VILJOEN ET AL.593
Fetal Alcohol Syndrome Epidemiology in a South African
Community: A Second Study of a Very High Prevalence Area*
DENIS L. VILJOEN, M.D., J. PHILLIP GOSSAGE, PH.D.,† LESLEY BROOKE, B.S. (HONS.),†
COLLEEN M. ADNAMS, M.D., F.C.P.,† KENNETH L. JONES, M.D.,† LUTHER K. ROBINSON, M.D.,†
H. EUGENE HOYME, M.D.,† CUDORE SNELL, D.S.W.,† NATHANIEL C.O. KHAOLE, M.D.,†
PIYADASA KODITUWAKKU, PH.D.,† KWADWO OHENE ASANTE, M.D.,† RICHARD FINDLAY, M.D.,†
BARBARA QUINTON, M.D.,† ANNA-SUSAN MARAIS, R.N.,† WENDY O. KALBERG, M.A., CED,† AND PHILIP A. MAY, PH.D.†
Department of Human Genetics, Faculty of Health Sciences, University of Witwatersrand, National Health Laboratory Services, South
Africa, and the Foundation for Alcohol Related Research
Received: August 2, 2004. Revision: March 23, 2005.
*This project was funded by the National Institute on Alcohol Abuse and
Alcoholism grants RO1 AA09440 and R01 AA11685, the National Institute
on Minority Health and Health Disparities and the Foundation for Alcohol
Related Research of South Africa.
†Philip A. May is with the University of New Mexico, Center on Alco-
holism, Substance Abuse and Addictions (CASAA), 2650 Yale SE, Albu-
querque, NM 87106. Correspondence should be sent to him at that address,
or via email at: firstname.lastname@example.org. J. Phillip Gossage, Piyadasa Kodituwakku
and Wendy O. Kalberg are with CASAA, the University of New Mexico.
Lesley Brooke, Nathaniel C.O. Khaole and Anna-Susan Marais are with the
ABSTRACT. Objective: The aim of the study was to determine the
prevalence and characteristics of fetal alcohol syndrome (FAS) in a sec-
ond primary school cohort in a community in South Africa. Method:
Active case ascertainment, two-tier screening, and Institute of Medicine
assessment methodology were employed among 857 first grade pupils,
most born in 1993. Characteristics of children with FAS were contrasted
with characteristics of a randomly selected control group from the same
classrooms. Physical growth and development, dysmorphology and psy-
chological characteristics of the children and measures of maternal al-
cohol use and smoking were analyzed. Results: The rate of FAS found
in this study is the highest yet reported in any overall community in the
world, 65.2-74.2 per 1,000 children in the first grade population. These
rates are 33-148 times greater than U.S. estimates and higher than in a
previous cohort study in this same community (40.5-46.4 per 1,000).
Detailed documentation of physical features indicates that FAS children
in South Africa have characteristics similar to those elsewhere: poor
growth and development, facial and limb dysmorphology, and lower in-
tellectual functioning. Frequent, severe episodic drinking of beer and
wine is common among mothers and fathers of FAS children. Their lives
are characterized by serious familial, social and economic challenges,
compared with controls. Heavy episodic maternal drinking is signifi-
cantly associated with negative outcomes of children in the area of non-
verbal intelligence but even more so in verbal intelligence, behavior and
overall dysmorphology (physical anomalies). Significantly more FAS
exists among children of women who were rural residents (odds ratio:
7.36, 95% confidence interval: 3.31-16.52), usually among workers on
local farms. Conclusion: A high rate of FAS was documented in this
community. Given social and economic similarities and racial admix-
ture, we suspect that other communities in the Western Cape have rates
that also are quite high. (J. Stud. Alcohol 66: 593-604, 2005)
(FAS) rate among first graders was 40.5-46.4 per 1,000
(May et al., 2000). This rate contrasts with estimated FAS
rates of 0.33-2.2 in the United States (Abel and Sokol, 1991;
May and Gossage, 2001) and with an average for the de-
veloped world of 0.97 per 1,000 (Abel, 1998; Abel and
Sokol, 1987). In a few high-risk American Indian reserva-
tion communities in the United States, the rate of FAS de-
rived from active case ascertainment methods seldom
exceeds 10 per 1,000 (Abel, 1995; May, 1991; May et al.,
1983), with an average rate of 8 per 1,000 from 1970 to
N A PREVIOUS STUDY in the community in South
Africa that was studied here, the fetal alcohol syndrome
1982 (May et al., 2002). The clinic-based rate of FAS for
African Americans of low socioeconomic status (SES) from
a few inner-city areas is 2.29 per 1000 (Abel, 1995, 1998).
Estimations of FAS prevalence in the United States come
from birth records, child disability registries, clinic-based
studies and a few population-based initiatives (Stratton et
al., 1996; May, 1996). Because of the wide variation in
methodologies, comparison of FAS prevalence and charac-
teristics among populations is difficult and almost impos-
sible. For example, all but three active case ascertainment
studies, where outreach in major geographical areas focuses
on aggressive case finding, were carried out among American
University of Cape Town and the Foundation for Alcohol Related Research.
Colleen M. Adnams is with the Department of Paediatrics, University of
Cape Town. Kenneth L. Jones is with the Division of Dysmorphology/Tera-
tology, Medical Center, University of California, San Diego. Luther K.
Robinson is with Dysmorphology and Clinical Genetics, State University of
New York at Buffalo. H. Eugene Hoyne is with the Division of Medical Ge-
netics, Stanford University School of Medicine. Cudore Snell is with the
Department of Social Work, Howard University. Kwadwo Ohene Asante is
in Pediatrics, British Columbia. Richard Findlay is with the Department of
Pediatrics, King/Drew Medical Center. Barbara Quinton is with the Depart-
ment of Pediatrics, Howard University.
