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MODERN
MEDICINE
Fetal alcohol syndrome
JOSEPH LOVELL, MD
Fetal alcohol syndrome occurs in its fully developed
form in about 6% of children born to women who
drink heavily during pregnancy. The principal features are growth and mental retardation, specific
craniofacial abnormalities and various central nervous system, limb, cardiac, and urogenital malformations. It is likely that l a r g e r n u m b e r s of less
severely damaged children with only partially developed fetal alcohol syndrome go unrecognized. The
pathogenic mechanism is not yet well understood.
The syndrome is not confined to childhood; there is
a progression of the disorder into adulthood with
mental retardation and behavioural problems. Fetal
alcohol syndrome is entirely preventable, thus publicity and counselling are of primary importance.
. . you will conceive and bear a son.
Now, then, be careful to tal<e no wine
or strong drinl< and to eat anything
unclean'
Old Testament, Judges 13:2-3.
•
Of all drugs and environmental agents, alcohol is the
leading known cause of mental
retardation and teratogenesis
in a society in which it is freely
available. Other drugs of abuse
do not increase the risk of fetal
damage on such a large scale as
Edcohol.'l
The disorder now known as
fetal cdcohol syndrome was first
described in 1968 in France by
P Lemoine^ and it was named
in 1973.' Fully developed fetal
alcohol syndrome has been
reported only in those children
whose mothers consumed cdcohol during pregnancy."^ Fetal
Dr Lovell is senior medical officer, medical
ward and drug and alcohol related brain
damage ward, Cumberland Hospital, North
Paramatta, New South Wales, Australia.
This article was written specially for
MODERN
Edcohol syndrome is a cUnicaUy
recognizable, specific disorder.
Clinical features
The main features of feted cdcohol syndrome are described
below and illustrated in the
Figures.
• Prenatal and postnatal
growth deficiency (neonatal
birth weight is usually less than
2 500g).
• Mental retardation, developmental delay with hyperactivity
and attention deficit. A great
variety of neurological abnormalities may occur, including
microcephaly, tremor, ataxia,
seizures, ptosis, cerebral palsy,
hypotonia, etc.®
• Specific craniofacial abnormalities^ — that is, small head,
flat midface (maxUlar hypoplasia), thinned upper lip with
smoothed philtrum, short
upturned nose with broad deep
bridge, widely spread eyes,
small palpebral fissure, epicanthal folds, high arched palate,
cleft palate and dental abnormalities.
Consultant's c o m m e n t
As ttiis paper indicates, fetal alcohol syndrome Is one of the major potential*
ty reversible causes of mental retardation and teratogenesis today. While
the US Surgeon-General and some other authorities have nscommended
total abstinence from alcohol during pregnancy, others have been less stringent. arguing that better results are more llltefy to be achieved by recommending guidelines that are more acceptable. As most of the damage from
alcohot to the embryo occurs during the firsi half of the first trimester of
pregnancy, during which time the mother-to-be Is unaware of her pregnant
status, recommendations on lowered alcotiol consumption levels dunng
pregnancy should be developed with the aim of implementation by all
women 'at risit of becoming pregnant'. This represents a large population. It
is likely that clinically recognized cases of fetal alcohol syndrome represent
only the clinical 'tip of the iceberg' and that a far larger number of undiagnosed but less severely damaged children go unrecognized. These
thoughts should galvanize the medical profession to worl< harder at reducing alcohol consumption in younger women.
DrAiex Woda)(
Director
Alcohol and Drug Service.
St Vincent's
Hospital,
Sydney, New South Wales.
MEDICINE.
