized in Table 3.
ACTIVITY AND ATTENTION
Hyperactivity and attentional deficits are hallmark features
of prenatal alcohol exposure. In fact, offspring activity level
may be a more sensitive indicator of alcohols teratogenicity
than physical Children with FAS have been de-
scribed as tremulous, hyperactive, and irritable.74 Caretakers
note that the children are always on the go, and never sit
In a long-term follow-up of children with FAS, hy-
perlanetic disorders were among the most frequently diag-
nosed disorders and persisted throughout ~hi l dhood?~ In ad-
dition, hyperactivity may occur in the absence of intellectual
impairment. One study of 15 alcohol-exposed children of
average intelligence (IQ range =82-113, mean =98.2) re-
ported all but one as being hyperactive? Even in the absence
of the diagnosis of FAS, moderate levels of alcohol exposure
(mean =0.45 AA/day) have caused offspring to be more
fidgety and less ~ompl i ant?~
Animal models of prenatal alcohol exposure have reiter-
ated and emphasized the effect of maternal alcohol expo-
sure on activity levels in of f ~pr i ng. ~~, ~~ In a review of the
literature concerning prenatal alcohol and hyperactivity,
Bond77 concluded that, if rats are exposed to alcohol
greater than 6-7 g/kg/day, and are tested prior to 70 days of
age, they exhibit an increase in activity in comparison with
control offspring. Hyperactivity in rats is easily tested in a
variety of ways, and all methods of prenatal treatment and
assessment appear to produce similar results.10778
In addition to hyperactivity, attentional deficits have long
been associated with FAS and prenatal alcohol exposure.
Early naturalistic observations of infants suggested that pre-
natal alcohol exposure was associated with an increased
nonalert state. That is, the infants spent more time with eyes
288 MATSON AND RILEY
open, but not attending.79 Such deficits in attention appear to
LEARNING AND MEMORY
continue through
and may be
to those Of
Although learning processes, per se, have not been system-
children with Attention Deficit Disorder (ADD).8o Both FAS/ atically addressed until recently, learning abilities, broadly
defined, have been described in alcohol-exposed infants and
FAE and ADD children showed deficits in investing, organiz-
ing, and maintaining attention and had an increase in impul-
children. The earliest studies of Streissguth and colleagues
sive responses. Similarly, adolescents and adults with FAS
measured early learning and behaviors thought to be related
demonstrated deficits in tasks involved in the focusing (Tal-
to learning. In an operant learning study, extinction after
reinforcement of two simple behaviors was measured in new-
land Letter Cancellation Test), encoding (WISC-R Digit
Span), and shifting [Wisconsin Card Sorting Test (WCST)] of
borns exposed to alcohol and nicotine prenatally? Alcohol
attention.8l Alternatively, in an examination of children with
and nicotine interacted to produce significantly poorer learn-
per-
ing in the infants. In the same sample, decreased habituation
formed similarly to controls and better than ADD children on
on the Brazelton Scale was related to alcohol use in mid
tests of reaction time and vigilance.
pregnancy.93 Deficits in learning continue to be reported from
Attentional deficits have also been related to prenatal
the Seattle cohort. Decreased academic achievement and in-
alcohol exposure in non-FAS children. Four-year-old chil-
creased parent and teacher ratings of learning problems at 7%
dren of social drinkers (mean consumption =0.45 AA/
years of age were related to maternal binge drinkinga and
day during pregnancy, 0.88 AA/day prior to pregnancy)
measures associated with learning ~kills.8~ In addition, learn-
were observed to have poorer attention spans than control
ing difficulties were also observed in children with IQ scores
children when parity, maternal smoking, home environ-
ment, and sex of the child were used as covariates.73 Stre-
within the average range who were born to alcoholic moth-
issguth et al.83 also examined 4-year-old children for sus- ers: although this sample was selected from a learning dis-
tained attention using a continuous performance task. abilities clinic.
and with ADD the
After covarying maternal smoking, caffeine use, nutrition,
education, and childs birth order, prenatal alcohol expo-
of omission, commission, and a decrease in the ratio of
Studies targeting more specific aspects Of learning and
learning
When compared with children matched for age, sex, and
are now being reported*
sure was significantly associated with an increase in errors
correct to total responses. Importantly, in this study the
level of activity did not differ from normal controls,
indicating that hyperactivity did not play a significant role
in the attentional problems noted in this sample. At age 7,
this cohort again demonstrated an increase in reaction
time, and errors of commission and vigilance84; and, at age
11, maternal binge drinking was associated with behavioral
difficulties at school, including hyperactivity and atten-
tional problems.85 At age 14, prenatal alcohol exposure was
again related to attentional measures,86 as well as perfor-
mance on the WISC-R Arithmetic ~ubtest, ~~ which is com-
monly thought of as a measure of attention and freedom
from Streissguths findings of deficits on
attentional measures were supported by Brown et al.,89 who
reported deficits in the ability to sustain attention following
alcohol exposure throughout pregnancy.
Not all studies find effects on attention, however. Fried and
colleaguesg0 found no relationship between alcohol exposure
and attentional measures at 6 years of age. In fact, there was
a decrease in impulsive responses and maternal perception of
behavior in relation to alcohol exposure. These authors sug-
gest differences between study cohorts and measures as pos-
sible reasons for the discrepancies between their findings and
those of Streissguth et al.83 Importantly, the alcohol exposure
levels in this cohort were very low. However, Boyd and col-
leagues also reported no effect of prenatal alcohol exposure
on sustained attention in preschool children of alcoholic
mothers who drank during pregnancy. The alcohol exposure
levels in this study, while still relatively low, were higher than
in the previous study.go
and memory were assessed in 2o with FAs.94
race, the children with FAS demonstrated deficits in both
learning and recalling a word list. Their recall was impaired
on both free and recognition recall trials, and they made an
increased number Of intIllSiOn, perseveration, and false-
positive errors. These errOr.5 are COnSiStent with deficits in
response inhibition. However, given their decreased level
Of learning, their retention Of the material Was relatively
intact. This Same pattern Of impaired learning and rela-
tively unimpaired retention was also dtmonstrated in
adults with FAS95 and are suggestive of pervasive deficits in
encoding verbal information.
