Fetal alcohol spectrum disorders are an umbrella term used to describe a pattern of disabilities and abnormalities that result from fetal exposure to ethanol during pregnancy and are the most common non-heritable causes of intellectual disability. The effects on the fetus may include physical, mental, behavioral, and/or learning disabilities, with possible lifelong implications, and encompass a phenotypic range that can greatly vary between individuals but reliably include one or more of the following: facial dysmorphism, fetal growth deficiency, central nervous system dysfunction, and neurobehavioral impairment. Five diagnoses fall under the term FASDs: FAS (fetal alcohol syndrome); partial FAS (partial fetal alcohol syndrome); alcohol-related neurodevelopmental disorder (ARND); neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE); and alcohol-related birth defects (ARBDs) [10]^[1]. This was the first systematic approach delineating the diagnostic categories introduced by the Institute of Medicine (IOM), which was revised in 2005 and 2016 and led to FASDs being divided into five subtypes. The fetal alcohol spectrum disorders’ four-letter diagnostic code was developed in 2000 to give greater diagnostic scope for describing children adversely affected by alcohol who did not fulfill the diagnostic criteria for FAS. One study assessed several diagnostic frameworks, wherein authors noted a lack of ascribed convergent validity, including the absence of a diagnostic gold standard against which to measure competing systems. Such a problem occurs when there is a debate between diagnoses. For instance, according to one diagnostic framework, a patient can be diagnosed with FAS and, according to another, receive no diagnosis. The authors noted that the concordance between systems is improved when diagnostic categories collapse into FASDs versus no diagnosis. Such an approach was designed for the 2016 Canadian system. The Canadian system introduces two subtypes of criteria: FASDs with sentinel facial features and FASDs without sentinel facial features [5]^[2]. Physical symptoms, which can be identified phenotypically, are characteristic facial features, such as short palpebral fissures, a thin vermilion border of the upper lip, and a smooth philtrum. Growth retardation is defined as being in the 10th percentile or less using height and weight measurements on standard growth curves adjusted for age, sex, race, or ethnicity [10]^[1]. Externally visible symptoms make it possible to notice possible disorders earlier, especially in early childhood; therefore, FAS and pFAS can be more recognizable compared with Alcohol-Related Neurodevelopmental Disorder (ARND), Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure (ND-PAE), and Alcohol-Related Birth Defects (ARBD) because of the characteristic facial dysmorphology and growth retardation [11]^[3]. 

2. Epidemiology

Despite many public education programs regarding alcohol consumption during pregnancy, the percentage of pregnant women consuming alcohol is increasing. According to data from the Centers for Disease Control and Prevention, alcohol consumption in pregnant women increased from 7.6% in 2012 to 10.2% in 2015 [10]^[1]. Furthermore, the number of pregnant women reporting binge drinking (four or more alcoholic beverages at once) increased from 1.4% to 3.1% [10]^[1]. In addition, data from the 2009 National Birth Defects Prevention Study of over 4000 women indicate that 30% of pregnant women use alcohol and 8% engage in binge drinking on at least one occasion ^[4]. High rates of alcohol consumption during pregnancy allow us to suspect a high prevalence of fetal alcohol spectrum disorders. The global prevalence of FASDs in children and youth in the general population is 7.7 per 1000 people. The highest prevalence ratio is in the European Region (19.8 per 1000 people) [14]^[5]. One study in the US indicated that 1.1 to 5% (depending on the community) of first-graders have FASDs, and the weighted prevalence estimates for FASDs in this population ranged from 31.1 to 98.5 per 1000 children [15]^[6].

3. Burden of FASDs

FASDs have an impact on various individual and social aspects. The outcomes caused by FASDs can be divided into primary and secondary disabilities. Primary disabilities comprise congenital conditions caused by the teratogenic effects of alcohol on the fetus’s brain and differences in behavior and cognition [16]^[7]. Delayed growth and craniofacial anomalies, including palpebral fissures, a smooth philtrum, and a thin upper lip vermilion, though infrequent, can help in terms of differential diagnoses [17]^[8]. In addition, FASDs have an increased risk of comorbidities, with ADHD, depression, anxiety disorder, oppositional defiant disorder, and receptive as well as expressive language disorders being commonly reported [18]^[9]. FASDs have been associated with adverse childhood experiences (ACEs), which begin with prenatal alcohol exposure and tend to continue across the lifespan. In one systematic review, it was estimated that ADHD had the highest prevalence of 50% among individuals diagnosed with FASDs [19]^[10]. The impairments described above as well as adverse childhood experiences (ACEs) can increase the risk of comorbidities. FASDs and subsequent exposure to ACEs, with neglect, parental substance abuse, parental separation or divorce, and physical abuse being the most prevalent, can lead to the development of additional neurobehavioral disorders. Moreover, children with FASDs living in foster care exhibited higher ACE scores than non-FASD subjects (RR = 9.05). Children diagnosed with FASDs were 9 times more likely to be placed in foster care and 6.7 times more likely to be placed in residential care compared with controls [20,21]^[11][12]. Secondary disabilities may include poorer school performance, unemployment, needing support from social welfare, an increase in psychiatric and medical comorbidities, problems with the law, and victimization [16,22]^[7][13]. Problems with the justice system, victimization, and incarceration may also be relevant to FASDs [22]^[13]. Disruptions in adaptive functioning, including poor communication and social and daily living skills, as well as an inability to properly regulate behavior and emotions, can lead to daily challenges at school, home, and community environments, increasing the risk of disrupted school experiences, alcohol or drug addictions, inappropriate sexual behavior, and a reduced capacity to live independently [16]^[7]. Primary and secondary disabilities make significant demands of foster parents, birth parents, schools, mental health care systems, and legal institutions [22]^[13]. The biopsychosocial burden of FASDs is summarized in Figure 1.

