Fetal Alcohol Spectrum Disorder

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Definitions

Fetal alcohol spectrum disorder (FASD) is a term used to describe a continuum of physical, mental, and behavioral changes that occur due to fetal alcohol exposure during gestation.

One common area of confusion is the use of the terms fetal alcohol spectrum disorder (FASD) and fetal alcohol syndrome (FAS). The term FAS was first implemented to describe the classic triad of characteristic facial abnormalities, growth retardation, and neurodevelopmental deficits found in children exposed to alcohol during gestation. However, recently there has been recognition that in utero alcohol exposure manifests as a wide range of adverse fetal outcomes and the term FASD has been coined to encompass this diversity. FASD is an umbrella term which includes FAS as its most severe clinical presentation.

Overview

It is estimated that a quarter of all newborns in Canada and the US are exposed to alcohol during early pregnancy. While there are no national statistics for FASD prevalence in Canada, the prevalence of FASD is reported as 9.1/1000 live births in the US. (CDC shows prevalence as 0.2 to 2 per 100 live births with 12.2 % of US women reporting EtOH use during 1995-2005 -http://www.cdc.gov/ncbddd/fasd/data.html) FASD is the leading known cause of mental retardation in Canada and the US and is entirely preventable.

Pathophysiology

Alcohol is a known teratogen. It is able to cross the placenta to affect fetal tissue as well as cross the blood-brain-barrier to affect the developing fetal brain. The exact mechanism of how alcohol toxicity leads to the characteristic features of FASD is unknown but many hypotheses have been proposed:

Alcohol acts as a vasoconstrictor to impair placental blood flow to the fetus, resulting in fetal hypoxia
Alcohol acts to disrupt cellular energetics by altering proteins used in glucose metabolism and transport
Alcohol impairs embryogenesis by dysregulating migration of embryonic cells
Alcohol disrupts proteins involved in cell-to-cell interactions
Alcohol alters regulation of gene expression
Alcohol disrupts cell signaling pathways
Alcohol induces cell damage/cell death

Risk Factors

Common risk factors for alcohol exposure in utero include advanced maternal age, lower parental education levels, lower parental socioeconomic status, exposure to cocaine and smoking prenatally, paternal drinking, and other drug use at the time of pregnancy. (also unmarried and employed women, EtOH use prior to pregnancy – again from CDC)

There is no known alcohol threshold for the development of FASD however studies have shown that any alcohol exposure during pregnancy can have adverse effects. Risk factors for development of FASD include maternal blood-alcohol levels, timing of alcohol exposure in relation to fetal development, frequency of alcohol usage, and the pattern of alcohol usage – binge drinking (≥4 drinks per session) being the worst.

Teratogen = any agent that can disturb the normal development of an embryo or fetus

Clinical Features

Classically, the FAS triad of clinical features are:

Growth Retardation

≤10th percentile for birth weight or birth length OR
≤10th percentile for height or weight OR
≤10th percentile weight-to-height ratio compared to the general population

Facial Features

3 characteristic facial dysmorphologies*
Short palpebral fissures
Smooth or flattened philtrum
Thin vermilion border of the upper lip
Facial features change with age and the diagnosis should be made according to when the features were most severely expressed
Other associated facial features such as midface hypoplasia, micrognathia, low set ears…etc) should be noted but are not included in the diagnostic criteria

*See Supplemental Information for diagrams of the facial dysmorphologies

Philtrum = space between upper lip and nose

Vermilion border = red, exposed surface of the lip

Neurobehavioral Dysfunction

Requires impairment of 3 domains

Domains of assessment

Hard and soft neurologic signs
Brain structure
Cognition/IQ
Communication
Academic achievement
Memory
Executive functioning and abstract reasoning
Attention deficit/hyperactivity
Adaptive behavior, social skills, social communication

A domain is considered as impaired if

Scores are ≤2 standard deviations below the mean

Classification

FASD is not a diagnosis by itself and the current Canadian guidelines for diagnosis of FASD has been subdivided into 4 diagnostic entities:

FAS with confirmed maternal alcohol exposure

Growth impairment
All 3 characteristic facial abnormalities
Impairment in ≥3 neurodevelopmental domains
Confirmed maternal alcohol exposure during gestation

FAS without confirmed maternal alcohol exposure

Growth impairment
All 3 characteristic facial abnormalities
Impairment in ≥3 neurodevelopmental domains
Unconfirmed maternal alcohol exposure during gestation

Partial FAS (p-FAS) with confirmed maternal alcohol exposure

≥2 characteristic facial abnormalities
Impairment in ≥3 neurodevelopmental domains
Confirmed maternal alcohol exposure during gestation

Alcohol-related neurodevelopmental disorder (ARND)

Impairment in ≥3 neurodevelopmental domains
Confirmed maternal alcohol exposure during gestation

Questions to Ask

Historical Investigation

Maternal alcohol use in current pregnancy

Number of alcoholic beverages
Pattern of drinking
Frequency of drinking
Timing of alcohol use (ie.1st, 2nd, 3rd trimester)
Use of TWEAK and/or T-ACE alcohol screening tools

Maternal drug use in current pregnancy

Smoking
Prescription medication
Over the counter medication
Illicit drug use

Previous pregnancy history

Alcohol usage
Number of previous pregnancies
Number of living children
FASD in current children

Neurodevelopmental history

How is the child doing in school?
How is the child interacting with peers?
Achievement of developmental milestones at the appropriate ages
Neurological signs
Neuroimaging (ie. MRI)

Physical Examination

Growth of the child

Monitor the child’s growth on the growth chart
Look for the height and weight percentile
Is the child maintaining their own percentile or falling off

Identify facial abnormalities in the child

Short palpebral fissures
Smooth or flattened philtrum
Thin vermilion border of the upper lip

Neurodevelopmental development of the child

Complete neurological exam
Previous neuroimaging (ie. MRI)
Developmental assessement

Differential Diagnosis

Teratogen exposure (other than alcohol) during pregnancy
Genetic syndromes
Multifactorial disorders

Diagnosis: The 4 Digit Diagnostic Code

The 4 digits in this code reflect the magnitude of expression of the 4 characteristic diagnostics features:

Growth deficiency
The FAS facial phenotype
Central nervous system damage/dysfunction
Prenatal exposure to alcohol

This system assigns numbers from 1 to 4 for each of the characteristics depending on the severity and then each produces a 4 number code.

References:

Kleigman RM, Behrman RE, Jenson HB, Stanton BF, ,. Nelson Textbook of Pediatrics 18th Edition. Elsevier Saunders, 2007.

Chudley AE, Conry J, Cook JL, et al. Fetal alcohol spectrum disorder: Canadian guidelines for diagnosis. Canadian Medical Association Journal 2005; 172 (supplement 5):S1-S14.

Koren G, Nulman I, Chudley AE, et al. Fetal alcohol spectrum disorder. Canadian Medical Association Journal. 2003; 169:1181-1185.

Goodlett CR, Horn KH, Zhou FC. Alcohol Teratogenesis: Mechanisms of Damage and Strategies for Intervention. Experimental Biology and Medicine 2005; 230: 394-406.

Sielski LA. Infants of Mothers with Substance Abuse. Up To Date ver.17.1. 2009.

Astley SJ and Clarren SK. Diagnosing the Full Spectrum of Fetal Alcohol-Exposed Individuals: Introducing the 4 Digit Diagnostic Code. Alcohol and Alcoholism 2000; 35(4): 400-410.

Acknowledgements

Written by: Peter Ao & Mitchell Lee

Edited by: Anne Marie Jekyll