Fetal alcohol spectrum disorders (FASDs) are a group of conditions that can occur in a person who is exposed to alcohol during gestation. FASDS affects 7.7 out of 1000 people globally, but is highly misdiagnosed and underdiagnosed. The several forms of the condition (in order of most severe to least severe) are: fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (pFAS), alcohol-related neurodevelopmental disorder (ARND), and neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE). Other terms used are fetal alcohol effects (FAE), partial fetal alcohol effects (PFAE), alcohol-related birth defects (ARBD), and static encephalopathy, but these terms have fallen out of favor and are no longer considered part of the spectrum. Not all infants exposed to alcohol in utero will have detectable FASD or pregnancy complications. The risk of FASD increases with the amount consumed, the frequency of consumption, and the longer duration of alcohol consumption during pregnancy, particularly binge drinking. The variance seen in outcomes of alcohol consumption during pregnancy is poorly understood. Diagnosis is based on an assessment of growth, facial features, central nervous system, and alcohol exposure by a multidisciplinary team of professionals. The main criteria for diagnosis of FASD are nervous system damage and alcohol exposure, with FAS including congenital malformations of the lips and growth deficiency. FASD is often misdiagnosed as or comorbid with ADHD. Almost all experts recommend that the mother abstain from alcohol use during pregnancy to prevent FASDs. As the woman may not become aware that she has conceived until several weeks into the pregnancy, it is also recommended to abstain while attempting to become pregnant. Although the condition has no known cure, treatment can improve outcomes. Treatment needs vary but include psychoactive medications, behavioral interventions, tailored accommodations, and case management.
Signs and symptoms
The key signs of fetal alcohol syndrome (FAS) required for diagnosis include:
Growth deficiency or failure to thrive: slow fetal growth low birth weight or height, small head circumference (microcephaly) Congenital malformations of lips: short palpebral fissure lengths, smooth philtrum, and thin upper lip. Nervous system damage: Clinically significant structural neurological, or functional impairment Popova et al. identified 428 ICD-10 conditions as co-occurring in individuals with FAS. Excluding conditions used in FAS diagnosis, co-occurring conditions with 50% prevalence or greater include:
Conduct disorder, behavioral problems, disruptive behavior, or impulsivity Developmental language disorder Hearing loss Visual impairment, including blindness or astigmatism Developmental delay, cognitive disorder, or mental deficiency Premature birth Substance dependence Congenital malformation of retina Congenital fusion of cervical vertebrae or cervical spine fusion Attention deficit hyperactivity disorder (ADHD) or otherwise impaired attention Small eye openings (blepharophimosis), or an abnormally increased distance between the eyes, or both (hypertelorism) Other FASD conditions are partial expressions of FAS, where the central nervous system shows clinical deficits. In these other FASD conditions, an individual may be at greater risk for adverse outcomes because brain damage is present without associated visual cues of poor growth or the "FAS face" that might ordinarily trigger an FASD evaluation. Such individuals may be misdiagnosed with primary mental health disorders such as ADHD or oppositional defiance disorder without appreciation that brain damage is the underlying cause of these disorders, which requires a different treatment paradigm than typical mental health disorders. While other FASD conditions may not yet be included as an ICD or DSM-IV-TR diagnosis, they nonetheless pose significant impairment in functional behavior because of underlying brain damage. Many indications of fetal alcohol spectrum disorders are developmental. Therefore, although a child may appear 'normal' at birth, intellectual disabilities caused by alcohol before birth may not appear until the child begins school. More broadly, alcohol use during pregnancy is also associated with:
Intellectual disability, both in overall IQ measurements and in many functional tests Fetal mortality, such as spontaneous abortion (miscarriage), stillbirth, and sudden infant death syndrome Domestic violence and potential harm to the infant Sleep and sucking problems as a baby Heart: A heart murmur that frequently disappears by one year of age. Ventricular septal defect, atrial septal defect, tetralogy of Fallot, coarctation of the aorta, or cardiac rhythm dysfunction. Bones: Joint anomalies including abnormal position and function, altered palmar crease patterns, small distal phalanges, and small fifth fingernails. Kidneys: Horseshoe, aplastic, dysplastic, or hypoplastic kidneys. Eyes: Strabismus, optic nerve hypoplasia (which may cause light sensitivity, decreased visual acuity, or involuntary eye movements). Cleft lip with or without a cleft palate: Alcohol is known to be a folic acid antagonist, and a baby's palate and lip develop during the first trimester of the pregnancy (first 12 weeks). Heavy alcohol consumption and binge drinking during this time have been linked to orofacial cleft. Occasional problems: ptosis of the eyelid, microphthalmia, webbed neck, short neck, radioulnar synostosis, spina bifida, and hydrocephalus. Alcohol can also harm the fertility of women who are planning for pregnancy. Adverse effects of alcohol can lead to malnutrition, seizures, vomiting, and dehydration. The mother can suffer from anxiety and depression, which can result in child abuse/neglect. It has also been observed that when the pregnant mother withdraws from alcohol, its effects are visible on the infant as well. The baby remains in an irritated mood, cries frequently, does not sleep properly, weakening of sucking ability and increased hunger. In 2019, a study found that individuals with FASD have a higher risk of hypertension independent of race/ethnicity and obesity.