4. Assessing Prenatal Alcohol Exposure

Documented prenatal alcohol exposure is a core component in making an FASD diagnosis. To effectively address alcohol consumption during pregnancy, an appropriate assessment of alcohol use as a routine component of prenatal care is essential. Many alcohol assessment tools in reproductive-age women and during pregnancy have been proposed (for example, CAGE, TWEAK, AUDIT-C, T-ACE, and T-ACER3) [23]^[14]. The biggest concern regarding such tools is their reliance on direct questioning and self-reporting, thus being prone to under-detection due to women’s unwillingness to admit to acts of alcohol consumption. Women who use substances during their pregnancies feel fear and stigma and, thus, are less willing to cooperate with physicians and more likely to avoid treatment [24]^[15]. The situation can be even more complicated in cases of maternal polysubstance abuse. There are efforts to create biomarkers that may be more valid than maternal self-reports. For example, one systematic review found that the detection of fatty acid ethyl esters in meconium indicated a more than four times higher prevalence of prenatal alcohol exposure compared with maternal self-reporting [25]^[16]. The latter findings indicate that maternal self-reports regarding PAE may not be sufficient as a sole information source [3,7]^[17][18].

5. Recognition of Signs over Time

Children with dysmorphic features of FASDs can be identified as early as 9 months of age, with a peak of identification at 18 months of age compared with an unaffected group of children. However, children with severe impairment of dysmorphic features can be identified at birth. The literature notes that although early behavioral and development impairment is usually noted between 18 and 42 months of age, CNS impairment may not be apparent until the child is in school [26]^[19]. Thus, early childhood assessment appears the most sensitive, as well as providing sometimes the only evidence of FASD phenotypes. Children with FASD phenotypes can be missed if they do not have an assessment of the disorder in time, primarily due to the diminishing prevalence of short palpebral features and a small head circumference, as well as the physical features of prenatal alcohol exposure being absent in as many as 75% of affected children [27]^[20]. This statement is supported by a US study highlighting that without early childhood screening, only one in seven children will be identified later in their lifetime. Therefore, this confirms the importance of early screening before children start pre- or primary school as early interventions are the most effective in improving children’s future quality of life [28]^[21].

6. Challenges in Follow-Up Care

Neurocognitive habilitation therapy and social skills improvement programs are especially recommended for patients with an FASD diagnosis. An effective neurocognitive habilitation program is “Alert” [29]^[22]. During the program, patients are encouraged to work in groups and introduced to learning concepts, creative activities, and the acknowledgment of sensory functions. Therefore, children learn to adapt to the community. If needed, medications can be administered (e.g., in the case of ADHD, depression, and anxiety disorders). Parents should also be educated on communicating with their children. Other interventions that aim to help patients to adapt may also be effective. For example, an analysis of one intervention, “MILE” (The Math Interactive Learning Experience), showed a significant gain in the patient’s math skills and behavior; another intervention, called “CFT” (Child Friendship Training), improves social skills, whereas “CPAT” (Computerized Progressive Attention Training) decreases reaction times and improves attention spans [30]^[23]. Cognitive control therapy significantly changes a child’s behavior. It teaches self-regulation, self-observation, and different thinking. The management of other comorbidities is chosen by a multidisciplinary team depending on the specific patient. Usually, a multidisciplinary team combines an audiologist, cardiologist, developmental pediatrician, developmental therapies, family therapist, nephrologist, neurologist, occupational therapist, ophthalmologist, physical therapist, primary care physician, psychiatrist, psychotherapist, sensory integration therapist, social worker, special education teachers, and speech-language pathologist. The literature shows that the lack of a functioning multidisciplinary team arises from the absence of FASD follow-up guidelines and neuropsychological help, and patients are left without proper care [2,3,10]^[1][17][24]. A summary of the challenges in evaluating prenatal alcohol exposure, diagnosing FASDs, and providing adequate care afterward is presented in Figure 2.