This document discusses alcohol intake during pregnancy and fetal alcohol spectrum disorders (FASD). It provides statistics on alcohol use during pregnancy from various studies. It notes that a safe level of alcohol during pregnancy has not been determined, as the effects of alcohol on the fetus are variable depending on factors like the mother's metabolism and drinking patterns. Low to moderate prenatal alcohol exposure has not shown effects in some studies, but other research has found children with FAS even with reported low alcohol intake. The document describes clinical features of FASD including facial abnormalities, growth issues, central nervous system anomalies, and functional impairments. It discusses diagnostic criteria from various organizations and guidelines for diagnosing FASD.

1. Alcohol Intake in Pregnancy
MOTHER SAFE ROUND
2016.05.17.
정 고 운

2. All About FASD?

3. • Alcohol intake in pregnancy
• Clinical features of FASD
• Diagnostic criteria of FASD

4. Alcohol Intake in Pregnancy
• CDC and Prevention surveillance system 2011-2013
– alcohol use within 1 mo 10.2%
– binge drinking 3.1%
• 2009 National Birth Defects Prevention Study
– any alcohol use during pregnancy 30%
– binge drinking 8%
• 2005 Pregnancy Risk Assessment Monitoring System
survey
– alcohol use in the 3 mo prior to pregnancy 50%

5. Safe Level of Alcohol Intake
• Alcohol is a teratogen that impacts fetal growth and
development at all stages of pregnancy
• A safe level of alcohol consumption during pregnancy
has not been determined

7. Variability of Adverse Fetal Outcomes
• The impact of alcohol on fetal development is variable
– variations in maternal alcohol clearance rate
– fetal developmental sensitivity
– genetic susceptibility
– drinking pattern (binge vs daily consumption)
– confounders such as polysubstance use
• There is no exact dose-response relationship

8. • No significant increase in risk of
– LBWI, SGA, up to 10g pure alcohol/day (1 drink/day)
– Preterm, up to 18 g pure alcohol/day (1.5 drinks/day)

9. Danish study
• Low to moderate alcohol consumption (<9 drink/week) in
early to mild pregnancy did not develop significant
effects on developmental outcomes in 5-year-old children

10. Washington State FAS Diagnostic & Prevention Network
clinics (2600 children with FAS)
• 1/7 children diagnosed with FAS had a reported exposure of
1–8 drinks/week
• 50% children with FAS had developmental scores in the
normal range as preschoolers. However, all had severe brain
dysfunction confirmed by the age of 10 years.
• Only 10% of the children with FAS had attention problems
by the age of 5 years; 60% had attention problems by the
age of 10 years.
• Only 30% of the children with FAS had an IQ below normal.
However, 100% had severe dysfunction in other areas, such
as language, memory and activity level.

11. Introduction of FASD
• Fetal alcohol syndrome (FAS)
– The most severe form of FASD
① Facial anomalies
② Growth retardation
③ CNS anomalies
• Fetal alcohol spectrum disorder (FASD)
– Effect of maternal alcohol consumption during
pregnancy
– Not a diagnostic term
– Umbrella terminology

12. Clinical Manifestations of FASD
• Facial Dysmorphism and minor anomalies
• Structural birth defects
• CNS involvement
• Growth retardation

13. Facial dysmorphism
• Characteristic facial features
– short palpebral fissures
– thin vermillion border
– smooth philtrum
• Others
– epicanthal folds
– short, upturned nose
– ear anomalies including “railroad track ears”
– micrognathia
– clinodactyly
– hockey stick configuration of the upper palmar crease

15. Facial Anomalies of FASD

16. • Palpebral fissure length

18. • Smooth or flattened phitrum
• Thin vermilian border of the upper lip
unaffected most severe
Lip-Phitrum Guide

19. Railroad track
configuration of the ear
Hockey stick crease

20. Structural birth defects
• ASD, VSD
• Conotruncal heart defects (ex. aberrant great vessels, TOF)
Cardiac
• flexion contractures, pectus excavatum/ carinatum,
Klippel-Feil syndrome, hemivertebrae, scoliosis
• radioulnar synostosis, hypoplastic nails, shortened 5th
digits, clinodactyly, camptodactyly
Skeletal
• aplastic/hypoplastic/dysplastic kidney, horseshoe kidney
• ureteral duplications, hydronephosis
Renal
• Strabismus, ptosis, retinal vascular anomalies
• optic nerve hypoplasia, vision problems
Ocular
• Conductive HL, SNHLAuditory

21. Differential Diagnosis
Williams syndrome Cornelia de Lange
syndrome
Velocardiofacial
syndrome
Dubowitz syndrome
Fetal anticonvulsant syndrome, especially hydantoin and valproate
Maternal PKU fetal effects
Noonan syndrome
Toluene embryopathy

22. CNS involvement - clinical manifestions
• Infancy
– irritability, jitteriness, autonomic instability, problems
regulating state (ex. sleep, attention, arousal)
• Children
– hyperactivity, inattention, cognitive impairment,
emotional reactivity, learning disability, hypotonia,
auditory and visual impairment, seizures, deficits in
memory and reasoning
• Adolescence and young adulthood
– primary deficits in social skills, adaptive function,
executive function (ex. school disruption, inability to
maintain employment, inappropriate sexual behavior)

23. CNS involvement - Structural
• 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
– visuospatialdeficits,verbalmemory,impulsiveness

24. • 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

25. CNS involvement - neurologic sign
• Hard neurologic signs
– abnormal reflexes, abnormal tone, cranial nerve
deficits
• Soft neurologic signs
– poor coordination or balance, visual-motor difficulties,
nystagmus, difficulty with motor sequencing or rapid
successive movements, right-left confusion
– seizure

