Developmental Language Disability As a Consequence of Prenatal Exposure to Ethanol

(1)

Developmental

Language

Disability

As a

Consequence

of Prenatal

Exposure

to Ethanol

Sally E. Shaywitz, MD, Barbara K. Caparulo, MA, and

Elizabeth Susan Hodgson, MD

From the Departments of Pediatrics and Psychology, Yale University School of Medicine and Yale Child Study Center, New Haven, Connecticut

ABSTRACT. Two pre-school-aged patients with a history of prenatal exposure to ethanol had abnormal head size and developmental delay. Both children were strikingly similar in physical appearance, behavior, and cognitive

dysfunction. Facial features were typical of fetal alcohol

syndrome. Head circumference >97th percentile without

hydrocephalus and no evidence of prenatal or postnatal

growth failure were unusual for ethanol teratogenicity. Each child had a similar pattern of verbal and behavioral dysfunctions characterized by (1) marked hypervigilence,

(2) distractability, and (3) cognitive confusion manifested as anxiety and behavioral disorganization. It is suggested that a history of prenatal exposure to ethanol associated with (1) large head circumference, (2) facial features of fetal alcohol syndrome, and (3) early developmental de-lay, particularly in language acquisition, and impaired modulation of attention and arousal may represent a possible new effect of alcohol teratogenicity. Pediatrics

68:850-855, 1981; fetal alcohol syndrome, fetal alcohol effects, teratogenicity, language dysfunction, develop-mental delay.

In 1968,

Lemoine et al,’ and later in 1973, Jones et al,2 described a cluster of abnormalities in chil-then born to alcoholic mothers. As awareness of the

problem has grown, more subtle effects and milder

cases have been described. At present, the criteria

to determine the most subtle expressions of ethanol teratogenicity have yet to be resolved. It has been

suggested that milder cases be grouped into an

“expanded fetal alcohol syndrome,”3 or into a

grouping with suspected fetal alcohol effects

(FAE).4

Central nervous system dysfunction may be the

most disabling of the varied effects of prenatal

alcohol exposure. Whereas the most severely

aS-fected subjects usually have less than average

in-telligence, mildly affected subjects may have

nor-mal IQs together with more subtle manifestations

of CNS dysfunction, such as significant academic, language, or behavioral disorders.3’5 Such learning and behavioral disorders are easily and frequently

overlooked when children are evaluated for the possibility of teratogen exposure. This is unfortu-nate because, potentially, the language and

concep-tual dysfunction in mild fetal alcohol syndrome

(FAS) may be the most remediable aspect of

ethanol teratogenicity, short of prevention.

In this study pre-school-aged children with mild

FAS who were seen in our Learning Disorders Unit

with abnormal head size and developmental delay

are described. Both children were strikingly similar in physical appearance, behavior, and cognitive dys-function. Both had experienced significant exposure

to alcohol during gestation, and each demonstrated facial features typically seen in FAS. However, both

had other similar physical findings not usually

as-sociated with FAS; that is, they had large heads

without hydrocephalus and had no evidence of

pre-natal or postnatal growth failure. We describe these

patients to emphasize a possible new effect of

al-cohol teratogenicity, expressed mainly through

marked behavioral and language dysfunction. The

unusual language and cognitive disorders found in

these children will be described in some detail to

provide pediatricians with an approach to the eval-uation of children with specific language disabilities

as typified by those we have now described in

children with fetal alcohol effects.

Received for publication Jan 5, 1981; accepted April 10, 1981. Reprint requests to (S.E.S.) Department of Pediatrics, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06510.

American Academy of Pediatrics.

CASE REPORTS

Case 1

(2)

white, married woman. Both his parents were college graduates. There was no family history ofverbal disability or mental retardation. The mother denied any illness or prenatal complications. She took no medications during

the pregnancy, did not smoke, and consumed only two

cups of coffee or tea per day. She drank 3 to 4 oz of bourbon daily during the pregnancy and occasionally drank beer. During the fifth month of gestation she had one episode of heavier drinking while attending a wed-ding.

