Approximately 5 % of the population world-wide is reported to have a diagnosis of attention deficit/hyperactivity disorder (ADHD) [
1], a disorder often associated with co-morbid conditions that can complicate identification and treatment [
2]; fetal alcohol spectrum disorders (FASD) are among those conditions that are commonly found to co-exist with ADHD [
3]. There is an established knowledge base with regards to identification and treatment guidelines for ADHD, and similarly, yet to a lesser degree, for FASD; there is also an increasing awareness and knowledge base of individuals having both disorders concurrently. There are not, however, formal guidelines for diagnosis, randomized controlled trials of any kind, or evidence-based treatment plans for this unique group of individuals with ADHD and associated FASD [
4]. Therefore, this multi-disciplinary meeting was organized to produce identification and treatment guidelines for patients with ADHD and associated FASD according to the clinical expertise and knowledge among the attendees based upon consensus.
In this article we refer to the co-existence of ADHD and FASD as—ADHD and associated FASD—and not FASD with associated or co-morbid ADHD because: 1) most alcohol affected individuals present with and are initially evaluated for attention and executive function deficits [
3,
5]; 2) management of ADHD symptoms in the FASD individual is integral to treatment and may minimize the potential impact of the common secondary disabilities associated with FASD [
3]; and 3) speculation remains as to the nature of the relationship of the co-existing disorders with each other [
3,
6]. The authors recognize that current formal guidelines for the management of ADHD symptoms do not account for the implications of prenatal alcohol exposure in affected individuals, thus the formulation of expanded guidelines for management of ADHD and associated FASD is the focus of this discussion. Firstly, we describe what is known about ADHD and FASD separately and then we describe what is known about the co-existing disorders. Next we discuss how our collaborative efforts led to consensus. Lastly, we present our recommended guidelines for clinicians, with specific regards to: identification and assessment, interventions and treatment, and multiagency liaisons and management. Included are three pertinent case studies that exemplify the need for individualized treatments and services, which commonly extend beyond medical care. A list of abbreviations can be found at the end of the manuscript.
ADHD
ADHD is a childhood onset, diagnosable neurobiological disorder with genetic and environmental origins [
7] characterized by pervasive behavioral symptoms of hyperactivity, inattentiveness, and impulsivity that interfere with functioning and development [
8]. In 1968 the American Psychiatric Association officially recognized hyperkinetic impulse disorder, which has since been renamed ADHD in the second edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-II). Symptoms present relatively early in childhood and persist over one’s lifespan for about half of individuals with childhood ADHD [
9,
10]. A systematic review and meta-regression analysis reported an overall worldwide-pooled estimate of 5.29 % [
11]. Structural brain MRI studies, comparing individuals with ADHD with controls, report overall reductions in brain volume of those having ADHD and reveal the largest differences in cerebellar regions, the splenium of the corpus callosum, total and right cerebral volume, and right caudate; several frontal regions assessed in two studies also showed large significant differences [
12]. In addition to academic and social impairments, children with ADHD are at risk for other psychological disorders and about half have additional behavioral disorders [
7,
13]. Meta-analyses of 42 international prison studies, based on data derived from symptom-based clinical instruments, reported 30 % of youth offenders and 26 % of adult offenders have clinically diagnosable ADHD [
14]. Furthermore, the adult offenders had higher rates of coexisting psychopathology and greater impairment due to mood, anxiety and personality disorders [
15].
Clear diagnostic criteria for ADHD are listed in the Diagnostic and Statistical Manual of Mental Disorders, 5
th edition, (DSM-5) [
8] and the World Health Organization’s International Statistical Classification of Diseases, 10
th edition, (ICD-10) [
16] (note that ADHD is the ICD-10 equivalent of hyperkinetic disorder). While the criteria have not changed from DSM-IV [
17], DSM- 5 has updated the definition of ADHD to more accurately characterize the experience of affected adults, and examples have been included to illustrate the types of behavior children, older adolescents, and adults with ADHD might exhibit. There is a strong evidence base in the literature regarding guidelines for identification, treatment, and management of individuals with ADHD, and the authors advocate use of the National Institute for Health Care Excellence (NICE) 2008 guidelines [
18].
FASD
FASD is a non-diagnostic descriptive term referring to the full range of diagnosable conditions caused by the deleterious effects of prenatal alcohol exposure (PAE), including neuropsychological, behavioral, and physical abnormalities [
19]. The range of clinical phenotypes varies in severity and outcome depending on the level, pattern, and timing of maternal alcohol consumption [
19,
20]. Fetal alcohol syndrome (FAS) was first described in 1973 [
21]. In 1996 the United States’ Institute of Medicine delineated useful classification terms including FAS, partial fetal alcohol syndrome (pFAS), alcohol related birth defects (ARBD), and alcohol related neuro-developmental disorder (ARND) [
22]. It wasn’t until 2000, however, that the term FASD was officially introduced [
23].