OCTOBER 1995 / MODERN MEDICINE OF SOUTH AFRICA
75
Reproduced by Sabinet Gateway under licence granted by the Publisher (dated 2012)
Fetal alcohol
syndrome
Alcohol is the leading cause of
mental retardation and
teratogenesis in a country
with free access to it.
continued
• A significantly increased
occurrence of a wide spectrum
of congenital malformations of
the central nervous, musculoskeletal, cardiovascular, and
urogenital systems. For exam-
pie, in one study, congenital
heart defects were fovmd in 29%
of children with fully developed
fetal alcohol sjnndrome; alcohol
is an essential cofactor within
the multifactorial aetiology of
congenital heart defects.®
• Ophthalmological signs occur
very often and include epicanthus, ptosis, myopia, optic
nerve hypoplasia, microphthalmus, coloboma, and tortuous
retinal vessels."
Pathogenesis
Figure 1a (left). Boy aged nme
months adniitted to tiospital for
repair of cleft palate (Figure lb
above). Mother fourid to be alcoholic on further enquiry by general
practitioner. Small for dates; on the
third pementlle for height, weight
and head circumference; developmentai delay. Note the short palpebral fissures.
I
'
A
J
Figure 2a. Adopted male at the age
of 18 months. Typical features are
present, including short palpebral
fissures, long
underdeveloped
philtrum, small upturned nose, maxillary and mandibular hypoplasia,
developmental delay. Mother, a
known alcoholic, has since died
from alcoholism.
76
4
Figure 2b. The same child four
years later. He has major behavioural and school problems.
tllu8traliOna reproduced by courtesy ol
Dr Tony Lipson.
MODERN MEDICINE OF SOUTH AFRICA / OCTOBER 1995
Fully developed fetal alcohol syndrome occurs in about 6% of
infants whose mothers consumed
more than 85g of absolute alcohol
(equivalent to six cans of beer)
daily during pregnancy. The
average incidence of the syndrome in developed countries
with unrestricted access to alcohol is one case per 2 000 or 3 000
live births, with variations of up
to one case per 600 births in
some commvmities.'""''^
No 'safe' level of alcohol consumption in pregnancy has yet
been established. The number of
abortions in women who consume more than lOg of alcohol
daily is greater than in those who
do not consume this level of alcohol [in Australia], and alcohol
withdrawal may occur in babies
born to mothers who consume
alcohol during pregnancy.'^
Prenatal alcohol exposure has
a profound effect on the development of the embryonic brain;
the effect is dose-related to
maternal drinking.'" The offspring of mothers who consvmied on average at least 15g
of alcohol per day during pregnancy are at risk of abnormal
mental development, behavioural problems, and other central nervous system effects.'®
Maternal consumption of at
least 30g of alcohol daily during
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Congenital heart defects were
found in 29% of children with
fully developed fetal alcohol
syndrome.
pregnancy is consistently associated with a low birthweight.
Consequently, every child with
a postnatal weight of less than
2 500g should be screened for
fetal
alcohol
syndrome.
Maternal consumption above
60g of alcohol daily is associated
with craniofacial abnormalities
specific to this syndrome.'"
The most critical period for the
development of alcohol teratogenicity is believed to be the
time of conception and the first
trimester, particularly during
the first month of pregnancy,
when the mother-to-be is often
unaware of her pregnant status.
Alcohol and its metabolite
acetaldehyde are toxic in embryo
culture and may decrease the
transfer of bloodfi-ommother to
embryo by reducing umbilical
blood flow and impairing the
placental uptake of amino acids
and other nutrients."*
Fetal alcohol syndrome can be
demonstrated in animals, such
as rats, mice and monkeys. The
main feature of experimental
fetal alcohol syndrome is microcephaly. The cerebral cortex is
especially vulnerable to prenatal alcohol exposure. Its total
mass is reduced, it contains
fewer neurones and glia, and
there is evidence of disordered
migration and decreased proliferation
of
neurones.
Developmental delay with various malformations of the central nervous system (for example, agenesis of corpus callosum) and craniofacial abnormalities similar to those seen in
human fetal alcohol syndrome
have been observed in the animal model.""
Diagnosis
The possibility of substance
abuse, including alcohol abuse,
should be considered in any
pregnant woman; screening
and counselling of all prospective mothers in this respect
should be routine. The neonate
at risk for fetal alcohol syndrome has to be identified and
f
evaluated with a knowledge of
the maternal drinking habit,
and specific risks, including
neonatal withdrawal syndrome,
have to be anticipated.