Labor was induced because the fetus was more than 42 weeks by dates. Labor

was

prolonged, ending in cesarean delivery under general anesthesia because of fetal brady-cardia. The infant had a nuchal cord, but required no resuscitation in the delivery room, and needed no inten-sive care. He developed transient neonatal jaundice

re-quiring no therapy and was discharged home with his mother.

J.E. was breast-fed for ten months. During this time his mother continued to drink cocktails in amounts sim-ilar to her daily prenatal alcohol consumption. J.E. was a passive, quiet infant, without feeding problems. His motor and language developmental milestones were all delayed. He walked independently at 22 months of age and did not

use

single words until almost 36 months of age. His parents became concerned and had him evalu-ated at a child development center at 37 months of age.

After testing he was given a developmental quotient (DQ) of 68, borderline range of developmental retardation. At 52 months of age he was again evaluated at that center and found to have an overall DQ of 69, with a language

DQ

of 61, the lowest score of all his developmental tests. Because his head seemed somewhat large, skull

roentgen-ograms were obtained and found to be normal. He was then referred to our Learning Disabilities Unit for further evaluation of his large head and developmental delay.

He was first evaluated at the Learning Disorders Unit at 410/,2 years of age. His physical examination was

re-markable for a number of dysmorphic features (Fig 1) that were strongly suggestive of fetal alcohol syndrome; these features

are

summarized in Table 1. Atypical for FAS were his height (118 cm, 50th percentile),9 weight (20 kg, 50th percentile),9 and head circumference (55 cm,

> 95th percentile).’#{176} His head showed prominent frontal bossing; palpebral fissure distance was 2.5 cm; distance

between the inner canthi was 2.5 cm. He had slight

hypotoma in all extremities; otherwise his neurologic examination was normal except for his language and cognitive dysfunction. Genitalia were normal. He showed some gross motor clumsiness when attempting to do tasks that required speed. He was ambidextrous. The remain-der of his physical examination was normal.

Chromosomal studies showed a normal karyotype and results of computed tomography (CT)

scan

were normal. However, his EEG

was

abnormal, with mild, generalized slowing and paroxysms of high voltage slow activity, posterior sharp activity, and one episode of three per

second spike and wave activity lasting six seconds, not accompanied by a clinical absence spell. Treatment with 50 mg of phenytoin sodium (Dilantin), twice a day, was started; the patient intermittently received the medica-tion for about a year. A subsequent EEG obtained after nine months of Dilantin therapy showed no epileptiform

activity. His family subsequently discontinued his

medi-cation.

J.E. had extensive and developmental testing that will

TABLE 1. Principal Features of Fetal Alc ohol Syndrome (FAS) Seen in Two Patients*

Feature Patient

J.E. A.J.

Craniofacial

Short palpebral fissurest + +

Hypoplastic philtrum + +

Thinned upper lip vermilion + +

Short, upturned noses -- +

Hypoplastic maxilla + +

Other dysmorphic facial features

occasionally reported in FAS

Highly arched palate + +

Small teeth with faulty enamel + +

Low set, posteriorly rotated ears + +

CNS dysfunction

Mild to moderate mental retardatioz4 Severe language and cognitive

dysfunction

Severe language and cognitive dysfunction

Microcephaly -

-Hyperactivity in childhoods Hyperacusis and distractability,

motor hyperactivity

Hyperacusis and distractabiity, motor hyperactivity

Poor coordination and hypotonia + +

Growth deficiency

Prenatal -

-Postnatalt -

-* Adapted from Streissguth et al.

t

As defined by Chouke,7 1929.

:1:Feature seen in >80% of patients with typical FAS.8

§

Feature seen in >50% of patients with typical FAS.8

(3)

be summarized later. At his initial evaluation at 410/12

years

of age, he had an adaptive DQ of 84, but his language development was between 1 #{189}to 2 years below the level expected for his chronologic age.

Case 2

A.J. was a 9 lb 13 oz term infant born to a 26-year-old white, married woman who was a high school graduate.

There was no known history of mental retardation or

language disability in the family. The mother drank ten to 12 cups of coffee per day during the pregnancy and admitted to drinking a quart of whiskey per day. Her excessive alcohol consumption was confirmed by outside sources. She smoked occasionally.

