Comorbidity of fetal alcohol spectrum disorder: A systematic review and meta-analysis

Abstract

Background:
Fetal alcohol spectrum disorder (FASD) is related to many comorbidities because of the permanent effects of prenatal alcohol exposure on the fetus. We aimed to identify the comorbid conditions that co-occur in individuals with FASD and estimate the pooled prevalence of comorbid conditions occurring in individuals with fetal alcohol syndrome (FAS).

Methods:
We did a systematic literature search of studies reporting on the comorbidity and cause of death in individuals with FASD using multiple electronic bibliographic databases, searching for studies published up to July, 2012. We included original research published in a peer-reviewed journal in the English language. We used the following criteria for determining study quality: use of an established FASD diagnostic guideline, study setting, method of data collection, and sample size. All comorbid disease conditions were coded according to the International Classification of Diseases, tenth revision (ICD-10). To estimate the pooled prevalence of comorbid conditions found to co-occur in individuals with FAS, we did meta-analyses assuming a random-effects model.

Findings:
Of 5068 studies found, 127 met eligibility criteria for data extraction. From those studies, we identified 428 comorbid conditions co-occurring in individuals with FASD, spanning across 18 of 22 chapters of the ICD-10. The most prevalent disease conditions were within the sections of congenital malformations, deformities, and chromosomal abnormalities, and mental and behavioural disorders. 33 studies reported data for frequency in a total of 1728 participants with FAS. The five comorbid conditions with the highest pooled prevalence (between 50% and 91%) included abnormal results of function studies of peripheral nervous system and special senses, conduct disorder, receptive language disorder, chronic serous otitis media, and expressive language disorder.

Interpretation:
The high prevalence of comorbid conditions in individuals with FASD highlights the importance of assessing prenatal alcohol exposure as a substantial clinical risk factor for comorbidity. The harmful effects of alcohol on a developing fetus represent many cases of preventable disability, and thus, alcohol use during pregnancy should be recognised as a public health problem globally.

Funding:
Public Health Agency of Canada.

Full text

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Published in The Lancet.
Comorbidity of fetal alcohol spectrum disorder: a systematic
review and meta-analysis
Svetlana Popova, Shannon Lange, Kevin Shield, Alanna Mihic, Albert E Chudley, Raja A S Mukherjee,
Dennis Bekmuradov, Jürgen Rehm
Social and Epidemiological Research Department, Centre for Addiction and Mental Health, Toronto, ON, Canada (S Popova
PhD, S Lange MPH, K Shield PhD, Prof J Rehm PhD); Dalla Lana School of Public Health (S Popova, A Mihic MSc, Prof J Rehm),
Factor-Inwentash Faculty of Social Work (S Popova), Institute of Medical Science (S Popova, S Lange, K Shield, Prof J Rehm),
University of Toronto, Toronto, ON, Canada; Program in Genetics and Metabolism, Children’s Hospital, Departments of
Pediatrics and Child Health and Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada (Prof A E
Chudley MD); FASD Specialist Behaviour Clinic, Surrey and Border’s Partnership NHS Foundation Trust, Oxted, UK (R A S
Mukherjee PhD); School of Occupational and Public Health, Ryerson University, Toronto, ON, Canada (D Bekmuradov BASc);
and Epidemiological Research Unit, Klinische Psychologie and Psychotherapie, Technische Universität Dresden, Dresden,
Germany (Prof J Rehm)
Correspondence to: Dr Svetlana Popova, Centre for Addiction and Mental Health, 33 Russell Street Toronto, ON M5S 2S1, Canada
lana.popova@camh.ca
Published Online January 5, 2016 http://dx.doi.org/10.1016/ S0140-6736(15)01345-8
See Online/Comment http://dx.doi.org/10.1016/ S0140-6736(15)01346-X
Summary
Background
Fetal alcohol spectrum disorder (FASD) is related to many comorbidities because of the permanent
effects of prenatal alcohol exposure on the fetus. We aimed to identify the comorbid conditions that co-
occur in individuals with FASD and estimate the pooled prevalence of comorbid conditions occurring
in individuals with fetal alcohol syndrome (FAS).
Methods
We did a systematic literature search of studies reporting on the comorbidity and cause of death in
individuals with FASD using multiple electronic bibliographic databases, searching for studies
published up to July, 2012. We included original research published in a peer-reviewed journal in the
English language. We used the following criteria for determining study quality: use of an established
FASD diagnostic guideline, study setting, method of data collection, and sample size. All comorbid
disease conditions were coded according to the International Classification of Diseases, tenth revision
(ICD-10). To estimate the pooled prevalence of comorbid conditions found to co-occur in individuals
with FAS, we did meta-analyses assuming a random-effects model.
Findings
Of 5068 studies found, 127 met eligibility criteria for data extraction. From those studies, we identified
428 comorbid conditions co-occurring in individuals with FASD, spanning across 18 of 22 chapters of
the ICD-10. The most prevalent disease conditions were within the sections of congenital
malformations, deformities, and chromosomal abnormalities, and mental and behavioural disorders. 33
studies reported data for frequency in a total of 1728 participants with FAS. The five comorbid
conditions with the highest pooled prevalence (between 50% and 91%) included abnormal results of
function studies of peripheral nervous system and special senses, conduct disorder, receptive language
disorder, chronic serous otitis media, and expressive language disorder.
Interpretation
The high prevalence of comorbid conditions in individuals with FASD highlights the importance of

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assessing prenatal alcohol exposure as a substantial clinical risk factor for comorbidity. The harmful
effects of alcohol on a developing fetus represent many cases of preventable disability, and thus,
alcohol use during pregnancy should be recognised as a public health problem globally.
Funding
Public Health Agency of Canada.
Introduction
Findings from the most recent Global Burden of Disease and Injury study
1
showed that alcohol was the
fifth leading contributor to disability and mortality—3!9% of global disability-adjusted life-years and
5!2% of all global deaths were attributable to alcohol in 2010. However, alcohol consumption often
results in harm not only to the drinker, but also to others around the drinker. A classic example of such
harm is the harm caused to the developing fetus by the consumption of alcohol during pregnancy.
Alcohol consumed by a pregnant woman interferes with normal developmental progression of
the fetus resulting in CNS and physical damage that subsequently has several lifelong health
consequences. This damage leads to fetal alcohol spectrum disorder (FASD; an umbrella term used to
describe individuals who experience disability as a result of prenatal alcohol exposure). FASD includes
fetal alcohol syndrome (FAS), partial FAS, and alcohol-related neurodevelopmental disorder.
2
Since the first description of FAS by Jones and Smith in 1973,
3
the terminology used, as well as the
diagnostic guidelines and recommendations have changed numerous times. Although the criteria for
FASD diagnoses have been described thoroughly in the guidelines put forth to date,
2,4–11
the diagnosis
of FASD remains challenging, and the specific assessment techniques used to make the definitive
diagnosis are still debated, especially for alcohol-related neurodevelopmental disorder.
FASD affects individuals from all socioeconomic and ethnic backgrounds, and in addition to
the individuals themselves, it can also greatly affect their families. In many cases, people with FASD
require lifelong assistance from a wide range of services including health, community, remedial
education, and many others. Hence, it is recognised that FASD has a substantial economic effect on
any society. In North America, the lifetime cost for some cases of FASD has been estimated to be more
than CAN$1 million.
12
In spite of a substantial and growing body of scientific literature on prenatal alcohol exposure
and FASD, epidemiological data for the prevalence of FASD from most countries, especially from low-
income and middle-income countries, is largely absent.
13
In the USA, the prevalence of FAS in typical,
mixed-racial, and mixed-socioeconomic populations was estimated to be at least two-to-seven cases per
1000 people and the prevalence of FASD in populations of younger school children might be as high as
20–50 cases per 1000 children.
14
There are no national statistics on the prevalence of FASD in Canada;
however, the crude prevalence in the general population has been roughly estimated to be about one-to-
two cases per 1000 people for FAS
15
and about nine-to-ten cases per 1000 people for FASD.
16
It is
postulated that the prevalence of FASD is at least ten times higher than the prevalence of FAS,
14,15,17,18
with alcohol-related neurodevelopmental disorder being the largest category of affected individuals; it
has been estimated that there are three-to-four cases of alcohol-related neurodevelopmental disorder for
every one case of FAS.
19
In Europe, two independent studies have found that the prevalence of FASD is 23–47 cases per
1000 people in first grade students in Italy
20
and 40 cases per 1000 people in elementary school
children in Croatia.
21
In some subpopulations, the prevalence of FASD is reported to be much higher
than in the general population. For example, although outdated, the prevalence of FASD in northern
communities of Canada
22
has been estimated to be about 20 times higher than the prevalence in the
general population. Further, the prevalence of FASD in the Western Cape Province of South Africa, a
region known for wine production and a high prevalence of binge drinking in women, has been
reported to be 135–208 cases per 1000 people among first grade students.
23

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Additionally, in special populations such as children residing in child-care settings (eg,
orphanages, foster care, and child welfare systems), the prevalence of FASD was estimated to be very
high.
24
For example, the prevalence of FAS in an orphanage for children with special needs in Russia
was reported to range from 427 to 680 cases per 1000 people.
25
The relatively high prevalence of FASD, especially in some susceptible populations
12,22,24
behoves physicians and other health-care professionals to recognise this spectrum of disorders and the
various clinical presentations that can be seen in individuals with FASD.
26
The deficits expressed by individuals with FASD vary broadly in severity and type. Even
though it is well documented that FASD is associated with a high number of comorbidities (defined
herein as any coexisting conditions, regardless of causality), the existing comorbid conditions and their
prevalence in individuals with FASD remain to be established. Therefore, using the existing
epidemiological and medical literature, the current study aimed to: identify the comorbid conditions
that co-occur in individuals with FASD, and estimate the pooled prevalence of comorbid conditions
found to co-occur in individuals with FAS.
The objective to estimate the prevalence was limited to FAS given that FAS is the only
expression of FASD in the WHO’s International Classification of Diseases (ICD): in the ICD, ninth
revision (ICD-9), Alcohol affecting fetus or newborn via placenta or breast milk 760!71, and in the
ICD, tenth revision (ICD-10), Fetal alcohol syndrome (dysmorphic) Q86.0.
27,28
Methods
Search strategy and selection criteria
The systematic literature review and meta-analyses were done and reported according to the standards
set out in Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).
29
We did a systematic literature search to locate original published studies that reported on the
comorbidities and primary cause of death in individuals with diagnosed FASD. This search was done in
the following electronic bibliographic databases: Ovid MEDLINE, PubMed, Embase, Web of Science
(including Science Citation Index, Social Sciences Citation Index, Arts and Humanities Citation
Index), PsycINFO, ERIC, Epscohost, CINAHL, Scopus, Campbell Collaboration, Cambridge
Scientific Abstracts Sociological Abstracts, Social Work Abstracts, Canadian Centre on Substance
Abuse Library Collection Database, and Centre for Addiction and Mental Health Library Database.
We used the following keywords: (fetal alcohol spectrum disorder* OR fetal alcohol syndrome
OR partial fetal alcohol syndrome OR fetal alcohol effects OR alcohol-related neurodevelopmental
disorder OR alcohol-related birth defects OR prenatal alcohol exposure) AND (death OR disabilit* OR
disease* OR disorder* OR co-morbidit* OR morbidit* OR cause of death OR mortality).
Additionally to the electronic search, we manually reviewed the content pages of the major
epidemiological and medical journals and the citations in the relevant articles (including all relevant
review articles identified via the electronic search). The search was not limited geographically, and was
done up to July, 2012, inclusively (with no restriction placed on the lower year limit).
Articles were retained if they met the following inclusion criteria: consisted of original research
published in a peer-reviewed journal; were published in the English language; and reported disease
conditions in individuals with diagnosed FASD or any of the diagnostic entities that fall within the
FASD spectrum (ie, FAS, partial FAS, alcohol-related neurodevelopmental disorder, and alcohol-
related birth defects). Articles were excluded if they were: review articles or discussion papers,
conference abstracts, or studies done on animals.
Data extraction and quality assessment
Three members of the study team independently extracted data. A fourth investigator checked table
entries for accuracy against the original articles. A fifth investigator, independent of the first process,

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reconciled all discrepancies. The following variables were abstracted from each study: reference,
country, sample size, age, and sex of participants, comorbid condition (as stated in the original paper),
ICD-10 code (if available), and frequency of the comorbid condition (if available). When an article
used a plain language description of the comorbid condition without stating a diagnostic code, we
coded the comorbid condition using the ICD-10.
We used the following criteria for determining study quality: use of an established FASD
diagnostic guideline, study setting, method of data collection, and sample size. We did not use the
overall quality of the study as an exclusion criterion; rather we used the quality rating (based on the
study characteristics) to investigate potential sources of heterogeneity between studies, if present.
Meta-analyses of the pooled prevalence of comorbid conditions
Additionally to the described above inclusion and exclusion criteria, to estimate a pooled prevalence of
the comorbid conditions found to co-occur, we included articles that reported the frequency of at least
one disease condition in a cohort of individuals with FAS in the meta-analyses. We did these meta-
analyses assuming that the data came from a hierarchy of different populations (ie, using a random-
effects model).
30
In instances in which only one study was found for a specific disease condition, the
estimate was accompanied by an exact 95% CI. To satisfy the assumption of normality when
statistically combining estimates by means of meta-analyses, we transformed prevalence estimates
using a double arcsine transformation so that the data followed a normal distribution.
31
We assessed
heterogeneity between prevalence estimates using the Cochrane Q-test and the I
2
statistic.
32,33
We
assessed the presence of publication bias (the possibility that studies that measured the prevalence of
specific comorbidities were not published because their results differed greatly from previous
estimations) using a ranked correlation test,
34
and by using a weighted regression test.
35
However, we
deemed publication bias to be unlikely because an observed prevalence of FAS comorbidities that was
substantially different than the previously estimated prevalence would probably have been published;
therefore, we did not do an adjustment for publication bias.
We compared a subset of pooled prevalence estimates of comorbidities found to co-occur in
individuals with FAS with the prevalence of the same disease conditions in the general population of
the USA, obtained from the available literature.
All analyses were done using STATA version 11.0 and R version 3.0.1.
Role of the funding source
The funder had no role in the design of the study, data gathering, analysis, interpretation, or writing up
the report. The corresponding author had full access to all the data and had final responsibility for the
decision to submit for publication.
Results
Of 5068 studies initially found, 127 studies met inclusion criteria, and were selected for data extraction
(the appendix contains the list of references). Figure 1 shows an overview of the results of the search
strategy used. Only two articles reported on cause of death data (ie, mortality data) in individuals with
FASD.
36,37
On the basis of the data reported in 127 studies, we identified 428 comorbid conditions that co-
occur in individuals with FASD (appendix pp 1–13), including both medical conditions and
dysmorphic features that discriminate individuals with FAS from those without. These comorbid
conditions co-occurring in individuals with FASD spanned across 18 of the 22 chapters of the ICD-10.
The most prevalent disease conditions were within the sections of congenital malformations,
deformities, and chromosomal abnormalities (Q00-Q99; chapter XVII), and mental and behavioural
disorders (F00-F99; chapter V).

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33 (26%) of the 127 studies reported data on the frequency of at least one disease condition in
individuals with FAS, and thus were eligible to be included in the meta-analyses.
20,22,38–68
Studies (ie,
study populations) were from the following countries: Canada (six studies
22,38,51,52,61,68
), Germany (four
studies
49,53,58,65
), Ireland (one study
43
), Italy (one study
20
), Norway (one study
60
), Portugal (one
study
64
), Scotland (one study
59
) South Africa (three studies
50,57,66
) Sweden (three studies
48,54,55
), and
USA (12 studies
39–42,44–47,56,62,63,67
).
The studies used different classifications or terms of FASD, which is reflective of the
modifications made to the classifications or terms over the years and the different terminology used
around the world. The following combinations of FASD diagnoses were observed in the examined
studies: FAS, partial FAS, and alcohol-related neurodevelopmental disorder; FAS and partial FAS;
partial FAS, alcohol-related neurodevelopmental disorder, and fetal alcohol effects; FAS and fetal
alcohol effects; FAS and prenatal alcohol exposure; and alcohol embryopathy.
The studies included in the meta-analyses used the following diagnostic guidelines: Hoyme
clarification of the Institute of Medicine (IOM) diagnostic criteria
8
(five studies
20,46,48,50,57
); the
diagnostic guidelines by Sokol and Clarren
9
(four studies
53,54,56,64
); the criteria put forth by the Fetal
Alcohol Study Group of the Research Society on Alcoholism
11
(two studies
22,40
); the guidelines by
Majewski
69,70
(two studies
58,65
); the IOM diagnostic criteria
10
(one study
66
); the Centre for Disease
Control FAS diagnostic guidelines
5
(one study
60
); the FASD Diagnostic Checklist
71
(one study
39
); the
Canadian Guidelines
2
(one study
38
); the guidelines by Clarren and Smith
7
(one study
43
); and the
guidelines by Sokol and Clarren
9
in combination with the criteria put forth by the Fetal Alcohol Study
Group of the Research Society on Alcoholism
11
(one study
61
). Lastly, 14
studies
41,42,44,45,47,49,51,52,55,59,62,63,67,68
claimed that they used diagnostic criteria for diagnosing FAS, but
the references were not stated. The appendix (pp 14–16) shows the study characteristics and quality
ratings of the studies included in the meta-analyses.
These 33 studies, selected for the meta-analyses, included 1728 participants with FAS and
reported frequencies for 183 comorbid conditions coded in ICD-10. Thus, to estimate a pooled
prevalence for each comorbid condition found to co-occur in individuals with FAS, we undertook 183
meta-analyses. The frequencies of comorbid conditions derived from the same sample and published in
iteration
47,51,52,63,68
were counted only once.
Figures 2–5 show the pooled prevalences of each comorbid condition (for which frequency data
exist) by ICD-10 chapters.
Table 1 presents 18 comorbid conditions (excluding conditions that are part of the diagnostic
criteria used for identifying FAS—ie, dysmorphic features) with a pooled prevalence higher than 50%
in individuals with FAS. The five comorbid conditions with the highest pooled prevalence include:
abnormal results of function studies of peripheral nervous system and special senses, conduct disorder,
receptive language disorder, chronic serous otitis media, and expressive language disorder.
The appendix (pp 17–19) presents the pooled prevalence and 95% CI of comorbid conditions in
individuals with FAS and the tests of heterogeneity. Heterogeneity (I
2
>75%; statistically significant Q
statistics [ie, p"0!1]) was present for the pooled analyses of 38 (21%) of 183 comorbid conditions that
co-occur in individuals with FAS, which is probably due to study differences with respect to patient
characteristics, definitions of comorbid condition used, study design, methodology, and sample size.
12 studies (36%) were done in the US population. Therefore, we compared the pooled
prevalence of the comorbid conditions estimated to have prevalence higher than 50% in individuals
with FAS with the prevalence of the same conditions in the general population of the USA, wherever
data for the general population were available (table 2).
The pooled prevalence of the comorbid conditions found to co-occur in individuals with FAS
was notably higher than in the general population (table 2).
72–79
For example, the pooled prevalence of
sensorineural hearing loss, unspecified (H90.5) and conductive hearing loss, unspecified (H90.2) was