The recently developed diagnostic test using ultrasound
enables the detection of even
mild craniofacial fetal abnormalities,'® and neuroimaging
may also assist in diagnosis.
Figures 3a (above left), 3b
(above). ar\d 3c (left). A 15-yearold boy witfi fetat alcofiol syndrome. Note maxillary tjypoplasia,
small nose, microcephaly. He has
mild mental retardation and is on
the fifth percentile for height. Head
circumference is less than the third
percentile.
Illusiraiions reproducad by courtesy of
Dr Tony Lipson.
OCTOBER 1995 / MODERN MEDICINE OF SOUTH AFRICA
77
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Fetal alcohol
syndrome
continued
Fully developed fetal alcohol syndrome
occurs in about 6% of mothers who
consumed more than 85g of alcohol
daily during pregnancy.
the assessment of alcoholic
patients. The incidence of psychiatric illness in mentally
retarded persons is high.
Certain specific syndromes
associated with mental retardation present with particular
neurocognitive, behavioural
and psychiatric profiles, a common example being fetal alcohol
syndrome.^"
i
Figure 4. Part-Aborigir\al child aged
14 mon/hs who was small tor dates
at birth and is on the third percentile for height, weight, and head
circumference with developmental
delay and squint. The squint is due
to right optic nerve hypoplasia.
i.
Figure 5. Twins aged seven years
suffering from developmental delay.
Twin 1 has a hypospadius and twin
2 a ventricular septal defect. The
alcoholic mother was found unconscious in the fourth month of pregnancy with a blood alcohd level of
520mg% (sun/ived).
Illustrations reproduced by courtesy o( Dr Tony Lipson.
O u t c o m e of c h i l d r e n w i t h
fetal alcohol syndrome
Despite the tendency for the
craniofacial dysmorphia to
diminish with time, fetal alcohol syndrome can still be identified in most patients in adolescence. Rarely, the face becomes
normal, illustrating the importance of childhood photographs
in the assessment of adults.
More often, the face is prolonged and the nose bulky, in
contrast with the appearance of
the affected infant. Sometimes
'small eyes' and a narrow upper
lip with smooth philtrum persist into adulthood. As a rule,
the weight normalizes in
80
women. In men, underweight
and short stature usually persist. Generally, there is no significant improvement in
intelligence.
In most cases, persistent
mental retardation, learning
disabilities with maladaptive
behaviour, irritability and
marked instability are the most
important sequelae of intrauterine exposure to alcohol.
Therefore, fetal alcohol syndrome is not confined to childhood only,^-and it should be
considered in the differential
diagnosis of any case of mental
and physical retardation and
general behaviour and learning
problems and, particularly, in
MODERN MEDICINE OF SOUTH AFRICA / OCTOBER 1995
Are affected children latent
alcoholics?
It is possible that children with
fetal alcohol syndrome are
latent alcoholics since aU conditions appropriate for the development of alcoholic dependency
are present, namely:
• the early use and adaptation
to alcohol in the prenatal period;
• the peculiar personality of the
syndrome — low intelligence
with emotional instability and
uncritical behaviour — which
presents a real risk for the
development of addiction;
• hereditary factors; and
• an 'alcohoKc' family and social
surroundings.
In our society it is difficult to
protect children from alcohol
exposure. It is up to the family
to help the child to cope with
the risk of addiction.
Prevention
Theoretically, the embryonic
damage caused by alcohol is
entirely preventable. The message is simple: women have to
cease drinking any alcohol during pregnancy. If this is not possible they should at least reduce
significantly their alcohol consimiption at the time of concep-
Reproduced by Sabinet Gateway under licence granted by the Publisher (dated 2012)
I
tion and during the first half of
pregnancy." Unfortunately, in
our society alcohol abuse is
often part of the mating ritual.
Widespread education of the
general public on the risk of
fetal alcohol sjmdrome during
the preconceptual and prenatal
period is of utmost importance.