Reports from the Seattle cohort also SukXest a relationship
between memory functioning and Prenatal alcohol exposure.
For example, deficits have been noted in auditory memo-
Iy,8196 memory for stories and designs97 and spatial memo-
ryF6 Other reports of spatial memory deficits have been re-
ported in chMren with FAS98 as have deficits on some
measures of working Alternatively, in the Ottawa
cohort, prenatal alcohol exposure was not related to perfor-
mance on the memory component of the McCarthy Scales of
Childrens Abilities in 3- or 4-year-old childred or 5- or
6-year-old children.51 In addition, prenatal alcohol exposure
was not related to Visual recognition memory in alcohol-
exposed infants in a study of the Detroit cohort.00
The animal literature is replete with studies of learning
deficits following prenatal alcohol exposure. lo Offspring of
rats given alcohol during gestation show learning deficits
that include active avoidance,75 passive avoidance, dis-
crimination and reversal, and taste aversion learning.lo3
Memory deficits have also been reported in rats exposed to
NEUROBEHAVIORAL FINDINGS IN FAS 289
alcohol prenatally. Specifically, deficits in spatial memo-
ry104,105 and retention of learned tasks'06 have been re-
ported following prenatal alcohol exposure. Other studies,
however, suggest that long-term retention of information
after learning is relatively i nt a~t . ~' " ' ~~' ~~~ Whereas a com-
plete discussion of the findings of animal studies, as well as
their strengths and limitations, is beyond the scope of this
paper, several reviews of the literature
LANGUAGE
The effects of prenatal alcohol exposure on language
have been mixed. Case reports suggest the presence of
speech and language disturbances resulting from prenatal
alcohol exposure. Abe122 lists 53 reports of speech delay or
impediment in 550 FAS cases published between 1973 to
1988. These reports range from complete lack of intelligible
speech"' to mild dysarthria"' or lisping."2 Both receptive
(e.g., Ref. 113) and expressive (e.g., Ref. 114) language
deficits have been noted as have articulation disor-
d e r ~ ~ ~ , ~ ~ , ~ ~ and developmental
Group studies of language functioning in children with
FAS also find deficits in speech and language functioning
(e.g., Refs. 38 and 118). Reported deficits include word
c o m p r e h e n s i ~ n , ~ ~ , ~ ~ ~ ~ ~ ~ ~ l9 naming ability,'" articulation,"'
and expressive and receptive language skills.68,'21 On tests
of verbal fluency, children with FAS display impairments in
letter fluency although category fluency appears to be less
affected.993122 In contrast, a recent report of eight children
with FAS documented relatively intact language develop-
ment, when compared with controls.'23
In prospective studies of children exposed to varying
amounts of alcohol, however, the results are not as clear. In
a sample of alcohol-exposed children from Ottawa, Can-
ada, decreases in language comprehension were found in
13-m0nth-old,~' 2-year-0ld,~' and 3-year-old5' children ex-
posed to relatively low levels of alcohol (mean exposure =
0.31 M day for the entire 2-year-old sample, 0.45 M day
for the "heavier" exposed group in the 3-year-old sample).
No deficits were found, however, in the same cohort at 4 ; '
5, or 651 years of age. Furthermore, no effect on expressive
or receptive language skills was found in a separate group
of alcohol-exposed children at 1, 2, or 3 years of age.124
Like the Ottawa cohort, this group of children were ex-
posed to relatively low levels of alcohol exposure (mean
exposure =0.07 Mday).
Other studies have documented effects of alcohol on
language, however. Russell and colleagues67 reported
deficits in offspring receptive language functioning re-
lated to indications of maternal problem drinking (e.g.,
an individual's perceptions of what others think about
their drinking or reported alcohol-related family prob-
lems). This same report also documented deficits in
WPPSI Verbal IQ, which has a significant language com-
ponent. Finally, a recent report from the Seattle prospec-
tive study demonstrated a dose-response relationship
between maternal alcohol use and offspring Word At-
tack performance at 14 years of age.87 Word Attack is a
subtest of the Woodcock Reading Mastery Tests and
involves reading of nonwords. This task requires a
knowledge of pronunciation rules and is related to read-
ing ability. To summarize, children with FAS appear to
have deficits in speech and language, and similar deficits
are noted in some groups of prospectively identified
alcohol-exposed children.
MOTOR ABILITIES
In addition to alcohol's effects on higher level cognitive
functions, there is also an effect on the developing motor
system. Although a few studies find no effect of prenatal
alcohol on motor devel ~pment, ~~- ~~. ' ~~ most studies of mo-
tor development and motor skills suggest an effect of pre-
natal alcohol exposure. Early descriptions of children of
chronic alcoholic mothers3 reported delayed motor devel-
opment and fine-motor dysfunction. One report noted a
"nonspecific dyscoordinated motor pattern," hemiplegia,
ataxia, and an increase in cerebral palsy in children of
alcohol abusing women.29 Later studies also noted delayed
motor development in infants and children exposed to
alcohol prenatall~9,'00,'26 and fine- and gross-motor dys-
functions were noted in children of alcoholic mothers127
and social drinkers.12' In addition, Marcus'" noted axial
ataxia and kinetic tremor in children with FAS. Finally,
several reports exist of deficits in motor speed/precision,
finger tapping speed, and grip strength in children with
Animal models have also provided evidence for motor
dysfunction following prenatal alcohol exposure. Gait dis-
turbance~,'~~ delays in reflex de~elopment,'~' and poor
bal an~e'~' have all been reported in rats exposed to alcohol
during the perinatal period.