A.J. was born by repeat cesarean section without fetal distress. There were no neonatal complications. His mo-tor and verbal milestones were delayed. His mother al-ways spoke of him as clumsy and accident prone. The patient was referred to our Learning Disorders Unit at

4/12

years

of age for evaluation of possible arrested hydro-cephalus. A physical examination and skull films obtained elsewhere several months prior to his first clinic visit had

revealed a large head.

A.J.’s physical examination also revealed a number of dysmorphic features suggestive of alcohol teratogenesis (Fig 2 and Table 1). His weight was 19 kg (75th

percent-ile),9 and his head circumference was 54.5 cm (> 97th

percentile).’#{176} He displayed a normal intercanthal dis-tance, but a small palpebral fissure measurement of 2.3 cm. His neurologic examination was normal except for his language and cognitive dysfunction. The remainder of his physical examination was normal. Cognitive and language evaluation will be detailed below.

Chromosome and CT scan studies were both normal.

His initial EEG showed a possibility of sharp waves in the posterior right region. An EEG repeated a year later

was normal. During the year between EEGs he was

treated with valproate because of staring spells associated with bizarre behavior, such as suddenly talking to imagi-nary objects in the midst of an ongoing conversation. He was not given his medication consistently.

COGNITIVE AND LANGUAGE EVALUATION

J.E., aged 5 years 1 1 months when administered

psy-chologic and linguistic assessment, received an overall

language reception score of 3.2 years on the Sequenced Inventory of Communicative Development 1 Sound discrimination was at the 32-month level for non-speech sounds. Comprehension of single words for con-crete objects was intact, but his understanding of size

relations was impaired. He was, however, able to carry

out concrete, two-stage commands. Although he could count and do simple addition and subtraction, he could not respond correctly to requests such as “Give me some

Fig 1. Patient J.E. Facial features of fetal alcohol syn- Fig 2. Patient A.J. Note marked resemblance to patient

(4)

of the pencils; give me all of the pencils.” His memory span for digits was age-appropriate.

J.E.’s overall language expression score on the SICD

was 2 years. His behavior during testing was marked by an unwillingness to speak and a failure to enjoy the give and take of conversation. When encouraged to speak, his utterances were highly articulated, and lacked fluency and appropriate intonation. Spontaneous language sam-ples were much like the productions of a 2 year old. However, he had a small repertoire of more

grammati-cally mature “canned” expressions. These “programmed” remarks showed no variation in tone, pitch, or intensity. Parental reports indicated that he had been taught cer-tam sentences, and, although he used them in the appro-priate contexts, he failed to vary the components of such

sentences creatively.

Testing of nonverbal intellectual abilities on the Leiter International Scales of Performance (Arthur

Adapta-tion)’2 yielded an IQ of 120.

Observations at school indicated a failure to engage in

play with peers and heightened use of the “canned”

expressions first observed in the clinic. He responded to the social initiations of peers by withdrawal into solitary play. Imitative behaviors were absent. He showed con-fusion and panic when the group moved to new games,

and was hypervigilent to auditory events, and to the comings and goings of people within the small classroom

setting. His behavior, both during structured teaching and on psychiatric evaluation in the clinic, showed several periods of conceptual confusion, blocking, and skipping

from one topic to another. Occasionally, he showed be-havior that was out of context and socially inappropriate.

A.J., aged 5 years 4 months at evaluation, was tested in the clinic on two occasions and was observed in his school program. Reliable assessment of intellectual com-petencies was precluded by his inability to carry through to completion his attempts at various tasks. Like J.E., he became confused, disoriented, and often shifted to topics that were only peripherally related to the tasks at hand. On the Wechsler Preschool and Primary Scale of Intelli-gence (WPPSI)’3 Block Design subtest, which correlates well with overall IQ, he performed at a level above that

for his chronologic age. Digit span memory was normal. On the SICD he showed a marked scattering of success and failure that appeared related to both shifts in atten-tion and to actual receptive and expressive language

deficits. Overall reception score was 3 years 3 months. Sound and speech discrimination was seriously impaired. He was unable to carry out two-stage commands involv-ing two objects and two actions (eg, “Put the cup in your lap and give me the ball”). Like J.E., he was able to count

up to six objects from an array of 11 objects, but could not correctly respond to commands involving words such as “some,” and “a few.” His syntactic development, re-ceptively, was at the 20- to 22-month level, slightly below that of J.E. Tense markers such as “-ing” and “-ed” were ignored, and he often confused the subject-object order of sentences.