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estimated to be up to 129 times higher in individuals with FAS than the prevalence of moderate to
severe hearing loss in the general population of the USA.
74
The pooled prevalence of unspecified
disorder of psychological development (F89) was estimated to be 97 times higher in individuals with
FAS than the prevalence of intellectual disabilities in the general population of the USA.
74
Further,
individuals with FAS have a prevalence of visual impairment including blindness (binocular or
monocular; H54) that is 31 times higher than the prevalence of low vision and 71 times higher than the
prevalence of blindness in the general US population.
72
Discussion
FASD, as indicated by the sheer number of conditions found to co-occur in this population, is a
multifaceted spectrum of disorders, affecting multiple organs and systems. Human and animal data
show that prenatal alcohol exposure is highly teratogenic and can alter growth and normal development
in most organs and tissues in the embryo and fetus through various well described mechanisms.
80
However, it must be acknowledged that the mere occurrence of FASD with any one of these disease
conditions does not necessarily represent causality.
81
Specifically, since FASD is common, other
common disorders will co-occur simply because of its high prevalence. However, the findings of this
study clearly demonstrate that individuals with FASD experience some comorbid disorders at rates
notably higher (in some cases more than a hundred times higher) than the prevalence in the general
population of the USA.
Not surprisingly, FASD is associated with staggering costs, especially to the health-care system
as reported from several different countries; for example, Canada,
82–84
South Africa,
85
and the USA.
86
Yet, the costs are underestimated given that FASD is largely underdiagnosed worldwide because of
limited capacity and expertise, and the need for a multidisciplinary team-based approach in diagnostic
evaluation.
2
For example, a Canadian survey of all FASD multidisciplinary diagnostic clinics revealed
that a 17-fold increase in diagnostic capacity is needed across Canada to diagnose the number of FASD
cases that currently exist (based on a prevalence of 1%).
87
Understandably, the number of comorbid disorders found to co-occur in individuals with FASD
can also account for the lower than expected prevalence estimates of FASD (ie, underdiagnosis),
probably because of the shadowing that might occur by the other disease conditions. It is likely that
clinicians report the condition or illness that has brought the individual in to seek medical attention,
rather than necessarily taking into consideration the potential associations and underlying causes of the
condition or illness (in this case, prenatal alcohol exposure).
Thus, it is hoped that the unveiling of the wide range of comorbid conditions that co-occur in
individuals with FASD will promote the routine investigation into whether or not prenatal alcohol
exposure occurred in a patient with any number of the identified comorbid conditions, thereby
improving screening and diagnosis. Improving screening and diagnosis would promote access to
interventions and resources that might subsequently reduce the occurrence of numerous “secondary
disabilities”, such as mental health problems, substance misuse, inappropriate sexual behaviour,
disrupted school experience, trouble with the law, and unemployment, just to list a few.
88
The harmful effects of alcohol on a fetus, representing many cases of preventable disability,
should be recognised globally as a large public health problem. The results of the present study clearly
demonstrate the need for such recognition. The number of comorbidities identified to co-occur in
individuals with FASD will not only raise awareness of FASD in general, but also will raise awareness
of the severe consequences of prenatal alcohol exposure and, hopefully, will prevent subsequent
alcohol-exposed pregnancies. This list of comorbidities will add to the armamentarium used by
clinicians, especially those clinicians working with individuals who are at greater risk to be prenatally
exposed to alcohol.
To our knowledge, this study is the first study to present a comprehensive list of the comorbid

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conditions (coded using the ICD-10) that co-occur in individuals with FASD and the pooled prevalence
of comorbid conditions in individuals with FAS. However, there are several limitations that must be
acknowledged. First, some studies had small samples from a clinical population or included individuals
from only one ethnic population, and are thus, limited in their generalisability. Second, all efforts were
made to include data from individuals with a diagnosed FASD only and exclude individuals with
prenatal alcohol exposure, without a specific diagnosis of an alcohol-related disorder; however, in
some cases it was not possible to separate the data. Third, the studies used different diagnostic systems,
which can affect the categorisation of the diagnostic entities of FASD.
It is imperative that prevention efforts be put in place to reduce the occurrence of alcohol
consumption during pregnancy. The prevalence findings of the current study highlight that there is an
urgent need to establish universal screening for prenatal alcohol exposure, using a standard screening
protocol, for all newborn babies, especially among at-risk populations. Such screening could: (1) lead
to close monitoring of a child’s development, which could in turn, facilitate early diagnosis, and the
implementation of timely interventions, if necessary; (2) prevent the occurrence of secondary
disabilities later in life, such as poor academic performance, mental health problems, alcohol and drug
use; and (3) provide an important opportunity to prevent the occurrence and/or recurrence of prenatal
and postnatal alcohol exposure within families and across generations.
Contributors
SP led the conception and design of the study, the development of the data collection instrument, data
collection, quality assessment, data analysis, and data interpretation, and wrote and revised the
manuscript; SL contributed to study design, the development of the data collection instrument,
performed data collection, quality assessment and extraction, assisted in data interpretation, and wrote
and revised the manuscript; KS performed the statistical analysis, assisted in data interpretation, and
contributed to revising the manuscript; AM and DB performed data collection, and reviewed and
revised the manuscript; AEC, RASM, and JR contributed to data interpretation and reviewed and
revised the manuscript.
Declaration of interests
We declare no competing interests.
Acknowledgments
This work was supported by the Public Health Agency of Canada. The authors of the current study
would like to thank Dr Jane Evans, University of Manitoba, for her helpful feedback on the first draft
of the manuscript.
References
1 Lim SS, Vos T, Flaxman AD, et al. A comparative risk assessment of burden of disease and injury
attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis
for the Global Burden of Disease Study 2010. Lancet 2012; 380: 2224–60. (Errata published in
Lancet 2013; 381: 1276; Lancet 2013; 381: 628).
2 Chudley AE, Conry J, Cook JL, Loock C, Rosales T, LeBlanc N, and the Public Health Agency of
Canada’s National Advisory Committee on Fetal Alcohol Spectrum Disorder. Fetal alcohol
spectrum disorder: Canadian guidelines for diagnosis. CMAJ 2005; 172 (suppl): S1–21.
3 Jones KL, Smith DW. Recognition of the fetal alcohol syndrome in early infancy. Lancet 1973; 302:
999–1001.
4 Astley SJ. Fetal alcohol syndrome prevention in Washington State: evidence of success. Paediatr

!
8!
Perinat Epidemiol 2004; 18: 344–51.
5 Bertrand J, Floyd RL, Weber MK, et al. National Task Force on FAS/FAE. Fetal Alcohol
Syndrome: Guidelines for Referral and Diagnosis. Atlanta, GA: Centers for Disease Control and
Prevention, 2004.
6 Burd L, Martsolf JT. Fetal alcohol syndrome: diagnosis and syndromal variability. Physiol Behav
1989; 46: 39–43.
7 Clarren SK, Smith DW. The fetal alcohol syndrome. N Engl J Med 1978; 298: 1063–67.
8 Hoyme HE, May PA, Kalberg WO, et al. A practical clinical approach to diagnosis of fetal alcohol
spectrum disorders: clarification of the 1996 institute of medicine criteria. Pediatrics 2005; 115: 39–
47.
9 Sokol RJ, Clarren SK. Guidelines for use of terminology describing the impact of prenatal alcohol
on the offspring. Alcohol Clin Exp Res 1989; 13: 597–98.
10 Stratton K, Howe C, Battaglia F. Fetal Alcohol Syndrome: diagnosis, epidemiology, prevention, and
treatment. Washington, DC: National Academy Press, 1996.
11 Rosett HL. A clinical perspective of the fetal alcohol syndrome. Alcohol Clin Exp Res 1980; 4: 119–
22.
12 Popova S, Stade B, Bekmuradov D, Lange S, Rehm J. What do we know about the economic impact
of fetal alcohol spectrum disorder? A systematic literature review. Alcohol Alcohol 2011; 46: 490–
97.
13 Popova S, Patra J, Rehm J. Prevalence of Fetal Alcohol Syndrome in the Global Burden of Disease
regions. Presented to the First European Conference on FASD: Growing Awareness in Europe.
Rolduc, Kerkrade, Netherlands, 2010.
14 May PA, Gossage JP, Kalberg WO, et al. Prevalence and epidemiologic characteristics of FASD
from various research methods with an emphasis on recent in-school studies. Dev Disabil Res Rev
2009; 15: 176–92.
15 Public Health Agency of Canada (PHAC). Fetal alcohol spectrum disorder (FASD): a framework
for action. Ottawa, Canada: PHAC, 2003.
16 Roberts G, Nanson J. Best practices. Fetal alcohol syndrome/fetal alcohol effects and the effects of
other substance use during pregnancy. Ottawa, ON: Health Canada, 2000.
17 May PA, Gossage JP. Estimating the prevalence of fetal alcohol syndrome. A summary. Alcohol
Res Health 2001; 25: 159–67.
18 Sampson PD, Streissguth AP, Bookstein FL, et al. Incidence of fetal alcohol syndrome and
prevalence of alcohol-related neurodevelopmental disorder. Teratology 1997; 56: 317–26.
19 Chudley AE. Fetal alcohol spectrum disorder: counting the invisible—mission impossible? Arch Dis
Child 2008; 93: 721–22.
20 May PA, Fiorentino D, Coriale G, et al. Prevalence of children with severe fetal alcohol spectrum
disorders in communities near Rome, Italy: new estimated rates are higher than previous estimates.
Int J Environ Res Public Health 2011; 8: 2331–51.
21 Petkovi# G, Barisi# I. FAS prevalence in a sample of urban schoolchildren in Croatia. Reprod
Toxicol 2010; 29: 237–41.
22 Robinson GC, Conry JL, Conry RF. Clinical profile and prevalence of fetal alcohol syndrome in an

!
9!
isolated community in British Columbia. CMAJ 1987; 137: 203–07.
23 May PA, Blankenship J, Marais AS, et al. Approaching the prevalence of the full spectrum of fetal
alcohol spectrum disorders in a South African population-based study. Alcohol Clin Exp Res 2013;
37: 818–30.
24 Lange S, Shield K, Rehm J, Popova S. Prevalence of fetal alcohol spectrum disorders in child care
settings: a meta-analysis. Pediatrics 2013; 132: e980–95.
25 Pal’chik AB, Legon’kova SV. Fetal’nyy alkogol’nyy sindrom: manifestatsia i dinamika [Fetal
Alcohol Syndrome: manifestation and dynamics]. Obozrenie psikhiatrii i meditsinskoi psikhologii
[Rev Psychiatry Med Psychol] 2011: 17–20.
26 Chudley AE, Longstaffe SE. Fetal Alcohol Syndrome and Fetal Alcohol Spectrum Disorder. In
Cassidy SB, Allanson JE, eds. Management of Genetic Syndromes. Hoboken, NY: Wiley-Blackwell;
2010; 363–80.
27 WHO. The International Classification of Diseases, Ninth Revision (ICD-9). Geneva, Switzerland:
World Health Organization, 1978.
28 WHO. The International Classification of Diseases and Related Health Problems, Tenth Revision.
Geneva, Switzerland: World Health Organization, 2007.
29 Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews
and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.
BMJ 2009; 399: b2700.
30 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177–88.
31 Freeman MF, Tukey JW. Transformations related to the angular and the square root. Ann Math Stat
1950; 21: 607–11.
32 Cochran WG. The combination of estimates from different experiments. Biometrics 1954; 8: 101–
29.
33 Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539–
58.
34 Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias.
Biometrics 1994; 50: 1088–101.
35 Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple,
graphical test. BMJ 1997; 315: 629–34.
36 Burd L, Klug MG, Bueling R, Martsolf J, Olson M, Kerbeshian J. Mortality rates in subjects with
fetal alcohol spectrum disorders and their siblings. Birth Defects Res A Clin Mol Teratol 2008; 82:
217–23.
37 Habbick BF, Nanson JL, Snyder RE, Casey RE. Mortality in foetal alcohol syndrome. Can J Public
Health 1997; 88: 181–83.
38 Bell SH, Stade B, Reynolds JN, et al. The remarkably high prevalence of epilepsy and seizure
history in fetal alcohol spectrum disorders. Alcohol Clin Exp Res 2010; 34: 1084–89.
39 Burd L, Klug MG, Martsolf JT, Kerbeshian J. Fetal alcohol syndrome: neuropsychiatric phenomics.
Neurotoxicol Teratol 2003; 25: 697–705.
40 Church MW, Eldis F, Blakley BW, Bawle EV. Hearing, language, speech, vestibular, and
dentofacial disorders in fetal alcohol syndrome. Alcohol Clin Exp Res 1997; 21: 227–37.

!
10!
41 Egeland GM, Perham-Hester KA, Gessner BD, Ingle D, Berner JE, Middaugh JP. Fetal alcohol
syndrome in Alaska, 1977 through 1992: an administrative prevalence derived from multiple data
sources. Am J Public Health 1998; 88: 781–86.
42 Famy C, Streissguth AP, Unis AS. Mental illness in adults with fetal alcohol syndrome or fetal
alcohol effects. Am J Psychiatry 1998; 155: 552–54.
43 Halliday HL, Reid MM, McClure G. Results of heavy drinking in pregnancy. Br J Obstet Gynaecol
1982; 89: 892–95.
44 Hug TE, Fitzgerald KM, Cibis GW. Clinical and electroretinographic findings in fetal alcohol
syndrome. J AAPOS 2000; 4: 200–04.
45 Jones KL, Hoyme HE, Robinson LK, et al. Fetal alcohol spectrum disorders: extending the range of
structural defects. Am J Med Genet A 2010; 152A: 2731–35.
46 Kalberg WO, Provost B, Tollison SJ, et al. Comparison of motor delays in young children with fetal
alcohol syndrome to those with prenatal alcohol exposure and with no prenatal alcohol exposure.
Alcohol Clin Exp Res 2006; 30: 2037–45.
47 Kvigne VL, Leonardson GR, Neff-Smith M, Brock E, Borzelleca J, Welty TK. Characteristics of
children who have full or incomplete fetal alcohol syndrome. J Pediatr 2004; 145: 635–40.
48 Landgren M, Svensson L, Strömland K, Andersson Grönlund M. Prenatal alcohol exposure and
neurodevelopmental disorders in children adopted from eastern Europe. Pediatrics 2010; 125:
e1178–85.
49 Löser H, Majewski F. Type and frequency of cardiac defects in embryofetal alcohol syndrome.
Report of 16 cases. Br Heart J 1977; 39: 1374–79.
50 May PA, Gossage JP, Marais AS, et al. The epidemiology of fetal alcohol syndrome and partial
FAS in a South African community. Drug Alcohol Depend 2007; 88: 259–71.
51 Sandor GG, Smith DF, MacLeod PM. Cardiac malformations in the fetal alcohol syndrome. J
Pediatr 1981; 98: 771–73.
52 Smith DF, Sandor GG, MacLeod PM, Tredwell S, Wood B, Newman DE. Intrinsic defects in the
fetal alcohol syndrome: studies on 76 cases from British Columbia and the Yukon Territory.
Neurobehav Toxicol Teratol 1981; 3: 145–52.
53 Spohr HL, Willms J, Steinhausen HC. Prenatal alcohol exposure and long-term developmental
consequences. Lancet 1993; 341: 907–10.
54 Strömland K, Hellström A. Fetal alcohol syndrome—an ophthalmological and socioeducational
prospective study. Pediatrics 1996; 97: 845–50.
55 Strömland K, Sundelin K. Paediatric and ophthalmologic observations in offspring of alcohol
abusing mothers. Acta Paediatr 1996; 85: 1463–68.
56 Swayze VW 2nd, Johnson VP, Hanson JW, et al. Magnetic resonance imaging of brain anomalies in
fetal alcohol syndrome. Pediatrics 1997; 99: 232–40.
57 Viljoen DL, Gossage JP, Brooke L, et al. Fetal alcohol syndrome epidemiology in a South African
community: a second study of a very high prevalence area. J Stud Alcohol 2005; 66: 593–604.
58 Steinhausen HC, Nestler V, Spohr HL. Development and psychopathology of children with the fetal
alcohol syndrome. J Dev Behav Pediatr 1982; 3: 49–54.
59 Beattie JO, Day RE, Cockburn F, Garg RA. Alcohol and the fetus in the west of Scotland. Br Med J

!
11!
(Clin Res Ed) 1983; 287: 17–20.
60 Elgen I, Bruaroy S, Laegreid LM. Lack of recognition and complexity of foetal alcohol
neuroimpairments. Acta Paediatr 2007; 96: 237–41.
61 Habbick BF, Nanson JL, Snyder RE, Casey RE, Schulman AL. Foetal alcohol syndrome in
Saskatchewan: unchanged incidence in a 20-year period. Can J Public Health 1996; 87: 204–07.
62 Hanson JW, Jones KL, Smith DW. Fetal alcohol syndrome. Experience with 41 patients. JAMA
1976; 235: 1458–60.
63 Kvigne VL, Leonardson GR, Borzelleca J, Neff-Smith M, Welty TK. Hospitalizations of children
who have fetal alcohol syndrome or incomplete fetal alcohol syndrome. S D Med 2009; 62: 97, 99,
101–03.
64 Ribeiro IM, Vale PJ, Tenedorio PA, Rodrigues PA, Bilhoto MA, Pereira HC. Ocular manifestations
in fetal alcohol syndrome. Eur J Ophthalmol 2007; 17: 104–09.
65 Rössig C, Wässer S, Oppermann P. Audiologic manifestations in fetal alcohol syndrome assessed
by brainstem auditory-evoked potentials. Neuropediatrics 1994; 25: 245–49.
66 Urban M, Chersich MF, Fourie LA, Chetty C, Olivier L, Viljoen D. Fetal alcohol syndrome among
grade 1 schoolchildren in Northern Cape Province: prevalence and risk factors. S Afr Med J 2008;
98: 877–82.
67 Centers for Disease Control and Prevention (CDC). Update: trends in fetal alcohol syndrome—
United States, 1979–1993. MMWR Morb Mortal Wkly Rep 1995; 44: 249–51.
68 Tredwell SJ, Smith DF, Macleod PJ, Wood BJ. Cervical spine anomalies in fetal alcohol syndrome.
Spine 1982; 7: 331–34.
69 Majewski F. Uber schädigende Einflüsse des Alkohols auf die Nachkommen. [The damaging effects
of alcoholism on the offspring (author’s transl in English)]. Nervenarzt 1978; 49: 410–16.
70 Majewski F. Die Alkoholembryopathie. Eine häufige und vermeidbare Schädigung bei Kindern
[The fetal alcohol syndrome. A common and preventable injury in children]. Der Kinderarzt 1986;
8: 1127–38. (The pediatrician).
71 Burd L, Cox C, Poitra B, et al. The FAS Screen: a rapid screening tool for fetal alcohol syndrome.
Addict Biol 1999; 4: 329–36.
72 Congdon N, O’Colmain B, Klaver CC, et al, and the Eye Diseases Prevalence Research Group.
Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol
2004; 122: 477–85.
73 Bluestone CD. Epidemiology and pathogenesis of chronic suppurative otitis media: implications for
prevention and treatment. Int J Pediatr Otorhinolaryngol 1998; 42: 207–23.
74 Boyle CA, Boulet S, Schieve LA, et al. Trends in the prevalence of developmental disabilities in US
children, 1997–2008. Pediatrics 2011; 127: 1034–42.
75 Hasin DS, Stinson FS, Ogburn E, Grant BF. Prevalence, correlates, disability, and comorbidity of
DSM-IV alcohol abuse and dependence in the United States: results from the National
Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry 2007; 64: 830–42.
76 Compton WM, Thomas YF, Stinson FS, Grant BF. Prevalence, correlates, disability, and
comorbidity of DSM-IV drug abuse and dependence in the United States: results from the national
epidemiologic survey on alcohol and related conditions. Arch Gen Psychiatry 2007; 64: 566–76.