Causes Fetal alcohol spectrum disorders are caused by alcohol exposure during gestational development. If an individual was not exposed to alcohol before birth, they will not have FASD. However, not all infants exposed to alcohol in utero will have detectable FAS, FASD, or pregnancy complications.
Exposure limit No safe level of fetal alcohol exposure has been established. Because alcohol is a known teratogen, it is considered unethical to do randomized controlled trials on pregnant women to determine the precise toxicity effects of alcohol. Among women who consume any quantity of alcohol during pregnancy, the risk of giving birth to a child with FASD is about 15%, and to a child with FAS about 1.5%. Drinking 2 standard drinks a day, or 6 standard drinks in a short time, carries a 4.3% risk of a FAS birth (i.e. one of every 23 heavy-drinking pregnant women will deliver a child with FAS). Furthermore, alcohol-related congenital abnormalities occur at an incidence of roughly one out of 67 women who drink alcohol during pregnancy. Among those mothers who have an alcohol use disorder, an estimated one-third of their children have FAS. The variance seen in outcomes of alcohol consumption during pregnancy is poorly understood. Aggravating factors may include low maternal weight, advanced maternal age, smoking, poor diet, genetics, and social risk factors. The risk of FASD increases with the amount consumed, the frequency of consumption, and a longer duration of alcohol consumption during pregnancy. Blood alcohol concentration has been identified as a relevant factor. All forms of alcohol, such as beer, wine, and liquor, pose similar risk. Binge drinking increases the chances and severity of FASD to such an extent that Svetlana Popova has stated that "binge drinking is the direct cause of FAS or FASD". Small amounts of alcohol may not cause an abnormal appearance, however, small amounts of alcohol consumption while pregnant may cause behavioral problems and also increases the risk of miscarriage. Quasi-experimental studies provide moderately strong evidence that prenatal alcohol exposure causes detrimental cognitive outcomes, and some evidence of reduced birthweight, although no study was fully rated at low risk of bias and quantity of studies was limited. The evidence is inconsistent and contradictory regarding the effects of low-to-moderate drinking, for example, less than 12 grams of ethanol per day. Many studies find no significant effect, but some find beneficial associations, and others find detrimental associations, even on the same outcomes. Summarizing studies by country shows some similarity in results, due to using the same data sources. The definition of low alcohol consumption varies significantly among studies and often fails to incorporate all aspects of timing, dose, and duration. Recall bias and socioeconomic and psychosocial factors have been controlled for in most studies, but it is likely that residual confounding due to missing factors and variation in methods still exists and is larger than any observed effects.
Paternal alcohol use Fathers who consume alcohol before conception may contribute to FASD through long-term epigenetic modification of the father's sperm, but this has been challenged; evidence it can cause complete FAS is inconclusive.