A.J.’s overall expressive development was at the 29-month level. Errors of syntax were common (eg, in plural

endings), as were problems in responding to “who,”

“what,” and “where” questions. For example, to the

ques-tion “When you go to bed, what do you wear?” he

answered “I sleep here tonight?,” demonstrating concep-tual confusion. Another example, however, documents the purely linguistic difficulty A.J. had with “wh” ques-tions: he asked at one point, “What are you going?”

Although A.J. engaged more frequently in spontaneous conversation than did J.E., he showed shallow interest in social interaction initiated by others and he was likely to approach strangers and speak with them as if they were friends. He expressed his needs and his wants, as well as his experiences, through language, and thus had a better sense of the functions of language than did J.E. In this regard, he created his

own

idioms to communicate; “to grow down” meant being younger than he, and “they go far longer in school” referred to children who traveled longer distances than he to get to school.

On psychiatric evaluation, his play and conversation

showed evidence of poor conceptual organization and

confused thought content, frequent shifting from topic to topic, and magical thinking, fantasies, and bizarre ideas.

On three separate occasions he stopped working on a

task, focused his attention on a distant object, and “talked” to someone whom he identified as Spiderman.

Observations of A.J. in school revealed a child inter-ested in his peers, but usually preoccupied with asking questions of his teacher about what people’s names were or where the other children lived. He did not appear to

be interested in these answers, however, or to

use

them as new information.

DISCUSSION

Usually the physical defects seen in fetal alcohol

syndrome provide the clue to the diagnosis.

How-ever, the most disabling consequences of alcohol

teratogenicity are CNS and behavior dysfunction.’4

Because fetal alcohol exposure may result in a

spectrum of abnormalities, some children with FAE

may have minimal physical anomalies but severe

CNS dysfunction. In the present report, two

un-usual cases of children with FAE have been

de-scribed who demonstrate previously unreported

ef-fects of prenatal alcohol exposure. Both boys had

significant exposure to alcohol in utero and had the

typical midfacial anomalies seen in FAS. They were

also alike in other physical, behavioral, language, and cognitive features. They shared some physical

findings atypical of narrowly defined FAS in that

both had large heads without hydrocephalus and

neither had pre- or postnatal growth failure. Both

were hyperactive, markedly hypervigilent to

audi-tory stimuli, and had poor sound discrimination.

Perhaps their auditory hypervigilence is an

exten-sion of the hyperacusis noted in newborns with

FAS.5 Their greatest disability and their greatest similarity were in their language and cognitive dys-functions.

Cognitive, linguistic, and developmental

(5)

type of disturbances presented. In addition to

defi-cits in language comprehension and syntactic-se-mantic errors in their spontaneous utterances, they

demonstrated symptoms of thought disorder

com-mon among youngsters with atypical childhood

psy-chosis or pervasive developmental disorder.’5”6 In

addition, both displayed unusually diminished

in-terest in social situations as a source of personal

gratification and pleasure, and both failed to

use

language appropriately as a means of initiating and

continuing social discourse. Although each had

de-veloped near age-appropriate self-help personal

skills in toileting, dressing, and table manners, their knowledge of the rules of interpersonal situations and discourse was grossly deficient.

Tangentiality and looseness of associations and

hypervigilence to environmental events appeared

to reflect underlying conceptual confusion. The sec-ond patient, A.J., appeared to adopt an organizing

strategy for himself, asking questions typically con-cerned with the future and the roles of people in his life. The first patient, J.E., however, withdrew from situations that were too perplexing and, especially,

attempted to reduce the frequency of his verbal

interactions. Both youngsters were susceptible to

episodes of panic and confusion brought about by

external stimuli (eg, school bells, sirens, noises from radiators); typically, such interruptions had a last-ing effect such that the child had to be reintroduced to the task at hand. Thus, self-modulation of atten-tion and arousal was rarely seen, and organization

of behavior had to be undertaken by the adult

present.