!
12!
77 Tomblin JB, Records NL, Buckwalter P, Zhang X, Smith E, O’Brien M. Prevalence of specific
language impairment in kindergarten children. J Speech Lang Hear Res 1997; 40: 1245–60.
78 Nock MK, Kazdin AE, Hiripi E, Kessler RC. Prevalence, subtypes, and correlates of DSM-IV
conduct disorder in the National Comorbidity Survey Replication. Psychol Med 2006; 36: 699–710.
79 Martin JA, Hamilton BE, Ventura SJ, Osterman MJ, Mathews TJ. Births: final data for 2011. Natl
Vital Stat Rep 2013; 62: 1–69, 72.
80 Goodlett CR, Horn KH, Zhou FC. Alcohol teratogenesis: mechanisms of damage and strategies for
intervention. Exp Biol Med (Maywood) 2005; 230: 394–406.
81 Rutter M. Epidemiological methods to tackle causal questions. Int J Epidemiol 2009; 38: 3–6.
82 Popova S, Lange S, Burd L, Rehm J. Health care burden and cost associated with fetal alcohol
syndrome: based on official Canadian data. PLoS ONE 2012; 7: e43024.
83 Popova S, Lange S, Burd L, Chudley AE, Clarren SK, Rehm J. Cost of fetal alcohol spectrum
disorder diagnosis in Canada. PLoS ONE 2013; 8: e60434.
84 Popova S, Lange S, Burd L, Urbanoski K, Rehm J. Cost of specialized addiction treatment of clients
with fetal alcohol spectrum disorder in Canada. BMC Public Health 2013; 13: 570.
85 Credé S, Sinanovic E, Adnams C, London L. The utilization of health care services by children with
Foetal Alcohol Syndrome in the Western Cape, South Africa. Drug Alcohol Depend 2011; 115:
175–82.
86 Amendah DD, Grosse SD, Bertrand J. Medical expenditures of children in the United States with
fetal alcohol syndrome. Neurotoxicol Teratol 2011; 33: 322–24.
87 Clarren SK, Lutke J, Sherbuck M. The Canadian guidelines and the interdisciplinary clinical
capacity of Canada to diagnose fetal alcohol spectrum disorder. J Popul Ther Clin Pharmacol 2011;
18: e494–99.
88 Streissguth AP, Barr HM, Kogan J, Bookstein FL. Understanding the occurrence of secondary
disabilities in clients with fetal alcohol syndrome (FAS) and fetal alcohol effects (FAE). Seattle,
Washington: University of Washington, Fetal Alcohol and Drug Unit, 1996.

!
Table 1: Comorbid disorders with an estimated pooled prevalence over 50% (excluding disorders that are part of fetal alcohol syndrome diagnostic
criteria) in individuals with fetal alcohol syndrome, by ICD-10 code
Disease condition
Disorder as stated in original paper
Pooled prevalence (95% CI)
R94.1
Abnormal results of function studies of peripheral nervous
system and special senses
Electrophysiological abnormalities in peripheral nerves
90!9%
(58!7%–99!8%)
F91
Conduct disorder
Conduct/behavioural problems/disruptive behaviour/impulsivity
90!7%
(77!9%–97!4%)
F80.2
Receptive language disorder
Receptive language deficits
81!8%
(59!7%–94!8%)
H65.2
Chronic serous otitis media
Chronic/recurrent (serous) otitis media
77!3%
(54!6%–92!2%)
F80.1
Expressive language disorder
Expressive language deficit
76!2%
(52!8%–91!8%)
H52.6
Other disorders of refraction
Refractive error(s)
71!4%
(47!8%–88!7%)
F89
Unspecified disorder of psychological development
Developmental/cognitive disorder/delay(s)/mental deficiency
69!2%
(47!7%–87!3%)
F80.9
Developmental disorder of speech and language, unspecified
Speech/language delay/disorder/retarded speech
development/speech defects/acquisition
67!2%
(43!1%–87!6%)
P07.3
Other preterm infants
Pre-mature birth/born prematurely/preterm birth
65!3%
(31!4%–100!0%)
H54
Visual impairment including blindness (binocular or
monocular)
Subnormal/decreased visual acuity/problems/visual impairment
61!9%
(38!4%–81!9%)
H90.5
Sensorineural hearing loss, unspecified
Central hearing loss
57!9%
(0!0%–100!0%)
H90.2
Conductive hearing loss, unspecified
Conductive hearing loss
56!8%
(43!9%–69!3%)
F10.2;
F19.2
Mental and behavioural disorders due to use of alcohol,
dependence syndrome; Mental and behavioural disorders due
to use of multiple drugs and use of other psychoactive
substances, dependence syndrome
Alcohol dependence/Drug dependence
54!5%
(23!4%–83!3%)
Q14.1
Congenital malformation of retina
Coccygeal fovea
54!1%
(43!5%-64!5%)
Q76.4
Other congenital malformations of spine, not associated with
scoliosis
Congenital fusion of cervical vertebrae/cervical spin fusion
52!6%
(40!8%-64!2%)
H65.0
Acute serous otitis media
(Acute/serous/serousmucous) otitis media
51!2%
(35!5%-66!7%)
F90.0
Disturbance of activity and attention
Attention deficit hyperactivity disorder
51!2%
(23!6%-78!4%)
Q75.2
Hypertelorism
Hypertelorism
50!0%
(18!7%-81!3%)
ICD-10=International Classification of Diseases, version 10.

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Table 2: Comparison of the pooled prevalence of comorbid disorders found in individuals with fetal alcohol syndrome versus the general population of
the USA, by ICD-10 code
Prevalence
Disease condition
Among individuals with fetal
alcohol syndrome
Among the US general
population
Fold change
H54
Visual impairment including blindness (binocular or monocular)
61.9%
0!87% (blind) and 1!98% (low
vision)
72
31 to 71
H65.2
Chronic serous otitis media
77.3%
<1!0%
73
77
H90.2
Conductive hearing loss, unspecified
56.8%
0.45% (moderate to severe
hearing loss)
74
126 to 129
H90.5
Sensorineural hearing loss, unspecified
57.9%
0.45% (moderate to severe
hearing loss)
74
126 to 129
F10.2
Mental and behavioural disorders due to use of alcohol, dependence
syndrome
54.5%
12!5% (lifetime alcohol
dependence)
75
4
F19.2
Mental and behavioural disorders due to multiple drug use and use of
other psychoactive substance, dependence syndrome
54.5%
2!6% (drug lifetime
dependence)
76
21
F80.1
Expressive language disorders
76.2%
7!4% (specific language
impairments)
77
10
F80.2
Receptive language disorders
81.8%
7!4% (specific language
impairments)
77
11
F89
Unspecified disorder of psychological development
69.2%
0!71% (intellectual disabilities)
74
97
F90
Disturbance of activity and attention
51.2%
6!7% (attention deficit
hyperactivity disorder)
74
8
F91
Conduct disorder
90.7%
9!5%
78
10
P07.3
Other preterm infants
65.3%
11!7%
79
6
ICD-10: International Classification of Diseases, version 10.

!
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Figure 1: Search strategy

!
16!
Figure 2: Prevalence of disease conditions belonging to ICD-10 chapters II, III, IV, V, and VI found to occur in individuals with fetal alcohol syndrome
Please note that each ICD-10 chapter is depicted by a unique colour. Each bar represents a single comorbid condition with its ICD-10 code. The height of the bar indicates the estimated pooled
prevalence, and the solid vertical line within each bar represents the 95% CI for each comorbid condition. D14.0=benign neoplasm of middle ear and respiratory systems: middle ear, nasal cavity, and
accessory sinuses. D18.0=haemangioma, any site. D64.9=Anaemia, unspecified. E86=volume depletion. F10.1/F19.1=mental and behavioural disorders due to use of alcohol, harmful use/mental and
behavioural disorders due to use of multiple drugs and use of other psychoactive substances, harmful use. F10.2/F19.2=mental and behavioural disorders due to use of alcohol, dependence
syndrome/mental and behavioural disorders due to use of multiple drugs and use of other psychoactive substances, dependence syndrome. F23.9=acute and transient psychotic disorder, unspecified.
F29=unspecified nonorganic psychosis. F31=bipolar affective disorder. F32.2/F32.3=severe depressive episode without psychotic symptoms/severe depressive episode with psychotic symptoms.
F33.8=other recurrent depressive disorders. F34.1=dysthymia. F34.8=other persistent mood (affective) disorders. F42=obsessive-compulsive disorder. F51=non-organic sleep disorders. F60.2=dissocial
personality disorder. F60.6=anxious (avoidant) personality disorder. F60.7=dependent personality disorder. F70–F79=mental retardation. F80=specific developmental disorders of speech and language.
F80.0=specific speech articulation disorder. F80.1=expressive language disorder. F80.2=receptive language disorder. F81=specific developmental disorder of scholastic skills. F82=specific
developmental disorder of motor function. F84.0=childhood autism. F89=unspecified disorder of psychological development. F90.0=disturbance of activity and attention. F91=conduct disorder.
F91.3=oppositional defiant disorder. F95=tic disorders. F95.8=other tic disorders. F98.5=stuttering (stammering). F98.6=cluttering. G40=epilepsy/seizure disorder. G40.2=localisation-related (focal)
(partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures. G81.1=spastic hemiplegia. Symbols are used to indicate conditions as stated in the original papers that cannot
clinically and/or statistically be grouped under one code. *Conduct/behavioural problems/disruptive behaviour/impulsivity (F91.0 conducts disorders). †Attention deficit hyperactivity disorder (F90.0
disturbance of activity and attention). ‡Hyperactivity/hyperactive and inattentiveness (F90.0 disturbance of activity and attention). §Short/impaired attention span/problems/distractibility (F90.0
disturbance of activity and attention).

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Figure 3: Prevalence of disease conditions belonging to ICD-10 chapters VII, VIII, IX, X, XI, XII, XIII, XIV, and XVI found to occur in individuals
with fetal alcohol syndrome
Please note that each ICD-10 chapter is depicted by a unique colour. Each bar represents a single comorbid condition with its ICD-10 code. The height of the bar indicates the estimated pooled
prevalence, and the solid vertical line within each bar represents the 95% CI for each comorbid condition. H30.9=chorioretinal inflammation, unspecified. H44.5=degenerated conditions of globe.
H47.0=disorders of optic nerve, not elsewhere classified. H50.0=convergent concomitant strabismus. H50.1=divergent concomitant strabismus. H50.5=heterophoria. H50.9=strabismus, unspecified.
H52.0=hypermetropia. H52.1=myopia. H52.2=astigmatism. H52.3=ansiometropia and aniseikonia. H52.6=other disorders of refraction. H53.0=amblyopia ex anopsia. H53.3=other disorders of
binocular vision. H54.2/54.5=visual impairment including blindness (binocular or monocular). H55=nystagmus and other irregular eye movements. H65.0=acute serous otitis media. H65.2=chronic
serous otitis media. H90.2=conductive hearing loss, unspecified. H90.5=sensorineural hearing loss, unspecified. H90.8=mixed conductive and sensorineural hearing loss, unspecified. H91.9=hearing
loss, unspecified. I27.8=other specified pulmonary heart diseases. J18.9=pneumonia, unspecified. J20=acute bronchitis. K00.4=disturbances in tooth formation. K07.0=major anomalies of jaw size.
K07.1=anomalies of jaw-cranial base relationship. K40=inguinal hernia. K40-K46=hernia. L68.9=hypertrichosis, unspecified. M20.0=deformity of finger(s). M21.2=flexion deformity.
M24.5=contracture of joint. M25.9=joint disorder, unspecified. M89.2=other disorders of bone development and growth. N13.3=other and unspecified hydonephrosis. N31.9=neuromuscular dysfunction
of bladder, unspecified. N39.0=urinary tract infection, site not specified. N47=redundant prepuce, phimosis and paraphimosis. P05.1=small for gestational age. P05.9=slow fetal growth, unspecified.
P07.1=other low birthweight. P07.3=other preterm infants. P92=feeding problems of newborn. P94.2=congenital hypotonia. Symbols are used to indicate conditions as stated in the original papers that
cannot clinically and/or statistically be grouped under one code. *Central hearing disorder (H90.5 sensorineural hearing loss, unspecified). †Incomplete extension of one or more digits (M25.9 joint
disorder, unspecified). ‡Camptodactyly (M21.2 flexion deformity). §Limited joint movement/decreased pronation/supination of elbow/limited movement of knee (M25.9 joint disorder, unspecified).
¶Bilateral pes calcaneovalgus (M21.2 flexion deformity). ||Hyperextension of joints/hyperextensible joints (M25.9 joint disorder, unspecified).

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Figure 4: Prevalence of disease conditions belonging to ICD-10 chapter XVII (Q00–Q28) found to occur in individuals with fetal alcohol syndrome
Please note that each ICD-10 chapter is depicted by a unique colour. Each bar represents a single comorbid condition with its ICD-10 code. The height of the bar indicates the estimated pooled
prevalence, and the solid vertical line within each bar represents the 95% CI for each comorbid condition. Q02=microcephaly. Q03=congenital hydrocephalus. Q04.0=congenital malformations of
corpus callosum. Q04.3=other reduction deformities of brain. Q04.6=congenital cerebral cysts. Q04.8=other specified congenital malformations of brain. Q04.9=congenital malformation of brain,
unspecified. Q05=spina bifida. Q06.8=other specified congenital malformations of spinal cord. Q10.0=congenital ptosis. Q10.3=other congenital malformations of eyelid. Q10.6=other congenital
malformations of lacrimal apparatus Q11.2=microphthalmos. Q12.0=congenital cataract. Q13.0=coloboma of iris. Q13.4=other congenital corneal malformation. Q14.0=congenital malformation of
vitreous humour. Q14.1=congenital malformation of retina. Q14.2=congenital malformation of optic disc. Q15.0=congenital glaucoma. Q15.8=other specified congenital malformations of eye.
Q16.9=congenital malformation of ear causing impairment of hearing, unspecified. Q17.8=other specified congenital malformations of ear. Q17.9=congenital malformations of ear, unspecified.
Q18.8=other specified congenital malformations of face and neck. Q20.1=Double outlet right ventricle. Q21.0=ventricular septal defect. Q21.1=atrial septal defect. Q21.2=atrioventricular septal defect.
Q21.3=tetralogy of Fallot. Q24.0=dextrocardia. Q24.3=pulmonary infundibular stenosis. Q24.8=other specified congenital malformations of heart. Q24.9=congenital malformation of heart, unspecified).
Q25.0=patent ductus arteriosus. Q25.1=coarctation of aorta. Q25.5=atresia of pulmonary artery. Q25.6=stenosis of pulmonary artery. Q25.7=other congenital malformations of pulmonary artery.
Q26.1=persistent left superior vena cava. Symbols are used to indicate conditions as stated in the original papers that cannot clinically and/or statistically be grouped under one code.
*Occipitofrontal/small head circumference (<10th percentile ; Q02 microcephaly). †Short/narrow palpebral fissures (Q10.3 other congenital malformations of eyelid). ‡Coccygeal fovea (Q14.1
congenital malformation of retina). §Retinal tortuosity/tortuosity of retinal vessels (Q14.1 congenital malformation of retina). ¶Blepharophimosis (Q10.0 congenital ptosis). ||Cardiac lesions (Q24.9
congenital malformation of heart, unspecified). **Epicanthal folds/broad epicanthus/prominent epicanthic folds (Q10.3 other congenital malformations of eyelid). ††Tortuosity of arteries in the eye
(Q15.8 other specified congenital malformations of eye). ‡‡Short inner canthal distance (Q10.6 other congenital malformations of lacrimal apparatus). §§Small optic disc (Q14.2 congenital
malformation of optic disc). ¶¶Hypoplastic optic discs/optic disc hypoplasia (Q14.2 congenital malformation of optic disc). ||||Extensive malformation of eye(s)/eye anomalies/intraocular defects (Q15.8
other specified congenital malformations of eye). ***Congenital heart disease (Q24.9 congenital malformation of heart, unspecified). †††Telecanthus (Q10.6 other congenital malformations of lacrimal
apparatus). ‡‡‡Bilateral maculopathy (Q14.1 congenital malformation of retina).