26. CNS involvements - functional
• Cognitive
– IQ range from 20 to 120
– difficulties in arithmetic (m/c)
– difficulties in reading and spelling
– impaired memory, and slow processing speed
• Executive function
– difficulty planning and relating cause and effect
– failure to consider consequences of actions
– poor organization, impaired judgment
– inability to generalize knowledge from one situation to
another

27. CNS involvement - functional
• Motor function
– poor gross/fine motor coordination
– poor visual-spatial coordination
– hypotonia
• Problems with hyperactivity, attention, or concentration
• Social skills and adaptive function
– poor understanding of social cues, seeming lack of
remorse after misbehaving, lack of appropriate
initiative, lack of reciprocal friendships, social
withdrawal, poor personal hygiene

28. 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

29. Growth Retardation
• Growth pattern characteristic of FASD usually presents in
the prenatal period and persists as a consistent
impairment over time
• Usually below 10 percentile
Growth delay may diminish
in adolescence and adult

30. Diagnosis of FASD

31. 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)

32. Discovery of FASD
• 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

33. Diagnostic Criteria of FASD
• 2000, Astley and Clarren
– 4-Digit Diagnostic Coding system
– To eliminate the ambiguities of IOM system
• 2005, Chudley et al.
– Canadian Diagnostic Guidelines
– IOM system + 4-Digit Diagnostic Code system
• 2005, Hoyme et al.
– Revised IOM Diagnostic Classification System

34. • Revised Institute of Medicine (IOM) criteria
• The University of Washington Four-Digit Diagnostic Code
• The National Task Force on Fetal Alcohol Syndrome/Fetal
Alcohol Effect (FAS/FAE)
• Fetal Alcohol Spectrum Disorders: Canadian Guidelines
for Diagnosis (updated in 2015)

35. Revised IOM Criteria for Diagnosis of FASD
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

36. 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 abnormalities
IV. Partial FAS Without confirmed Maternal Alcohol Exposure
IIIB and IIIC, as above

37. V. ARBD (all of 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) Congenital structural defect (≥1)
if the patient displays minor anomalies only, X 2 must be present)
cardiac/skeletal/renal/eyes/ears/minor anomalies
VI. ARND (both A and B)
(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

38. AAP Diagnostic criteria for FASD
1. FAS
• All three characteristic facial features
• Growth retardation
• CNS involvement
• Confirmed or unconfirmed prenatal alcohol exposure
2. Partial FAS
• Two key facial features
• Growth retardation or CNS involvement
• Confirmed prenatal alcohol exposure

39. 3. Neurobehavioral disorder a/w prenatal alcohol exposure
• CNS involvement with functional impairment (ex. social, academic)
and onset in childhood
• Facial features and growth retardation not necessary (but may be
present)
• Not better explained by other teratogens; genetic or medical
conditions; or environmental neglect
• Confirmed history of prenatal alcohol exposure

40. 2015 Canadian Diagnostic Guidelines
1. FASD with sentinel facial features
• All of the following:
– Prenatal alcohol exposure confirmed or unknown
– All three sentinel facial features
– Meets criteria for CNS involvement:
• Any age: Severe impairment in ≥3 neurodevelopmental
domains
• For children ≤6 years: Microcephaly
2. FASD without sentinel facial features
• Both of the following:
– Confirmed prenatal alcohol exposure
– Severe impairment in ≥3 neurodevelopmental domains

41. 3. At risk for neurodevelopmental disorder and FASD associated
with prenatal alcohol exposure (whether or not child has all
three sentinel facial features)
• All three of the following:
– Confirmed prenatal alcohol exposure, and
– Some indication of neurodevelopmental disorder, but does not
meet CNS criteria as described above, and
– Plausible explanation for lack of meeting CNS criteria (eg,
incomplete evaluation, child is too young for adequate assessment)

42. *Sentinel facial features
The following three sentinel facial features must be present because of
their specificity to prenatal alcohol exposure:
1. Palpebral fissure length ≥ 2 SDs below the mean (< 3 percentile).
2. Philtrum rated 4 or 5 on 5-point scale of the University of Washington
Lip–Philtrum Guide.
3. Upper lip rated 4 or 5 on 5-point scale of the University of Washington
Lip–Philtrum Guide.

43. §Neurodevelopmental assessment
1. A diagnosis of FASD is made only when there is evidence of pervasive
brain dysfunction, which is defined by severe impairment in three of
more of the following neurodevelopmental domains: motor skills;
neuroanatomy/neurophysiology; cognition; language; academic
achievement; memory; attention; executive function, including
impulse control and hyperactivity; affect regulation; and adaptive
behavior, social skills or social communication.
2. Severe impairment is defined as a global score or a major subdomain
score on a standardized neurodevelopmental measure that is ≥ 2 SDs
below the mean, with appropriate allowance for test error. In some
domains, large discrepancies among subdomain scores may be
considered when a difference of this size occurs with a very low base
rate in the population (≤ 3% of the population).

44. Summary of specific updates in this guideline
• The use of FASD as a diagnostic term
• The inclusion of special considerations for diagnosing FASD in infants,
young children and adults
• The deletion of “growth” as a diagnostic criterion
• The addition of a new “at-risk” category that will capture individuals
who do not meet the diagnostic criteria but are still at risk of FASD
• The revision and refinement of brain domains evaluated in the
neurodevelopmental assessment; specific changes and additions
include:
– “Hard and soft neurological signs including sensory motor” was
renamed “motor skills” and redefined
– “Brain structure” was renamed “neuroanatomy/neurophysiology”
and redefined
– “Communication” was renamed “language”
– “Attention deficit/hyperactivity” was renamed “Attention” and
redefined
– “Affect regulation” was added
– “Executive function” was expanded and clarified

45. Thank you for attention