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. 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 problems are expressed as either hard signs, or diagnosable disorders, such as epilepsy or other seizure disorders, or soft signs. soft signs are broader, nonspecific neurological impairments, or symptoms, such as impaired fine motor skills, neurosensory hearing loss, poor gait, clumsiness, and poor eye–hand coordination. many soft signs have norm-referenced criteria, while others are determined through clinical judgment. "clinical judgment" is only as good as the clinician, and soft signs should be assessed by either a pediatric neurologist, a pediatric neuropsychologist, or both. 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 that 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 related signs other conditions may commonly co-occur with fasd, stemming from prenatal alcohol exposure. however, these conditions are considered alcohol-related birth defects and not diagnostic criteria for fas. 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, and/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). occasional problems: ptosis of the eyelid, microphthalmia, cleft lip with or without a cleft palate, webbed neck, short neck, radioulnar synostosis, spina bifida, and hydrocephalus. in 2019, a study discovered that individuals with fasd have a higher risk of hypertension independent of race/ethnicity and obesity. cause fetal alcohol syndrome 1) alcohol consumed (etoh) 2) alcohol crosses into the placenta 3) alcohol metabolizes 4) fatty acid ethyl esters (faee) detected in meconium fetal alcohol spectrum disorder is caused by a woman consuming alcohol while pregnant. alcohol crosses through the placenta to the unborn child and can interfere with normal development. alcohol is a teratogen (causes birth defects) and there is no known safe amount of alcohol to consume while pregnant and there is no known safe time during pregnancy to consume alcohol to prevent birth defects such as fasd. evidence of harm from low levels of alcohol consumption is not clear and since there are not known safe amounts of alcohol, women are suggested to completely abstain from drinking when trying to get pregnant and while pregnant. small amounts of alcohol may not cause an abnormal appearance, however, small amounts of alcohol consumption while pregnant may cause milder symptoms such as behavioral problems and also increases the risk of miscarriage. among those women who are alcoholic, an estimated one-third of their children have fas. fetal alcohol syndrome occurs when a fetus is exposed to alcohol during conception. although traditionally believed through the mother who is pregnant woman has more than four standard drinks per day, there is evidence as of 2019 supporting that the father before conception can cause fas through long term epigenetic mutation of the father's sperm as well during conception. mechanism despite intense research efforts, the exact mechanism for the development of fas or fasd is unknown. on the contrary, 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. 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 with respect to ethanol. the developing fetal nervous system appears particularly sensitive to ethanol toxicity. the latter interferes with proliferation, differentiation, neuronal migration, axonic 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 detoxicating 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 glutathion peroxidases, resulting in antioxidant protection being much less effective. additionally, ethanol may alter fetal development by interfering with retinoic acid signaling as acetaldehydecan competes with retinaldehyde and prevents its oxidation to retinoic acid. diagnosis because admission of alcohol use during pregnancy can stigmatize birth mothers, many are reluctant to admit to drinking or to provide an accurate report of the quantity they drank. this complicates diagnosis and treatment of the syndrome. as a result, diagnosis of the severity of fasd relies on protocols of observation of the child's physiology and behavior rather than maternal self-reporting. 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 university of washington's systems. each diagnostic system requires that a complete fasd evaluation includes an assessment of the four key features of fasd, described below. a positive finding on all four features is required for a diagnosis of fas. however, 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 that is not "full-blown fas". while the four diagnostic systems essentially agree on criteria for fetal alcohol syndrome (fas), there are still differences when full criteria for fas are not met. this has resulted in differing and evolving nomenclature for other conditions across the spectrum of fasd, which may account for such a wide variety of terminology. 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. thus, other fasd conditions are partial expressions of fas. however, these other fasd conditions may create disabilities similar to fas if the key area of central nervous system damage shows clinical deficits in two or more of ten domains of brain functioning. essentially, even though growth deficiency and/or fas facial features may be mild or nonexistent in other fasd conditions, yet clinically significant brain damage of the central nervous system is present. 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. fetal alcohol syndrome the