594JOURNAL OF STUDIES ON ALCOHOL / SEPTEMBER 2005
Indians (Clarren et al., 2001; May et al., 2002). Passive,
record-based systems and clinic-based methods that inves-
tigate FAS among clients presenting for medical services
(e.g., in prenatal clinics) are most commonly used in other
U.S. and European populations (Abel, 1995; Abel and Sokol,
1987, 1991; Chavez et al., 1988; Egeland et al., 1995, 1998;
May, 1996). Active case ascertainment for FAS studies was
endorsed by a study committee of the Institute of Medicine
(IOM) as the most accurate method for epidemiological stud-
ies of FAS, but such studies are logistically challenging, ex-
pensive and time consuming (Stratton et al., 1996).
This article summarizes a second active case ascertain-
ment initiative in a first grade cohort to assess the preva-
lence of FAS in the Western Cape Province (WCP) of the
Republic of South Africa. Although FAS had been diag-
nosed in South Africa before (Palmer, 1985), a first study
in this community was prompted by a binational (United
States and South African) commission initiated by the vice
presidents of the two countries (National Institute on
Alcohol Abuse and Alcoholism, 1996, 1998). An initial,
comprehensive inquiry in 1997 produced the highest rate
of FAS ever reported, more than 40 per 1,000, and raised
many issues regarding the exact conditions produc-
ing FAS in South Africa and generally in human popu-
lations (Adnams, 2001; May et al., 2000; Viljoen et al.,
Fruit, grape and wine production dominate the region.
Wine production over the past 300 years has influenced the
modal drinking patterns. Wine was historically distributed
daily to workers as partial payment for labor, under what
was called the “Dop” system. Dop was outlawed by mul-
tiple statutes, and there is general public sentiment against
its practice, but residual patterns of regular, heavy episodic
alcohol consumption by some are a legacy. Furthermore,
increased contemporary availability of inexpensive com-
mercial beer, wine and distilled spirits, primarily in “take-
away”(carry-out) sources and shebeens (illegal bars),
has maintained or exacerbated severe drinking (London
et al., 1995; Mager, 2004; Parry, 1998). Episodic drinking
is a major form of recreation among subsegments of the
WCP population, causing many problems (King et al.,
The population of the WCP is 3,721,200: 57% “Cape
Coloured” (mixed race), 18% black, 25% white and 1%
of other races. Cape Town is the major city, but 40% of
the population lives outside of the metropolitan area in small
towns and rural areas. The study community is similar
in social and economic character to others in the Wine-
lands of WCP, with a 1996 population of 45,255 (35,364
urban and 9,861 rural; Bureau of Census, 1997). The vast
majority are classified as Coloured. Coloured denotes peo-
ple in South Africa originating from intermarriage of
African tribal populations (particularly the Khoi and San),
European whites and Asians (primarily Malaysians).
Although indications that alcohol was teratogenic had
been raised earlier in Europe (Sullivan, 1899; Lemoine et
al., 1968), the diagnosis of FAS was formulated by Jones
and Smith in 1973 (Jones and Smith, 1973), with further
delineation in recent years (Aase, 1994; Aase et al., 1995;
Hoyme et al., 2005; Stratton et al., 1996; Rossett, 1980;
Sokol and Clarren, 1989, 1995). FAS is a pattern of anoma-
lies and developmental deficits in children who were ex-
posed prenatally to large amounts of alcohol. Children with
FAS have a characteristic pattern of facial and body
dysmorphology and delayed physical growth and develop-
ment, as well as specific mental and behavioral deficits
(Stratton et al., 1996). For a diagnosis of FAS, all three
categories of problems must be present (Stratton et al.,
1996), and the diagnosis should be made only after excluding
other genetic and teratogenic anomalies (Hoyme et al., 2005).
Even though an FAS diagnosis can be made without confir-
mation of maternal drinking (Stratton et al., 1996), a detailed
maternal history is best to confirm gestational drinking.
In this study, no attempt was made to diagnose lower-
severity fetal alcohol outcomes, previously called “fetal al-
cohol effects.” Currently these other diagnoses are referred
to as “alcohol-related birth defects” or “alcohol-related
neurodevelopmental deficits” (Stratton et al., 1996). The
continuum of effects, from mild to severe, is called “fetal
alcohol spectrum disorder.” Only the most definite diagno-
sis was used in this study—full-blown FAS/not FAS. Di-
agnostic components of the IOM were strictly used: (1)
facial and other dysmorphology, recorded using a quanti-
fied checklist (see Hoyme et al., 2005), where high scores
indicate more features consistent with FAS; (2) diminished
growth for age (occipitofrontal head circumference [OFC],
weight and height; (3) developmental delay (in intelligence,
behavioral functioning and social skills); and, if possible,
(4) confirmation of maternal alcohol consumption from ma-
ternal or collateral sources.
Once data were collected and analyzed by independent
examiners for each component, a structured case confer-
ence was held (Figure 1) for final diagnoses (see Hoyme et
al., 2005). Every child with an FAS diagnosis met each of
the IOM criteria 1-3 above, and criteria for number 4 were
met in 90.6% of cases.
