Criteria

Introduction

A number of diagnostic criteria are currently in use. The choice of diagnostic criteria varies within and between countries.[44] There are a number of subtle but important differences between the criteria, particularly with regard to facial features and central nervous system (CNS) criteria. Terminology, diagnostic categories, and cut-points for abnormality also vary. 

In recent survey of specialist fetal alcohol spectrum disorder (FASD) clinics,[44] the most commonly used diagnostic criteria in the US were the 4-digit diagnostic code,[34] followed by the Clarification of Institute of Medicine (IOM) criteria for fetal alcohol syndrome (FAS),[37] and the Centers for Disease Control and Prevention (CDC) criteria for FAS.[35] Subsequent to publication of the IOM criteria, various groups have published revised criteria, with the aim of making the diagnosis more specific, rigorous, and clinically useful.[33][36][47]

Institute of Medicine criteria for fetal alcohol syndrome[33]

Developed by a panel of experts, based on review of a large number of children with clinical abnormalities who were born following confirmed alcohol exposure in utero. These criteria provided the first systematic approach to delineating diagnostic categories for children adversely affected by alcohol exposure in utero. The categories are as follows: FAS, partial FAS, alcohol-related neurodevelopmental disorder (ARND), and alcohol-related birth defects (ARBDs).

FAS (diagnosis requires all 4 criteria):

1. Confirmed or unconfirmed maternal alcohol exposure.

2. Facial features - evidence of a characteristic pattern of facial anomalies that includes features such as short palpebral fissures and anomalies in the premaxillary zone (e.g., flat upper lip, flattened philtrum, and flat midface).

3. Growth retardation - at least one of the following:

  • Low birth weight for gestational age

  • Decelerating weight over time not due to nutrition

  • Disproportional low weight to height.

4. CNS neurodevelopmental abnormalities - at least one of the following:

  • Decreased cranial size at birth

  • Structural brain anomalies

  • Neurological hard or soft signs (age appropriate).

Partial FAS (diagnosis requires sections 1 and 2, and one other):

1. Confirmed maternal alcohol exposure.

2. Facial features - evidence of some components of the pattern of characteristic facial anomalies.

3. Growth retardation - at least one of the following:

  • Low birth weight for gestational age

  • Decelerating weight over time not due to nutrition

  • Disproportional low weight to height.

4. CNS neurodevelopmental abnormalities - at least one of the following:

  • Decreased cranial size at birth

  • Structural brain anomalies

  • Neurological hard or soft signs (age appropriate).

5. Evidence of a complex pattern of behaviour or cognitive abnormalities that are inconsistent with developmental level and cannot be explained by familial background or environment alone, such as learning difficulties; deficits in higher-level receptive and expressive language; poor capacity for abstraction or metacognition; specific deficits in mathematical skills; or problems in memory, attention, or judgement.

ARND disorder (diagnosis requires section 1, and one other):

1. Confirmed maternal alcohol exposure.

2. CNS neurodevelopmental abnormalities - any one of the following:

  • Decreased cranial size at birth

  • Structural brain anomalies

  • Neurological hard or soft signs (age appropriate).

3. Evidence of a complex pattern of behaviour or cognitive abnormalities that are inconsistent with developmental level and cannot be explained by familial background or environment alone, such as learning difficulties; deficits in higher-level receptive and expressive language; poor capacity for abstraction or metacognition; specific deficits in mathematical skills; or problems in memory, attention, or judgement.

ARBD:

Confirmed maternal alcohol exposure and one or more birth defects:

  • Cardiac anomalies:

    • Atrial septal defects

    • Ventricular septal defects

    • Aberrant great vessels

    • Tetralogy of Fallot.

  • Skeletal anomalies:

    • Hypoplastic nails

    • Shortened fifth fingers

    • Radioulnar synostosis

    • Flexion contractures

    • Camptodactyly

    • Clinodactyly

    • Pectus excavatum and carinatum

    • Klippel-Feil syndrome

    • Hemivertebrae

    • Scoliosis.

  • Renal anomalies:

    • Aplastic, dysplastic, or hypoplastic kidneys

    • Ureteral duplication

    • Hydronephrosis

    • Horseshoe kidneys.

  • Ocular anomalies:

    • Strabismus

    • Retinal vascular anomalies

    • Refractive problems secondary to small globes.

  • Auditory anomalies:

    • Conductive hearing loss

    • Sensorineural hearing loss.

Other malformations.