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19!
Figure 5: Prevalence of disease conditions belonging to ICD-10 chapters XVII (Q30-Q99), XVIII, XX, and XXI found to occur in individuals with fetal
alcohol syndrome
Please note that each ICD-10 chapter is depicted by a unique colour. Each bar represents a single comorbid condition with its ICD-10 code. The height of the bar indicates the estimated pooled
prevalence, and the solid vertical line within each bar represents the 95% CI for each comorbid condition. Q30.8=other congenital malformations of nose. Q35.9=cleft palate, unspecified. Q36=cleft lip.
Q38.0=congenital malformations of lip, not elsewhere classified. Q38.5=congenital malformations of palate, not elsewhere classified. Q52.8=other specified congenital malformations of female
genitalia. Q52.9/Q55.9=congenital malformation of female genitalia, unspecified/congenital malformation of male genital organ, unspecified. Q53.9=undescended testicle, unspecified.
Q54.1=hypospadias, penile. Q54.9=hypospadias, unspecified. Q60.2=renal agenesis, unspecified. Q62.0=congenital hydronephrosis. Q62.1=atresia and stenosis of ureter. Q62.5=duplication of ureter.
Q63.2=ectopic kidney. Q63.9=congenital malformation of kidney, unspecified. Q65. 2=congenital dislocation of hip, unspecified. Q68.1=congenital deformity of hand. Q68.8=other specified congenital
musculoskeletal deformities. Q74.0=other congential malformations of upper limb(s), including shoulder girdle. Q75.2=hypertelorism. Q75.8=other specified congenital malformations of skull and face
bones. Q76.4=other congenital malformations of spin, not associated with scoliosis. Q76.6=other congenital malformations of ribs. Q82.8=other specified congenital malformations of skin. Q84.6=other
congenital malformations of nails. R01.0=benign and innocent cardiac murmurs. R25.1=tremor, unspecified. R27.0=ataxia, unspecified. R45.4/R45.5=irritability and anger/hostility.
R49.2=hypernasality and hyponasality. R62.8=other lack of expected normal physiological development. R68.1=nonspecific symptoms peculiar to infancy. R94.0=abnormal results of function studies of
CNS. R94.1=abnormal results of function studies of peripheral nervous system and special senses. X60-X84=intentional self-harm. Z55.3=underachievement in school. Symbols are used to indicate
conditions as stated in the original papers that cannot clinically and/or statistically be grouped under one code.*Narrow vermilion border/thin upper lip (Q38.0 congenital malformations of lip, not
elsewhere classified). †Long/smooth/indistinct/poorly developed philtrum (Q38.0 congenital malformations of lip, not elsewhere classified). ‡Flat/low/broad/deep nasal bridge (Q30.8 other congenital
malformations of nose). §Short/small upturned nose (Q30.8 other congenital malformations of nose). ¶Hypoplastic radial head (Q74.0 other congential malformations of upper limb(s), including
shoulder girdle). ||Anteverted nares/nostrils (Q30.8 other congenital malformations of nose). **Radio-ulnar synostosis/deformity/terminal transverse defect of forearm/hand (Q74.0 other congential
malformations of upper limb(s), including shoulder girdle). ††Prenatal/postnatal growth retardation/deficiency (R62.8 other lack of expected normal physiological development). ‡‡Height <10th
percentile (R62.8 other lack of expected normal physiological development). §§Weight <10th percentile (R62.8 other lack of expected normal physiological development). ¶¶Failure to thrive (R62.8
other lack of expected normal physiological development).

1!
Appendix
Comorbidity of fetal alcohol spectrum disorder: a systematic review and meta-analysis
Svetlana Popova, Shannon Lange, Kevin Shield, Alanna Mihic, Albert E Chudley, Raja A S Mukherjee, Dennis Bekmuradov, Jürgen Rehm
Table A1. Comprehensive list of comorbid conditions found to occur among individuals with fetal alcohol spectrum disorder
Authors’ adjustment for ICD-10, if not specified in the study
Condition as stated in original paper
Source
Condition
Code
CHAPTER II: Neoplasms
C00-D48
Malignant neoplasms, stated or presumed to be primary, of specified sites, except of lymphoid, haematopoietic and related tissue
(C00-C75)
Hepatoblastoma
1
C22!2
Rhabdomyosarcoma (of bladder)
2
Connective and soft tissue, unspecified
C49!9
Wilms’ tumour/Nephroblastoma
2,3
Malignant neoplasm of kidney, except renal pelvis
C64
Adrenal carcinoma
4
Cortex of adrenal gland
C74!0
(Adrenal) neuroblastoma/ Ganglioneuroblastoma
5–9
Adrenal gland, unspecified
C74!9
Acute lymphocytic leukaemia
2
Acute lymphoblastic leukaemia [ALL]
C91!0
Malignant neoplasms, states or presumed to be primary, of lymphoid, haematopoletic and related tissue
C81-C96
Hodgkin lymphoma
10
C81
Benign neoplasms
D10-D36
Splenic flexure
11
Transverse colon
D12!3
Polyp in auditory canal
12
Middle ear, nasal cavity and accessory sinuses
D14!0
Haemangioma(s)
4,10,13–17
Capillary hemangiomata
18
Haemangioma, any site
D18!0
Pigmented nevi
16
Malanocytic naevi
D22
CHAPTER III: Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism
D50-D89
Aplastic and other anaemias
D60-D64
Anemia
19
Anaemia, unspecified
D64!9
Coagulation defects, purpura and other haemorrhagic conditions
D65-D69
Bleeding disorder
20
Coagulation defect, unspecified
D68!9
Thrombocytopenia/thrombopenia
20,21
Thrombocytopenia, unspecified
D69!6
CHAPTER IV: Endocrine, nutritional and metabolic diseases
E00-E90
Metabolic disorders
E70-E90
Dehydration
19
Volume depletion
E86
Hyponatraemia
20
Hypo-osmolality and hyponatraemia
E87!1
CHAPTER V: Mental and behavioural disorders
F00-F99
Mental and behavioral disorders due to psychoactive substance use
F10-F19
Alcohol abuse/use
22–28
Mental and behavioural disorders due to use of alcohol, harmful use
F10!1
Alcohol dependence
24,29,30
Mental and behavioural disorders due to use of alcohol, dependence syndrome
F10!2
Drug abuse/use
26–28
Mental and behavioural disorders due to multiple drug use and use of other
psychoactive substances, harmful use
F19!1
Drug dependence
30
Mental and behavioural disorders due to multiple drug use and use of other
psychoactive substances, dependence syndrome
F19!2
Schizophrenia, schizotypal and delusional disorder
F20-F29
Schizophrenia
27,31,32
Schizophrenia, unspecified
F20!9
Schizotypal personality disorder
30
Schizotypal disorder
F21
Delusional disorder
30
F22!0
Brief psychotic disorder
30
Acute and transient psychotic disorder, unspecified
F23!9
Schizoaffective disorder, depressive type
33
F25!1
Schizoaffective disorder
30
Schizoaffective disorder, unspecified
F25!9

2!
Authors’ adjustment for ICD-10, if not specified in the study
Condition as stated in original paper
Source
Condition
Code
Psychotic disorder not otherwise specified
30
Psychotic features
34
Unspecified nonorganic psychosis
F29
Mood [affective] disorders
F30-F39
Hypomania
35
F30!0
Mania/manic
31,35
Manic episode, unspecified
F30!9
Bipolar disorder/manic depressive
26,27,30,36,37
Bipolar affective disorder
F31
Major depressive disorder
30,31,35,36,38
Severe depressive episode without psychotic symptoms/Severe depressive episode
with psychotic symptoms
F32!2/F32!3
Depressive disorder/depression/depressive symptoms
14,26,27,34,37,39–44
Other recurrent depressive disorders
F33!8
Severe persistent melancholic depression
33
Recurrent depressive disorder, unspecified
F33!9
Emotional/affective instability
33
Cyclothymia
F34!0
Dysthymia/dysthymic disorder
30,37,38
Dysthymia
F34!1
Mood/emotional disorder/problems
14,25,45
Other persistent mood [affective] disorders
F34!8
Neurotic, stress-related and somatoform disorders
F40-F48
Social phobias
31,38
F40!1
Specific phobia
15,38
Clastrophobia
30
Specific (isolated) phobias
F40!2
Panic disorder/attacks
14,26,30,38
Panic disorder [episodic paroxysmal anxiety]
F41!0
Generalized anxiety disorder
30,31,38
Anxiety/anxiety disorder
14,35,37,44
Generalized anxiety disorder
F41!1
Obsessive-compulsive disorder
26,31,37,38,46
F42
Obsessive-compulsive symptomatology
47
Predominantly compulsive acts [obsessional rituals]
F42!1
Post-traumatic stress disorder
14,26,27,30,31,37,39
F43!1
Adjustment disorder(s)
36,37
F43!2
Behavioral syndromes associated with physiological disturbances and physical factors
F50-F59
Anorexia nervosa
30
F50!0
Bulimia nervosa
30
F50!2
Binge eating
30
Other eating disorders
F50!8
Eating disorders/abnormal eating behaviours
14,15,44,45
Eating disorder, unspecified
F50!9
Sleep problems/disturbances/disorder
15,25,44,45,48
Nonorganic sleep disorders
F51
Sleep anxiety
48
Parasomnias
48
Other nonorganic sleep disorders
F51!8
Disorders of adult personality and behaviour
F60-F69
Paranoid personality disorder
30
F60!0
Antisocial personality disorder
30
Dissocial personality disorder
F60!2
Borderline personality disorder
30
Emotionally unstable personality disorder
F60!3
Avoidant personality disorder
30
Anxious [avoidant] personality disorder
F60!6
Dependent personality disorder
30
F60!7
Mental retardation
F70-F79
Mental retardation/intellectual impairment
2,8,9,12–15,34,46,49–60
Mental retardation
F70-F79
Disorders of psychological development
F80-F89
Marked dysarticulation
61
Specific speech articulation disorder
F80!0
Expressive language deficit
53,61
Expressive language disorder
F80!1
Receptive language deficit
53,61
Receptive language disorder
F80!2
Reduced vocabulary and clarity of speech
15,61
Other developmental disorders of speech and language
F80!8
Speech/language delay/disorder/retarded speech development/speech
defects/acquisition
3–5,14,15,18,45,49,50,53, 54,59,61-–64
Developmental disorders of speech and language, unspecified
F80!9
Learning disability/disorders
25,50,65,66
Developmental disorders of scholastic skills, unspecified
F81!9

3!
Authors’ adjustment for ICD-10, if not specified in the study
Condition as stated in original paper
Source
Condition
Code
Psychomotor delay/abnormal motor function
1,18,47
Fine and/or gross motor development delays/dysfunction/clumsiness/developmental
coordination disorder
2,4,6,8,9,12,14,15,46,49,50,
52,59,60,63,64,67
Specific developmental disorder of motor function
F82
Pervasive developmental disorder
36
F84
Autism/autistic/autism spectrum disorder/autistic behaviour
14,34,39,46,57,68
Childhood autism
F84!0
Atypical autism
68
F84!1
Asperger syndrome
68
F84!5
Developmental/cognitive disorder/delay(s)/mental deficiency
2,4–6,16–18,25,49–53,63, 64,69–73
Unspecified disorder of psychological development
F89
Behavioral and emotional disorders with onset usually occurring in childhood and adolescence
F90-F98
Attention deficit hyperactivity disorder/attention deficit disorder
14,25,26,31,33–39,45–
47,50,55,60,64,66,71,74
(Short/impaired) attention span/problems/distractibility
14,15,47,49,50,59,70
Hyperactivity/hyperactive (and inattentiveness)
2,8,9,12–15,50,52, 57,59,60, 63–
65,69,70,75,76
Disturbance of activity and attention
F90!0
Hyperkinetic syndrome/disorder
44,45
Hyperkinetic disorders, unspecified
F90!9
Conduct disorder
31,34,35,37,38,44–46,50
Conduct/behavioural problems/disruptive behaviour/impulsivity
14,26,50,71
Conduct disorders
F91
Delinquency
43,77
Poor socialization/social competence/antisocial
78,79
Socialized conduct disorder
F91!2
Opposition defiant disorder/oppositional behaviour
14,25,26,31,35,37–39,47
Opposition defiant disorder
F91!3
Separation anxiety disorder
31,35,38
Separation anxiety disorder of childhood
F93!0
Insecure attachment/reactive attachment disorder
36,37,39,80
Reactive attachment disorder of childhood
F94!1
Tic disorders/tics
38,44-46
Tic disorders
F95
Tourettes/Gilles de la Tourette’s syndrome
47,60
Combined vocal and multiple motor tic disorder [de la Tourette]
F95!2
Spasticity
52
Other tic disorders
F95!8
Enuresis
44,45
Nonorganic enuresis
F98!0
Enkopresis
44,45
Nonorganic encopresis
F98!1
Severe stutter(ing)/stammer
15,61
Stuttering [stammering]
F98!5
Cluttering/dysrhythmia
61
Cluttering
F98!6
CHAPTER VI: Diseases of the nervous system
G00-G99
Episodic and paroxysmal disorders
G40-G47
Epilepsy/seizure disorder
14,27,37,39
Epilepsy
G40
Epileptiform seizures
51
Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes
with simple partial seizures
G40!1
(Partial) Seizure(s)
25,39,49,50,52,57,64,71,75, 81
Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes
with complex partial seizures
G40!2
Myoclonic seizures
17
Generalized epileptic seizures
82
Generalized idiopathic epilepsy and epileptic syndromes
G40!3
Cerebral palsy and other paralytic syndromes
G80-G83
(Peri/pre-natally acquired) Cerebral palsy
34,57,83
G80
Spastic cerebral palsy
57
Spastic hemiplegic cerebral palsy
G80!2
Mixed dystonic and spastic cerebral palsy
72
Other cerebral palsy
G80!8
Spastic hemiplegia
75
G81!1
CHAPTER VII: Diseases of the eye and adnexa
H00-H59
Disorders of sclera, cornea, iris and ciliary body
H15-H22
Keratoconus
62
H18!6
Disorders of choroid and retina
H30-H35
Myopia choroidosis
84
Other chorioretinal inflammations
H30!8

4!
Authors’ adjustment for ICD-10, if not specified in the study
Condition as stated in original paper
Source
Condition
Code
Chorioretinal atrophy
72
Choroidal degeneration
H31!1
Retinal tortuosity/tortuosity of retinal vessels
62,72,75,84
Other specified retinal disorders
H35!8
Disorders of vitreous body and globe
H43-H45
Ocular phthisis
85
Degenerated conditions of globe
H44!5
Disorders of optic nerve and visual pathways
H46-H48
Optic nerve hypoplasia/double ring sign
46,51,72,74,75,84–87
Disorders of optic nerve, not elsewhere classified
H47!0
Optic nerve atrophy
51,52
Optic atrophy
H47!2
Disorders of ocular muscles, binocular movement, accommodation and refraction
H49-H52
Esotropia
4,72,75,84–86
Convergent concomitant strabismus
H50!0
Exotropia
84,85
Divergent concomitant strabismus
H50!1
Exophoria
84,85
Heterophoria
H50!5
Strabismus
4,9,15,16,45,46,49,53,65,74,
76,84,85,87–93
Strabismus, unspecified
H50!9
Inferolateral deviation of eye
7
Other specified disorders of binocular movement
H51!8
Ocular motility disorder
72
Disorder of binocular movement, unspecified
H51!9
Hypermetropia/hyperopia/hypertropic
53,62,84
Hypermetropia
H52!0
Myopia
53,55,62,74,84,86
H52!1
Astigmatism
53,62,84,86
H52!2
Ansiometropia
84
Ansiometropia and aniseikonia
H52!3
Ciclopegic refraction
62
Disorders of accommodation
H52!5
Refractive error(s)
14,46,88
Other disorders of refraction
H52!6
Visual disturbances and blindness
H53-H54
Amblyopia
53,84
Amblyopia ex anopsia
H53!0
Photophobia
53
Subjective visual disturbances
H53!1
Visual perceptual problems
46
Other disorders of binocular vision
H53!3
Subnormal/decreased visual acuity/problems/visual impairment
14,37,46,62,84
Focusing defects
53
Visual impairment including blindness (binocular or monocular)
H54
Other disorders of eye and adnexa
H55-H59
Nystagmus/nystagmoid eye movements
14,52,53,72,75,84–86
Nystagmus and other irregular eye movements
H55
CHAPTER VIII: Diseases of the ear and mastoid process
H60-H95
Diseases of middle ear and mastoid
H65-H75
(Acute/serous/serousmucous) otitis media
12,19,74,94
Acute serous otitis media
H65!0
Chronic/recurrent (serous) otitis media
53,61,94
Chronic serous otitis media
H65!2
Secretory otitis media
94
Middle ear fluid
94
Nonsuppurative otitis media, unspecified
H65!9
Eustachian tube dysfunction
74
Eustachian tube disorder, unspecified
H69!9
Perforated tympanic membrane
94
Perforation of tympanic membrane
H72
Other disorders of ear
H90-H95
Bilateral conductive hearing loss
62
Conductive hearing loss, bilateral
H90!0
Congenital deafness
95
Conductive hearing loss
12,61,96
Conductive hearing loss, unspecified
H90!2
Sensorineural hearing loss
12,14,61
Cental hearing disorder
12,61
Sensorineural hearing loss, unspecified
H90!5
Conductive and sensorineural hearing loss/central hearing disorder with conductive
hearing loss
12,61
Mixed conductive and sensorineural hearing loss, unspecified
H90!8
(Chronic) Hearing loss/impairment
15,18,37,50,51,74,75,88
Hearing loss, unspecified
H91!9
Hyperacusia
17
Other abnormal auditory preceptions
H93!2
CHAPTER IX: Diseases of the circulatory system
I00-I99

5!
Authors’ adjustment for ICD-10, if not specified in the study
Condition as stated in original paper
Source
Condition
Code
Pulmonary heart disease and diseases of pulmonary circulation
I26-I28
Cor pulmonale
97
Other specified pulmonary heart diseases
I27!8
Other forms of heart disease
I30-I52
Mitral regurgitation
58
Mitral (valve) insufficiency
I34!0
Mitral valve prolapse
53,57
I34!1
Arrhythmia
53
Cardiac arrhythmia, unspecified
I49!9
Congestive heart failure
98
I50!0
Cardiomegaly/ventricular dilatation
53,58,72,98
Cardiomegaly
I51!7
Diseases of veins, lymphatic vessels and lymph nodes, not elsewhere classified
I80-I89
Oesophageal varices
56,99
I85
Gastric varices
99
I86!4
CHAPTER X: Diseases of the respiratory system
J00-J99
Acute upper respiratory infections
J00-J06
Recurrent (upper) respiratory infection
53,72
Acute upper respiratory infection, unspecified
J06!9
Influenze and pneumonia
J09-J18
(Bilateral actue) Bronchopneumonia
56
Viral pneumonia, not elsewhere classified
J12
Pneumonia
19
Pneumonia, unspecified
J18!9
Other acute lower respiratory infections
J20-J22
Bronchitis
19
Acute bronchitis
J20
Other diseases of upper respiratory tract
J30-J39
Recurrent tonsilitis
53
Chronic tonsilitis
J35!0
Adenoidal hypertrophy
63
Hypertrophy of adenoids
J35!2
Chronic upper airway obstruction
63
Other specified diseases of upper respiratory tract
J39!8
Chronic lower respiratory diseases
J40-J47
Asthma
27,53
J45
Other respiratory disease principally affecting the interstitium
J80-J84
Pulmonary edema
53
Pulmonary oedema
J81
Other diseases of the respiratory system
J95-J99
Focal pulmonary atelectasis
17
Pulmonary collapse
J98!1
Pulmonary disease
88
Respiratory disorder, unspecified
J98!9
CHAPTER XI: Diseases of the digestive system
K00-K93
Diseases of the oral cavity, salivary glands and jaws
K00-K14
Hypoplastic teeth
15,45,59
Faulty tooth enamel
59
Disturbances in tooth formation
K00!4
Small chin (micrognathia)/micrognathic mandible
11,12,18,45,47,51,53,54,58, 63,99,100
Hypoplasia of mandible
13
Major anomalies of jaw size
K07!0
Retrognathia/prognathism
15,76,90
Anomalies of jaw-cranial base relationship
K07!1
Dental crowding/poor dental alignment/separated teeth/abnormal dental
configuration
47,53,74,88
Anomalies of tooth position
K07!3
Malocclusion
74
Malocclusion, unspecified
K07!4
Diseases of oesophagus, stomach and duodenum
K20-K31
Duodenal hypomotility
101
Other specified diseases of stomach and duodenum
K31!8
Hernia
K40-K46
Hernia
2,7,9,11,12,13,15,20,52,57,
65,69,72,75,99
K40-K46
Other diseases of intestines
K55-K63
Chronic intestinal psuedoobstruction
101
Other and unspecified intestinal obstruction
K56!6
Diseases of liver
K70-K77