Two-tier screening system
In the previous study in this community (May et al.,
2000), dysmorphology, growth and developmental data for
more than 406 unselected first grade children were col-
lected initially to provide norms for this particular popula-
tion relative to National Center for Health Statistics growth
charts and clinical presentation. The unique racial mixture
of the WCP necessitated this first step. For example, pre-
VILJOEN ET AL. 595
liminary information suggested that the interpupillary dis-
tance (IPD) and the inner canthal distance (ICD) in local
subpopulations were greater than U.S. norms; and in many
children the proximal portion of the philtral columns were
smoother than found in America. Small head size is more
common in this population, but a child with isolated micro-
cephaly (or another single trait) and no additional features
of FAS was diagnosed with microcephaly (or the isolated
trait). The growth and clinical data from the first study
were utilized primarily to calibrate the expectations of the
clinicians and to set the cutoff criteria for Tier II screening
in all phases of the study (see below).
Four two-person teams (one expert pediatric dysmorpho-
logist and a physician being trained in FAS diagnosis) worked
independently but simultaneously, using standardized as-
sessment criteria. Twelve of the 13 elementary schools of
the community were accessed in both studies. The school
that declined participation was a private, all-white school
with 60 first graders. More than 90% of the children in the
study were Coloured; the remainder were black or white.
Relatively low mobility of the local population ensured that
most of the study children underwent gestation locally.
In the previous South Africa study, cutoff points were
set to ensure capture of all FAS children, and they were
used again in this study. In this study, 863 (93.6%) of 922
children on the rolls in first grade classrooms had parental
consent to participate and received Tier I screening, where
height, weight and OFC were measured. If a child was at
or below the 10th centile on OFC and/or on both height
and weight, he or she was referred for a complete physical
examination (Tier II). Two hundred and ninety-nine (34.9%)
children met these criteria (see Figure 1). In our first study,
one child with FAS from the community was not in a stan-
dard school (<2% error), and in this study no FAS cases
were found out of standard schools.
Every child receiving a complete (Tier II) dysmorphology
screen was examined completely by two of the physician
teams. Each two-member team measured OFC, palpebral
fissure length (PFL) and philtral length (PL) as well as
ICD and outer canthal distance, and examined other indica-
tors such as joint abnormalities, heart function and palmar
creases. Findings were recorded, and physicians within each
team verified one another’s findings (the expert checked
those of the trainee). All physicians were blinded from prior
knowledge of the child and the mother. After one team
examined them, a second team repeated the examination.
Interrater reliability was checked for the expert dys-
morphologists’ (not trainees) independent measurements,
rounded to the nearest 0.1 cm, using the square root of the
Pearson correlation (r). Results were 0.86 for ICD, 0.92 for
IPD, 0.91 for PFL and 0.82 for PL, indicating substantial
reliability among experienced examiners.
Complete diagnostic sequence—case and control
After the dysmorphology examinations, a child was as-
signed a preliminary diagnosis of not-FAS, deferred or FAS.
Only those with the classic FAS phenotype and measure-
ments were assigned a preliminary diagnosis of FAS. Chil-
dren with a deferred diagnosis had the appearance, growth
deficits and some anomalies of FAS, but developmental
tests and maternal interviews were especially necessary for
final diagnosis of these children. Children with a preliminary
FIGURE 1. The Methodological Flow of the Wave II Western Cape, South Africa FAS Study
596JOURNAL OF STUDIES ON ALCOHOL / SEPTEMBER 2005
FAS or a deferred diagnosis (n = 92) were advanced to
developmental and prenatal risk assessment.
A child with a final diagnosis of FAS had sufficient
dysmorphology, was approximately two standard deviations
below the mean on either verbal or nonverbal intelligence
quotient (IQ) tests, had substantial behavioral problems as
measured by the Personal Behavior Checklist (PBCL) and
had confirmation of prenatal alcohol consumption. In less
than 10% of cases were IOM criteria permitting an FAS
diagnosis without confirmation of alcohol exposure invoked
Control children (n = 146) were randomly selected from
first grade students without a preliminary diagnosis of FAS
or a deferred diagnosis. Identical examinations and testing
were performed on subjects and controls. Developmental
tests included Tests of the Reception of Grammar (TROG),
Ravens Colored Progressive Matrices and the PBCL-36,
providing measures of nonverbal and verbal IQ, cognitive
skills and behavioral problems. One hundred twenty-four
(84.9%) of the randomly selected controls were located and
agreed to participate.
The mothers of control children became maternal con-
trols. Structured interviews contained items covering repro-
duction, alcohol use before and during the index pregnancy,
SES, demographic variables, nutrition, physical status of
the mother and social context.
Protocols utilized drinking questions in a Timeline
Followback methodology (Sobell et al., 1988, 2001) de-
signed to elicit accurate reporting of alcohol consumed from
both Dop and commercial sources (London, 2000; London
et al., 1998; Parry and Bennetts, 1998). Photographs of stan-
dard beer, wine and spirit containers and tobacco products
sold locally were shown to respondents for accurate assess-
ment of quantity, frequency, and variability (Kaskutas and
Graves, 2000, 2001). A 7-day current drinking log was used
as a benchmark to calibrate extant quantity and frequency
of drinking and for accurate recall of drinking during the
pregnancy with the index child (see May et al., 2000, 2005;
Viljoen et al., 2002). This method is used because prenatal
drinking is underreported with direct reporting (Czarnecki
et al., 1990; Jacobson et al., 1991, 2002; Jacobson and
Jacobson, 1994) unless information is gathered through
unique questions, methods and contextual frameworks, such
as a part of general nutrition screen (King, 1994). Drinking
questions followed nutrition questions. All maternal inter-
views were administered by Afrikaans-speaking interview-
ers in the field.
Because mothers of FAS children often lead chaotic lives,
death or mobility obviated some interviews (May et al.,
1983; Streissguth et al., 1985). Specifically, 54 of the 64
mothers of the FAS children were contacted; 53 agreed to
be interviewed. For the remaining 10, data were obtained
via collaterals (usually relatives). Only one (1.6%) of the
64 case mothers was deceased, likely from tuberculosis.