~~s. 68~71~119
VlSUOSPATlAL ABILITIES
Visuospatial abilities in children with FAS have not been
well documented. Many studies report deficits in simple
drawing tasks like the Beery Developmental Test of Visual
Motor I ntegr ati ~n~~, ~~, ~~, " ~ and the Frostig Developmental
Test of Visual Per~epti on~~~"~, '~~; however, very few stud-
ies have addressed more complex visuospatial abilities in
FAS. As mentioned previously, spatial memory appears to
be impaired in children with FAS.81,96,98 Interestingly, the
study of Uecker and Nadel suggested deficits in memory
for the location of objects but not for the objects them-
selves. In addition, this study documented alcohol-associ-
ated deficits in clock drawing, a traditional measure of
visuospatial ability.133 In a recent of more specific
visuospatial ability, children with FAS displayed deficits in
local processing of hierarchical stimuli. These children
were impaired in recalling and copying local (details) but
not global (configural) features of the stimuli. These defi-
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NEUROBEHAVIORAL FINDINGS IN FAS 291
cits were not due to the size of the stimuli or to deficits in
memory, and suggested a specific impairment in processing
local features of hierarchical visual information. Similar
deficits have been noted in other de~el opmental ~~ and
dementi ~~g ~~ disorders.
OTHER NEUROPSYCHOLOGICAL ABILITIES
In addition to the abilities already discussed, a few stud-
ies have documented other specific neuropsychological def-
icits in individuals with FAS. The WCST is a test of non-
verbal problem solving, which requires both problem
solving and cognitive flexibility, and has been proposed to
be sensitive to frontal system dysfunction. Adolescents and
adults with FAS display decreased accuracy,81 achieve
fewer categories, and make more perseverative responses99
on the WCST. Alternatively, the computerized version of
the WCST was found to be only moderately sensitive to
prenatal alcohol exposure in the 14-year assessment of the
Seattle cohort.s6 Our data suggest that, whereas children
with FAS perform more poorly than controls, these deficits
are considerably less severe than we would expect, given
their overall level of ability (i.e., IQ).i37
Finally, tests of planning ability are also thought to be
sensitive to frontal systems dysfunction, although few such
studies have been done in individuals with FAS. On the
Progressive Planning Testy9 which is similar to the Tower
of London Test, children with FASFAE had difficulty
with planning ahead and tended to perseverate on incorrect
strategies.
SUM MARY
In summary, FAS is a devastating developmental disor-
der that is associated with a wide variety of neurobehavioral
deficits. Studies of FAS have documented consistent defi-
cits in language, motor, learning, and visuospatial function-
ing. Memory seems to also be affected; however, studies
that include a comparison of learning and recall suggest
that, at least in the verbal domain, retention is fairly nor-
mal. That is, learning deficits (i.e., encoding) may be at the
root of observed memory deficits and that once informa-
tion is learned it can be retained. In addition, most studies
of attention suggest deficits in this domain, although the
study of Coles et a1.82 suggests that further, more specific
evaluation of the components of attention is necessary. In
addition, visuospatial functioning and problem solving are
two, as yet, understudied areas in FAS. Existing studies
suggest deficits in simple visuospatial functioning, but more
complex abilities are yet to be described. Similarly, several
studies show deficits on the WCST, although it is unclear
how these deficits relate to overall cognitive ability. Many
of these deficits have been supported by cohort studies that
provide invaluable information about the role of prenatal
alcohol exposure in the development of neurobehavioral
abilities. Future research is required to more clearly delin-
eate whether areas of relative strength or weakness exist in
children with FAS and how their cognitive abilities relate to
other types of mental retardation. In addition, correlation
of neuropsychological and neuroanatomical data may help
us understand the role of abnormal brain development in
cognitive ability. Taken together, results from these two
types of studies can help provide the background for edu-
cational and training programs specific to individuals with
FAS or prenatal alcohol exposure.
REFERENCES
1. Warner RH, Rosett HL The effects of drinking on offspring.
J Stud Alcohol 36:1395-1420, 1975
2. Lemoine P, Harousseau H, Borteyru J -P, Menuet J -C: Les enfants
de parents aicooliques: Anomalies observkes. A proposos de 127 cas
[Children of alcoholic parents: Abnormalities observed in 127 cases].
Ouest Med 21:476-482, 1968
3. J ones KL, Smith DW, Ulleland CN, Streissguth AP: Pattern of
malformation in offspring of chronic alcoholic mothers. Lancet 1:1267-
1271, 1973
4. J ones KL, Smith DW: Recognition of the fetal alcohol syndrome
in early infancy. Lancet 2:999-1001, 1973
5. Abel EL, Sokol RJ : A revised conservative estimate of the inci-
dence of FAS and its economic impact. Alcohol Clin Exp Res 15:514-524,
1991
6. Streissguth AP, Clarren SK, J ones KL: Natural history of the fetal
alcohol syndrome: A 10 year follow-up of eleven patients. Lancet 2:85-91,
1985
7. Streissguth AP, Aase J M, Clarren SK, Randels SP, LaDue RA,
Smith DF: Fetal alcohol syndrome in adolescents and adults. JAh4A
8. Streissguth AP: The behavioral teratology of alcohol: Perfor-
mance, behavioral, and intellectual deficits in prenatally exposed children,
in West J R (ed): Alcohol and Brain Development. New York, Oxford,
1986, pp 3-44
9. Abel EL, Sokol RJ : Incidence of fetal alcohol syndrome and
economic impact of FAS-related anomalies. Drug Alcohol Depend 1951-
70, 1987
10. Meyer LS, Riley EP: Behavioral teratology of alcohol, in Riley EP,
Vorhees CV (eds): Handbook of Behavioral Teratology. New York, Ple-
num Press, 1986, pp 101-140
11. Palmer RH, Ouellette EM, Warner L, Leichtman SR: Congenital
malformations in offspring of a chronic alcoholic mother. Pediatrics 53:
12. Root AW, Reiter EO, Andriola M, Duckett G: Hypothalamic-
pituitary function in the fetal alcohol syndrome. J Pediatr 87585-588,
1975
13. Kousseff B: KI-A possible new syndrome. Birth Defects 11:
14. Majewski F, Bierich J , Loeser H, Michaelis R, Leiber B, Bettecken
F: Zur Klinik und pathogenese der alkohol-embryopathie. Bericht uber 68
falle [Diagnosis and pathogenesis of alcohol embryopathy: Report of 68
cases]. Munchener Medizinische Wochenschrift 118:1635-1642,1976
15. Majewski F, Majewski B: Alcohol embryopathy: Symptoms, auxo-
logical data, frequency among the offspring and pathogenesis, in
Kuriyama K, Takada A, Ishii H (eds): Biomedical and Social Aspects of
Alcohol and Alcoholism. Elsevier Science Publishers, 1988, pp 837-844
16. Char F: Fetal alcohol syndrome with Noonan phenotype. Birth
Defects 12:81-82, 1976
17. Ballesta F, Cruz M: Sindrome alcoholico fetal y alteraciones
cromosomicas [Fetal alcohol syndrome and chromosome aberrations].
