Alcohol Intake in PregnancyMOTHER SAFE ROUND

2016.05.17.정 고 운

All About FASD?

• Alcohol intake in pregnancy

• Clinical features of FASD

• Diagnostic criteria of FASD

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%

Safe Level of Alcohol Intake

• Alcohol is a teratogen that impacts fetal growth and de-velopment at all stages of pregnancy

• A safe level of alcohol consumption during pregnancy has not been determined

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

• 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)

Danish study• Low to moderate alcohol consumption (<9 drink/week) in

early to mild pregnancy did not develop significant ef-fects on developmental outcomes in 5-year-old children

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.

Introduction of FASD

• Fetal alcohol syndrome (FAS)– The most severe form of FASD① Facial anomalies② Growth retardation③ CNS anomalies

• Fetal alcohol spectrum disorder (FASD)– Effect of maternal alcohol consumption during preg-

nancy– Not a diagnostic term– Umbrella terminology

Clinical Manifestations of FASD

• Facial Dysmorphism and minor anomalies

• Structural birth defects

• CNS involvement

• Growth retardation

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

Facial Anomalies of FASD

• Palpebral fissure length

• Smooth or flattened phitrum• Thin vermilian border of the upper lip

unaffected most severe

Lip-Phitrum Guide

Railroad track configura-tion of the ear

Hockey stick crease

Structural birth defects

•ASD, VSD•Conotruncal heart defects (ex. aberrant great vessels, TOF)Cardiac• flexion contractures, pectus excavatum/ car-

inatum, Klippel-Feil syndrome, hemiverte-brae, scoliosis

• radioulnar synostosis, hypoplastic nails, shortened 5th digits, clinodactyly, campto-dactyly

Skeletal

• aplastic/hypoplastic/dysplastic kidney, horseshoe kidney

• ureteral duplications, hydronephosisRenal

• Strabismus, ptosis, retinal vascular anom-alies

• optic nerve hypoplasia, vision problemsOcular

• Conductive HL, SNHLAuditory

Differential Diagnosis

Williams syndrome Cornelia de Lange syndrome

Velocardiofacial syn-drome

Dubowitz syndromeFetal anticonvulsant syndrome, especially hydantoin and valproateMaternal PKU fetal effectsNoonan syndromeToluene embryopathy

CNS involvement - clinical manifestions

• Infancy– irritability, jitteriness, autonomic instability, problems

regulating state (ex. sleep, attention, arousal)• Children

– hyperactivity, inattention, cognitive impairment, emo-tional 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, ex-

ecutive function (ex. school disruption, inability to maintain employment, inappropriate sexual behavior)

CNS involvement - Structural

• Cerebrumvolume 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, perse-

verative behavior

• Corpus callosum– role in the coordination of various functions– Agenesis, thinning, hypoplasia, partial agenesis

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

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

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 initia-tive, lack of reciprocal friendships, social withdrawal, poor personal hygiene

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

Growth Retardation

• Growth pattern characteristic of FASD usually presents in the prenatal period and persists as a consistent impair-ment over time

• Usually below 10 percentile

Growth delay may diminish in adolescence and adult

Diagnosis of FASD

Historical Background

‘You will conceive and give birth to a sonDrink no wine or other fermented drink’

(Holy Bible, Judges 13:7)

‘Foolish, drunken and harebrained women most oftenbring forth children like morose and languid.’

(Aristotle, BC 384-322)

‘Offspring of imprisoned alcoholic women, 55.8% borndead or died before age 2.’

(Sullivan, 1899)

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

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

• 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)

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 ExposureIB, 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 abnormalities

IV. Partial FAS Without confirmed Maternal Alcohol ExposureIIIB and IIIC, as above

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

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

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 condi-

tions; or environmental neglect• Confirmed history of prenatal alcohol exposure

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 do-mains

• 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

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, incom-

plete evaluation, child is too young for adequate assessment)

*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.

§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; neu-roanatomy/neurophysiology; cognition; language; academic achieve-ment; memory; attention; executive function, including impulse con-trol 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 con-sidered when a difference of this size occurs with a very low base rate in the population (≤ 3% of the population).

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 neurodevel-opmental assessment; specific changes and additions include: – “Hard and soft neurological signs including sensory motor” was re-

named “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

Thank you for attention