Both youngsters exhibited oddities of prosodic

functioning, with hyperarticulation, forcing of

speech sometimes to the point of explosiveness,

whispering, and failure to use variations in pitch

and tone to express meaning appearing during both

formal assessment and free play. These prosodic

dysfunctions are of special significance because, in

normal development, children learn to understand

and to express intention through these nonverbal

means before they acquire the linguistic means to

do

so.

In

view of both patients’ intact nonverbal intel-lectual competencies, the disabilities in almost all areas of psycholinguistic functioning are notable.

However, these youngsters differ from those with

developmental dysphasia.’5”6 Such children, despite their language handicaps, are interested in and take

pleasure from personal and social interactions. A

further distinction between the picture of young

dysphasic children and the two patients reported

here lies in the evidence of thought disorder. Children like the

two

presented here, with

signif-icant antenatal exposure to alcohol who exhibit

minor physical effects and more subtle CNS

dys-function, may escape detection until they exhibit

learning problems in school,3 at which time they

may be stigmatized as mentally retarded if their

learning disorder is not defined. These two boys

were detected earlier, as preschoolers, because of

their unusually severe language and behavioral dis-order, disabilities not reported previously in chil-then with FAE. On verbal tests of intelligence, both

boys performed within the borderline retarded

range, but on nonverbal intelligence tests, both

demonstrated average or above performance. This

TABLE 2. Principal Cognitive, Linguistic, and Behavior Markers Observed in Patients J.E. and A.J.

Cognitive Characteristics Behavioral Characteristics Linguistic Characteristics

Intelligence Anxiety Intact

Intact nonverbal Poor modulation of arousal Articulatory skills

Borderline verbal Poor regulation of attention No history of echolalia

Short-term memory Hypervigilence, especially to audi- Major deficits

Intact for digits tory stimuli Sound and speech discrimination

Body awareness Panic reactions to minor changes Comprehension of: prepositions,

Normal knowledge of body parts in routine or to minor stresses complex, two-stage commands,

Good personal, self-help skill de- Peer relationships references to abstract qualities

velopment Poor (distance, size relationships)

Disturbance in thought Marked by withdrawal, immatu- Syntactic development

Blocking rity or affectless interpersonal Prosodic features of language

(in-Tangentiality exchanges tonation, pitch, stress)

Looseness of associations Play Knowledge of rules of dialogue

Perseveration Inappropriate, unimaginative, im- Reduced sentence length for

On familiar routines, themes of mature chronologic age

play, topics Overall

Failure to appreciate communica-tion function of language, and to enjoy engaging in dialogue Diminished or inappropriate

(6)

suggests that children with possible FAE should receive very broad inteffigence testing to best define any CNS dysfunction.

These patients also point out the significance of

a thorough assessment oflanguage in any child with

significant antenatal exposure to alcohol or

dys-morphogenesis and behavior suggestive of FAE.

Siblings of any child with known FAE should also

be assessed for undetected learning disorders.

While differential diagnosis among many of the

disorders of development may require careful

as-sessment by multidisciplinary specialists, the

pedia-trician can be alerted to possible learning problems

associated with maternal alcoholism by careful

ob-servations and the use of a few relatively simple assessment procedures. The specific clinical char-acteristics that were useful in this study in the early identification of possible FAS-related learning and behavior disturbances were: (1) marked

hypervigil-ence; (2) distractabiity to even normal levels of

auditory and visual stimulation; (3) cognitive

con-fusion manifested as anxiety and behavioral

disor-ganization. In order to determine the presence of

these difficulties, observation in the physician’s

of-fice should concentrate on the child’s level of

arousal and attention and his ability to regulate the

flow of his attention and to follow the pattern of

activities going on in the office. Attempting to

en-gage the child in conversation during the course of

a routine pediatric examination, eg, asking him to

tell a story about a picture and to describe common

objects, provide for the physician impressions of

both attentional development and overall language

development. The specific markers summarized in

Table 2 may further help primary care providers

organize questions and tasks during a routine office

examination so that early language disorders may

be detected. Prognosis for such children can be

altered by thorough testing and early identification.