Arch Pediatr 29:435-443, 1978
18. Qazi QH, Madahar C, Masakawa A, McGann B: Chromosome
abnormality in a patient with fetal alcohol syndrome, in Galanter M (ed):
265:1961-1967, 1991
490-494, 1974
459-463, 1975
292 MATTSON AND RILEY
Currents in Alcoholism, vol 5. New York, Grunc & Stratton, 1979, pp
155-1 61
19. Slavncy PR, Grdu J G: Fetal alcohol damage and schizophrenia.
J Clin Psychiatry 39:782-783, 1978
20. Neidengard L, Carter TE. Smith DW: Klippel-Feil malformation
complex in fetal alcohol syndrome. Am J Dis Children 132:929-930, 1978
21. Qazi Q, Masakawa A, Milman D, McGann B, Chua A, Haller J :
Renal anomalies in fetal alcohol syndrome. Pediatrics 63:886-889, 1979
22. Abcl EL: Fctal Alcohol Syndromc. New J ersey, Mcdical Econom-
ics Company, Inc., 1990
23. Ticha R, Santavy J , Matlocha Z: Fetal alcohol syndrome: Amino
acid pattern. Acta Paediatr Hungar 24:143-148, 1983
24. Aronson M, Olegird R: Fetal alcohol effects in pediatrics and
child psychology, in Rydberg U (ed): Alcohol and the Developing Brain.
New York, Raven Press, 1985, pp 135-145
25. Strcissguth AP, Rohsenow DJ : Intellectual development in off-
spring of chronic alcoholic mothers and matched controls. Paper prc-
sented at the Western Psychological Association, San Francisco, 1974
26. Streissguth AP, Herman CS, Smith DW: Intelligence, behavior,
and dysmorphogenesis in the fetal alcohol syndrome: A report on 20
patients. J Pediatr 92:363-367, 1978
27. Majewski F: Uber schadigende einfliisse des alkohols auf die
nachkommen [The damaging effects of alcohol on offspring]. Der Nerve-
narzt 49:410-416, 1978
28. Majewski F: Unterzuchungen zur alkohol-embryopathie [Studies
on alcohol embryopathy]. Fortschritte der Medizin 96:2207-2213, 1978
29. Oleglrd R, Sabel K-G, Aronsson M, Sandin B, J ohansson PR,
Carlsson C, Kyllerman M, Iversen K, Hrbek A: Effects on the child of
alcohol abuse during pregnancy. Acta Paediatr Scand 275:112-121, 1979
30. Shaywitz SE, Cohen DJ , Shaywitz BA: Behavioral learning diffi-
culties in children of normal intelligence born to alcoholic mothers. J Pe-
diatr 96978-982, 1980
31. Iosub S, Fuchs M, Bingol N, Gromisch DS: Fetal alcohol syn-
drome revisited. Pediatrics 68:475-479, 1981
32. Aronson M, Kyllerman M, Sabel K-G, Sandin B, Olegird R:
Children of alcoholic mothers: Developmental, perceptual, and behav-
ioural characteristics as compared to matched controls. Acta Pzdiatr
Scand 74:27-35, 1985
33. Mattson SN, Riley EP, Gramling L, Delis DC, J ones KL: Heavy
prenatal alcohol exposure with or without physical features of fetal alcohol
syndrome leads to IQ deficits. J Pediatr 131:718-721, 1997
34. Streissguth AP, Randels SP, Smith DF: A test-retest study of
intelligence in patients with fetal alcohol syndrome: Implications for care.
J Am Acad Child Adolesc Psychiatry 30584-587, 1991
35. Streissguth AP, Barr HM, Sampson PD, Bookstein FL: Prenatal
alcohol and offspring development: The first fourteen years. Drug Alcohol
Depend 36:89-99, 1994
36. Golden NL, Sokol RJ , Kuhnert BR, Bottoms S: Maternal alcohol
use and infant development. Pediatrics 70:931-934, 1982
37. Ioffe S, Chernick V: Prediction of subsequent motor and mental
retardation in newborn infants exposed to alcohol in utero by computer-
ized EEG analysis. Neuropediatrics 21:11-17, 1990
38. Autti-Ram0 I, Korkman K, Hilakivi-Clarke L, Lehtonen M,
Halmesmaki E, Granstrom M-L: Mental development of 2-year-old chil-
dren exposed to alcohol in utero. J Pediatr 120:740-746, 1992
39. Streissguth AP, Barr HM, Martin DC, Herman CS: Effects of
maternal alcohol, nicotine, and caffeine use during pregnancy on infant
mental and motor development at eight months. Alcohol Clin Exp Res
40. OConnor MJ , Brill NJ , Sigman M: Alcohol use in primiparous
women older than 30 years of age: Relation to infant development.