Eight (12.5%) were nomadic or had moved from the area.
Drinking data were obtained from collateral sources on 9
of the 10 women not located. All 10 of the children of
mothers not interviewed were in foster or adoptive place-
ment (2 in an orphanage and 4 with relatives). Maternal
data presented here are focused primarily on confirmation
of maternal drinking for case assessment/diagnosis. A de-
tailed profile and discussion of a variety of maternal risk
factors for FAS in this setting are given elsewhere (Viljoen,
et al., 2002; May et al., 2005). Four (7.5%) of the 53 moth-
ers of children with FAS denied drinking during the index
pregnancy. To ensure accuracy, two dysmorphologists re-
visited these four children to rule out other anomalies and
to confirm the diagnosis. After further review of all results,
five (9.4%) children were diagnosed without confirmed al-
The maternal control group consisted of the 116 moth-
ers of the randomly selected control children located alive
and agreeing to interviews. Of the 30 mothers not inter-
viewed, 15 (10.3%) were not located, 3 (2.1%) refused and
12 (8.2%) had their children in foster placement.
Case conferences for final diagnoses
Final diagnoses were made only after case conferences
were held for each child. Results from dysmorphology ex-
aminations, developmental testing and maternal interviews
(each domain completed by independent investigators) were
presented at the structured case conference.
Data were entered and analyzed using the Epi Info soft-
ware of the U.S. Centers for Disease Control and Preven-
tion (Dean et al., 1994). Categorical variables comparing
cases with controls were analyzed by chi-square and Fisher’s
exact tests. Odds ratios (ORs) were calculated in 2 × 2
comparisons. Confidence intervals for ORs were computed
for 95% confidence levels by the Cornfield technique. For
continuous variables, t tests, one-way analysis of variance
and difference of proportions tests (Blalock, 1972) were
used. In Table 4, Pearson correlation coefficients are used
to compare selected variables, two of which were utilized as
dummy variables (3 and 5 or more drinks per occasion). With
certain variables, comparisons are made between subsets of
cases and controls, based on current drinking and smoking.
As shown in Table 1 (data column 1), of 863 children
examined, 50.8% were male. The overall mean (SD) age
VILJOEN ET AL. 597
was 6.5 years, or 77.6 months. The children averaged 113.7
cm (3 feet, 8 inches) in height, weighed 19.1 kg (42 lbs, 3
oz) on average and had an OFC of 50.6 cm. After the
dysmorphology examination, 28 children had a preliminary
diagnosis of FAS, and 64 were classified as deferred. These
92, along with the 146 control children, were the subjects
of further research (see Figure 1).
Sixty-four of the school children received a final diag-
nosis of FAS. Also at final diagnosis, five initially deferred
children were considered “still deferred” because of an in-
ability to locate them for testing. None of the control chil-
dren had FAS or indicators sufficient for deferral. In Table
1 (data columns 2 and 3), more FAS children and controls
were females (53.1% and 52.1%, respectively) than in the
entire school population (49.2%), but the difference was
not statistically significant. The average age was 6.5 years
for FAS children and 6.4 years for the controls. Height,
weight, OFC, PFL and almost every variable used in the
clinical examination were significantly different between
subjects and controls, including total dysmorphology scores
(14.0 vs 2.2, p < .001). Higher scores indicate more fea-
tures of FAS. The only variables not significantly different
in Table 1 are peripheral to the dysmorphology examina-
tion for FAS diagnosis: observations of gross hyperactiv-
ity, fine motor coordination, strabismus, long philtrum (by
observation, although actual measurements did differ), prog-
nathism, limited elbow supination, clinodactyly (usually of
the fifth finger) and hypertrichosis. More of the children
with FAS were in foster or adoptive placement (17.5% vs
10.7%), a nonsignificant difference.
Scores on neurodevelopmental tests (Table 2) are re-
ported for two FAS groups and the controls. One group
with FAS consists of children with consistent and severe
FAS and randomly selected controls: Western Cape Community, South Africa
Demographic and growth parameters for all sub-A (first grade) children, children with
(n = 863)
(n = 64)
(n = 146)Variable
Gender, % male
Age, in months, mean (SD)
Height, cm, mean (SD)
Weight, kg, mean (SD)
cm, mean (SD)
Palpebral fissure length, cm,
Philtrum length, mm,
Short intercanthal distance, %
Short interpupilary distance, %
Fine motor, %
Hypoplastic midface, %
“Railroad track” ears, %
Epicanthal folds, %
Flat nasal bridge, %
Anteverted nostrils, %
Long philtrum, %
Smooth philtrum, %
Narrow vermillion border, %
Heart murmur, %
Limited elbow supination, %
50.6 (1.67)48.2 (1.28)51.4 (1.63)c
.– 2.3 (0.13)2.6 (0.14)d
Palmar crease alteration, %
Foster care or adopted, %
Notes: NS = not significant; aχ2 test; bt test; cmeasurements at time of Tier I screen; therefore they are
directly comparable to all other groups; dpalpebral fissure length and philtrum length was 7 months
after exam of children with FAS; other variables are age-corrected by percentile; eOR = 1.76 (95%
confidence interval [CI]: 0.68-4.54); 95% CI calculated via Cornfield technique.
598JOURNAL OF STUDIES ON ALCOHOL / SEPTEMBER 2005
enough dysmorphology for a preliminary diagnosis of FAS
(prior to psychological screening or maternal interview).