Prevention and stigma
Almost all experts recommend that the mother abstain from alcohol use during pregnancy to prevent FASDs. A pregnant woman may not become aware that she has conceived until several weeks into the pregnancy, so it is also recommended to abstain from alcohol while attempting to become pregnant. The recommendations of abstaining from alcohol during pregnancy and while attempting to become have been made by the Surgeon General of the United States, the Centers for Disease Control, the American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, the World Health Organization, the United Kingdom's National Institute for Health and Clinical Excellence, and many others. In the United States, federal legislation has required that warning labels be placed on all alcoholic beverage containers since 1988 under the Alcoholic Beverage Labeling Act.
Stigma The most current advocacy perspectives encourage people and systems to approach FASD with interventions and support for individuals already living with FASD. Focusing on prevention often only further stigmatizes individuals with FASD and their birth parents. Advocates say, if a person is supporting people currently living with FASD, then that person is spreading the awareness needed for successful prevention efforts; "Intervention is Prevention". Many social determinants of health impact the effects of PAE:
Genetics Poverty/Access to nutritious food Malnutrition Poor social support networks Lack of personal autonomy Access to healthcare Generational and sociocultural traumas Access to mental health care and treatment
Medication Women can experience serious symptoms that accompany alcohol withdrawal during pregnancy. According to the World Health Organization, these symptoms can be treated during pregnancy with brief use of benzodiazepine tranquilizers. Currently, the FDA has approved three medications—naltrexone, acamprosate, and disulfiram—for the treatment of alcohol use disorder (AUD). However, there is insufficient data regarding the safety of these medications for pregnant women.
Naltrexone is a nonselective opioid antagonist that is used to treat AUD and opioid use disorder. The long-term effects of naltrexone on the fetus are currently unknown. Animal studies show that naltrexone administered during pregnancy increases the incidence of early fetal loss; however, there are insufficient data available to identify the extent to which this is a risk in pregnant women. Acamprosate functions as both an antagonist of NMDA and glutamate and an agonist at GABAA receptors, although its molecular mechanism is not completely understood. Acamprosate is effective at preventing alcohol relapse during abstinence. Animal data, however, suggest that acamprosate can have possible teratogenic effects on fetuses. Disulfiram prevents relapse by blocking the metabolism of acetaldehyde after consumption of alcohol, which leads to headache, nausea, and vomiting. Some evidence suggests that disulfiram use during the first trimester is associated with an increased risk of congenital malformations such as reduction defects and cleft palate. Additionally, the effects of disulfiram can involve hypertension, which can be harmful to both the pregnant woman and the fetus. American Psychiatric Association guidelines recommend that medications not be used to treat alcohol use disorder in pregnant women except in cases of acute alcohol withdrawals or other co-existing conditions. Instead, behavioral interventions are usually preferred as treatments for pregnant women with AUD. Medications should only be used for pregnant women after carefully considering the potential risks and harms of the medications versus the benefits of alcohol cessation.
Mechanism After a pregnant woman consumes alcohol, the alcohol crosses through the placenta and umbilical cord to the developing fetus. Alcohol metabolizes slowly in the fetus and remains for a long time when compared to an adult. A human fetus appears to be at triple risk from maternal alcohol consumption:
The placenta allows free entry of ethanol and toxic metabolites like acetaldehyde into the fetal compartment. The so-called placental barrier is practically absent concerning ethanol. The developing fetal nervous system appears particularly sensitive to ethanol toxicity. The latter interferes with proliferation, differentiation, neuronal migration, axonal outgrowth, integration, and fine-tuning of the synaptic network. In short, all major processes in the developing central nervous system appear compromised. Fetal tissues are quite different from adult tissues in function and purpose. For example, the main detoxifying organ in adults is the liver, whereas the fetal liver is incapable of detoxifying ethanol, as the ADH and ALDH enzymes have not yet been brought to expression at this early stage. Up to term, fetal tissues do not have significant capacity for the detoxification of ethanol, and the fetus remains exposed to ethanol in the amniotic fluid for periods far longer than the decay time of ethanol in the maternal circulation. The lack of significant quantities of ADH and ALDH means that fetal tissues have much lower quantities of antioxidant enzymes, like SOD, glutathione transferases, and glutathione peroxidases, resulting in antioxidant protection being much less effective. Although alcohol is known to be a teratogen (causing birth defects), the exact biological mechanisms for the development of FAS or FASD are unknown. However, clinical and animal studies have identified a broad spectrum of pathways through which maternal alcohol can negatively affect the outcome of a pregnancy. Clear conclusions with universal validity are difficult to draw, since different ethnic groups show considerable genetic polymorphism for the hepatic enzymes responsible for ethanol detoxification. Genetic examinations have revealed a continuum of long-lasting molecular effects that are not only timing specific but are also dosage specific; with even moderate amounts being able to cause alterations. Additionally, ethanol may alter fetal development by interfering with retinoic acid signaling as acetaldehyde can compete with retinaldehyde and prevents its oxidation to retinoic acid.
