Fetal Alcohol Spectrum Disorder: Pathogenesis and clinical findings
Authors: Preeti Kar Reviewers: Nicola Adderley Chandandeep Bal* Danielle Nelson* * MD at time of publication
Genetic Factors
Disadvantaged prenatal and/or postnatal environment
Maternal factors (age, metabolism, stress, other substance use)
Maternal alcohol consumption during pregnancy (greatest risk with binge drinking and daily/chronic intake)
Prenatal alcohol exposure to fetus via placenta-umbilical transport
Fetal Alcohol Spectrum Disorder with Sentinel Facial Features (confirmed or unknown PAE)
Fetal Alcohol Spectrum Disorder without Sentinel Facial Features
• There is no known safe amount of prenatal alcohol exposure
(PAE). Although PAE below the threshold of >7 drinks/week or > 2 binge episodes (one binge episode is >4 drinks in one sitting) has not been associated with neurodevelopmental effects, there is insufficient objective evidence to deem this level of alcohol exposure safe.
Sentinel Facial Features
(confirmed PAE) Alcohol exposure between Alcohol acts directly as a teratogen
Vasoconstriction of placental-umbilical unit ̄ blood flow and ̄ oxygen delivery to fetus
Notes (continued):
• A multidisciplinary team is necessary for an accurate and comprehensive diagnosis and subsequent recommendations. Canadian Guidelines for diagnosis, 4-digit code, the APP Toolkit, University of Washington Lip- Philtrum Guide are different methods of assessing and diagnosing patients.
• While not specific to FASD, congenital abnormalities (e.g. heart defects, renal problems, auditory/visual impairments, skeletal defects) and growth deficits (prenatal and/or postnatal height or weight ≤ 10th percentile) are often associated with this disorder.
Smooth philtrum
Thin upper lip
day 15 and 22 of & indirectly via its metabolites pregnancy (most often)
Neuronal cell death & disruption of migration & proliferation Altered signaling, neurotransmitter imbalance, & neural connectivity Evidence of impairment in 3+ neurodevelopmental domains
Small palpebral fissures
(≥2 SDs below the mean for age & sex or < 3rd percentile) Language Memory Attention Motor skills Cognition Affect regulation Academic achievement Executive function (including hyperactivity & impulsivity) Neuroanatomy/ Neurophysiology (e.g. seizure disorder, abnormal brain structure as seen on brain imaging, microcephaly (head circumference ≤ 10th percentile)) Adaptive behavior, social skills, or social communication Failure to reach age-appropriate milestones, challenges at school, aggression, delinquency, mental health challenges, substance use disorders Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 30, 2018 on www.thecalgaryguide.com