A recent Canadian survey
foimd that a surprising number
of adults have but a meagre or
no knowledge of the risk connected with maternal alcohol
consumption.^'^ It is likely that
the situation in South Afiica is
not much better. Only a great
deal of widespread health education can hopefully improve
the situation. However, it is well
known that it is notoriously difficult to alter drinking habits.
Sm-veys conducted in Sweden,
New York and Scotland have
shown a continued high incidence of fetal alcohol sjmdrome
in some populations despite
publicity.'^
FuUy developed, clinically recognizable fetal alcohol syndrome probably represents only
the tip of the iceberg. It is Hkely
that larger numbers of less
severely damaged children with
only partially developed fetal
alcohol syndrome (sometimes
called fetal alcohol effect) go
unrecognized.
Conclusion
The current estimate of annual
costs related to fetal alcohol
syndrome in the USA is over
US$300 million, with mental
retardation accounting for
almost 60% of this amoimt.'^
One can only speculate what
Prenatal alcohol exposure has a
profound dose-related effect on
the development of the brain.
Figure 6a. Neonate witi^ typical features. Further enquiries from the
paediatrician revealed a history of
alcohol abuse by the mother dunng
pregnancy.
Figure 6b. Lateral X-ray of heel
showing epiphyseal stippling which
can be associated with the fetal
alcohol syndrome.
Illustrations reproduced tiy courtesy ot Dr Tony Upson.
Key points
• Of all drug and environmental agents, alcofiol is the leading Itnown cause
of mental retardation and teratogenicity in a society in which it is freely
available.
• Fully developed fetal alcohol syndrome occurs in about 6% of infants
whose mothers consumed more than 85g of aJcohol dally during pregnancy.
• Alcohol has a dose-related effect on the development of the embryonic
brain.
• The time of conception and the first trimester of pregnancy are the most
critical to the development of alcohol teratogenicity, The mother-to-be is
often unaware of her status during the critical first month of pregnancy.
• The possibility of substance abuse should be considered in all pregnant
women.
• Although craniofacial dysmorphia tends to diminish with time, fetal alcohol syndrome can still be identified in most patients in adolescence.
• Theoretically, embryonic damage caused by alcohol Is entirely preventable.
• Women should be encouraged to cease drinking alcohol during pregnancy; if they are unable to do this, they should at least reduce their consumption al the time of conception and during the first hall of pregnancy.
the total costs of alcohol embryonic damage in South Afiica are,
but whatever thefinancialcost,
the price in terms of human suf-
fering is overwhelming. •
References available on request from The
Editor at PO Box 2271, Clareinch 7700.
OCTOBER 1995 / MODERN MEDICINE OF SOUTH AFRICA
81
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MODERN MEDICINE
OPHTHALMOLOGY CLINIC
The child with leucocoria
(white pupil)
Leucocoria is a serious eye condition requiring immediate
referral. The general practitioner has a crucial role
in obtaining an early diagnosis which, in some cases,
may prove to he life saving.
GLEN A GOLE, MD BS, FRACO, FRACS, FRCOphth
•
Leucocoria is an uncommon
condition with a large differential diagnosis, that almost
always indicates severe eye disease. Early diagnosis by the
general practitioner can be life
saving. Parents frequently
Dr Gole is senior visiting specialist, Royal
Children's and Royal Women's Hospitals,
consultant ophthalmologist, paediatric low
vision clinic, and clinical associate
professor. University of Queensland,
Brisbane, Queensland, Australia. This
article was written specially for MODERN
MEDICINE.
Figure 1. 'Cat's eye' reflex In the
right eye of a child with retinoblastoma.
Illusiraiion reproduced by courtesy of G
Frank Judisch, MD.
notice an 'abnormal' appearance to the pupil or eye before a
white pupil is obvious.
Retinoblastoma
Retinoblastoma is the most
common intraocular malignancy in childhood. It usually presents within the first three
years of life with a white pupil
or 'cat's eye' reflex (Figure 1).