Developmental stages Different body systems in the infant grow, mature, and develop at specific times during gestation. The effect of consumption of alcohol differs during each of these developmental stages:
From conception to the third week, the most susceptible systems and organs are the brain, spinal cord, and heart. The effects of alcohol consumption early in the pregnancy can result in defects in these systems and organs. During the third week, alcohol can also damage the central nervous system of the fetus. During the fourth week of gestation, the limbs are being formed, and it is at this point that alcohol can affect the development of arms, legs, fingers, and toes. The eyes and ears also form during the fourth week and are more susceptible to the effects of alcohol. By the sixth week of gestation, the teeth and palate are forming, and alcohol consumption at this time will affect these structures. Alcohol use in this window is responsible for many of the facial characteristics of fetal alcohol syndrome. During the twelfth week, frequent alcohol exposure can negatively impact brain development, which affects cognitive, learning, and behavioral skills before birth. By the 20th week of gestation, the formation of organs and organ systems is well-developed. The infant is still susceptible to the damaging effects of alcohol. Ethanol exposure in the second trimester reduces nutrition levels and can affect the functioning of the endocrine system in both fetus and mother. This is because blood flow via the umbilical artery to the fetal brain is reduced.
Diagnosis Fetal alcohol spectrum disorders encompass a range of physical and neurodevelopmental problems which can result from prenatal alcohol exposure. Diagnosis is based on the signs and symptoms in the person and evidence of alcohol use. These diagnoses of fetal alcohol spectrum disorders are currently recognized:
Fetal alcohol syndrome (FAS) Partial fetal alcohol syndrome (pFAS) refers to individuals with a known, or highly suspected, history of prenatal alcohol exposure who have alcohol-related physical and neurodevelopmental deficits that do not meet the full criteria for FAS. Alcohol-related neurodevelopmental disorder (ARND) Neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE) As of 2016, the Swedish Agency for Health Technology Assessment and Assessment of Social Services accepts only FAS as a diagnosis, seeing the evidence as inconclusive for other types. The agency feels it is unclear if identifying a FASD-related condition benefits the diagnosed individual.
Classification Presently, four FASD diagnostic systems that diagnose FAS and other FASD conditions have been developed in North America:
The Institute of Medicine's guidelines for FAS, the first system to standardize diagnoses of individuals with prenatal alcohol exposure; The University of Washington's "The 4-Digit Diagnostic Code", which ranks the four key features of FASD on a Likert scale of one to four and yields 256 descriptive codes that can be categorized into 22 distinct clinical categories, ranging from FAS to no findings; The Centers for Disease Control's "Fetal Alcohol Syndrome: Guidelines for Referral and Diagnosis", which established consensus on the diagnosis FAS in the U.S. but deferred addressing other FASD conditions; and Canadian guidelines for FASD diagnoses, which established criteria for diagnosing FASD in Canada and harmonized most differences between the IOM and the University of Washington's systems. Each diagnostic system requires an assessment of four key features: growth, facial features, central nervous system, and alcohol exposure. To determine any FASD condition, a multi-disciplinary evaluation is necessary to assess each of the four key features for assessment. Generally, a trained physician will determine growth deficiency and FAS facial features. While a qualified physician may also assess central nervous system structural abnormalities or neurological problems, usually central nervous system damage is determined through psychological, speech-language, and occupational therapy assessments to ascertain clinically significant impairments in three or more of the Ten Brain Domains. Prenatal alcohol exposure risk may be assessed by a qualified physician, psychologist, social worker, or chemical health counselor. These professionals work together as a team to assess and interpret data of each key feature for assessment and develop an integrative, multi-disciplinary report to diagnose FAS (or other FASD conditions) in an individual. A positive finding on all four features is required for a diagnosis of FAS, and the four diagnostic systems essentially agree on criteria for fetal alcohol syndrome (FAS). However, there are differences among systems when full criteria for FAS are not met. Prenatal alcohol exposure and central nervous system damage are the critical elements of the spectrum of FASD, and a positive finding in these two features is sufficient for an FASD diagnosis in all FASD systems. But different researchers and systems may use a wide variety of terminology to describe an individual's FASD condition, as the nomenclature is still evolving. Most individuals with deficits resulting from prenatal alcohol exposure do not express all features of FAS and fall into other FASD conditions. The Canadian guidelines recommend the assessment and descriptive approach of the "4-Digit Diagnostic Code" for each key feature of FASD and the terminology of the IOM in diagnostic categories, excepting ARBD.