The second FAS group consists of children who have quali-
fying dysmorphology but whose diagnosis of FAS was more
formally deferred until the case conference. Average IQ
scores were worse for children with FAS. Verbal ability
was significantly lower for both groups of children with
FAS as measured (in Afrikaans) by the TROG (p < .001).
The differences in nonverbal performance were not as great
and not statistically significant between the three groups,
although approaching significance (p = .057). The scores
of the controls and the deferred/then FAS group were quite
similar, yet the preliminary FAS group and controls dif-
fered significantly on nonverbal performance. Problem be-
haviors were highly divergent between both FAS groups
and controls. The importance of local population controls
is underscored by the data, as all children from this popula-
tion are performing below the norm of 100.
The overall dysmorphology scores, indicating severity
of physical deformity and lack of physical development,
form a spectrum in Table 2. Children with preliminary FAS
had the highest average score of 17.8; the children first
deferred had an average score of 12.3; and the controls had
an average score of 3.6. Therefore, behavioral indicators
and dysmorphology were concordant in pattern, especially
regarding verbal IQ, behavioral problems and total
dysmorphology. Finally in Table 2, reported maternal drink-
ing also supports the spectrum of damage associated with
both physical development and behavioral problems. The
mothers of children with preliminary FAS reported the most
drinking; the mothers of preliminarily deferred children were
intermediate; and the control mothers were lowest on all
three maternal drinking measures.
Maternal drinking and smoking
Maternal drinking variables (Table 3) indicate that
the mothers of all children with FAS were likely to be
drinking more at the time of the interview. Further-
more, almost 90% of all alcohol consumed at the time of
the interview by both groups was on weekend days. From
the reference drinking level (current 7-day drinking log),
92.3% of the case mothers reported drinking during preg-
nancy, and 88.7%-92.5% reported drinking about the same
amount throughout the trimesters. Among controls, 25.7%
drank prior to pregnancy, and 13%-20% drank in the first
through third trimesters. The beverage of choice reported
by the mothers of FAS children (not in Table 3) was beer
(58.5%), followed by wine (45.3%), and a few preferred
distilled spirits (5.7%). These percentages exceed 100
because several mothers reported more than one favorite
More mothers of FAS children used tobacco at the time
of the interview (67.9% vs 28.6%; OR = 5.29) and during
the index pregnancy (75.5% vs 26.8%; OR = 8.41). By
American and European standards, however, smokers con-
sumed low weekly quantities: 27.9-38.2 hand-rolled ciga-
rettes (1 g of tobacco each).
Fathers of children with FAS drank heavily. Ninety-six
percent of the case fathers currently drink, compared with
73% of the controls. Drinking fathers of the FAS children
consumed 84.6 drinks per month, compared with 47.5 for
drinking controls. Fathers of children with FAS were more
likely to be reported as having a drinking problem than
controls (OR = 28.33) and to be farm laborers (OR = 6.55).
In Table 4, zero-order correlations are presented on the
association between four drinking measures and specific
and randomly selected controls
Developmental and behavioral indicatorsa of children with FAS (by preliminary diagnosis after dysmorphology exam)
Final Dx FAS
Child developmental traits
Verbal IQ, mean (SD)b
Nonverbal IQ, mean (SD)e
Behavior, mean (SD)f
Total dysmorphology score,
During pregnancy, %
Current drinks/week, mean
No. drinks per
drinking day, mean (SD)g
(n = 28)
(n = 36)
(n = 123)
F = 15.9, 2/185 df, p < .001
F = 2.90, 2/187 df, NS (p = .057)
F = 21.0, 2/185 df, p < .001
(n = 18)
(n = 22)
(n = 28)
F = 119.3, 2/67 df, p < .001
χ2 = 61.3, p < .001
21.4 (13.96) 10.2 (9.06)3.8 (4.66)
F = 19.9, 2/67 df, p < .001
7.6 (5.82)4.8 (3.80) 3.0 (3.63)
F = 6.05, 2/67 df, p < .004
Notes: Dx = diagnosis; FAS = fetal alcohol syndrome; ANOVA = analysis of variance; IQ = intelligence quotient. aAll scores
standardized for age of child at time of testing; bTests of the Reception of Grammar (TROG); ct test significantly different from
both children with preliminary diagnosis of deferred and controls, significance < .002; dt test significantly different from controls,
significance < .02; eRavens Colored Progressive Matrices; fPersonal Behavior Checklist (PBCL-36); gof those who report drink-
ing during pregnancy in a full interview.
VILJOEN ET AL. 599
outcomes. Verbal and nonverbal ability are, as expected,
negatively correlated with the mother’s drinks per month,
drinks per day and reported episodes of three or five alco-
holic drinks per day. Verbal behavior is most highly corre-
lated with drinks per day on weekends (r = -.31) and heavy
episodic drinking (r = -.35 for three drinks per occasion
and -.29 for five drinks per occasion). The more the re-
ported maternal drinking per day was during pregnancy,
the lower the child’s IQ was, especially the verbal IQ. Prob-
lem behaviors were significantly correlated with heavy
drinking mothers (r = .38-.40). The highest correlations were
found between dysmorphology scores and drinks per day
on weekends and two other measures of episodic drinking
(r = .60-.61).