Pediatrics 78:444-450, 1986
41. Fried PA, Wathnson B: 12- and 24-month neurobehavioural fol-
low-up of children prenatally exposed to marihuana, cigarettes and alco-
hol. Neurotoxicol Teratol 10:305-313, 1988
42. Coles CD, Brown RT, Smith IE, Platzman KA, Erickson S, Falek
4152-164, 1980
A Effects of prenatal alcohol exposure at school age. I. Physical and
cognitive development. Neurotoxicol Teratol 13:357-367, 1991
43. Streissguth AP, Barr HM, Sampson PD, Darby BL, Martin DC:
I Q at age 4 in rclation to maternal alcohol use and smoking during
pregnancy. Dev Psycho1 25:3-11, 1989
44. Streissguth AP, Barr HM, Sampson PD: Moderate prenatal alco-
hol exposure: Effects on child I Q and learning problems at age 7% years.
Alcohol Clin Exp Res 14:662-669, 1990
45. Goodlett CR, Lundahl KR: Temporal determinants of neonatal
alcohol-induced cerebellar damage and motor performance deficits. Phar-
macol Biochcm Behav 55531-540, 1996
46. Thomas J D, Wasserman EA, West J R, Goodlett CR: Behavioral
deficits induced by bingelike exposure to alcohol in neonatal rats: Impor-
tance of developmental timing and number of episodes. Dev Psychobiol
29:433-452, 1996
47. Clarren SK, Astley SJ, Gunderson VM, Spellman D: Cognitive
and behavioral deficits in nonhuman primates associated with very early
embryonic binge exposures to ethanol. J Pediatr 121:789-796, 1992
48. Goldschmidt L, Richardson GA, Stoffer DS, Geva D, Day NL:
Prenatal alcohol exposure and academic achievement at age six: A non-
linear fit. Alcohol Clin Exp Res 20:763-770, 1996
49. Forrest F, Florey C du V, Taylor D, McPherson F, Young J A:
Reported social alcohol consumption during pregnancy and infants de-
velopment at 18 months. Br Med J 303:22-26, 1991
50. Fried PA, Watkinson B: 36- and 48-month neurobehavioral fol-
low-up of children prenatally exposed to marijuana, cigarettes, and alco-
hol. J Dev Behav Pediatr 11:49-58, 1990
51. Fried PA, OConnell CM, Watkinson B: 60- and 72-month fol-
low-up of children prenatally exposed to marijuana, cigarettes, and alco-
hol: Cognitive and language assessment. J Dev Behav Pediatr 13:383-391,
1992
52. Greene T, Ernhart CB, Ager J , Sokol R, Martier S, Boyd T:
Prenatal alcohol exposure and cognitive development in the preschool
years. Neurotoxicol Teratol 1357-68, 1991
53. Streissguth AP, Dehaene P: Fetal alcohol syndrome in twins of
alcoholic mothers: Concordance of diagnosis and IQ. Am J Med Genet
54. Streissguth AP, Herman CS, Smith DW Stability of intelligence in
the fetal alcohol syndrome: A preliminary report. Alcohol Clin Exp Res
55. Van Biervliet J P: The foetal alcohol syndrome. Acta Paediatr Belg
56. Iosub S, Fuchs M, Bingol N, Stone RK, Gromisch DS: Long-term
follow-up of three siblings with fetal alcohol syndrome. Alcohol Clin Exp
Res 5523-527, 1981
57. Steinhausen H-C, Gobel D, Nestler V: Psychopathology in the
offspring of alcoholic parents. J Am Acad Child Psychiatry 23:465-471,
1984
58. Spohr H-L, Steinhausen H-C Clinical, psychopathological and
developmental aspects in children with the fetal alcohol syndrome: A
four-year follow-up study, in Ciba Foundation Symposium: Mechanisms of
Alcohol Damage In Utero. London, Pitman, 1984, pp 197-211
59. Steinhausen H-C, Willms J , Spohr H-L Long-term psychopatho-
logical and cognitive outcome of children with fetal alcohol syndrome.
J Am Acad Child Adolesc Psychiatry 32:990-994, 1993
60. Don A, Rourke BP: Fetal alcohol syndrome, in Rourke BP (ed):
Syndrome of Nonverbal Learning Disabilities: Neurodevelopmental Man-
ifestations. New York, Guilford Press, 1995, pp 372-406
61. LaDue RA, Streissguth AP, Randels SP: Clinical considerations
pertaining to adolescents and adults with fetal alcohol syndrome, in Son-
deregger TB (ed): Perinatal Substance Abuse: Research Findings and
Clinical Implications. Baltimore, J ohns Hopkins Press, 1992, pp 104-131
62. Usowicz AG, Golabi M, Curry C: Upper airway obstruction in
infants with fetal alcohol syndrome. Am J Dis Children 140:1039-1041,
1986
63. Mattson SN, Riley EP, J ernigan TL, Ehlers CL, Delis DC, J ones
KL, Stern C, J ohnson KA, Hesselink J R, Bellugi U: Fetal alcohol syn-
47357-861, 1993
2:165-170, 1978
30~113-116, 1977
NEUROBEHAVIORAL FINDINGS IN FAS 2Y.7
drome: A case report of neuropsychological, MRI, and EEG assessment
of two children. Alcohol Clin Exp Rcs 16:lOOl-1003. 1992
64. Naselli A, De Toni T, Vignolo M, Di Battista E, Aicardi G:
Auxological findings and endocrine function in a case of fetal alcohol
syndrome. Acta Med Auxolog 14:23-30, 1982
65. Harris SR, MacKay LLJ , Osborn J A: Autistic behaviors in off-
spring of mothers abusing alcohol and other drugs: A series of case
reports. Alcohol Clin Exp Res 19:660-665. 1995
66. Coles CD, Smith IE, Falek A: Prenatal alcohol exposure and
infant behavior: Immediate effects and implications for later development.