6!
Authors’ adjustment for ICD-10, if not specified in the study
Condition as stated in original paper
Source
Condition
Code
(Congenital) Hepatic fibrosis
56,102
Hepatic fibrosis
K74!0
(Peri)portal fibrosis
99,102,103
Portal hypertension
K76!6
Liver disease
104
Liver disease, unspecified
K76!9
Disorders of gallbladder, biliary tract and pancreas
K80-K87
Cholestasis
99
Obstruction of bile duct
K83!1
CHAPTER XII: Diseases of the skin and subcutaneous tissue
L00-L99
Disorders of skin appendages
L60-L75
Hirsutism
9,16,17,99,105,106
L68!0
Hypertrichosis/excess (body) hair
76,90,106
Hypertrichosis, unspecified
L68!9
CHAPTER XIII: Diseases of the musculoskeletal system and connective tissue
M00-M99
Arthropathies
M00-M25
Phalangeal anomalies/tapering of phalanges/small fifth finger
9,13,15,17,32,69,73,107,108
Shortened fingers
49
Deformity of finger(s)
M20!0
Camptodactyly
13,17,49,69,76,88–90,92,93, 96
Bilateral pes calcaneovalgus
75
Flexion deformity
M21!2
Other joint contractures
109
Contracture of joint
M24!5
Limited joint movement/decreased pronation/supination of elbow/limited movement
of knee
13,15,17,32,54,69,70,76,88–
90,92,109,110
Incomplete extension of one or more digits
49,109
Hyperextension of joints/hyperextensible joints
81,106
Joint disorder, unspecified
M25!9
Dorsopathies
M40-M54
Scoliosis
111
M41
Soft tissue disorders
M60-M79
Abnormal muscle tone
14
Disorder of muscle, unspecified
M62!9
Abnormal deep tendon reflexes
14
Other specified disorders of synovium and tendon
M67!8
Osteopathies and chondropathies
M80-M94
Generalized non-specific osteoporosis
51
Osteoporosis, unspecified
M81!9
Delayed bone age
18,107,108
Other disorders of bone development and growth
M89!2
CHAPTER XIV: Diseases of the genitourinary system
N00-N99
Renal tubulo-interstitial diseases
N10-N16
Acute pyelonephritis
112
Acute tubulo-interstitial nephritis
N10
Pelvicaliceal dilation
52
Other and unspecified hydronephrosis
N13!3
Hydroureter
112
N13!4
Vesicoureteral reflux
112
Vesicoureteral-reflux-associated uropathy
N13!7
Other disorders of kidney and ureter
N25-N29
Superior calyectasis
18
Hypertropied kidney/hypertrophy/enlarged kidney
11,103,112
Caliceal diverticulum
11
Other specified disorders of kidney and ureter
N28!8
Other diseases of urinary system
N30-N39
Neurogenic bladder
107
Neuromuscular dysfunction of bladder, unspecified
N31!9
Recurrent urinary tract infection
52
Urinary tract infection, site not specified
N39!0
Diseases of male genital organs
N40-N51
Phimosis
52
Redundant prepuce, phimosis and paraphimosis
N47
Noninflammatory disorders of female genital tract
N80-N98
Vesicovaginal fistula
51,112
N82!0
CHAPTER XVI: Certain conditions originating in the perinatal period
P00-P96
Disorders related to length of gestation and fetal growth
P05-P08
Small for gestational age
2,3,9,49,64,75,81
P05!1

7!
Authors’ adjustment for ICD-10, if not specified in the study
Condition as stated in original paper
Source
Condition
Code
Intrauterine growth retardation
12,13,18,21,110
Slow fetal growth, unspecified
P05!9
Birth weight <10th percentile/low birth weight*
3,21,32,49,50,54,55,62,64,
96,99,106,113
Other low birth weight
P07!1
Pre-mature birth/born prematurely/preterm birth
21,49,75,88,99,113,114
Other preterm infants
P07!3
Respiratory and cardiovascular disorders specific to the perinatal period
P20-P29
Birth asphyxia/perinatal asphyxia
20
Birth asphyxia
P21
Hypoxic episode
72
Birth asphyxia, unspecified
P21!9
Respiratory distress syndrome/Respiratory distress/Hyaline membrane disease
9,20,21
Respiratory distress syndrome of newborn
P22!0
Meconium aspiration syndrome
20
Neonatal aspiration of meconium
P24!0
Bronchopulmonary dysplasia
20
Bronchopulmonary dysplasia originating in the perinatal period
P27!1
Atelectasus
53
Other and unspecified ateletasis of newborn
P28!1
Apnoeic attacks/episodes
17,20
Obstructive apnea
63
Other apnoea of newborn
P28!4
Bigeminy
58
Neonatal cardiac dysrhythmia
P29!1
Cardiac disorders
21
Cardiac disorders originating in the perinatal period, unspecified
P29!9
Haemorrhagic and haematological disorders of fetus and newborn
P50-P61
Neonatal hyperbilirubinaemia/jaundice (premature infant)
17,21,115,116
Neonatal jaundice associated with preterm delivery
P59!0
Neonatal hyperbilirubinemia/jaundice
17,59,99,103
Neonatal jaundice, unspecified
P59!9
Polycythaemia
20
Polycythaemia neonatorum
P61!1
Anemia due to prematurity
21
Anaemia of prematurity
P61!2
Transitory endocrine and metabolic disorders specific to fetus and newborn
P70-P74
Hypoglycaemia
9,17,20
Other neonatal hypoglycaemia
P70!4
Hypocalcaemia
17,20
Other neonatal hypocalcaemia
P71!1
Digestive system disorders of fetus and newborn
P75-P78
Necrotizing enterocolitis
20
Necrotizing enterocolitis of fetus and newborn
P77
Congenital cirrhosis
103
Other specified perinatal digestive system disorders
P78!8
Other disorders originating in the perinatal period
P90-P96
Periventricular leukomalacia
71
Neonatal cerebral leukomalacia
P91!2
Feeding difficulties/problems/slow feeding/sucking difficulties
19,20,50,51,54,73,81,116
Feeding problem of newborn
P92
Hypertonia/hypertonic
17,20,63
Congenital hypertonia
P94!1
(Muscular/generalized) Hypotonia/hypotonicity
12,13,15,34,50,52,54,59,65,
69,70,73,96,117
Congenital hypotonia
P94!2
Newborn abstinence syndrome
21
Neonatal withdrawal symptoms from materal use of drugs of addiction
P96!1
CHAPTER XVII: Congenital malformations, deformations and chromosomal abnormalities
Q00-Q99
Congenital malformation of the nervous system
Q00-Q07
Microcephaly/micrencephaly/microcephalic
2,7,9,10,12–18,20,31,32,37,
45,47,49,50,55,56,60,63,64, 69–
71,82,88,100,107,108, 118–120)
Occipitofrontal/small head circumference (<10th percentile)*
7,9,12,21,32,45,50,52,54,55,
62,63,65,69,73,82,89,91,96, 99,106
Microcephaly
Q02
(Congenital) Hydrocephalus
52,121
Congenital hydrocephalus
Q03
Displacement/abnormalities/agenesis of the corpus callosum/hypoplastic corpus
collosum
6,7,17,51,55,87,100,118
Congenital malformations of corpus callosum
Q04!0
Cerebral/neurological/cortical volume reduction/hypoplasia/atrophy/
underdevelopment
17,55,72,87,100,118,122
Other reduction deformities of brain
Q04!3
Schizencephaly
87
Congenital cerebral cysts
Q04!6
Heterotopias
17
Small brainstem
72
Other specified congenital malformations of brain
Q04!8

8!
Authors’ adjustment for ICD-10, if not specified in the study
Condition as stated in original paper
Source
Condition
Code
Polymicrogyria
82
Dandy-Walker cyst (cyst of the fourth ventricle)
117
Dilated lateral ventricles
55,81
Structural/neurologic abnormality
31
Cerebral/neurological displacement/asymmetry/abnormalities
106,118,122
Congenital malformations of brain, unspecified
Q04!9
Meningomyelocele (Lumbar/Sacral)
13,54,81,107
Spina bifida
Q05
(Pre)sacral/coccygeal dimple
12,13,51,65
Other specified congenital malformations of spinal cord
Q06!8
Congeital malformations of eye, ear, face and neck
Q10-Q18
Ptosis/blepharoptosis
2,8,9,11–13,15,16,18,46,50,
54,69,72,74,84,85,87,88, 91–
93,95,99,100,105,106
Blepharophimosis
13,15,62,65
Congenital ptosis
Q10!0
Epicanthal folds/broad epicanthus/prominent epicanthic folds
2,4,5,8–13,15–18,32,45,50, 52–
54,62,69,72,73,76,81,84, 88–
90,92,100,117
Short/narrow palpebral fissures*
9–12,14,16,17,32,37,45–47,
49,50,53,54,56,58,63,64,69,
72,73,76,81,82,84,86,88,89,
91,96,99,100,106,110,117, 119
(Anti)mongoloid fissures/slant/slanted palpebral fissures/downward slanted eyes
2,9,11,13,18,51,72
Other congenital malformations of eyelid
Q10!3
Telecanthus/short inner canthal distance
37,62,72,76,84,89,90,92,93
Other congenital malformations of lacrimal apparatus
Q10!6
Microphthalmos/microphthalmia
14,16,17,32,50,53,72,85,106
Microphthalmos
Q11!2
Cataract/lens opaification
72,75,84,85
Congenital cataract
Q12!0
Coloboma of iris
85
Q13!0
Clouded cornea/corneal opacity
53,81
Congenital corneal opacity
Q13!3
Microcornea
85,86
Peters’ anomaly
72
Axenfeld’s anomaly
72
Corneal atresia
53
Other congenital corneal malformations
Q13!4
Scleral defect
53
Other congenital malformations of anterior segment of eye
Q13!8
Hyperplastic primary vitreous
75,85
Congenital malformation of vitreous humour
Q14!0
Coccygeal fovea
15,69
Bilateral maculopathy
75
Dysplastic retina
75
Retinal tortuosity/tortuosity of retinal vessels
55,63,75,84
Congenital malformation of retina
Q14!1
Hypoplastic optic discs/optic disc hypoplasia
55,63,84
Small optic disc(s)
55,63,84
Congenital malformation of optic disc
Q14!2
Buphthalmos
85
Congenital glaucoma
Q15!0
Extensive malformation of eye(s)/eye anomalies/intraocular defects
16,55,85
Tortuosity of arteries in the eye
85
Other specified congenital malformation of eye
Q15!8
Dysfunction of auditory pathway
12
Congenital malformation of ear causing impairment of hearing, unspecified
Q16!9
Microtia
53
Q17!2
Railroad track ear(s)
76,88–90,92,109
Other specified congenital malformations of ear
Q17!8
Low set/seated ears
2,5,7,18,53,59,73,99
Ear malformation/anomalies/poorly formed/malformed/abnormal ears
9,15–17,45,50,51,106
Posterior rotation of ears/intrarotated ears
3,5,7,53,59
Congenital malformation of ear, unspecified
Q17!9
Webbing of neck
32
Q18!3
(Marked) Nasolabial fold
2,12
Other specified congenital malformations of face and neck
Q18!8

9!
Authors’ adjustment for ICD-10, if not specified in the study
Condition as stated in original paper
Source
Condition
Code
Congenital malformations of the circulatory system
Q20-Q28
Double outlet right ventricle
97
Q20!1
Artial abnormality
32
Other congenital malformations of cardiac chambers and connections
Q20!8
Ventricular septal defect
9,12–14,17,52,57,63,70,74,
75,81,88,95,97,98,107,113
Q21!0
Atrial septal defect
7,12–14,52,63,74,75,88,91, 95,97,113
Patent foramen ovale
58
Atrial septal defect
Q21!1
Atrioventricular septal defect
13,98,113,117
Q21!2
Tetralogy of Fallot/Fallot’s teratology
12,13,57,75,97,107
Tetralogy of Fallot
Q21!3
Pentalogy of fallot
13
Other congenital malformations of cardiac septa
Q21!8
Dysplastic/polypoid pulmonary valve
58
Other congenital malformations of pulmonary valve
Q22!3
Aortic stenosis
58
Congenital stenosis of aortic valve
Q23!0
Dextrocardia
97
Q24!0
Pulmonary (artery) stenosis
14,52–54,56,58,63,97,113
Pulmonary infundibular stenosis
Q24!3
Cardiac/heart malformation defect/congenital heart defect/abnormalities/anomalies
11,13,15,16,20,21,25,34,50,
65,69,88,90,96,97
Right/left ventricle hypertrophy
5
Axial deviation
53
Other specified congenital malformations of heart
Q24!8
Cardiac lesions
107,108
Congenital heart disease
9,49,52,106
Conotruncal heart defects
95
Congenital malformation of heart, unspecified
Q24!9
Patent ductus arteriosus/persistent ductus of Botalli
12,14,52,75,88,91,97
Patent ductus arteriosus
Q25!0
Coarctation of aorta
88,97
Q25!1
Hypoplasia of aorta
88
Deformed sinus Valsalva
58
Vascular ring abnormality
14
Other congenital malformations of aorta
Q25!4
Atresia of pulmonary artery
97
Q25!5
Peripheral pulmonary artery stenosis
97
Stenosis of pulmonary artery
Q25!6
Aplasia of pulmonary artery
13,113
Other congenital malformations of pulmonary artery
Q25!7
Persistent left superior vena cava
52
Q26!1
Profunda femoris artery
14
Other specified congenital malformations of circulatory system
Q28!8
Congenital malformations of the respiratory system
Q30-Q34
Choanal stenosis
63
Choanal atresia
Q30!0
Nasal hypoplasia
63
Agenesis and underdevelopment of nose
Q30!1
Anteverted nares/nostrils
2,9,53,58,76,88–90,92,100
Flat/low/broad/deep nasal bridge
2,3,5,7,9–12,45,49,50,52–
54,64,73,76,81,88–90,99, 100
Short/small upturned nose
13,15,45,49–52,54,58,63,65,
69,70,73,100,110
Other congenital malformations of nose
Q30!8
Hypoplastic lungs
53
Hypoplasia and dysplasia of lung
Q33!6
Cleft lip and cleft palate
Q35-Q37
Submuscous cleft palate/cleft of soft palate
17,53
Cleft soft palate
Q35!3
Cleft palate
7,11–17,20,50,53,55,57,61,
69,70,74,75,100
Cleft palate, unspecified
Q35!9
Cleft lip
7,55,57,61,62,100
Q36
Other congnital malformations of the digestive system
Q38-Q45
Long/smooth/indistinct/poorly developed/hypoplastic philtrum*
5,9,11,14,31,37,45,47,49,50, 52–
54,56,58,62–64,73,76, 82,88–
Congenital malformations of lips, not elsewhere classified
Q38!0

10!
Authors’ adjustment for ICD-10, if not specified in the study
Condition as stated in original paper
Source
Condition
Code
90,92,93,100,106, 117,119,123
Narrow vermillion border/thin upper lip*
5,10,12,14,15,31,37,45,47,
49,50,52,54,58,62–64,65,69,
70,73,76,82,88–90,92,93,
100,110,117,119,123
High arched palate/gothic palate/palatal anomaly
2,3,8,12,13,15,18,51,53,59, 61,69,73
Congenital malformation of palate, not elsewhere classified
Q38!5
Small hypopharynx
63
Other congenital malformations of pharynx
Q38!8
Hiatus hernia
51
Congenital hiatus hernia
Q40!1
Rudimentary gallbladder
99
Agenesis, aplasia and hypoplasia of gallbladder
Q44!0
(Congenital) Extra-hepatic biliary atresia
99,103
Atresia of bile ducts
Q44!2
Bile duct hypoplasia
99
Other congenital malformations of bile ducts
Q44!5
Congenital malformations of genital organs
Q50-Q56
Biseptate vagina
17
Doubling of vagina
Q52!1
Hypoplastic labia majora
17
Other congenital malformations of the vulva
Q52!7
Labial hypoplasia/hypoplastic labia
52
Other specified congenital malformations of female genitalia
Q52!8
Congenital malformations of female genitalia, unspecified
Q52!9
Minor/anomalous external genital anomalies
12,13,15–18,65,69,70
Congenital malformations of male genital organs, unspecified
Q55!9
Cryptorchism/undescended testis/testes
2,7,52,54,63,75
Undescended testicle, unspecified
Q53!9
Hypospadias – penile abnormalities
20,52
Hypospadias, penile
Q54!1
Hypospadias
12,20,52
Hypospadias, unspecified
Q54!9
Small phallus
63
Other congenital malformations of penis
Q55!6
Hooded prepuce
54
Other specified congenital malformations of male genital organs
Q55!8
Congenital malformations of the urinary system
Q60-Q64
Renal agenesis
20
Renal agenesis, unspecified
Q60!2
11,103,112
Renal hypoplasi, unilateral
Q60!3
11
Renal hypoplasia, bilateral
Q60!4
Renal/kidney hypoplasia/aplasia
13,95
Renal hypoplasia, unspecified
Q60!5
Cystic disease of the kidneys
56
Cystic kidney disease
Q61
Kidney caliceal cyst
112
Congenital single renal cyst
Q61!0
Renal/kidney dysplasia/dysplastic kidney
11,14,95
Renal dysplasia
Q61!4
Hydronephrosis/hydronephrotic kidney
1,5,11,13,16,52,72,81,112
Congenital hydronephrosis
Q62!0
Ureteropelvic anomalies/ ureteropelvic junction constriction/obstruction
11,81,107,108
Atresia and stenosis of ureter
Q62!1
Megaloureteral duplication
112
Congenital megaloureter
Q62!2
Double/duplex ureter/ureteral duplication/duplication of upper renal tract
2,13,52,95
Third ureter
11
Duplication of ureter
Q62!5
Vesicoureteral/vesicoureteric reflux
13,14
Congenital vesico-uretero-renal reflux
Q62!7
Double/duplex kidney
2,13
Accessory kidney
Q63!0
Horseshoe kidney (renal fusion)
11,14,95
Lobulated, fused and horseshoe kidney
Q63!1
Malrotation of the kidney
11,107,108
Ectopic kidney
Q63!2
Renal pelviectasis
18
Double/duplication of collecting system
9,112
Dysplasia of renal calyces
3
Other specified congenital malformations of kidney
Q63!8
Renal anomalies
11,15,65,69,96
Congenital malformation of kidney, unspecified
Q63!9
Bladder diverticulum
13,112
Congenital diverticulum of bladder
Q64!6
Trabeculated bladder
112
Other congenital malformations of bladder and urethra
Q64!7
Urinary tract malformation
13
Congenital malformation of urinary system, unspecified
Q64!9
Congenital malformations and deformities of the musculoskeletal system
Q65-Q79
Congenital hip dislocation/hip instability
2,13,15,17,72,81
Congenital dislocation of hip, unspecified
Q65! 2