TABLE 3. Substance use by mothers and fathers of the children with FAS and randomly selected controls
(n = 53)
(n = 116)Variable
p, OR (95% CI)b
Current drinker, in last year, %69.821.1 <.001c, OR = 8.14
(n = 53)
(n = 35)
(n = 109)
(n = 19)
Current use of alcohol, drinks
last week, mean (SD)
Current consumption on weekends,
Fri., Sat., Sun., mean (SD)
Percentage on weekends
12.6 (13.1)15.2 (11.2) 1.0 (2.9) 5.4 (4.7)Whole sample < .001d
Drinkers only < .001d
Whole sample < .001d
Drinkers only < .001d
Whole sample NSe
Drinkers only NSe
<.001c, OR = 34.76
11.1 (11.1) 13.6 (8.9)0.9 (2.7)5.0 (4.2)
Drank before pregnancy with
index child, %f
Did not drink or stopped
Drank during index pregnancy, %
19.5<.001c, OR = 39.71
<.001c, OR = 50.67
<.001c, OR = 80.03
<.001c, OR = 51.18
<.001c, OR = 5.29
Drank during 1st trimester, %f
Did not drink or stopped
Drank during 2nd trimester, %f
Did not drink or stopped
Drank during 3rd trimester, %f
Did not drink or stopped
Current user of tobacco, %
(n = 52)
(n = 34)
(n = 99)
(n = 33)
Current users, quantity tobacco
used each week, g, mean (SD)
Used tobacco during index
Tobacco use during index
pregnancy, used same or more,
than current use, %
27.5 (32.0)38.2 (32.4)9.3 (17.1)27.9 (19.1) Whole sample < .000c
Smokers only NSc
<.001c, OR = 8.41
(n = 49)
(n = 47)
(n = 96)
(n = 70)
Drinks consumed by father
during index pregnancy 30
day, mean (SD)
Fathers with drinking problems
in past, %
Fathers currently have drinking
Usual occupation, % farm laborer
81.1 (81.7)84.6 (81.7) 34.6 (45.9)47.5 (47.8)Whole sample < .001d
Drinkers only < .002d
<.001c, OR = 28.33
.001c, OR = 6.55
Notes: FAS = fetal alcohol syndrome; OR = odds ratio; CI = confidence interval. aMortality and mobility reduced the number of
available mothers of FAS children by 10, see Method section text for details; b95% CIs calculated via the Cornfield technique;
cχ2 test; dt test; edifference of proportions test; fdrank “less,” the “same amount” or “more” than use at time of interview; gfour
women did not admit to drinking during the index pregnancy, but reexamination confirmed a diagnosis of FAS.
600 JOURNAL OF STUDIES ON ALCOHOL / SEPTEMBER 2005
Urban/rural distribution and prevalence of FAS
The mothers of FAS children were much more likely
than the controls to have resided in rural areas during ges-
tation of the index child (66.0% vs 20.9%; OR = 7.36;
Table 5). They also were more likely to be farm workers
than the controls. The urban/rural distribution of FAS cases
(Table 5) also was tested against the overall residence pat-
tern through indirect standardization (Barclay, 1958). Be-
cause 66.0% (n = 35) of the FAS cases underwent gestation
in the rural areas, this is a significant departure from ran-
dom distribution (p < .001, OR = 5.42), as only 26% of the
population lived in rural areas.
The prevalence of FAS among children screened was
74.2 per 1,000, or 69.4 if all 922 first graders in public
schools are used as the denominator (Table 5). One child
with FAS was white, as were three controls, making this
rate the predominantly Coloured/black rate. There were few
older children in first grade in this study cohort; therefore,
there was no need to correct for age. If the approximately
60 children in first grade from the all-white school that did
not participate are added to the denominator, and if it is
assumed that none have FAS, the most conservative, in-
school prevalence is 65.2 per 1,000. Because no out-of-
school children were identified with FAS, the range of FAS
prevalence for the community was 65.2-74.2 per 1,000.
Active case ascertainment of FAS through population-
based screening has rarely been reported except for Ameri-
can Indian and Alaska Native populations (May, 1996; May
et al., 2002). Furthermore, screening of all children in a
particular school or grade has been reported in only two
other published studies (Clarren et al., 2001; May et al.,
2000), and one of these was the previous study of this
particular South African population.
Active case ascertainment in schools with skilled
dysmorphologists, psychologists and maternal interviewers
can effectively and efficiently identify children with FAS
in the particular age range from 3 years to the early teens.
The interdisciplinary, multiple-domain, control-group design
described here produced what we believe is complete, accu-
rate and reliable knowledge of the prevalence and charac-
teristics of FAS. This study was rather unique because it
was population-based; consent to participate was very high;
the host community has a very high prevalence of FAS;
and there was relatively low mobility among cases of
Limitations exist, however. First, the diagnosis of FAS
is best made when children are between 3 and 12 years of
age, so maternal interviews carried out in this time frame
standardization and overall prevalence of FAS
Distribution of FAS cases by rural and urban calculated from interviews and by indirect
(n = 53)
(n = 116)
Residence during index
pregnancy, from interview (%)
Residence of FAS mothers (indirect
standardization by frequency)
1st grade children screened
1st grade children per all enrolled
in 12 schools
1st grade children per all enrolled
in all schools
66.0 (n = 35)
34.0 (n = 18)
20.9 (n = 28)
79.1 (n = 87)
<.001c, OR = 7.36
<.001c, OR = 5.42
74.2 per 1,000
69.4 per 1,000
65.2 per 1,000
Notes: FAS = fetal alcohol syndrome; OR = odds ratio; CI = confidence interval; NS = not significant.
aMortality and mobility reduced the number of available mothers of FAS children by 10, see Method
section text for details; b95% CIs calculated via the Cornfield technique; cχ2 test.
cal dysmorphology versus selected maternal drinking measures (n = 164)
Pearson correlation coefficients for developmentala and physi-
per day on
aAll scores standardized for age of child at time of testing; bTests of the
Reception of Grammar (TROG); cRavens Colored Progressive Matrices;
dPersonal Behavior Checklist (PBCL-36).
*p < .05; †p < .01; ‡p < .001.
