Fetal Alcohol Spectrum Disorder 제일 병원 주산기 분과 전임의 안계형
Introduction Fetal alcohol spectrum disorder (FASD) • Effect of maternal alcohol consumption during pregnancy • Physical, mental, behavioral, and/or learning disabilities with possible lifelong implications • Not a diagnostic term : Diagnoses like FAS, partial FAS and ARND fall under the umbrella of FASD
Fetal alcohol syndrome (FAS) birth defect syndrome caused by maternal alcohol consumption during pregnancy • The most severe form of FASD ① Facial anomalies ② Growth retardation ③ CNS anomalies
Partial FAS- diagnostic classification for patients who present with most, but not all, of the growth deficiency and/or facial features of FAS. central nervous system damage(structural, neurological, and/or functional impairment). prenatal alcohol exposure.
Alcohol Related Neurodevelopmental Disorders (ARND) - diagnostic classification coined by the Institute of Medicine in 1996- for patients who present with central nervous system damage (structural, neurological, and/or functional impairment). prenatal alcohol exposure.
Fetal Alcohol Effects (FAE) Introduced in 1978 used to describe abnormalities seen in individuals that were compatible with those caused by prenatal alcohol exposure but the pattern was not sufficiently complete to render a diagnosis of FAS. "We propose abandoning the clinical use of the term FAE with its implications of causation, and urge simple recording of the verifiable conclusions concerning the individual patient." Aase et al (1995)
Historical Background„You will conceive and give birth to a son Drink no wine or other fermented drink‟ (Holy Bible, Judges 13:7)„Foolish, drunken and harebrained women most often bring forth children like morose and languid.‟ (Aristotle, BC 384-322)„Offspring of imprisoned alcoholic women, 55.8% born dead or died before age 2.‟ (Sullivan, 1899)
The discovery of FAS 1968, Lemoine et al. • Outcome of children of alcoholic mothers 1973, Jones and Smith • „Fetal alcohol syndrome‟ was first introduced 1978, Clare and Smith • „Fetal alcohol effects‟ 1996, Institute of Medicine (IOM) • replaced FAE with ARBD and ARND • New classification of FASD
Cause of FASD The sole cause of FASD is women drinking alcohol beverages during pregnancy Alcohol is a teratogen “ Of all the substance of abuse (including cocaine, heroin, and marijuana), alcohol produces by far the most serious neurobehavioral effects in the fetus.” -IOM Report to congress, 1996
Prenatal alcohol exposure is a 100% preventable cause of birth defects and developmental disabilities.
Epidemiology Prevalence • FAS: 0.5-2.0/1000 birth in US • FASD: 9.1/1000 birth in US (1%) Economic impact • average lifetime costs for 1 FAS pt: $2.9 million • annual cost: $ 6 billion
The reasons for variable prevalence rates • variable poverty rates • genetic and ethnic difference: level of enzyme activity • lack of uniformly accepted diagnostic criteria • lack of knowledge, skill, training and misconceptions among primary care providers
CNS anomalies Cerebrum volume reduction of the cranial vault and brain • 12% compared to control • Parietal, Temporal, Inferior frontal lobe • Lt hemisphere > Rt hemisphere • white matter hypoplasia • visuospatial deficits, verbal ,memory, impulsiveness
Cerebellum • reduction in the anterior vermis (lobule I-V) • motor coordination and balance impairments Basal ganglia • caudate nucleus • connection with cortical and subcortical motor areas • control voluntary motor function • executive function, motivation, social behavior, perseverative behavior
Corpus callosum • role in the coordination of various functions • agenesis • thinning, hypoplasia, partial agenesis
Overall difficulties for persons with FASD Taking in information Storing information Recalling information when necessary Using information appropriately in a specific situation
Primary difficulties for persons with FASD Lower IQ Impaired ability in reading, spelling, and arithmetic Lower level of adaptive functioning ; more significantly impaired than IQ Streissguth, et al. (1996)
Typical difficulties for persons with FASD Sensory integration issues Are overly sensitive to sensory input Upset by bright or loud noise Annoyed tags in shirts or seams in socks Bothered by certain textures of food Have problems sensing where their body is in space (i.e., clumsy) Memory problems Multiplication Time sequencing
Information processing problems Do not use complete tasks or chores and may appear to be oppositional Have trouble determining what to do in a given situation Do not ask questions because they want fit in Say they understand when they do not Have verbal expressive skills that often exceed their level of understanding Misinterpret others, words, actions, or body movement Have trouble following multiple directions