Both boys reported here had benefitted as

pre-schoolers from early participation in special public

education programs, with individualized

instruc-tion, consistent routines, and small teacher-to-pupil ratio, and parent training. Visual and auditory

dis-tractions were limited, and daily therapy in

lan-guage, speech, and social interaction was provided.

In summary, a history of antenatal exposure to

ethanol associated with (1) large (greater than 97th percentile) head circumference without hydroceph-alus, (2) facial features of FAS, (3) early

develop-mental delay, particularly in language acquisition

and the

use of language for communicative pur-poses, and (4) impaired modulation of attention and arousal expressed as hypervigilence, distractibility,

and anxiety are presented as possible effects of

alcohol on the fetus.

ACKNOWLEDGMENTS

This work was supported in part by grants from the National Institutes of Health, NS 12384, AA 03599; Clin-ical Center grant RR00125; a grant from the National Council on Alcoholism; and grant No. 1 P50 MH-30929

from the Mental Health Clinical Research Center.

REFERENCES

1. Lemoine P, Harousseau H, Borteyru JP, et al: Les enfants de parents alcoholiques: Anomalies observee. Quest Medical 25:476, 1968

2. Jones KL, Smith DW, Ulleland CN, et al: Pattern of malfor-mation in offspring of chronic alcoholic mothers. Lancet 1:

1267, 1973

3. Shaywitz SE, Cohen DJ, Shaywitz BA: Behavior and learn-ing difficulties in children of normal intelligence born to alcoholic mothers. J Pediatr 96:978, 1980

4. Loeser H, Majewski F: Type and frequency ofcardiac defects

in embryo-fetal alcohol syndrome: Report of 16 cases. Br Heart J 39:1374, 1977

5. Streissguth AP, Herman CS, Smith DW: Intelligence,

be-havior and dysmorphogenesis in the fetal alcohol syndrome:

A

report

on 20 patients. J Pediatr 92:363, 1976

6. Streissguth AP, Landesman-Dwyer 5, Martin JC, et al: Teratogenic effects of alcohol in humans and laboratory animals. Science 209: 353, 1980

7. Chouke KS: The epicanthus or Mongolian fold in caucasion children. Am J Phys Anthropol 13:255, 1929

8. Clarren 5K, Smith DW: The fetal alcohol syndrome. N Engi

J Med 298:1063, 1978

9. National Center for Health Statistics: NCHS Growth Charts, 1976. Monthly Vital Statistics Report. Vol 25, No. 3, Suppl (HRA) 76-1120. Rockville, MD, Health Resources

Administration, June 1976

10. Tanner JM: Physical growth and development, in Forfar JO, Arneil GC (eds): Textbook of Pediatrics. Edinburgh, Churchill Livingstone, 1973

11. Hendrick DL, Prather EM, Tobin AR: Sequenced Inventory of Communicative Development. Seattle, WA, Seattle Uni-versity Press, 1975

12. Leiter International Performance Scales (Arthur Adapta-tion). Chicago, Stoelting Publishing Co, 1948

13. Wechsler D: Wechsler Intelligence Scale for

Children-Re-vised. New York, The Psychological Corp, 1974

14. Smithells RW: Fetal alcohol syndrome. Dev Med Child

Neurol 21:244, 1979

15. Caparulo BK, Cohen DJ: Cognitive structures, language and emerging social competence in autistic and aphasic children. JAm Acad Child Psychiatry 16:620, 1977

16. Cohen DJ, Caparulo BK, Shaywitz BA: Primary childhood aphasia and childhood autism: Clinical, biological and

con-ceptual observations. J Am Acad Child Psychiatry 15:604,

(7)

1981;68;850

Pediatrics

Sally E. Shaywitz, Barbara K. Caparulo and Elizabeth Susan Hodgson

Ethanol