VILJOEN ET AL.601
are challenged by recall. We used Timeline Followback
and 7-day drinking logs of current consumption to cali-
brate reporting, refresh memory and estimate alcohol con-
sumption during index pregnancies.
Second, a study such as this depends on the honesty of
mothers—a problem that has presented challenges else-
where. In South Africa, however, mothers interviewed are
highly forthcoming, and we have confidence in informa-
tion obtained from 90% of those interviewed.
Third, the fact that one private, all-white school did not
participate in this study leaves a gap in our knowledge of
the whole community, as 11 of the 13 schools in the com-
munity are predominantly Coloured. In the one public pre-
dominantly white school participating in the study, only
one white child was diagnosed with FAS. We suspect that
the rate of FAS among whites in South Africa is low, but a
larger sample of whites is desirable.
Fourth, generalizing from the conditions in this small
South African town may be difficult. How comparable is
the situation to that in other countries, populations and races?
We suspect that it is highly generalizable to other towns in
the WCP and to some other parts of South Africa (Viljoen
et al., 2003). Unique historical and sociocultural conditions
in South Africa may limit the broader generalizability of
some findings, however.
Child characteristics and their implications to a spectrum
Even though the focus of this study was exclusively on
full-blown FAS, a spectrum of severity emerged from the
process of screening and diagnosis. Forty-four percent were
correctly believed to have FAS at the time of the
dysmorphology examination, even before psychological test-
ing and maternal interviews. The remaining 56% had physi-
cal symptoms that were less severe (e.g., a lower total
dysmorphology score), and their preliminary diagnosis was
less definite at the dysmorphology examination. This pat-
tern of findings has occurred in our other field trials and
has led to an improved operational definition of physical
features of fetal alcohol spectrum disorder (Hoyme et al.,
2005). In the article, we have aggregated data for the chil-
dren by preliminary dysmorphology diagnosis when pre-
senting the findings on the developmental tests, which
illustrated that physical anomalies are associated signifi-
cantly with IQ and development. The more severe the
dysmorphology is, the poorer are the IQ (especially verbal)
and behavior. Furthermore, this spectrum is clearly associ-
ated with drinking severity.
Implications of the prevalence findings
Much drinking in this community is heavy episodic
drinking, with alcohol consumed primarily on weekends.
On weekends, the women and men on the farms frequently
have means to purchase alcohol and unencumbered time to
consume it heavily. Fridays are paydays. Thus, even though
the current drinking quantities reported by subjects are not
outrageously high in absolute quantity, when compared with
heavy drinking in the United States (May et al., 2004),
most attention should be paid to the episodic nature of the
drinking and the large differential between subjects and con-
trols. Subjects drink more than controls, drink rapidly and
drink heavily in an episodic fashion. Given their small body
size (see May et al., 2005), high blood alcohol concentra-
tions are produced (Khaole et al., 2004). Furthermore, it is
clearly shown here that mothers of children with FAS do
not quit or cut down during pregnancy. Drinkers in this
study are more prone to episodic drinking during pregnancy
than U.S. women (Tsai and Floyd, 2004). Case mothers
drank sufficiently to produce cases of FAS as severe as
any we have experienced anywhere in the United States. In
two recent articles (May et al., 2004, 2005), we have pre-
sented evidence of specific cofactors that combine with epi-
sodic drinking in this WCP town to produce FAS. Low
SES and the despair of poverty and powerlessness are cer-
tainly overarching factors. As presented in our other ar-
ticles, specific and quantifiable measures of poverty and
despair are (1) poor current and lifelong nutrition and (2)
multiple generations of fetal alcohol exposure. Episodic
drinking was documented, along with poor nutrition, small
maternal body size (providing less mass to which the alco-
hol can be distributed) and the social and economic despair
endured by some South African Coloured women (see also
May et al., 2000; Viljoen et al., 2002). These findings com-
bine to produce very high rates of FAS in this community.
Most of the children were born in 1993, one year before
the end of apartheid.
Because of past apartheid policy (enforced segregation
by ethnicity), darker-skinned peoples are overrepresented
in lower SES, as is clearly reflected by the concentration of
cases in the poorer, rural areas. All but one of the children
with FAS was Coloured, and those with the lowest SES
indicators were overrepresented. High rates also exist in
other low-SES, urban areas of South Africa (Viljoen et al.,
2003), but rates published to date for those areas are no
higher than 20 per 1,000. The legacy of Dop is influential
in the drinking pattern and in a very high rate of FAS. The
fact that FAS was more common in the rural areas may
reflect higher SES among urban dwellers, or urban areas
may simply provide escape from extreme poverty and a
heavy drinking social milieu/culture. Other recreational
activities are available in town that do not involve alco-
hol to the same degree. Clearly, residing on some of the
fruit and wine-producing farms is a grave risk factor, as
severe episodic drinking is perpetuated by norms within
a context of despair. Prevention is most needed in rural
602 JOURNAL OF STUDIES ON ALCOHOL / SEPTEMBER 2005
Why is the rate of FAS increasing?
The rate of FAS in this second study in this community
is another record rate for any functional community (65-74
per 1,000) to date. It is 60% higher than reported in our
previous South African study (40.5-46.4 per 1,000) of an-
other cohort born 2-3 years earlier (May et al., 2000). There-
fore, the increase in an already alarming rate is cause for
concern. Much of this increase in rate is likely real, be-
cause similar, although slightly refined, methods of diag-
nosis were used. There was also minimal change in the
population composition through migration, social and eco-
nomic improvement or other forces. It is possible that there
was among our physicians some increased sensitivity to
and familiarity with the recognition of subtle clinical fea-
tures of FAS in this population and to the fact that FAS is
very prevalent locally. But the psychological/developmen-
tal and maternal data provide verification that FAS diag-
noses are accurate.