The implications of heavy PAE are long term and pervasive, affecting the individual, mother, family, and community throughout one’s lifespan [
24‐
26]. FASD are considered a “hidden disability” because most individuals affected by PAE are not identified until adolescence or adulthood, if at all [
27]. Although FAS is estimated to occur in 2 to 7 per 1000 live births in young children in the United States, and up to 68 per 1000 in high-risk populations [
28,
29], FASD are more prevalent and may occur in as many as 2–5 % of younger school children in the US and some western European countries [
30], which means that as many as 6 to 16 million young children in the US may have FASD, based upon the current US population of 320 million [
31]. Meta-analyses of children and youth in a child-care system revealed a 6.0 % pooled prevalence of FAS and a 16.9 % pooled prevalence of FASD [
32]. A recent study reported a significantly high proportion (86.5 %) of FASD among foster and adopted youth referred to a mental health center, which were previously mis- or undiagnosed [
33]. Furthermore, a retrospective assessment of children in the United Kingdom reported prenatal alcohol exposure rates of 34 % among “looked after children” and 75 % among those awaiting adoption [
34]. Brain imaging techniques have shown that PAE causes permanent structural alterations to the brain, and reduced overall volume [
35,
36]. Studies have demonstrated damage to the corpus callosum, cerebellar vermis, basal ganglia, as well as perislyvian, orbito-frontal, and parietal brain regions of individuals with FASD [
35]. Additionally, a review of individuals with FASD reported a pooled prevalence of 90.9 % having abnormal peripheral nervous system function results [
37].
There is a high prevalence of co-morbid conditions in individuals with FASD [
37]. Long term studies report that adolescents and young adults with FASD have major problems with adaptive behavior, with high rates of disrupted education (61 %), trouble with the law (60 %), confinement (50 %), inappropriate sexual behavior on repeated occasions (49 %), and drug and alcohol related problems (35 %) [
26]. Deficits in adaptive functioning can often help clinicians identify individuals with prenatal alcohol exposure [
26]. Individuals with FASD present with specific behavioral impairments that make them especially vulnerable to manipulation. They are easily coerced into producing false confessions thereby making them more likely to become involved with the criminal justice system [
38]; and one study reported 35 % of individuals with FASD have been in jail or prison at some point [
39].
The diagnostic criteria for FAS is well established in the ICD-10 and DSM-5, but the diagnostic criteria for PAE conditions other than FAS are less precise and subject to considerable debate due to lack of available published evidence [
40]. Several FASD diagnostic approaches have been designed to promote best practices, but accurate clinical diagnoses remain, for the most part, to be made by expert clinicians who have wider experience with complex neurobehavioral findings. According to the ICD-10 and DSM-5 diagnostic criteria sets, in the absence of confirmed PAE, the signs and symptoms of FAS fall into three categories: 1) a characteristic pattern of facial anomalies (short palpebral fissure, smooth philtrum, thin vermilion border of the upper lip); 2) evidence of growth retardation (pre-and/or postnatal); and 3) evidence of central nervous system (CNS) abnormalities [
19‐
21]. While the presence of facial anomalies enables diagnosis in some children with histories of heavy prenatal alcohol exposure, most PAE affected individuals do not exhibit obvious dysmorphology [
41] and/or lack reliable PAE history [
42], which greatly hinders identification. Although useful for classification, the IOM’s terms are not listed as diagnosable conditions in the ICD or DSM criteria sets. DSM-5 has proposed a diagnostic criteria set for neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE), but is not yet intended for clinical use. A recent paper on FASD [
43] (which thoroughly elucidates the diagnostic terms and includes the proposed DSM-5 criteria on ND-PAE) and recent book on ARND [
44], together explain why a more accessible diagnosis is needed. Until the DSM-5 or ICD-11 have established criteria sets, the authors advocate using the 2005 Canadian Guidelines for the Diagnosis of FASD [
20]. These guidelines focus more on the neurobehavioral assessment over growth deficiencies and recommend using a multidisciplinary approach to diagnosis [
20].
ADHD and associated FASD
Individuals with histories of heavy PAE or ADHD are at risk for a wide range of impairments including behavioral and neuropsychological deficits [
37,
45,
46]. Children with a diagnosis of ADHD present with impairments similar to those apparent in alcohol-exposed children especially with regards to executive functioning and attention deficits [
47]. There are, however, clear distinctions between the two groups; individuals with ADHD with PAE perform worse on conventional tests sensitive to attentional problems and conduct disorder, compared with individuals with FASD [
46]. ADHD is the most common psychiatric disorder diagnosed in children with PAE in the United States at a rate of 41 % [
48] and in individuals with FASD world-wide at a rate of 48 % [
49]. Given the range of a 2–5 % prevalence rate of FASD in the US and some western European countries and the 41–48 % prevalence rate of co-occurring ADHD, we estimate the prevalence of ADHD and associated FASD to be 0.8–2.4 % among children in the US and some western European countries. Although, because many affected individuals are un-diagnosed, we speculate that the two disorders occur together at far higher rates than estimates suggest. Despite the depth of knowledge on the separate disorders and an increasing amount on the concurrence, the exact relationship between the two remains unclear and there is a debate over whether or not the presentation necessarily constitutes separate entities [
3,
6,
25]. Furthermore, evidence indicates that ADHD symptoms in individuals identified with FASD may be a specific clinical phenotype [
3]. Understanding the relationship between the disorders is complicated by the fact that ADHD is primarily defined descriptively (without a clear etiology) and FASD are primarily defined mechanistically (with a clear etiology). The clinical quality of ADHD in children with FASD often differs from that of children having only ADHD [
50]; behavioral studies report exacerbated effects of having both PAE and ADHD compared with alcohol exposure alone [
45]. The majority of individuals with PAE lack the physical and facial dysmorphology commonly associated with FAS [
41] and many lack reliable histories of PAE [
42], which further increases the difficulty in making a clear diagnosis. According to the National Organization of Fetal Alcohol Spectrum (NOFAS), most individuals affected by FASD are often only identified ─ if at all─ subsequent to a referral for learning disabilities or for co-occurring ADHD [
27], likely resulting in many mis- or undiagnosed individuals. In the absence of high quality studies examining the relationship between ADHD and FASD and reporting on effective treatments, the authors have produced identification and treatment guidelines for clinicians, based upon expert consensus.