11!
Authors’ adjustment for ICD-10, if not specified in the study
Condition as stated in original paper
Source
Condition
Code
Talipes (Club foot/feet)/per equinovarus
3,14,49,54,73
Talipes equinovarus
Q66!0
Metatarsus varus
57
Q66!2
Feet malformations/positional foot deformities
2
Congenital malformations of feet, unspecified
Q66!9
Facial asymmetry
4
Q67!0
Dolichocephalic head
9
Dolichocephaly
Q67!2
Plagiocephaly
51
Q67!3
Hemihypertrophy of left side of face
4
Other congenital defomities of skull, face and jaw
Q67!4
Veterbral segmentation defects
95
Congenital deformity of spine
Q67!5
Pectus excavatum
13,16,32,51,63,73
Q67!6
Pectus carinatum/pigeon-shaped chest
14,54
Pectus carinatum
Q67!7
Chest asymmetry/prominent hemithorax
2,7
Other congenital defomities of chest
Q67!8
Clinodactyly
2,12,13,47,49,50,65,76,88–93,96
Proximal placement of thumbs
14
Minor hand anomalies/hand malformations
74
Congenital deformity of hand
Q68!1
Tibial bowing/femoral or tibial torsion
49,73
Congenital bowing of tibia and fibula
Q68!4
Joint anomalies/synostosis of joints/valgus alignment of limbs
16,17,49,91,96
Other specified congenital musculoskeletal deformities
Q68!8
Polydactyly
6,49
Q69
Extra toe
54
Accessory toe(s)
Q69!2
Syndactyly
32,49
Q70
Syndactyly of toes
7,54
Fused toes
Q70!2
Radio-ulnar synostosis/deformity/terminal transverse defect of forearm/hand
7,12,74,106,108
Hypoplastic radial head
108
Other congenital malformations of upper limb(s), including shoulder girdle
Q74!0
Brachycephaly
72,73
Craniosynostosis
Q75!0
Hypertelorism
3,4,7-9,11,53,54,73,100
Q75!2
Midface hypoplasia/flat midface/maxilla hypoplasia/flattened maxilla/maxillary
hypoplasia
16,17,32,45,47,49,50,56,64,
65,69,70,73,76,81,88–90,92,
93,99,100,117
Metopic ridge
9
Bulged forehead/frontal bossing
8,51,59
Large posterior/anterior fontanelle
51,117
Persistently patent frontanelles
14
Narrow forehead
54
Other specified congenital malformations of skull and face bones
Q75!8
Spina bifida occulta
14
Q76!0
Congenital fusion of cervical vertebrae/cervical spin fusion
107,108
Thoracic kyphosis
14
Sacral dysgenesis
3
Other congenital malformations of spine, not associated with scoliosis
Q76!4
Cervical rib
14
Q76!5
Abnormal thoracic cage (development)/rib anomalies
32,107,108
Other congenital malformations of ribs
Q76!6
Tibial exostoses (bilateral)
51
Multiple congenital exostoses
Q78!6
Diaphramatic hernia
7,57
Congenital diaphragmatic hernia
Q79!0
Diaphragmatic anomalies
16
Eventration of diaphragm
8
Other congenital malformations of diaphragm
Q79!1
Gastroschisis
110
Q79!3
Other congenital malformations
Q80-Q89
Abnormal/altered crease(s) anomalies (e!g!, hockey stick)
1,2,5,9,11–13,15–18,49,52,
58,65,69,73,76,88–90,92,99, 109,123
(Bridged/bilateral) Simian crease
7,17,51,54,81
Other specified congenital malformations of skin
Q82!8
Wide-set/hypoplastic nipples
2,7,10,11,99
Other congenital malformations of breast
Q83!8

12!
Authors’ adjustment for ICD-10, if not specified in the study
Condition as stated in original paper
Source
Condition
Code
Hair whorls (two or more)
73
Fine (electric) hair
18
Congenital morphological disturbances of hair, not elsewhere classified
Q84!1
Nail hypoplasia/hypoplastic/small nails
7,9,11,12,16,51,63,88–90, 95,117
Dysplastic toenails
73,81
Other congenital malformations of nails
Q84!6
Glossoptosis
2
Congenital malformation syndromes predominantly affecting facial appearance
Q87!0
CHAPTER XVIII: Symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified
R00-R99
Symptoms and signs involving the circulatory and respiratory systems
R00-R09
Functional murmurs/cardiac/heart murmur
8,9,17,52,53,56,58,63,74,76,81, 89-
91,93,97,107,109,116,117
Benign and innocent cardiac murmurs
R01!0
Rhonchi
53
Abnormal breathing
63
Other and unspecified abnormalities of breathing
R06!8
Symptoms and signs involving the digestive system and abdomen
R10-R19
Hepatomegaly
99,102,104
Hepatomegaly, not elsewhere classified
R16!0
Symptoms and signs involving the nervous and musculoskeletal systems
R25-R29
Tremulousness/tremor
14,17,50,63,73
Tremor, unspecified
R25!1
Ataxia
52
Ataxia, unspecified
R27!0
Poor coordination/abnormal motor coordination
14,59,73
Other and unspecified lack of coordination
R27!8
Persistent primitive reflexes
73
Abnormal reflex
R29!2
Decorticate rigidity
17
Abnormal posture
R29!3
Symptoms and signs involving cognition, perception, emotional state and behaviour
R40-R46
Irritability and anger
R45!4
Anger (control) problem(s)
25
Hostility
R45!5
Aggressive behaviour/aggression/violence
14,47,70,71
Physical violence
R45!6
Symptoms and signs involving speech and voice
R47-R49
Echolalia
18,53
Other and unspecified symbolic dysfunctions
R48!8
Aphonic
63
Aphonia
Q49!1
Hypernasality
61
Hypernasality and hyponasality
R49!2
General symptoms and signs
R50-R69
Febrile seizures
39,71
Febrile convulsions
R56!0
Profuse sweating (diaphoresis)
73
Hyperhidrosis, unspecified
R61!9
Delayed milestones
11,59,73
Deficits in the development of standing/walking/astasia
3,18,73,78,124
Delayed milestone
R62!0
Prenatal/postnatal growth retardation/deficiency
2,9,15–18,50,54,62–64,69,70,
72,75,87,88
Height <10th percentile* /short stature/stunted
2,3,7,9,12,18,21,45,49,50,52,55,
60,63,65, 69,71,73,82,89,91,96, 120
Weight <10th percentile* / underweight
2,3,7,9,12,18,21,45,49,50,52,55,
63,65,69,71,73,82,89,91,106,120
Failure to thrive
15,18,19,49,50,72,101
Other lack of expected normal physiological development
R62!8
Irritable infant/neonatal irritability/ hyperexcitability
14,21,50,51,58,73,81,125
Nonspecific symptoms peculiar to infancy
R68!1
Abnormal findings on diagnostic Imaging and in function studies, without diagnosis
R90-R94
Abnormal MRI
37
Abnormal finding on diagnostic imaging of central nervous system
R90
EEG abnormality
13,50
Abnormal results of function studies of central nervous system (Abnormal
electroencephalogram [EEG])
R94!0
Abnormal retinal function - ERG records
87
Abnormal results of function studies of peripheral nervous system and special senses
(Abnormal electroretinogram [ERG])
R94!1
CHAPTER XX: External causes of morbidity and mortality
V01-Y98
Intentional self-harm/Sequelae of external causes of morbidity and mortality
X60-X84

13!
Authors’ adjustment for ICD-10, if not specified in the study
Condition as stated in original paper
Source
Condition
Code
Self-injury/self-harm/suicidal/suicide threats/attempts
14,25,33,37,126,127
Intentional self-harm
X60-X84
CHAPTER XXI: Factors influencing health status and contact with health services
Z00-Z99
Persons with potential health hazards related to socioeconomic and psychosocial circumstances
Z55-Z65
School failure/problems/poor scholastic performance/dropped out
14,28,32,50,96,126,127
Underachievement in school
Z55!3
Problems (adjusting to new careers) with employment/unemployed
14,70,127
Problems related to employment and unemployment
Z56
ICD-10=International Classification of Diseases, version 10.
*Diagnostic features that
discriminate individuals
with and without fetal alcohol syndrome.

14!
Table A2. Study characteristics and quality rating of the studies included in the meta-analyses
Reference
Country
Year of
publication
Year of
study
Setting
Study design
Method of data
collection
Sample
size
Gender
(% Male)
Age range (mean,
if available)
Diagnostic system used
Total quality
rating score
Quality
rating scores
Population-
based – 2
Clinic-based – 1
Active (ACA; Clinical
assessment) – 2
Passive (RCR, Birth
defects registry) – 1
< 20 – 1
20-49 – 2
50+ – 3
No – 0
Yes – 1
Maximum
score = 8
Bell et al!
39
Canada
2010
n/a
Clinic-based
Retrospective
cohort study
RCR
86
59!8
*
2 to 49 (15!2)
*
Canadian guidelines
2
Score
1
1
3
1
6
Beattie et al!
52
Scotland
1983
1971-
1981
Population-
based
Retrospective
cohort study
RCR
40
52!5
0 to 10 (2!2)
Not specified
Score
2
1
2
0
5
Burd et al!
25
United States
2003
n/a
Clinic-based
Retrospective
cohort study
RCR
152
58!9
*
1m to 56 (8!2)
*
FASD Diagnostic
Checklist
5
Score
1
1
3
1
6
CDC
64
United States
1995
1981-
1993
Population-
based
Retrospective
cohort study
Birth defects registry
60
58!3
0 to 31 (8!0)
Not specified
Score
2
1
3
0
6
Church et al!
61
United States
1997
n/a
Clinic-based
Retrospective
cohort study
RCR
22
36!4
3 to 27 (11!5)
Criteria of the Fetal
Alcohol Study Group of
the Research Society on
Alcoholism
8
Score
1
1
2
1
5
Egeland et
al!
49
United States
1998
1977-
1992
Population-
based
Retrospective
cohort study
RCR (multi-source)
145
53!1
0 to 16
Not specified
Score
2
1
3
0
6
Elgen et al!
55
Norway
2007
1999-
2004
Clinic-based
Prospective
cohort study
Clinical assessment
25
59!6
*
0 to 16 (7!7)
*
CDC FAS diagnostic
guidelines
11
Score
1
2
2
1
6
Famy et al!
30
United States
1998
n/a
Clinic-based
Prospective
cohort study
(nested)
Clinical assessment
11
60!0
*
19 to 51 (28!8)
*
Not specified
Score
1
2
1
0
4
Habbick et
al!
34
Canada
1996
1992-
1994
Population-
based
Cross-
sectional study
ACA
207
52!7
n/a
Guidelines by Sokol and
Clarren
14
with the criteria
of the Fetal Alcohol
Study Group of the
Research Society on
Alcoholism
8
Score
2
2
3
1
8
Halliday et
al!
20
Ireland
1982
n/a
Clinic-based
Prospective
cohort study
Clinical assessment
10
52!2
*
0 to 4
*
Guidelines by Clarren
and Smith
16
Score
1
2
1
1
5
Hanson et
al!
16
United States
1976
n/a
Clinic-based
Retrospective
case series
RCR
41
n/a
n/a
Not specified
Score
1
1
2
0
4
Hug et al!
87
United States
2000
n/a
Clinic-based
Retrospective
case series
RCR
11
81!8
0 to 12 (4!5)
Not specified

15!
Reference
Country
Year of
publication
Year of
study
Setting
Study design
Method of data
collection
Sample
size
Gender
(% Male)
Age range (mean,
if available)
Diagnostic system used
Total quality
rating score
Quality
rating scores
Population-
based – 2
Clinic-based – 1
Active (ACA; Clinical
assessment) – 2
Passive (RCR, Birth
defects registry) – 1
< 20 – 1
20-49 – 2
50+ – 3
No – 0
Yes – 1
Maximum
score = 8
Score
1
1
1
0
3
Jones et al!
109
United States
2010
2009
Population-
based
Cross-
sectional study
ACA
245
51!8
n/a
Not specified
Score
2
2
3
0
7
Kalberg et
al!
67
United States
2006
n/a
Population-
based
Cross-
sectional study
ACA
14
50!0
1!7 to 5!7 (3!7)
Hoyme clarification of
the IOM diagnostic
criteria
21
Score
2
2
1
1
6
Kvigne et al!
50
United States
2004
1981-
1993
Clinic-based
Retrospective
case-control
study
RCR
43
53!8
*
4 to 21
*
(10!0)
Not specified
Score
1
1
2
0
4
Kvigne et al!
19
United States
2009
1981-
1993
Clinic-based
Retrospective
case-control
study
RCR
43
53!8
*
4 to 21
*
(10!0)
Not specified
Score
1
1
2
0
4
Landgren et
al!
46
Sweden
2010
n/a
Population-
based
Cross-
sectional study
ACA
21
56!8
*
4!8 to 10!5 (7!5)
*
Hoyme clarification of
the IOM diagnostic
criteria
21
Score
2
2
2
1
7
Löser &
Majewski
113
Germany
1977
n/a
Clinic-based
Retrospective
case series
RCR
16
56!3
0 to 6 (1!8)
Not specified
Score
1
1
1
0
3
May et al!
90
South Africa
2007
2002
Population-
based
Cross-
sectional study
ACA
55
58!9
*
(7!7)
*
Hoyme clarification of
the IOM diagnostic
criteria
21
Score
2
2
3
1
8
May et al!
93
Italy
2011
2005-
2007
Population-
based
Cross-
sectional study
ACA
8
50!0
(6!7)
*
Hoyme clarification of
the IOM diagnostic
criteria
21
Score
2
2
1
1
6
Ribeiro et al!
84
Portugal
2007
n/a
Clinic-based
Retrospective
cohort study
RCR
32
71!9
1 to 17 (9!6)
Guidelines by Sokol &
Clarren
14
Score
1
1
2
1
5
Robinson et
al!
106
Canada
1987
1984-
1985
Population-
based
Cross-
sectional study
ACA
14
59!1
*
3 to 18 (9!7)
*
Criteria of the Fetal
Alcohol Study Group of
the Research Society on
Alcoholism
8
Score
2
2
1
1
6
Rössig et al!
12
Germany
1994
1980-
1993
Clinic-based
Retrospective
cohort study
RCR
36
52!8
0 to 17!4 (8!0)
Guidelines by
Majewski
31,32
Score
1
1
2
1
5
Sandor et al!
97
Canada
1981
n/a
Clinic-based
Retrospective
cohort study
RCR
76
56!6
0 to 18
Not specified

16!
Reference
Country
Year of
publication
Year of
study
Setting
Study design
Method of data
collection
Sample
size
Gender
(% Male)
Age range (mean,
if available)
Diagnostic system used
Total quality
rating score
Quality
rating scores
Population-
based – 2
Clinic-based – 1
Active (ACA; Clinical
assessment) – 2
Passive (RCR, Birth
defects registry) – 1
< 20 – 1
20-49 – 2
50+ – 3
No – 0
Yes – 1
Maximum
score = 8
Score
1
1
3
0
5
Smith et al!
107
Canada
1981
n/a
Clinic-based
Retrospective
cohort study
RCR
76
56!6
0 to 18
Not specified
Score
1
1
3
0
5
Spohr et al!
69
Germany
1993
1977-
1979
Clinic-based
Retrospective
cohort study
RCR
60
60!0
0!5 to 11!4 (3!1)
Guidelines by Sokol &
Clarren
14
Score
1
1
3
1
6
Steinhausen et
al!
15
Germany
1982
1977-
1979
Clinic-based
Retrospective
cohort study
RCR
71
n/a
0 to 15!5 (4!3)
Guidelines by
Majewski
31,32
Score
1
1
3
1
6
Strömland &
Hellström
85
Sweden
1996
n/a
Clinic-based
Prospective
cohort study
RCR
25
64!0
n/a
Guidelines by Sokol &
Clarren
14
Score
1
1
2
1
5
Strömland &
Sundelin
75
Sweden
1996
n/a
Clinic-based
Retrospective
case series
RCR
5
60!9
n/a
Not specified
Score
1
1
1
0
3
Swayze et
al!
100
United States
1997
n/a
Clinic-based
Retrospective
cohort study
Clinical assessment
10
60!0
4 to 26 (15!0)
Guidelines by Sokol &
Clarren
14
Score
1
2
1
1
5
Tredwell et
al!
108
Canada
1982
n/a
Clinic-based
Retrospective
cohort study
RCR
50
56!6
0 to 18
Not specified
Score
1
1
3
0
5
Urban et al!
120
South Africa
2008
2001-
2004
Population-
based
Cross-
sectional study
ACA
123
49!7
(7!1)
*
IOM diagnostic criteria
42
Score
2
2
3
1
8
Viljoen et al!
76
South Africa
2005
n/a
Population-
based
Cross-
sectional study
ACA
64
46!9
(6!5)
Hoyme clarification of
the IOM diagnostic
criteria
21
Score
2
2
3
1
8
ACA=Active case ascertainment. CDC=Centre for Disease Control. IOM=Institute of Medicine. RCR=Retrospective chart review.
*
Inclusive of individuals with other FASD-related diagnoses.