Some of the increase in the FAS rate might be attributed
to liberating social changes and an increase in the supply
of commercially available alcohol. Both cohorts of chil-
dren studied thus far underwent gestation during the weak-
ening of the apartheid era, which officially ended in 1994.
Therefore, change in individual freedoms has affected the
Coloured and Black population, and social liberation seems
to have resulted in increased quantity of drinking in indi-
viduals or small subsegments of the population. To exam-
ine this hypothesis, we reviewed average drinks per drinking
day reported by the control groups in the 1997 study and in
this later study (1999-2000). The average number of drinks
per drinking day was indeed higher among the controls in
this study, as it went from 2.2 per day in 1997 to 3.0. On
the other hand, some other variables of drinking quantity
and frequency among controls in Studies I and II have pro-
vided mixed changes. Nevertheless, the daily consumption
data and our observations lead us to believe that much of
this increase in FAS is real.
Comparison of these findings with those of other studies
The results of previous studies have provided insight
into the epidemiology of FAS, paralleling our findings here.
Population-based, clinic and laboratory studies all indicate
that major risk factors for FAS are associated with the
mother’s individual characteristics, her environment and her
social milieu. Specific traits—such as advancing maternal
age; high gravidity and parity; and the quantity, frequency
and timing of drinking during gestation—are all important
explanations for the prevalence of FAS (May, 1995;
Streissguth et al., 1985). All of these risk factors exist in
some South African women with a rapid and severe drink-
ing pattern that produces a very high blood alcohol con-
centration (Khaole et al., 2004), and drinking persists
throughout pregnancy in mothers of FAS children. Further-
more, SES is a major risk factor in both the United States
and South Africa (Abel, 1998, 1995; Abel and Hannigan,
1995; Bingol et al., 1987; Viljoen et al., 2003). These vari-
ables, however, have rarely been studied simultaneously in
nonclinic populations. Rather, passive case ascertainment
methods are commonly used with existing data sources that
are frequently incomplete and selective (Chavez et al., 1988;
Little et al., 1990; Pierog et al., 1979). The proactive meth-
odology used in South Africa has yielded rich epidemio-
logical data useful for prevention. Furthermore, as of the
completion of this second wave of research in this commu-
nity, these studies have identified 110 “gold standard” cases
for further research and for clinical services.
Unlike one previous study of a very high rate in an
Indian community in Canada (Robinson et al., 1987), this
South African community is economically and socially
stable. As an established community with a viable economy
undergoing moderate rates of modernization, such a high rate
of FAS is an extreme public health concern. Furthermore, a
large number of mothers in this community give birth to chil-
dren with FAS (approximately 69 per 1,000 of childbearing
age), rather than the relatively small number of U.S. women
(0.3-3.3) who bear one or more children with FAS (Abel
and Sokol, 1987; May and Gossage, 2001; Streissguth et
al., 1985). The reasons for such a high rate are found in the
socioeconomic milieu, individual drinking patterns, subcul-
tural drinking norms and other cofactors of risk.
In a departure from the U.S. literature, there was no
significant difference in cases versus controls in the per-
centage of children in foster or adoptive placement. In the
United States, a much higher percentage of children with
FAS are not raised by biological parents (May et al., 1983;
Streissguth et al., 1985).
Comprehensive, community-wide prevention programs
are needed in this area and in other towns and rural areas
of WCP. With a small amount of money available in South
Africa for public health, however, and with other pressing
needs (e.g., tuberculosis and HIV/AIDS), it is unlikely that
well-funded, comprehensive prevention initiatives will be
undertaken utilizing South African resources alone. Models
of comprehensive prevention exist in the literature (Stratton
et al., 1996; May, 1995), which can be applied to this problem.
Thus, it is imperative that the high rate of FAS gain the
attention of international groups and other resource-bearing
constituents. The implications of this study and its findings
may be important for other parts of the developing world.
This article adds to the knowledge about FAS in a very
high-risk population, in many ways confirming facts already
VILJOEN ET AL.603
understood in any human population. For example, severe
episodic drinking is the pattern of drinking that leads to
FAS in low-SES populations, and maybe in any popula-
tion. This study provided a unique opportunity to employ,
test and refine epidemiology research methods applicable
to almost any population. Furthermore, psychological test-
ing, interview and diagnostic methodologies are relevant to
studies of other populations and cultures. In many ways,
the South African studies have opened a new era in the
study of FAS. Similar studies are currently under way in
other parts of South Africa, in Washington, D.C., and in
We extend our deepest thanks to Mayor Herman Bailey, the (Western
Cape Community) Town Council, Cecil Driver and the other principals of
the twelve primary schools where research was performed. Jon M. Aase,
M.D., helped design the first clinical screening and training protocols
used, and Phyllis Trujillo supported this project with manuscript prepara-
tion, administrative help and logistical energy. Carolyn Tullet, Loretta
Hendricks, Julie Croxford, Andrea Hay, Ansie Kitching, Chris Shaw, Chan
Makan, Ph.D., Sandra Hawk, and other colleagues participated with dedi-
cation and energy in the data collection and local research process.
Protocols and consent forms were approved by the University of New
Mexico (UNM) Medical School (HRRC 96-209), the UNM College of
Arts and Sciences (01-93-86-9908), the Research Ethics Committee of the
University of Cape Town, the Office for Human Research Protection of
the National Institutes of Health and a single-site assurance committee in
the local town. Active consent for children to participate in this study was
obtained from parents or other legal guardians. Mothers interviewed also
consented to participate.
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