Adv Alcohol Subst Abuse 697-104, 1987
67. Russell M, Czarnecki DM, Cowan R, McPherson E, Mudar PJ :
Measures of maternal alcohol use as predictors of development in early
childhood. Alcohol Clin Exp Res 15:991-1000, 1991
68. J anzen LA, Nanson J L, Block GW: Neuropsychological evalua-
tion of preschoolers with fetal alcohol syndrome. Neurotoxicol Teratol
69. Larroque B, Kaminski M, Dehaene P, Subtil D, Delfosse M-J ,
Querleu D: Moderate prenatal alcohol exposurc and psychomotor devel-
opment at preschool age. Am J Public Health 85:1654-1661, 1995
70. Gusella J L, Fried PA: Effects of maternal social drinking and
smoking on offspring at 13 months. Neurobehav Toxicol Teratol6:13-17,
1984
71. Conry J : Neuropsychological deficits in fetal alcohol syndrome
and fetal alcohol effects. Alcohol Clin Exp Res 14:650-655, 1990
72. J acobson J L, J acobson SW, Sokol RJ , Martier SS, Ager J W,
Kaplan-Estrin MG: Teratogenic effects of alcohol on infant development.
Alcohol Clin Exp Res 17:174-183, 1993
73. Landesman-Dwyer S, Ragozin AS, Little RE: Behavioral corre-
lates of prenatal alcohol exposure: A four-year follow-up study. Neurobe-
hav Toxicol Teratol 3:187-193, 1981
74. Hanson J W, J ones KL, Smith DW: Fetal alcohol syndrome: Ex-
perience with 41 patients. J AMA 235:1458-1460, 1976
75. Bond NW, DiGiusto EL: Avoidance conditioning and Hebb-Wil-
liams maze performance in rats treated prenatally with alcohol. Psychop-
harmacology 58:69-71, 1978
76. Ulug S, Riley EP: The effect of methylphenidate on overactivity in
rats prenatally exposed to alcohol. Neurobehav Toxicol Teratol 5:35-39,
1983
77. Bond NW: Prenatal alcohol exposure in rodents: A review of its
effects on offspring activity and learning ability. Austral J Psychol 33:331-
344, 1981
78. Bond NW: Behavioural teratology: Fetal alcohol exposure and
hyperactivity, in Bond NW (ed): Animal Models in Psychopathology.
Sydney, Academic Press, 1984, pp 279-311
79. Landesman-Dwyer S, Keller LS, Streissguth AP: Naturalistic ob-
servations of newborns: Effects of maternal alcohol intake. Alcohol Clin
Exp Res 2171-177, 1978
80. Nanson J L, Hiscock M: Attention deficits in children exposed to
alcohol prenatally. Alcohol Clin Exp Res 14:656-661, 1990
81. Carmichael Olson H, Feldman J J , Streissguth AP, Gonzalez RD:
Neuropsychological deficits and life adjustment in adolescents and adults
with fetal alcohol syndrome. Alcohol Clin Exp Res 16:380, 1992
82. Coles CD, Platzman KA, Raskind-Hood CL, Brown RT, Falek A,
Smith I E A comparison of children affected by prenatal alcohol exposure
and attention deficit, hyperactivity disorder. Alcohol Clin Exp Res 21:
150-161, 1997
83. Streissguth AP, Martin DC, Barr HM, Sandman BM, Kirchner
GL, Darby BL Intrauterine alcohol and nicotine exposure: Attention and
reaction time in 4-year old children. Dev Psychol 20:53>541, 1984
84. Streissguth AP, Barr HM, Sampson PD, Parrish-J ohnson J C,
Kirchner GL, Martin DC: Attention, distraction and reaction time at age
7 years and prenatal alcohol exposure. Neurobehav Toxicol Teratol8:717-
725, 1986
85. Carmichael Olson H, Sampson PD, Barr H, Streissguth AP, Book-
stein F L Prenatal exposure to alcohol and school problems in late child-
hood: A longitudinal prospective study. Dev Psychopath01 4:341-359,1992
17:273-279, 1995
86. Streissguth AP, Sampson PD, farmichacl Olson 1 i. Bookstcin FL.
Barr HM, Scott M, Feldman J , Mirsky AF: Maternal drinking during
pregnancy: Attention and short-term memory in 14-year old offspring-A
longitudinal prospective study. Alcohol Clin Exp Rcs 18:202-218. I994
87. Streissguth AP, Barr HM, Carmichael Olson H, Sampson PD.
Bookstein FL, Burgess DM: Drinking during pregnancy dccrcascs word
attack and arithmetic scorcs on standardized tests: Adolcsccnt data from
a population-based prospective study. Alcohol Clin Exp Rcs 18:238-251.
1994
88. Sattler J M: Assessmcnt of Childrcn. San Dicgo. J cromc M. Sat-
tler, 1992
89. Brown RT, Coles CD, Smith IE. Platzman KA, Silvcrstcin J .
Erickson S, Falck A: Effccts of prenatal alcohol cxposurc at school age. 11.