Fetal alcohol syndrome The most severe condition is called Fetal Alcohol Syndrome (FAS), which refers to individuals who have a specific set of birth defects and neurodevelopmental disorders characteristic of the diagnosis. The following criteria must be fully met for an FAS diagnosis:
Prenatal or postnatal height or weight (or both) at or below the 10th percentile All three FAS facial features present Clinically significant structural, neurological, or functional impairment of the central nervous system Confirmed or Unknown prenatal alcohol exposure FAS is the only expression of FASD that has garnered consensus among experts to become an official ICD-9 and ICD-10 diagnosis.
Partial FAS Partial FAS (pFAS) was previously known as atypical FAS in the 1997 edition of the "4-Digit Diagnostic Code". People with pFAS have a confirmed history of prenatal alcohol exposure, but may lack growth deficiency or the complete facial stigmata. Central nervous system damage is present at the same level as FAS. These individuals have the same functional disabilities but "look" less like FAS. The following criteria must be fully met for a diagnosis of Partial FAS:
Two or three FAS facial features present Clinically significant structural, neurological, or functional impairment in three or more of the Ten Brain Domains Confirmed prenatal alcohol exposure Growth or height may range from normal to deficient.
Alcohol-related neurodevelopmental disorder Alcohol-related neurodevelopmental disorder (ARND) is the specific diagnosis of the non-dysmorphic type of FASD, where a majority of the symptoms are witnessed. The diagnosis was initially suggested by the Institute of Medicine to replace the terms FAE (fetal alcohol effects). It focuses on central nervous system damage, rather than growth deficiency or FAS facial features. The Canadian guidelines also use this diagnosis and the same criteria. While the "4-Digit Diagnostic Code" includes these criteria for three of its diagnostic categories, it refers to this condition as static encephalopathy. The behavioral effects of ARND are not necessarily unique to alcohol however, so use of the term must be within the context of confirmed prenatal alcohol exposure. ARND may be gaining acceptance over the terms FAE and ARBD to describe FASD conditions with central nervous system abnormalities or behavioral or cognitive abnormalities or both due to prenatal alcohol exposure without regard to growth deficiency or FAS facial features. The following criteria must be fully met for a diagnosis of ARND or static encephalopathy:
Minimal or no FAS facial features present Clinically significant structural, neurological, or functional impairment in three or more of the Ten Brain Domains Confirmed prenatal alcohol exposure Growth or height may range from normal to minimally deficient.
Neurobehavioral disorder associated with prenatal alcohol exposure Neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE) is the spectrum-wide term for the psychiatric, behavioral, and neurological symptoms of all FASDs. It was introduced into the DSM-5 as a "condition for further study" and as a specified condition under, "other specified neurodevelopmental disorders" as a way to better study the behavioral aspects of all FASD disorders.