The tumour assumes several
forms within the eye, but it
usually looks like a whitish
Figure 2. Bilateral
cataracts.
congenital
mass on the retina. The other
common presenting sign is a
squint, caused by loss of the fixation reflex when the tumour
involves the macula.
Most cases of retinoblastoma
arise as new mutations. If both
eyes are involved or if the disease is mvdtifocal in one eye, it
may be assumed that the disease has arisen as a result of a
germinal mutation. In these
cases, the tumour will be subsequently transmitted as an
autosomal dominant condition
Figure 3. Congenital cataract seen
against the red reflex.
The
cataract may often be seen as a
dark, rather than a white, shadow.
OCTOBER 1995 / MODERN MEDICINE OF SOUTH AFRICA
85
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MODERN MEDICINE
OPHTHALMOLOGY CLINIC
with greater than 80% penetrance to the patient's children.
In 6 to 8% of patients there will
be a positive family history.
Advances in the understanding
of the molecular biology of the
retinoblastoma gene are
presently at the forefront of
genetic research. In utero identification of carriers of the gene
within affected families is Kkely in the near future. Carriers
of the gene have a long-term
risk of developing a second
malignancy such as an osteogenic sarcoma.
If retinoblastoma is suspected, urgent referral to an ophthalmologist versed in the
management of retinoblastoma
is indicated. Treatment undertaken at an early stage is life
saving. After confirmation of
the diagnosis, management
usually involves enucleation of
the affected eye if the sight cannot be saved or, if there is visual potential, local irradiation or
irradiation of the whole eye.
Laser therapy and cryotherapy
can be used for small tumours
or local recurrences.
Congenital cataract
Congenital cataract is the most
common cause of leucocoria. It
may be unilateral or bilateral
(Figure 2). The aetiology of congenital cataracts can be hereditary, infectious (e.g. rubella),
metabolic (e.g. galactosaemia)
or associated with a syndrome
(e.g. Down's syndrome).
The trend towards early
diagnosis and treatment in
paediatric ophthalmology is
nowhere better illustrated than
86
in the case of congenital
cataract. Vitrectomy instruments, developed for use in
retinal detachment surgery,
have revolutionized congenital
cataract surgery. This, together
with advances in contact lenses, has changed the outlook for
the child with congenital
cataract. Seventy percent of
children with bilateral congenital cataracts will achieve a final
vision of 6/18 or better. Even
patients with unilateral cataract, which causes severe
amblyopia if untreated, have a
50% chance of having good
vision if treated by three
months of age. However, good
visual results are by no means
universal after congenital
cataract surgery. Fitting and
maintaining contact lenses is
extraordinarily time-consuming, expensive and often frustrating for the parents.
Nevertheless, the cost of intervention, with its prospect of
useful vision, pales into
insignificance when measured
against the economic cost to the
individual and the community
of blindness from birth.
Prevention of the tragedy of
congenital rubella syndrome by
COMING
COMING
MODERN MEDICINE OF SOUTH AFRICA / OCTOBER 1995
immunization lies firmly within the province of the family
doctor. Congenital cataract
should be excluded in all newbom children by confirming the
presence of a normal red fundus reflex in both eyes (use a
direct ophthalmoscope at arm's
length in a darkened room —
see Figure 3) prior to discharge
home. Early treatment (before
three months of age) of congenital cataract gets results — late
treatment is doomed to failure
because of the development of
deprivation amblyopia.
Any child who has had
cataract surgery in infancy
must have follow-up for his or
her whole life because of the
long-term risk of glaucoma and
retinal detachment.
Intraocular lenses are not
used in babies because of the
dramatic changes in the
refractive power of the eye in
the first three years of life
and because of the significant
postoperative opacification in
the posterior lens capsule,
which necessitates a large
posterior capsulotomy and
anterior vitrectomy at the
time of primary surgery. •
Joint injections:
Intra-articufar and
periarticular techniques
l\Auscuiar dystrophies
In childhood