Attention and behavior. Neurotoxicol Teratol 13:369-376. 1991
90. Fried PA, Watkinson B, Gray R: A follow-up study of attcntional
behavior in 6-year-old children cxposed prenatally to niarihuana, ciga-
rettes, and alcohol. Neurotoxicol Tcratol 14:299-311, 1992
91. Boyd TA, Ernhart CB, Greene TH, Sokol RJ , Martier S: Prcnatal
alcohol exposure and sustained attention in the preschool years. Ncuro-
toxicol Teratol 13:49-55, 1991
92. Martin J , Martin DC. Lund CA, Streissguth AP: Matcrnal alcohol
ingestion and cigarette smoking and their cffccts on ncwborn condition-
ing. Alcohol Clin Exp Res 1:243-247, 1977
93. Streissguth AP, Barr HM, Martin DC: Matcrnal alcohol use and
neonatal habituation asscsscd with the Brazclton scalc. Child Dev 54:
1109-1118, 1983
94. Mattson SN, Riley EP, Dclis DC, Stern C, J ones KL: Verbal
learning and memory in children with fctal alcohol syndrome. Alcohol
CIin Exp Res 20510-816, 1996
95. Don A, Kerns K, Matecr CA, Streissguth AP: Cognitive deficits in
normal IQ and borderline I Q adults with fetal alcohol syndrome. Alcohol
Clin Exp Res 17:458, 1993
96. Gray J K, Streissguth AP: Memory deficits and life adjustment in
adults with fetal alcohol syndrome: A case control study. Alcohol Clin Exp
Res 14:294, 1990
97. Streissguth AP, Bookstein FL, Sampson PD, Barr HM: Ncurobe-
havioral effects of prenatal alcohol. Part 111. PLS analyses of ncuropsy-
chologic tests. Neurotoxicol Teratol 11:493-507, 1989
98. Uecker A, Nadel L: Spatial locations gone awry: Objcct and
spatial memory deficits in children with fetal alcohol syndrome. Ncuro-
psychologia 34:209-223, 1996
99. Kodituwakku PW, Handmaker NS, Cutler SK, Weathersby EK.
Handmaker SD: Specific impairments in self-regulation in children cx-
posed to alcohol prenatally. Alcohol Clin Exp Res 19:1558-1564, 1995
100. J acobson SW, J acobson J L, Sokol RJ , Martier SS, Ager J W:
Prenatal alcohol exposure and infant information processing ability. Child
Dev 64:1706-1721, 1993
101. Riley EP, Lochry EA, Shapiro NR: Lack of response inhibition in
rats prenatally exposed to alcohol. Psychopharmacology 62:47-52, 1979
102. Anandam N, Stern J M: Alcohol in utero: Effects on preweanling
appetitive learning. Neurobehav Toxicol 2:199-205, 1980
103. Driscoll CD, Riley EP, Mcyer LS: Delayed taste aversion learning
in preweanling rats exposed to alcohol prenatally. Alcohol 2:277-280, 1985
104. Gianoulakis C: Rats exposed prenatally to alcohol exhibit impair-
ment in spatial navigation test. Behav Brain Res 36:217-228, 1990
105. Reyes E, Wolfe J , Savage DD: The effects of prenatal alcohol
exposure on radial arm maze performance in adult rats. Physiol Behav
106. Lochry EA, Riley EP: Retention of passive avoidance and T-maze
escape in rats exposed to alcohol prenatally. Neurobehav Toxicol 2:107-
115, 1980
107. Hall J L, Church MW, Berman RF: Radial arm maze deficits in
rats exposed to alcohol during midgestation. Psychobiology 22:181-185,
1994
108. Driscoll CD, Streissguth AP, Riley EP: Prenatal alcohol exposure:
Comparability of effects in humans and animal models. Neurotoxicol
Teratol 12231-237, 1990
46~45-48, 1989
294 MATSON AND RILEY
109. Becker HC, Randall CL, Salo AL, Saulnier J L, Weathersby RT:
Animal research: Charting the course for FAS. Alcohol Health Res World
18:lO-16, 1994
110. Tsukahara M, Kajii T: Severe skeletal dysplasias following intra-
uterine exposure to ethanol. Teratology 37:79-80, 1988
111. Marcus J C: Neurological findings in the fetal alcohol syndrome.
Neuropediatrics 18:158-160, 1987
112. Koranyi G, Csiky E: Az embryopathia alcoholica gyermekkorban
eszlelheto tuneteirol [Signs of alcohol embryopathy apparent in child-
hood]. Orvosi Hetilap 119:2923-2929, 1978
113. Shaywitz SE, Caparulo BK, Hodgson ES: Developmental lan-
guage disability as a consequence of prenatal exposure to ethanol. Pedi-
atrics 685350-855, 1981
114. Tenbrinck MS, Buchin SY: Fetal alcohol syndrome: Report of a
case. J AMA 232:1144-1147, 1975
115. Church MW, Gerkin KP: Hearing disorders in children with fetal
alcohol syndrome: Findings from case reports. Pediatrics 82147-154,1988
116. Collins E, Turner G: Six children affected by maternal alcoholism.
Med J Austral 2:606-608, 1978
117. Seeler RA, Israel J N, Royal J E, Kaye CI, Rao S, Abulaban M:
Ganglioneuroblastoma and fetal hydantoin-alcohol syndromes. Pediatrics
118. Steinhausen H-C, Nestler V, Spohr H-L Development and psy-
chopathology of children with the fetal alcohol syndrome. J Dev Behav
Pediatr 3:49-54, 1982
119. Mattson SN, Riley EP, Gramling L, Delis DC, J ones KL: Neuro-
psychological comparison of alcohol-exposed children with or without
physical features of fetal alcohol syndrome. Neuropsychology 12:146-153,
1998
120. Becker M, Warr-Leeper GA, Leeper HA: Fetal alcohol syndrome:
A description of oral motor, articulatory, short-term memory, grammati-
cal, and semantic abilities. J Commun Disord 23:97-124, 1990
121. Carney LJ, Chermak GD: Performance of American Indian chil-
dren with fetal alcohol syndrome on the test of language development.