Executive function deficits Go with strangers Repeatedly break the rules Do not learn from mistakes or natural consequences Frequently do not respond to point, level, or sticker systems Have trouble with time and money Give in to peer pressure
Self esteem and personal issues Multiple issues Cannot entertain themselves Have trouble changing tasks Do not accurately pick up social cues
Secondary Disabilities Psychiatric problem • ADHD • schizophrenia, depression, personality disorders Disrupted school experience Dependent living Trouble with the law Confinement Inappropriate sexual behavior Alcohol or drug problems
Paternal exposure Male drinking did not have a significant effect but at 10 or more drinks per week the hazard ratio was 5.0 (CI 1.2-21.4) Henriksen et al. (1978) Paternal alcohol use have no association with gestational age or birth weight Savitz et al. (1992) Analyzed preconceptional drinking by fathers and found no birth weight association Spohr et al. (1993) No association was found between couple fecundity and male alcohol intake Jesen TK et al. (1998)
Fertility and miscarrage Reduction in fecundability was evident even among women with a weekly alcohol intake corresponding to five or fewer drinks Jesen TK et al. (1998) Maternal alcohol use during pregnancy has been associated with an increased risk of miscarriage, stillbirth, and extremely premature delivery in some studies Henriksen et al.(2004), Maconochie et al.(2007), Aliyu et al.(2008)
Diagnostic criteria Institute of Medicine (IOM, 1996) 4-Digit Diagnostic Coding Sytem (Astley, 2004) Center for Disease Control and Prevention (CDC, 2004) Canadian FASD Guidelines (Chudley, 2005) Revised IOM Diagnostic Classification System (Hoyme, 2005)
Revised IOM criteria for diagnosis of FASD (Hoyme et al., 2005)I. FAS With Confirmed Maternal Alcohol Exposure (all of A–D) (A) Confirmed maternal alcohol exposure (B) Minor facial anomalies (≥2) (1) Short palpebral fissures (p10%) (2) Thin vermilion border of the upper lip (score 4 or 5) (3) Smooth philtrum (score 4 or 5) (C) Prenatal and/or postnatal growth retardation (1) Height and/or weight p10% (D) Deficient brain growth and/or abnormal morphogenesis (≥1) (1) Structural brain abnormalities (2) Head circumference p10%II. FAS Without Confirmed Maternal Alcohol Exposure IB, IC, and ID as above
III. Partial FAS With Confirmed Maternal Alcohol Exposure (all A-C) (A) Confirmed maternal alcohol exposure (B) Minor facial anomalies (≥2) (1) Short palpebral fissures (p10%) (2) Thin vermilion border of the upper lip (score 4 or 5) (3) Smooth philtrum (score 4 or 5) (C) One of the following other characteristics: (1) Prenatal and/or postnatal growth retardation (a) Height and/or weight p10% (2) Deficient brain growth or abnormal morphogenesis (≥1) (a) Structural brain abnormalities (b) Head circumference p10% (3) Complex pattern of behavioral or cognitive abnormalitiesIV. Partial FAS Without confirmed Maternal Alcohol Exposure IIIB and IIIC, as above
V. ARBD (all of A-C): Alcohol related birth defect (A) Confirmed maternal alcohol exposure (B) Minor facial anomalies (≥2) (1) Short palpebral fissures (p10%) (2) Thin vermilion border of the upper lip (score 4 or 5) (3) Smooth philtrum (score 4 or 5) (C) Congenital structural defect (≥1) if the patient displays minor anomalies only, X 2 must be present) cardiac/skeletal/renal/eyes/ears/minor anomaliesVI. ARND (both A and B): Alcohol related neurodevelopmental disorder (A) Confirmed maternal alcohol exposure (B) At least 1 of the following: (1) Deficient brain growth or abnormal morphogenesis (≥1) (a) Structural brain abnormalities (b) Head circumference p10% (2) Complex pattern of behavioral or cognitive abnormalities
Approach to the diagnosis1. Screening for maternal alcohol consumption2. Biomarkers for in utero alcohol exposure3. Meconium FAEE screening (fatty acid ethyl esters)4. Hair FAEE screening
FAEE Fatty acid ethyl esters Non-oxidative metabolites Esterification of ethanol FAEE synthase, AEAT in all human tissue Produced by the fetus itself from the ethanol
Fatty acid ethyl esters in meconium are useful biomarkers for FAS and fetal alcohol disorder Bearer et al. (2006) This chemicals accumulate in meconium during the last trimester.
Further evaluation Neurocognitive function test Brain MRI Functional Brain imaging Digital photography EEG
No safe amount of alcoholdrinking during pregnancy has been determined.