17!
Table A3. Pooled prevalence of comorbid conditions among individuals with fetal alcohol syndrome and results of the tests of heterogeneity
ICD-10
Tests of heterogeneity
95% Confidence
interval
Q statistic
Code
Condition
Prevalence
estimate
LE
UE
Included studies
Q
df
P-value
I
2
test
D18!0
Haemangioma, any site
0!209
0!082
0!370
15,16,20
6!42
2
0!040
66!5%
F70-F79
Mental retardation
0!433
0!211
0!669
15,34,46,49,50,52,55
157!56
6
0!000
95!8%
F80
Specific developmental disorders of speech and language
0!672
0!431
0!876
15,49,50,61,64
70!91
4
0!000
94!0%
F81
Specific developmental disorders of scholastic skills
0!309
0!195
0!437
25,50
2!51
1
0!113
60!1%
F82
Specific developmental disorder of motor function
0!436
0!231
0!652
15,46,49,50,52,64,67
100!34
6
0!000
93!6%
F84!0
Childhood autism
0!041
0!000
0!127
34,46
2!11
1
0!146
52!7%
F89
Unspecified disorder of psychological development
0!692
0!477
0!873
16,25,49,50,64,69
123!20
5
0!000
95!3%
Disturbance of activity and attention
Attention deficit hyperactivity disorder
0!512
0!236
0!784
25,34,46,50,55,64
125!50
5
0!000
96!9%
Hyperactivity/hyperactive and inattentiveness
0!251
0!170
0!342
49,50
1!55
1
0!214
35!3%
F90!0
Short/impaired attention span/problems/distractibility
0!274
0!000
0!514
12,15,50,52,64,69,75,76
154!14
7
0!000
95!1%
F91
Conduct disorder
0!074
0!029
0!137
34,46,50
3!28
2
0!194
43!4%
F91!3
Oppositional defiant disorder
0!233
0!000
0!487
25,46
5!05
1
0!025
80!2%
G40!2
Localization-related (focal) (partial) symptomatic epilepsy and epileptic
syndromes with complex partial seizures
0!215
0!147
0!293
25,49,50,52,64,75
13!72
5
0!018
63!9%
H47!0
Disorders of optic nerve, not elsewhere classified
0!441
0!000
0!782
46,52,75,84,85,87
58!51
5
0!000
91!5%
H50!0
Convergent concomitant strabismus
0!312
0!000
0!601
75,84,85
8!07
2
0!018
75!1%
H50!1
Divergent concomitant strabismus
0!111
0!041
0!207
84,85
0!23
1
0!629
0!0%
H50!5
Heterophoria
0!042
0!000
0!113
84,85
0!04
1
0!836
0!0%
H50!9
Strabismus, unspecified
0!188
0!093
0!305
15,46,49,76,84,87,90,93
41!67
7
0!000
84!0%
H52!1
Myopia
0!107
0!000
0!218
55,84
1!30
1
0!254
23!3%
H55
Nystagmus and other irregular eye movements
0!066
0!023
0!126
52,75,84,85
5!09
3
0!165
0!0%
H90!2
Conductive hearing loss, unspecified
0!568
0!439
0!693
12,61
0!66
1
0!416
0!0%
Sensorineural hearing loss, unspecified
0!154
0!000
0!404
12,61
4!96
1
0!026
79!8%
H90!5
Central hearing disorder
0!579
0!000
1!000
12,61
46!59
1
0!000
97!9%
H90!8
Mixed conductive and sensorineural hearing loss, unspecified
0!153
0!000
0!379
12,61
3!43
1
0!064
70!9%
H91!9
Hearing loss, unspecified
0!149
0!000
0!355
50,75
1!45
1
0!228
31!2%
K07!0
Major anomalies of jaw size
0!383
0!000
0!746
12,100
3!90
1
0!048
74!4%
K07!1
Anomalies of jaw-cranial base relationship
0!237
0!000
1!000
15,76,90
154!79
2
0!000
98!6%
K40
Inguinal hernia
0!117
0!044
0!216
20,52,75
0!53
2
0!765
0!0%
K40-K46
Hernia
0!242
0!180
0!310
15,67,69
0!89
2
0!640
0!0%
L68!9
Hypertrichosis, unspecified
0!053
0!000
0!184
76,90,106
8!95
2
0!011
84!2%
M20!0
Deformity of finger(s)
0!329
0!000
1!000
15,69,107
75!90
2
0!000
97!2%
Flexion deformity
M21!2
Camptodactyly
0!132
0!057
0!231
69,76,90,93
8!06
3
0!045
62!7%
Joint disorder, unspecified
M25!9
Limited joint movement/decreased pronation/supination of elbow/limited
movement of knee
0!094
0!051
0!149
15,69,76,90,109
12!18
4
0!016
66!3%
P05!1
Small for gestational age
0!405
0!332
0!480
49,64
1!08
1
0!299
7!3%
P07!1
Other low birth weight
0!605
0!409
0!786
49,50,55,64,106,113
44!94
5
0!000
87!8%
P07!3
Other preterm infants
0!653
0!314
1!000
49,75,113
6!96
2
0!031
82!5%
P94!2
Congenital hypotonia
0!407
0!149
0!693
12,15,50,52,69
67!99
4
0!000
94!5%
Microcephaly
0!619
0!452
0!773
12,15,16,20,49,50,55,64,69, 100,107,120
165!85
11
0!000
94!2%
Q02
Occipitofrontal/Small head circumference [<10th percentile]
0!781
0!662
0!881
12,50,52,55,
7!63
3
0!054
60!8%
Q04!0
Congenital malformations of corpus callosum
0!311
0!171
0!471
55,87,100
1!33
2
0!513
0!0%

18!
ICD-10
Tests of heterogeneity
95% Confidence
interval
Q statistic
Code
Condition
Prevalence
estimate
LE
UE
Included studies
Q
df
P-value
I
2
test
Q04!3
Other reduction deformities of brain
0!373
0!000
0!682
55,87,100
6!34
2
0!042
69!0%
Q10!0
Congenital ptosis
0!133
0!104
0!165
12,15,46,50,69,76,84,85,87,
90,93,100,106,109
22!74
13
0!045
17!7%
Other congenital malformations of eyelid
Epicanthal folds/broad epicanthus/prominent epicanthic folds
0!405
0!279
0!538
12,15,16,50,69,76,84,90,100
56!39
8
0!000
85!9%
Q10!3
Short/narrow palpebral fissures
0!597
0!436
0!749
12,16,46,49,50,64,69,84,100
70!15
8
0!000
90!4%
Other congenital malformations of lacrimal apparatus
Q10!6
Short inner canthal distance
0!188
0!000
0!387
76,90,93
11!08
2
0!004
78!2%
Q11!2
Microphthalmos
0!078
0!024
0!155
50,85
0!47
1
0!491
0!0%
Q12!0
Congenital cataract
0!070
0!000
0!148
75,84,85
1!97
2
0!374
0!0%
Congenital malformation of vitreous humour
0!096
0!000
0!267
75,85
1!41
1
0!236
28!9%
Coccygeal fovea
0!541
0!435
0!645
15,69
1!51
1
0!220
33!6%
Retinal tortuosity/tortuosity of retinal vessels
0!499
0!000
1!000
75,84
3!87
1
0!049
74!2%
Q14!0
Hypoplastic optic discs/optic disc hypoplasia
0!179
0!000
0!551
55,84
7!31
1
0!007
86!3%
Q17!8
Other specified congenital malformations of ear
0!106
0!076
0!140
76,90,109
1!26
2
0!532
0!0%
Q17!9
Congenital malformations of ear, unspecified
0!395
0!222
0!582
15,16,50,106
18!46
3
0!000
81!0%
Q21!0
Ventricular septal defect
0!151
0!075
0!246
12,52,75,97,113
8!45
4
0!077
51!3%
Q21!1
Atrial septal defect
0!131
0!000
0!337
12,52,75,97,113
27!21
4
0!000
90!2%
Q21!3
Tetralogy of Fallot
0!054
0!019
0!104
12,75,97
1!94
2
0!380
0!0%
Q24!3
Pulmonary infundibular stenosis
0!034
0!000
0!081
52,97,113
2!14
2
0!343
17!9%
Q24!8
Other specified congenital malformations of heart
0!246
0!124
0!391
15,16,20,34,69,90
51!75
6
0!000
90!0%
Congenital malformation of heart, unspecified
Q24!9
Congenital heart disease
0!144
0!079
0!224
49,52,106
2!64
2
0!267
33!9%
Q25!0
Patent ductus arteriosus
0!025
0!000
0!056
12,52,75,97
0!54
3
0!910
0!0%
Other congenital malformations of nose
Anteverted nares/nostrils
0!128
0!076
0!192
76,90,100
0!77
2
0!681
0!0%
Flat/low/broad/deep nasal bridge
0!427
0!342
0!514
12,49,50,64,76,90,100
15!21
6
0!019
64!2%
Q30!8
Short/small upturned nose
0!370
0!218
0!535
15,49,50,69,100
27!62
4
0!000
86!9%
Q35!9
Cleft palate, unspecified
0!144
0!053
0!268
12,15,20,50,55,61,69,75,100
37!24
8
0!000
82!5%
Q36
Cleft lip
0!120
0!000
0!265
55,61,100
3!52
2
0!172
45!0%
Congenital malformations of lip, not elsewhere classified
Long/smooth/indistinct/poorly developed philtrum
0!577
0!450
0!698
49,50,64,76,90,93,100,106
32!37
7
0!000
81!0%
Q38!0
Narrow vermilion border/thin upper lip
0!615
0!462
0!758
12,15,49,50,64,69,76,90,93, 1000
75!00
9
0!000
91!6%
Q38!5
Congenital malformations of palate, not elsewhere classified
0!266
0!124
0!436
12,15,61,69
16!38
3
0!001
82!0%
Q52!9/Q55!9
Congenital malformation of female genitalia, unspecified/Congenital
malformation of male genital organ, unspecified
0!246
0!108
0!415
12,15,16,69
17!45
3
0!001
84!5%
Q53!9
Undescended testicle, unspecified
0!163
0!000
0!332
52,75
0!21
1
0!649
0!0%
Q54!9
Hypospadias, unspecified
0!071
0!000
0!167
12,20
0!41
1
0!524
0!0%
Q63!9
Congenital malformation of kidney, unspecified
0!071
0!032
0!122
15,69
0!53
1
0!466
0!0%
Q68!1
Congenital deformity of hand
0!251
0!178
0!332
12,50,76,90,93
7!10
4
0!131
35!8%
Other congenital malformations of upper limb(s), including shoulder girdle
Q74!0
Radio-ulnar synostosis/deformity/terminal transverse defect of
forearm/hand
0!043
0!014
0!087
12,106,108
0!69
2
0!707
0!0%
Q75!8
Other specified congenital malformations of skull and face bones
0!380
0!255
0!513
16,49,50,64,69,76,90,93,100
43!51
8
0!000
87!2%
Q82!8
Other specified congenital malformations of skin
0!329
0!222
0!446
12,15,16,49,52,69,76,90,109
72!02
8
0!000
90!0%
Q84!6
Other congenital malformations of nails
0!079
0!031
0!145
12,90
0!95
1
0!331
0!0%
R01!0
Benign and innocent cardiac murmurs
0!124
0!079
0!177
52,76,90,93,97,109,
9!52
5
0!090
52!0%

19!
ICD-10
Tests of heterogeneity
95% Confidence
interval
Q statistic
Code
Condition
Prevalence
estimate
LE
UE
Included studies
Q
df
P-value
I
2
test
R62!8
Other lack of expected normal physiological development
Prenatal/postnatal growth retardation/deficiency
0!901
0!766
1!000
15,16,50,63,69,87
37!49
5
0!000
87!4%
Height <10th percentile
0!784
0!445
1!000
49,50,52,55,106
57!26
4
0!000
95!7%
Weight <10th percentile
0!771
0!457
1!000
12,49,50,52,55,106
75!58
5
0!000
95!9%
Failure to thrive
0!566
0!000
1!000
15,49,50
98!09
2
0!000
97!4%
df=degrees of freedom. ICD-10=International Classification of Diseases, version 10. LE=lower estimate. UE=upper estimate.
Note. Conditions in italics are as stated in the original papers and cannot clinically and/or statistically be grouped together; therefore, each condition was
analyzed separately. Conditions with only one study are not listed.

20!
References
1 Khan A, Bader JL, Hoy GR, Sinks LF. Hepatoblastoma in child with fetal alcohol syndrome. Lancet 1979;
313: 1403–4.
2 Zaunschirm A, Muntean W. Fetal alcohol syndrome and malignant disease. Eur J Pediatr 1984; 141: 256.
3 Kiess W, Linderkamp O, Hadom HB, Haas R. Fetal alcohol syndrome and malignant disease. Eur J Pediatr
1984; 143: 160–1.
4 Hornstein L, Crowe C, Gruppo R. Adrenal carcinoma in child with history of fetal alcohol syndrome.
Lancet 1977; 2: 1292–3.
5 Battisti L, Degani D, Rugolotto S, Brogna-Pignatti C. Fetal alcohol syndrome and malignant disease: A
case report. Am J Pediatr Hematol Oncol 1993; 15: 136–7.
6 Kiley VA, Lazerson J. Agenesis of the corpus callosum and neural crest tumors. Pediatr Hematol Oncol
1986; 3: 179–82.
7 Kinney H, Faix R, Brazy J. The fetal alcohol syndrome and neuroblastoma. Pediatrics 1980; 66: 130–2.
8 Ramilo J, Harris VJ. Neuroblastoma in a child with the hydantoin and fetal alcohol syndrome: The
radiographic fetures. Br J Radiol 1979; 52: 993–5.
9 Seeler RA, Isreal JN, Royal JE, Kaye CI, Rao S, Abulaban M. Ganglioneuroblastoma and fetal haydantoin-
alcohol syndromes. Pediatrics 1979; 63: 524–7.
10 Bostrom B, Nesbit MEJ. Hodgkin disease in a child with fetal alcohol-hydantoin syndrome. J Pediatr
1983; 103: 760–2.
11 Qazi Q, Masakawa A, Milman D, McGann B, Chua A, Haller J. Renal anomalies in fetal alcohol
syndrome. Pediatrics 1979; 63: 886–9.
12 Rössig C, Wasser S, Oppermann P. Audiologic manifestations in fetal alcohol syndrome assessed by
brainstem auditory-evoked potentials. Neuropediatrics 1994; 25: 245–9.
13 Majewski F. Alcohol embryopathy: Some facts and speculations about pathogenesis. Neurobehav Toxicol
Teratol 1981; 3: 129–44.
14 Elliott E, Payne JM, Morris A, Haan E, Bower C. Fetal alcohol syndrome: A prospective national
surveillance study. Arch Dis Child 2008; 93: 732–7.
15 Steinhausen HC, Nestler V, Spohr HL. Development and psychopathology of children with the fetal
alcohol syndrome. J Dev Behav Pediatr 1982; 3: 49–54.
16 Hanson JW, Jones KL, Smith DW. Fetal alcohol syndrome. Experience with 41 patients. JAMA 1976; 235:
1458–60.
17 Jones KL, Smith DW. Recognition of the fetal alcohol syndrome in early infancy. Lancet 1973; 2: 999–
1001.
18 Tenbrinck MS, Buchin SY. Fetal alcohol syndrome: Report of a case. JAMA 1975; 232: 1144–7.
19 Kvigne VL, Leonardson GR, Borzelleca J, Neff-Smith M, Welty TK. Hospitalizations of children who
have fetal alcohol syndrome or incomplete fetal alcohol syndrome. S D Med 2009; 62: 97, 99, 101–3.
20 Halliday HL, Reid MM, McClure G. Results of heavy drinking in pregnancy. BJOG 1982; 89: 892–5.
21 Toutain S, Lejeune C. Family management of infants with fetal alcohol syndrome or fetal alcohol spectrum
disorders. J Dev Phys Disabil 2008; 20: 425–36.
22 Alati R, MacLeod J, Hickman M, et al. Intrauterine exposure to alcohol and tobacco use and childhood IQ:
Findings from a parental-offspring comparison within the Avon Longitudinal Study of Parents and
Children. Pediatr Res 2008; 64: 659–66.
23 Baer JS, Barr HM, Bookstein FL, Sampson PD, Streissguth AP. Prenatal alcohol exposure and family
history of alcoholism in the etiology of adolescent alcohol problems. J Stud Alcohol 1998; 59: 533–43.

21!
24 Baer JS, Sampson PD, Barr HM, Connor PD, Streissguth AP. A 21-year longitudinal analysis of the effects
of prenatal alcohol exposure on young adult drinking. Arch Gen Psychiatry 2003; 60: 377–85.
25 Burd L, Klug MG, Martsolf JT, Kerbeshian J. Fetal alcohol syndrome: Neuropsychiatric phenomics.
Neurotoxicol Teratol 2003; 25: 697–705.
26 Clark E, Lutke J, Minnes P, Ouellette-Kuntz H. Secondary disabilities among adults with fetal alcohol
spectrum disorder in British Columbia. J FAS Int 2004; 2: e13.
27 Grant T, Huggins J, Connor P, Pedersen JY, Whitney N, Streissguth A. A pilot community intervention for
young women with fetal alcohol spectrum disorders. Community Ment Health J 2004; 40: 499–511.
28 Streissguth AP, Bookstein FL, Barr HM, Sampson PD, O'Mally D, Young JK. Risk factors for adverse life
outcomes in fetal alcohol syndrome and fetal alcohol effects. J Dev Behav Pediatr 2004; 25: 228–38.
29 Alati R, Al Mamun A, Williams GM, O'Callaghan M, Najman JM, Bor W. In utero alcohol exposure and
prediction of alcohol disorders in early adulthood: a birth cohort study. Arch Gen Psychiatry 2006; 63:
1009–16.
30 Famy C, Streissguth AP, Unis AS. Mental illness in adults with fetal alcohol syndrome or fetal alcohol
effects. Am J Psychiatry 1998; 155: 552–4.
31 Astley SJ, Olson HC, Kerns K, et al. Neuropyschological and behavioral outcomes from a comprehensive
magnetic resonance study of children with fetal alcohol spectrum disorders. Can J Pharmacol 2009; 16:
e178–201.
32 Slavney PR, Grau JG. Fetal alcohol damage and schizophrenia. J Clin Psychiatry 1978; 39: 782–3.
33 O'Mally K, Huggins J. Suicidality in adolescents and adults with fetal alcohol spectrum disorders. Can J
Psychiatry 2005; 50: 125.
34 Habbick BF, Nanson JL, Snyder RE, Casey RE, Schulman AL. Fetal alcohol syndrome in Saskatchewan:
unchanged incidence in a 20-year period. Can J Public Health 1996; 87: 204–7.
35 Walthall JC, O'Connor MJ, Paley B. A comparison of psychopathology in children with and without
prenatal alcohol exposure. Ment Health Aspects Dev Disabil 2008; 11: 69–78.
36 O'Connor MJ, Shah B, Whaley S, Cronin P, Gunderson B, Graham J. Psychiatric illness in a clinical
sample of children with prenatal alcohol exposure. Am J Drug Alcohol Abuse 2002; 28: 743–54.
37 Astley SJ. Profile of the first 1,400 patients receiving diagnostic evaluations for fetal alcohol spectrum
disorder at the Washington State Fetal Alcohol Syndrome Diagnostic & Prevention Network. Can J Clin
Pharmacol 2010; 17: e132–64.
38 Fryer SL, McGee CL, Matt GE, Riley EP, Mattson SN. Evaluation of psychopathological conditions in
children with heavy prenatal alcohol exposure. Pediatrics 2007; 119: e733–41.
39 Bell SH, Stade B, Reynolds JN, et al. The remarkably high prevalence of epilepsy and seizure history in
fetal alcohol spectrum disorder. Alcohol Clin Exp Res 2010; 34: 1084–9.
40 O'Connor MJ. Prenatal alcohol exposure and infant negative affect as precursors of depressive features in
children. Inf Mental Hlth J 2001; 22: 291–9.
41 O'Connor MJ, Kasari C. Prenatal alcohol exposure and depressive features in children. Alcohol Clin Exp
Res 2000; 24: 1084–92.
42 O'Connor MJ, Paley B. The relationship of prenatal alcohol exposure and the postnatal environment to
child depressive symptoms. J Pediatr Psychol 2006; 31: 50–64.
43 Roebuck TM, Mattson SN, Riley EP. Behavioral and psychosocial profiles of alcohol-exposed children.
Alcohol Clin Exp Res 1999; 23: 1070–6.
44 Steinhausen HC, Willms J, Spohr HL. Long-term psychopathologies and cognitive outcome of children
with fetal alcohol syndrome. J Am Acad Child Adolesc Psychiatry 1993; 32: 990–4.