Specific criteria
Growth In terms of FASD, growth deficiency is defined as significantly below average height, weight or both due to prenatal alcohol exposure and can be assessed at any point in the lifespan. Growth measurements must be adjusted for parental height, gestational age (for a premature infant), and other postnatal insults (e.g., poor nutrition), although birth height and weight are the preferred measurements. Deficiencies are documented when height or weight falls at or below the 10th percentile of standardized growth charts appropriate to the population. Prenatal or postnatal presentation of growth deficits can occur, but are most often postnatal. Criteria for FASD are least specific in the Institute of Medicine (IOM) diagnostic system ("low birth weight..., decelerating weight not due to nutrition..., [or] disproportional low weight to height" p. 4 of executive summary), while the CDC use the 10th percentile as a cut-off to determine growth deficiency. The "4-Digit Diagnostic Code" allows for mid-range gradations in growth deficiency (between the 3rd and 10th percentiles) and severe growth deficiency at or below the 3rd percentile. Growth deficiency, which may range from mild to severe, is one of the diagnostic features of fetal alcohol syndrome (FAS) and partial fetal alcohol syndrome (pFAS), but is not required for diagnoses of alcohol-related neurodevelopmental disorder (ARND) under the diagnostic systems in which ARND is recognized. The "4-Digit Diagnostic Code" from 2004 ranks growth deficiency as follows:
Severe: Height and weight at or below the 3rd percentile. Moderate: Either height or weight at or below the 3rd percentile, but not both. Mild: Either height or weight or both between the 3rd and 10th percentiles. None: Height and weight both above the 10th percentile. In the initial studies that described FAS, growth deficiency was a requirement for inclusion in the studies; thus, all the original people with FAS had growth deficiency as an artifact of sampling characteristics used to establish criteria for the syndrome. That is, growth deficiency is a key feature of FASD because growth deficiency was a criterion for inclusion in the study that defined FAS. Growth deficiency may be less critical for understanding the disabilities of FASD than the neurobehavioral sequelae to the brain damage. Canadian guidelines updated in 2016 deleted growth as a diagnostic criterion.
Facial features
Several characteristic craniofacial abnormalities are often visible in individuals with FAS. The presence of FAS facial features indicates brain damage, although brain damage may also exist in their absence. FAS facial features (and most other visible, but non-diagnostic, deformities) are believed to be caused mainly during the 10th to 20th week of gestation. Refinements in diagnostic criteria since 1975 have yielded three distinctive and diagnostically significant facial features which distinguish FAS from other disorders with partially overlapping characteristics. The three FAS facial features are:
A smooth philtrum: The divot or groove between the nose and upper lip flattens with increased prenatal alcohol exposure. Thin vermilion: The upper lip thins with increased prenatal alcohol exposure. Small palpebral fissures: Eye width decreases with increased prenatal alcohol exposure. Measurement of FAS facial features uses criteria developed by the University of Washington. The lip and philtrum are measured by a trained physician with the Lip-Philtrum Guide, a five-point Likert scale with representative photographs of lip and philtrum combinations ranging from normal (ranked 1) to severe (ranked 5). Palpebral fissure length (PFL) is measured in millimeters with either calipers or a clear ruler and then compared to a PFL growth chart, also developed by the University of Washington. Ranking FAS facial features is complicated because the three separate facial features can be affected independently by prenatal alcohol. A summary of the criteria follows:
Severe: All three facial features ranked independently as severe (lip ranked at 4 or 5, philtrum ranked at 4 or 5, and PFL two or more standard deviations below average). Moderate: Two facial features ranked as severe and one feature ranked as moderate (lip or philtrum ranked at 3, or PFL between one and two standard deviations below average). Mild: A mild ranking of FAS facial features covers a broad range of facial feature combinations: Two facial features ranked severe, and one ranked within normal limits, One facial feature ranked severe, and two ranked moderate, or One facial feature ranked severe, one ranked moderate, and one ranked within normal limits. None: All three facial features ranked within normal limits.
