Early Diagnosis of

Fetal Alcohol Spectrum Disorder

Cheil General Hospital & Women’s Healthcare Center,

Kwandong University College of Medicine, Seoul, Korea

Goun Jeong, M.D.

Department of Pediatrics

2010.04.27.

Introduction

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

Prenatal alcohol exposure is a 100% preventable

cause of birth defects and developmental disabilities.

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

Epidemiology

Prevalence

– FAS: 0.5-2.0/1000 birth in US

– FASD: 9.1/1000 birth in US (1%)

>4% in South Africa

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

Variability of adverse fetal outcomes

– the amount of alcohol

– genetic variation

– nutrition

– maternal age

– socioeconomic status

– the timing of exposure

Clinical manifestations of FASD

FASD related birth defects

• Midface hypoplasia, Hypertelosism, High arched palate

• Micrognathia,Joint contracture, Scoliosis, Hemivertebrae, Radioulnar synostosis, Brachydactyly, Clinodactyly, Camptodactyly

Skeletal

• Septal defects, Hypoplastic pulmonary arteries, TOF

• Pectus excavatum or carinatumCardiac

• Pyelonephritis, Hydronephrosis, Dysplastic kidney

• Ureteral duplications, uni/bilateral hypoplasiaRenal

• Strabismus, Retinal vascular anomaliesOcular

• Conductive hearing loss, neurosensory hearing lossAuditory

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

– visuospatialdeficits, 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

Neuropsychological and Behavioral changes

Overall IQ

Learning and Memory

Language

Attention

Visuospatial abilities

Executive functioning

Fine and Gross motor skills

Adaptive and Social skills

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

Diagnosis

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 abnormalities

IV. Partial FAS Without confirmed Maternal Alcohol Exposure

IIIB 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

Physical examination

Palpebral fissure length

Lip-Philtrum Guide

unaffected most severe

Approach to the diagnosis

1. Screening for maternal alcohol consumption

2. Biomarkers for in utero alcohol exposure

3. Meconium FAEE screening

4. Hair FAEE screening

Screening Questionnaires

TWEAK (≥ score 3, heavy or problem drinker)

T

(tolerance)

How many drinks does it take before you begin to feel the first effects of

alcohol?

(3 or more drinks = 2 points)

W

(worried)

Have close friends or relatives worried or complained about your

drinking in the past year?

(yes = 2 points)

E

(eye-opener)

Do you sometimes take a drink in the morning when you first get up?

(yes = 2 points)

A

(amnesia)

Has a friend of family member ever told you about things you said or

did while you were drinking that you could not remember?

(yes = 1 point)

K

(kut-down)

Do you sometimes feel the need to cut down on your drinking?

(yes = 1 point)

Timeline followback calendar: TLFB

SUN MON TUE WED THU FRI SAT

1 2 3

4 5 6 7 8 9 10

11 12 13 14 15 16 17

18 19 20 21 22 23 24

25 26 27 28 29 30

소주 3잒

와인 1잒

Biomarkers

GGT (gamma-glutamyl transferase) ↑

MCV (mean corpuscular volume) <98 fL

HAA (hemoglobin-associated acetaldehyde) ↑

CDT (carbohydrate deficient transferrin) ↑

FAEE (fatty acid ethyl esters)

FAEE

Non-oxidative metabolites

Esterification of ethanol

FAEE synthase, AEAT in all human tissue

Produced by the fetus itself from the ethanol

Meconium as a matrix

Discarded material: noninvasive and easy collection

Cumulative matrix from 13th week GA until birth

Wider window of opportunity for detection

Detected in the meconium of neonates born to both

drinking and non-drinking mothers

FAEE accumulation in hair

Neonatal hair grows at the 4th week of fetal life

Collected up to 3 months

Accumulation in hair is dose-dependent

Long-term biomarker

Further evaluation

Neurocognitive function test

Brain MRI

Functional Brain imaging

Digital photography

EEG

Bayley III

베일리 발달척도는 대표적인 발달평가 도구로, 영유아를 대상으로

전반적인 발달 상태 및 정상적인 발달 상태로부터의 이탈 정도를 평가하기위해 개발되었음

1969년 초판이 개발된 이후, 1993년에 개정판이 나왔고,

2004년 3판이 나온 상태이며, 아직 국내 표준화는 되어있지 않음

Bayley-III (Bayley Scales of Infant Development, Third edition)

인지, 언어, 운동, 사회-정서, 적응적 행동의 총 5개 하위 영역으로 구성

Bayley Content (1)

인지(Cognitive) : 외부 세상에 대해 생각하고, 반응하고, 학습하는 정도

언어(Language) : 수용성 언어와 표현성 언어로 구성

– 수용성 언어: 소리를 인식하고 단어와 지시를 이해하는 정도를 평가

– 표현성 언어: 소리, 몸동작, 단어를 사용해 의사소통 하는 정도를 평가

운동(Motor) : 소근육 운동과 대근육 운동으로 구성됨

– 소근육 운동(Fine Motor) : 손과 손가락을 움직이고 사용하는 정도를 평가

– 대근육 운동(Gross Motor) : 싞체를 움직이는 정도를 평가

위의 인지, 언어, 운동은 과제를 이용하여 평가자에 의해 이루어짐

Bayley Content (2)

사회-정서(Social-Emotional)

– 연령에 따라 정상적으로 도달해야 하는 사회-정서적 측면을 평가

적응적 행동(Adaptive Behavior)

– 적응적 행동 영역은 일상생활에서 주어지는 다양핚 요구에 적응하는 능력을 평가함

– 10개의 소영역으로 구성되어 있음

– 의사소통, 기초학습(단어 인식과 수 세기), 자기지도(스스로를 통제, 지시따르기), 놀이, 사회관계(사람들과 어울리기), 외부활동, 가정생활(갂단핚집안일 돕기, 개인 소지품 관리), 건강/안전(기본적인 건강 및 안전 행동), 자기관리(먹기, 배변, 씻기 등), 운동기능(움직임과 도구 다루기) 등

– 적응적 행동의 소영역은 유아의 연령에 따라 해당되지 않는 영역이 있을수 있음

위의 사회-정서, 적응적 행동은 보호자의 보고에 의해 이루어짐

보조적인 평가를 위함

Report example

인지, 언어, 운동 등의 영역에서 원점수를 통해 척도점수(10점이 50p)가산출되고, 최종적으로 표준점수(100점이 50%ile) 및 백분위가 산출됨

표준점수에 따라 [발달지연, 경계, 평균 하, 평균, 평균 상, 우수, 최우수]

등으로 분류됨

척도원점수

(raw score)

척도 점수

(scaled score)

표준 점수

(composite score)

백분위

(percentile)분류

인지 48 9 95 37 평균

수용성 언어 19 10

100 50 평균표현성 언어 20 10

소근육 운동 32 979 8 경계

대근육 운동 39 4

사회-정서 87 9 95 37 평균

Thank you for

your attention