22!
45 Spohr HL, Willms J, Steinhausen HC. The fetal alcohol syndrome in adolescence. Acta Paediatrics 1994;
404: 19–26.
46 Landgren M, Svensson L, Strömland K, Andersson-Grönlund M. Prenatal alcohol exposure and
neurodevelopmental disorders in children adopted from eastern Europe. Pediatrics 2010; 125: e1178–85.
47 Fernández-Mayoralas DM, Fernández-Jaén A, Muñoz-Jareño N, Pérez B, Arroyo-González R. Fetal
alcohol syndrome, tourette syndrome, and hyperactivity in nine adopted children. Pediatr Neurol 2010; 43:
110–6.
48 Wengel T, Hanlon-Dearman AC, Fjeldsted B. Sleep and sensory characteristics in young children with fetal
alcohol spectrum disorder. J Dev Behav Pediatr 2011; 32: 384–92.
49 Egeland GM, Perhain-Hestet KA, Gessnet BD, Ingle D, Berne JE, Miclcldalgh JP. Alcohol syndrome in
Alaska, 1977 through 1992: an administrative prevalence derived from multiple data sources. Am J Public
Health 1998; 88: 781–6.
50 Kvigne VL, Leonardson GR, Neff-Smith M, Brock E, Borzelleca J, Welty TK. Characteristics of children
who have full or incomplete fetal alcohol syndrome. J Pediatr 2004; 145: 635–40.
51 Azouz EM, Kavianian G, Der Kaloustian VM. Fetal alcohol syndrome and bilateral tibial exostoses: A case
report. Pediatr Radiol 1993; 23: 615–6.
52 Beattie JO, Day RE, Cocburn F, Garg RA. Alcohol and the fetus in the west of Scotland. Br Med J (Clin
Res Ed) 1983; 287: 17–20.
53 Church MW, Gerkin KP. Hearing disorders in children with fetal alcohol syndrome: Findings from case
reports. Pediatrics 1988; 82: 147–54.
54 Collins E, Turner G. Six children affected by maternal alcoholism. Med J Aust 1978; 2: 606–8.
55 Elgen I, Bruaroy S, Laegreid LM. Lack of recognition and complexity of foetal alcohol neuroimpairments.
Acta Paediatr 2007; 96: 237–41.
56 Habbick BF, Zaleski WA, Casey R, Murphy F. Liver abnormalities in three patients with fetal alcohol
syndrome. Lancet. 1979; 1: 580–1.
57 Nanson JL. Autism in fetal alcohol syndrome: a report of six cases. Alcohol Clin Exp Res 1992;16:558–65.
58 Sonoda T, Ohdo S, Sennari E. Congenital heart disease in a case with fetal alcohol syndrome: Clinical and
postmortem findings. Acta Paediatr Jpn 1984; 26: 241–7.
59 Shaywitz SE, Caparulo BK, Hodgson ES. Developmental language disability as a consequence of prenatal
exposure to ethanol. Pediatrics 1981; 68: 850–5.
60 von Gontard A, Deget F. Gilles de la Tourette's syndrome in a girl with fetal alcohol syndrome. J Stud
Alcohol 1996; 57: 219–20.
61 Church MW, Eldis F, Blakley BW, Bawle EV. Hearing, language, speech, vestibular, and dentofacial
disorders in fetal alcohol syndrome. Alcohol Clin Exp Res 1997; 21: 227–37.
62 Pensiero S, Manna F, Michieletto P, Perissutti P. Cleft palate and keratoconus in a child affected by fetal
alcohol syndrome: An accidental association? Cleft Palate Craniofac J 2007; 44: 95–7.
63 Usowicz AG, Golabi M, Curry C. Upper airway obstruction in infants with fetal alcohol syndrome. Am J
Dis Child 1986; 140: 1039–41.
64 Centers for Disease Control and Prevention (CDC). Update: Trends in fetal alcohol syndrome - United
States, 1979-1993. Morb Mortal Wkly Rep 1995; 44: 249–51.
65 Steinhausen HC, Willms J, Winkler-Metzke C, Spohr HL. Behavioual phenotype in foetal alcohol
syndrome and foetal alcohol effects. Dev Med Child Neurol 2003; 45: 179–82.
66 Fuchs D, Burnside L, Marchenski S, Murdy A. Children with disabilities receiving services from child
welfare agencies in Manitoba. Toronto, ON: Centre of Excellence for Child Welfare, 2005.

23!
67 Kalberg WO, Provost B, Tollison SJ, et al. Comparison of motor delays in young children with fetal
alcohol syndrome to those with prenatal alcohol exposure and with no prenatal alcohol exposure. Alcohol
Clin Exp Res 2006; 30: 2037–45.
68 Mukherjee R, Layton M, Yacoub E, Turk J. Autism and autistic traits in people exposed to heavy prenatal
alcohol: data from a clinical series of 21 individuals and nested case control study. Adv Ment Health
Intellect Disabil 2011; 5: 42–9.
69 Spohr HL, Willms J, Steinhausen HC. Prenatal alcohol exposure and long-term development consequences.
Lancet 1993; 341: 907–10.
70 Spohr HL, Willms J, Steinhausen HC. Fetal alcohol spectrum disorders in young adulthood. J Pediatr
2007; 150: 175–9.
71 Bhang SY, Ahn DH, Lee YJ, An HY, Ahn JH. The first report of fetal alcohol effect in a 12-year-old child
in Korea. Psychiatry Investig 2009; 6: 50–3.
72 Chan T, Bowell R, O'Keefe M, Lanigan B. Ocular manifestations in fetal alcohol syndrome. Br J
Ophthalmol 1991; 75: 524–6.
73 Harris SR, Osborn JA, Weinberg J, Loock C, Junaid K. Effects of prenatal alcohol exposure on neuromotor
and cognitive development during early childhood: A series of case reports. Phys Ther 1993; 73: 608–17.
74 Streissguth AP, Clarren SK, Jones KL. Natural history of the fetal alcohol syndrome: A 10-year follow-up
of eleven patients. Lancet 1985; 13: 85–91.
75 Strömland K, Sundelin K. Paediatric and ophthalmological observations in offspring of alcohol abusing
mothers. Acta Paediatrica 1996; 85: 1463–8.
76 Viljoen DL, Gossage JP, Brooke L, et al. Fetal alcohol syndrome epidemiology in a South African
community: A second study of a very high prevalence area. J Stud Alcohol 2005; 66: 593–604.
77 Schonfeld AM, Mattson SN, Riley EP. Moral maturity and delinquency after prenatal alcohol exposure. J
Stud Alcohol 2005; 66: 545–54.
78 Olson HC, Fledman JJ, Streissguth AP, Sampson PD, Bookstein FL. Neuropsychological deficits in
adolescents with fetal alcohol syndrome: Clinical findings. Alcohol Clin Exp Res 1998; 22: 1998–2012.
79 Whaley SE, O'Connor MJ, Gunderson B. Comparison of the adaptive functioning of children prenatally
exposed to alcohol to a nonexposed clinical sample. Alcohol Clin Exp Res 2001; 25: 1018–24.
80 O'Connor MJ, Sigman M, Kasari C. Attachment behavior of infants exposed prenatally to alcohol:
Mediating effects of infant affect and mother-infant interaction. Dev Psychopathol 1992; 4: 243–56.
81 Goldstein G, Arulanantham K. Neural tube defect and renal anomalies in a child with fetal alcohol
syndrome. J Pediatr 1978; 93: 636–7.
82 Reinhardt K, Mohr A, Gartner J, Spohr H, Brockmann K. Polymicrogyria in fetal alcohol syndrome. Birth
Defects Res A Clin Mol Teratol 2010; 88: 128–31.
83 Burd L, Klug MG, Bueling R, Martsolf J, Olson M, Kerbeshian J. Mortality rates in subjects with fetal
alcohol spectrum disorders and their siblings. Birth Defects Res A Clin Mol Teratol 2008; 82: 217–23.
84 Ribeiro SBA, Vale PJ, Tenedorio PA, Rodrigues PA, Bilhoto MA, Pereira HC. Ocular manifestations in
fetal alcohol syndrome. Eur J Ophthalmol 2007; 17: 104–9.
85 Strömland K, Hellström A. Fetal alcohol syndrome--an ophthalmological and socioeducational prospective
study. Pediatrics 1996; 97: 845–50.
86 Chan DQ. Fetal alcohol syndrome. Optom Vis Sci 1999; 76: 678–85.
87 Hug TE, Fitzgerald KM, Cibis GW. Clinical and electroretinographic findings in fetal alcohol syndrome. J
AAPOS 2000; 4: 200–4.

24!
88 Autti-Rämö I, Fagerlaud A, Ervalahti N, Loimu L, Korkman M, Hoyme HE. Fetal alcohol spectrum
disorders in Finland: clinical delineation of 77 older children and adolescents. Am J Med Genet A 2006;
140A: 137–43.
89 Ervalahti N, Korkman M, Fagerlund A, Autti-Rämö I, Loimu L, Hoyme HE. Relationship between
dysmorphic features and general cognitive function in children with fetal alcohol syndrome. Am J Med
Genet A 2007; 143A: 2916–23.
90 May PA, Gossage JP, Marais AS, et al. The epidemiology of fetal alcohol syndrome and partial FAS in a
South African community. Drug Alcohol Depend 2007; 88: 259–71.
91 Jones K, Smith D. The fetal alcohol syndrome. Tetratology 1975; 12: 1–10.
92 May PA, Fiorentino DJ, Gossage P, Kalberg WO, Hoyme HE, Robinson LK. Epidemiology of FASD in a
province in Italy: Prevalence and characteristics of children in a random sample of schools. Alcohol Clin
Exp Res 2006; 30: 1562–75.
93 May PA, Fiorentino D, Coriale G, et al. Prevalence of children with severe fetal alcohol spectrum disorders
in communities near Rome, Italy: New estimated rates are higher than previous estimates. Int J Environ Res
Public Health 2011; 8: 2331–51.
94 Cohen-Kerem R, Bar-Oz B, Nulman I, Papaioannou VA, Koren G. Hearing in children with fetal alcohol
spectrum disorder (FASD). Can J Clin Pharmacol 2007; 14: e307–12.
95 O'Leary CM, Nassar N, Kurinczuk JJ, et al. Prenatal alcohol exposure and risk of birth defects. Pediatrics
2010; 126: e843–50.
96 Shaywitz SE, Cohen DJ, Shaywitz BA. Behavior and learning difficulties in children of normal intelligence
born to alcoholic mothers. J Pediatr 1980; 96: 978–82.
97 Sandor GG, Smith DF, MacLeod PM. Cardiac malformations in the fetal alcohol syndrome. J Pediatr
1981; 98: 771–3.
98 Steeg CN, Woolf P. Cardiovascular malformations in the fetal alcohol syndrome. Am Heart J 1979; 98:
635–7.
99 Newman SL, Flannery DB, Caplan DB. Simultaneous occurrence of extrahepatic biliary atresia and fetal
alcohol syndrome. Am J Dis Child 1979; 133: 101.
100 Swayze VW, Johnson VP, Hanson JW, et al. Magnetic resonance imaging of brain anomalies in fetal
alcohol syndrome. Pediatrics 1997; 99: 232–40.
101 Uc A, Vasiliauskas E, Piccoli DA, Flores AF, DiLorenzo C, Hyman PE. Chronic intestinal
psueuoobstruction associated with fetal alcohol syndrome. Dig Dis Sci 1997; 42: 1163–2267.
102 Lefkowitch JH, Rushton AR, Feng-Chen KC. Hepatic fibrosis in fetal alcohol syndrome. Pathologic
similarities to adult alcoholic liver disease. Gastroenterology 1983; 85: 951–7.
103 Dunigan TH, Werlin SL. Extrahepatic biliary atresia and renal anomalies in fetal alcohol syndrome. Am J
Dis Child 1981; 135: 1067–8.
104 Mooller J, Brandt NJ, Tygstrup I. Hepatic dysfunction in patient with fetal alcohol syndrome. Lancet 1979;
1: 605–6.
105 Manning MA, Hoyme HE. Fetal alcohol spectrum disorders: A practical approach to diagnosis. Neurosci
Biobehav Rev 2007; 31: 230–8.
106 Robinson GC, Conry JL, Conry RF. Clinical profile and prevalence of fetal alcohol syndrome in an isolated
community in British Columbia. Can Med Assoc J 1987; 137: 203–7.
107 Smith DF, Sandor GG, MacLeod PM, Tredwell S, Wood B, Newman DE. Intrinsic defects in fetal alcohol
syndrome: Studies on 76 cases from British Columbia and the Yukon Territory. Neurbehav Toxicol Teratol
1981; 3: 145–52.

25!
108 Tredwell SJ, Smith DF, MacLeod PJ, Wood BJ. Cervical spine anomalies in fetal alcohol syndrome. Spine
1982; 7: 331–4.
109 Jones KL, Hoyme HE, Robinson LK, et al. Fetal alcohol spectrum disorders: Extending the range of
structural defects. Am J Med Genet A 2010; 152A: 2731–5.
110 Sarda P, Bard H. Gastroschisis in a case of dizygotic twins: The possible role of maternal alcohol
consumption. Pediatrics 1984; 74: 94–6.
111 de Cornulier M, de Lacour F, Avet-Loiseau H, et al. Vertebral involvement and fetal acohol syndrome.
Pediatrie 1991; 46: 685–9.
112 Havers W, Majewski F, Olbing H, Eickenberg HU. Anomalies of the kidneys and genitourinary tract in
alcoholic embryopathy. J Urol 1980; 124: 108–10.
113 Löser H, Majewski F. Type and frequency of cardiac defects in embryofetal alcohol syndrome. Report of
16 cases. Br Heart J 1977; 39: 1374–9.
114 Sokol RJ, Janisse JJ, Louis JM, et al. Extreme prematurity: An alcohol-related birth effect. Alchol Clin Exp
Res 2007; 31: 1037.
115 Christoffel KK, Salafsky I. Fetal alcohol syndrome in dizygotic twins. J Pediatr 1975; 87: 963–7.
116 Van Dyke DC, Mackay L, Ziaylek EN. Management of severe feeding dysfunction in children with fetal
alcohol syndrome. Clin Pediatr 1982; 21: 339.
117 Johnson CAC, Hill ID, Bowie MD. Fetal alcohol syndrome with hydrocephalus: A case report. S Afr Med J
1984; 65: 738–9.
118 Riley EP, McGee CL, Sowell ER. Teratogenic effects of alcohol: A decade of brain imaging. Am J Med
Genet C Semin Med Genet 2004; 127C: 35–41.
119 Autti-Rämö I, Gaily E, Granstrom ML. Dysmorphic features in offspring of alcoholic mothers. Arch Dis
Child 1992; 67: 712–6.
120 Urban M, Chersich MF, Fourie LA, Chetty C, Olivier L, Viljoen D. Fetal alcohol syndrome among grade 1
schoolchildren in Northern Cape Province: Prevalence and risk factors. S Afr Med J 2008; 98: 877–82.
121 Clarren SK, Alvord EC, Sumi SM, Streissguth AP, Smith DW. Brain malformations related to prenatal
exposure to ethanol. J Pediatr 1978; 92: 64–7.
122 O'Hare ED, Kan E, Yoshii J, et al. Mapping cerebellar vermal morphology and cognitive correlates in
prenatal alcohol exposure. Neuroreport 2005; 16: 1285–90.
123 Ceccanti M, Spangnolo AP, Tarani L, et al. Clinical delination of fetal alcohol spectrum disorder (FASD)
in Italian children: Comparison and contrast with other racial/ethnic groups and implications for diagnosis
and prevention. Neurosci Biobehav Rev 2007; 31: 270–7.
124 Jacobson JL, Jacobson SW, Sokol RJ, Martier SS, Ager JW, Kaplan-Estrin MG. Teratogenic effects of
alcohol on infant development. Alcohol Clin Exp Res 1993; 17: 174–83.
125 Lemola S, Stadlmayr W, Crob A. Infant irritability: The impact of fetal alcohol exposure, maternal
depressive symptoms, and low emotional support from the husband. Inf Mental Hlth J 2009; 30: 57–81.
126 Huggins JE, Grant T, O'Malley K, Streissguth AP. Suicide attempts among adults with fetal alcohol
spectrum disorders: Clinical considerations. Ment Health Aspects Dev Disabil 2008; 11: 33–41.
127 Streissguth AP, Barr HM, Kogan J, Bookstein FL. Understanding the occurrence of secondary disabilities
in clients with fetal alcohol syndrome (FAS) and fetal alcohol effects (FAE). Seattle, Washington:
University of Washington, Fetal Alcohol and Drug Unit, 1996.