Central nervous system Central nervous system (CNS) damage is the primary feature of any FASD diagnosis. Prenatal alcohol exposure, which is classified as a teratogen, can damage the brain across a continuum of gross to subtle impairments, depending on the amount, timing, and frequency of the exposure as well as genetic predispositions of the fetus and mother. While functional abnormalities are the behavioral and cognitive expressions of the FASD disability, CNS damage can be assessed in three areas: structural, neurological, and functional impairments. All four diagnostic systems allow for assessment of CNS damage in these areas, but the criteria vary. The IOM system requires structural or neurological impairment for a diagnosis of FAS, but also allows a "complex pattern" of functional anomalies for diagnosing PFAS and ARND. The "4-Digit Diagnostic Code" and CDC guidelines allow for a positive CNS finding in any of the three areas for any FASD diagnosis, but functional anomalies must measure at two standard deviations or worse in three or more functional domains for a diagnosis of FAS, PFAS, and ARND. The "4-Digit Diagnostic Code" also allows for an FASD diagnosis when only two functional domains are measured at two standard deviations or worse. The "4-Digit Diagnostic Code" further elaborates the degree of CNS damage according to four ranks:
Definite: Structural impairments or neurological impairments for FAS or static encephalopathy. Probable: Significant dysfunction of two standard deviations or worse in three or more functional domains. Possible: Mild to moderate dysfunction of two standard deviations or worse in one or two functional domains or by judgment of the clinical evaluation team that CNS damage cannot be dismissed. Unlikely: No evidence of CNS damage.
Structural Structural abnormalities of the brain are observable, and physical damage to the brain or brain structures caused by prenatal alcohol exposure. Structural impairments may include microcephaly (small head size) of two or more standard deviations below the average, or other abnormalities in brain structure (e.g., agenesis of the corpus callosum, cerebellar hypoplasia). Microcephaly is determined by comparing head circumference (often called occipitofrontal circumference, or OFC) to appropriate OFC growth charts. Other structural impairments must be observed through medical imaging techniques by a trained physician. Because imaging procedures are expensive and relatively inaccessible to most people, diagnosis of FAS is not frequently made via structural impairments, except for microcephaly. Evidence of a CNS structural impairment due to prenatal alcohol exposure will result in a diagnosis of FAS, and neurological and functional impairments are highly likely. During the first trimester of pregnancy, alcohol interferes with the migration and organization of brain cells, which can create structural deformities or deficits within the brain. During the third trimester, damage can be caused to the hippocampus, which plays a role in memory, learning, emotion, and encoding visual and auditory information, all of which can create neurological and functional CNS impairments as well. As of 2002, there were 25 reports of autopsies on infants known to have FAS. The first was in 1973, on an infant who died shortly after birth. The examination revealed extensive brain damage, including microcephaly, migration anomalies, corpus callosum dysgenesis, and a massive neuroglial, leptomeningeal heterotopia covering the left hemisphere. In 1977, Clarren described a second infant whose mother was a binge drinker. The infant died ten days after birth. The autopsy showed severe hydrocephalus, abnormal neuronal migration, and a small corpus callosum. FAS has also been linked to brainstem and cerebellar changes, agenesis of the corpus callosum and anterior commissure, neuronal migration errors, absent olfactory bulbs, meningomyelocele, and porencephaly. Additional structural defects were identified in various autopsies since then, including: Ulegyria, microgyria, Hypoxic-Ischemic and/or Hemorrhagic lesions due to Perinatal stroke, ventriculomegaly, and cerebellar atrophy.
Neurological When structural impairments are not observable or do not exist, neurological impairments are assessed. In the context of FASD, neurological impairments are caused by prenatal alcohol exposure, which causes general neurological damage to the central nervous system (CNS), the peripheral nervous system, or the autonomic nervous system. A determination of a neurological problem must be made by a trained physician, and must not be due to a postnatal insult, such as meningitis, concussion, traumatic brain injury, etc. All four diagnostic systems show virtual agreement on their criteria for CNS damage at the neurological level, and evidence of a CNS neurological impairment due to prenatal alcohol exposure will result in a diagnosis of FAS or pFAS, and functional impairments are highly likely. Neurological abnormalities in fetal alcohol spectrum disorders may present as either hard neurological signs, such as epilepsy or other seizure disorders, or as soft neurological signs. Soft signs include nonspecific neurological abnormalities such as impaired fine motor skills, sensory deficits, poor gait, clumsiness, and impaired eye–hand coordination. While some soft neurological signs can be assessed using standardized, norm-referenced measures, others require clinical evaluation by qualified healthcare professionals with expertise in neurodevelopmental disorders.