J Commun Disord 24123-134, 1991
122. Mattson SN: The Role of the Basal Ganglia in the Behavioral
Teratogenicity of Alcohol. San Diego, SDSURJ CSD J oint Doctoral Pro-
gram in Clinical Psychology, 1994, pp 144
123. Ernhart CB, Greene T, Sokol RJ, Martier S, Boyd TA, Ager J:
Neonatal diagnosis of fetal alcohol syndrome: Not necessarily a hopeless
prognosis. Alcohol Clin Exp Res 19:1550-1557, 1995
124. Greene T, Ernhart CB, Martier S, Sokol R, Ager J : Prenatal
alcohol exposure and language development. Alcohol Clin Exp Res 14:
125. Chandler LS, Richardson GA, Gallagher J D, Day N L Prenatal
exposure to alcohol and marijuana: Effects on motor development of
preschool children. Alcohol Clin Exp Res 20:455-461, 1996
126. Autti-Ramo I, Granstrom M-L: The psychomotor development
during the first year of life of infants exposed to intrauterine alcohol of
various duration. Neuropediatrics 22:59-64, 1991
127. Kyllerman M, Aronson M, Sabel K-G, Karlberg E, Sandin B,
Olegird R: Children of alcoholic mothers: Growth and motor perfor-
mance compared to matched controls. Acta Paediatr Scand 7420-26,
1985
128. Barr HM, Streissguth AP, Darby BL, Sampson PD: Prenatal
exposure to alcohol, caffeine, tobacco, and aspirin: Effects on fine and
gross motor performance in 4-year-old children. Dev Psycho1 26:339-348,
1990
129. Hannigan J H, Riley EP: Prenatal ethanol alters gait in rats. Al-
130. Lee MH, Haddad R, Rabe A: Developmental impairments in the
631524-527, 1979
937-945, 1990
cohol 5~451-454, 1989
progeny of rats consuming ethanol during pregnancy. Neurobehav Toxicol
2:189-198, 1980
131. Meyer LS, Kotch LE, Riley EP: Neonatal ethanol exposure: Func-
tional alterations associated with cerebellar growth retardation. Neuro-
toxic01 Teratol 12:15-22, 1990
132. Aronson M, Olegird R: Children of alcoholic mothers. Pediatri-
cian 1457-61, 1987
133. Spreen 0, Strauss E: A Compendium of Ncuropsychological
Tests. New York, Oxford University Press, 1991
134. Mattson SN, Gramling L, Delis DC, J ones KL, Riley EP: Global-
local processing in children prenatally exposed to alcohol. Child Neuro-
psycho1 2:165-175, 1996
135. Bihrle AM, Bellugi U, Delis D, Marks S: Seeing either the forest
or the trees: Dissociation in visuospatial processing. Brain Cogn 11:37-49,
1989
136. Delis DC, Massman PJ , Butters N, Salmon DP, Shear PK, Derna-
dura T, Filoteo J V: Spatial cognition in Alzheimer's disease: Subtypes of
global-local impairment. J Clin Exp Neuropsychol 14:463-477, 1992
137. Mattson SN, Roebuck TM, Riley EP: Wisconsin card sorting
performance in children prenatally exposed to alcohol. Alcohol Clin Exp
Res 20:74A, 1996
138. Shallice T, Burgess P: Higher-order cognitive impairments and
frontal lobe lesions in man, in Levin HS, Eisenberg HM, Benton AL (eds):
Frontal Lobe Function and Dysfunction. New York, Oxford University
Press, 1991, pp 125-138
139. Mulvihill J J , Klimas J T, Stokes DC, Risemberg HM: Fetal alcohol
syndrome: Seven new cases. Am J Obstet Gynecol 125:937-941, 1976
140. Bierich J R, Majewski F, Michaelis R, Tillner I: Uber das embryo-
fetale alkoholsyndrom [On the embryofetal alcohol syndrome]. Eur J Pe-
diatr 121:155-177, 1976
141. Ijaiya K, Schwenk A, Gladtke E Fetales Alkoholsyndrom [Fetal
alcohol syndrome]. Deutsche Medizinische Wochenschrift 101:1563-1568,
1976
142. Fryns J P, Deroover J , Parloir C, Goffaw P, Lebas E, Van Den
Berghe H: The foetal alcohol syndrome. Acta Paediatr Belg 30117-121,
1977
143. Dehaene P, Walbaum R, Titran M, Samaille-Villette C, Samaille
P, Crepin G, Delahousse G, Decocq J , Delcroix M, Caquant F, Querleu D:
La descendance des mitres alcoliques chroniques: A propos de 16 cas
d'alcoolisme foetal [The offspring of alcoholic mothers: A report of 16
cases of fetal alcohol syndrome]. Revue Francaise de Gyntcologie et
d'ObstCtrique 72:491-498, 1977
144. M~l l er J , Brandt NJ , Tygstrup I: Hepatic dysfunction in patient
with fetal alcohol syndrome. Lancet 1:605-606, 1979
145. Mattson SN, Riley EP, J ernigan TL, Garcia A, Kaneko WM,
Ehlers CL, J ones KL: A decrease in the size of the basal ganglia following
prenatal alcohol exposure: A preliminary report. Neurotoxicol Teratol
146. Dehaene P, Samaille-Villette C, Samaille P-P, Crepin G, Wal-
baum R, Deroubaix P, Blanc-Garin A-P: Le syndrome d'alcoolisme foetal
dans le nord de la France [Fetal alcohol syndrome in the north of France].
Revue de L'Alcoolisme 23:145-158, 1977
147. Majewski F Alcohol embryopathy: Some facts and speculations
about pathogenesis. Neurobehav Toxicol Teratol 3:129-144, 1981
148. O'Connor MJ , Sigman M, Kasari C: Interactional model for the
association among maternal alcohol use, mother-infant interaction, and
infant cognitive development. Infant Behav Dev 16:177-192, 1993
149. Caruso K, ten Bensel R: Fetal alcohol syndrome and fetal alcohol
effects. Minn Med 76:25-29, 1993
150. Spohr HL, Willms J , Steinhausen HC. The fetal alcohol syndrome
in adolescence. Acta Pediatr 404:19-26, 1994
16~283-289, 1994