Functional When structural or neurological impairments are not observed, all four diagnostic systems allow CNS damage due to prenatal alcohol exposure to be assessed in terms of functional impairments. Functional impairments are deficits, problems, delays, or abnormalities due to prenatal alcohol exposure (rather than hereditary causes or postnatal insults) in observable and measurable domains related to daily functioning, often referred to as developmental disabilities. There is no consensus on a specific pattern of functional impairments due to prenatal alcohol exposure and only CDC guidelines label developmental delays as such, so criteria (and FASD diagnoses) vary somewhat across diagnostic systems. The four diagnostic systems list various CNS domains that can qualify for functional impairment, which can determine an FASD diagnosis:
Evidence of a complex pattern of behavior or cognitive abnormalities inconsistent with developmental level in the following CNS domains – Sufficient for a pFAS or ARND diagnosis using IOM guidelines Learning disabilities, academic achievement, impulse control, social perception, communication, abstraction, math skills, memory, attention, judgment Performance at two or more standard deviations on standardized testing in three or more of the following CNS domains – Sufficient for an FAS, pFAS or static encephalopathy diagnosis using 4-Digit Diagnostic Code Executive functioning, memory, cognition, social/adaptive skills, academic achievement, language, motor skills, attention, activity level General cognitive deficits (e.g., IQ) at or below the 3rd percentile on standardized testing – Sufficient for an FAS diagnosis using CDC guidelines Performance at or below the 16th percentile on standardized testing in three or more of the following CNS domains – Sufficient for an FAS diagnosis using CDC guidelines Cognition, executive functioning, motor functioning, attention and hyperactive problems, social skills, sensory processing disorder, social communication, memory, difficulties responding to common parenting practices Performance at two or more standard deviations on standardized testing in three or more of the following CNS domains – Sufficient for an FAS diagnosis using Canadian guidelines Cognition, communication, academic achievement, memory, executive functioning, adaptive behavior, motor skills, social skills, social communication
Ten brain domains A recent effort to standardize assessment of functional CNS damage has been suggested by an experienced FASD diagnostic team in Minnesota. The proposed framework attempts to harmonize IOM, 4-Digit Diagnostic Code, CDC, and Canadian guidelines for measuring CNS damage vis-à-vis FASD evaluations and diagnosis. The standardized approach is referred to as the Ten Brain Domains and encompasses aspects of all four diagnostic systems' recommendations for assessing CNS damage due to prenatal alcohol exposure. The framework provides clear definitions of brain dysfunction, specifies empirical data needed for accurate diagnosis, and defines intervention considerations that address the complex nature of FASD with the intention to avoid common secondary disabilities. The proposed Ten Brain Domains include:
Achievement Adaptive behavior Attention Cognition Executive functioning Language Memory Motor skills Multisensory integration or soft neurological problems Social communication The Fetal Alcohol Diagnostic Program (FADP) uses unpublished Minnesota state criteria of performance at 1.5 or more standard deviations on standardized testing in three or more of the Ten Brain Domains to determine CNS damage. However, the Ten Brain Domains are easily incorporated into any of the four diagnostic systems' CNS damage criteria, as the framework only proposes the domains, rather than the cut-off criteria for FASD.
Alcohol exposure Prenatal alcohol exposure is determined by interview of the biological mother or other family members knowledgeable of the mother's alcohol use during the pregnancy (if available), prenatal health records (if available), and review of available birth records, court records (if applicable), chemical dependency treatment records (if applicable), chemical biomarkers, or other reliable sources. Assessment of prenatal alcohol exposure varies among diagnostic systems. The Institute of Medicine (IOM), the U.S. Centers for Disease Control and Prevention (CDC), and the Canadian guidelines classify exposure as confirmed, absent, or unknown when relevant to diagnosis, although specific criteria differ among systems. The 4-Digit Diagnostic Code further categorizes confirmed prenatal alcohol exposure according to estimated level of risk.
Confirmed exposure: The CDC guidelines are silent on using information on the amount, frequency, and timing of prenatal alcohol use for diagnostic purposes. The IOM and Canadian guidelines explore this further, acknowledging the importance o