Fetal alcohol spectrum disorders 4-digit diagnostic code[34][58]

These criteria were developed to ensure objectivity and reproducibility in the diagnosis of FAS through specifying cut-off points (e.g., for growth parameters and palpebral fissure length). The concept of the 4-digit diagnostic code was introduced to give greater diagnostic scope for describing children adversely affected by alcohol but who did not fulfil the diagnostic criteria for FAS. This system introduces the use of a number of other terms to describe clinical patterns, including the terms 'static encephalopathy - alcohol exposed', and 'neurobehavioural disorder - alcohol exposed'.

FAS (diagnosis requires all 4 criteria):

1. Confirmed or unconfirmed maternal alcohol exposure.

2. Facial features - all 3 of:

  • Philtrum rank 4 or 5

  • Upper lip rank 4 or 5

  • Palpebral fissure length <3rd percentile.

3. Growth retardation: antenatal or postnatal height or weight ≤10th percentile.

4. CNS - at least one of:

  • Structural evidence of CNS damage (e.g., head circumference <3rd percentile, significant brain abnormalities on neuroimaging)

  • Neurological evidence of CNS damage

  • Significant impairment across 3 or more domains of brain function (generally ≤2 standard deviations). Domains include executive function, memory, cognition, social/adaptive skills, academic achievement, language, motor, attention, and activity level.

Partial FAS (diagnosis requires 1 and 2 and 3):

1. Confirmed maternal alcohol exposure.

2. Facial features - at least 2 of:

  • Philtrum rank 4 or 5

  • Upper lip rank 4 or 5

  • Palpebral fissure length <3rd percentile.

3. CNS - at least one of:

  • Structural evidence of CNS damage (e.g., head circumference <3rd percentile, significant brain abnormalities on neuroimaging)

  • Neurological evidence of CNS damage

  • Significant impairment across 3 or more domains of brain function (generally ≤2 standard deviations). Domains include executive function, memory, cognition, social/adaptive skills, academic achievement, language, motor, attention, and activity level.

ARND or ARBD:

  • The 4-digit code uses different categories and terminology to describe children with neurodevelopmental problems, some of which may be comparable with ARND.

Centers for Disease Control and Prevention criteria for fetal alcohol syndrome[35]

A committee of experts, mandated by US federal law, was convened by the CDC to update and refine the diagnostic criteria for FAS. Criteria were only developed for FAS because there was deemed to be lack of evidence to support the development of reliable diagnostic criteria for the rest of the spectrum.

FAS (diagnosis requires all 4 criteria):

1. Confirmed or unconfirmed maternal alcohol exposure.

2. Facial features - all 3 of the following:

  • Philtrum rank 4 or 5

  • Upper lip rank 4 or 5

  • Palpebral fissure length ≤10th percentile.

3. Growth retardation: antenatal or postnatal height or weight ≤10th percentile.

4. CNS - at least one of the following:

  • Structural abnormalities: head circumference ≤10th percentile (or ≤3rd percentile for children whose height and weight are ≤10th percentile) or clinically significant brain abnormalities on neuroimaging

  • Neurological abnormalities: seizures not due to postnatal causes, or soft neurological signs

  • Functional abnormalities: global cognitive deficit or significant developmental delay (IQ assessment ≤2 standard deviations), or deficits in ≥3 specific functional domains (≤ 16th percentile or 1 standard deviation). Domains include cognitive deficits or significant developmental discrepancies, executive functioning, motor functioning delay or deficits, attention and hyperactivity problems, social skills problems, sensory problems, memory deficits, or pragmatic language problems.

Clarification of Institute of Medicine criteria for fetal alcohol syndrome[38]

The authors sought to clarify the criteria for diagnostic categories described in these guidelines in order to make them both more specific and more useful for clinicians. In particular, these criteria included specified cut-off points for measurements such as growth and palpebral fissure length. The criteria for ARBD were made stricter, requiring 2 or more of the facial features of FAS in addition to specified birth defects. An updated guideline based on these criteria has been published.[38]

FAS (diagnosis requires all 4 criteria):

1. Confirmed or unconfirmed maternal alcohol exposure.

2. Facial features - 2 or more of:

  • Philtrum rank 4 or 5

  • Upper lip rank 4 or 5

  • Palpebral fissure length ≤10th percentile.

3. Growth retardation: antenatal or postnatal weight or height ≤10th percentile.

4. CNS - at least one of:

  • Structural brain abnormalities

  • Head circumference ≤10th percentile.

Partial FAS (diagnosis requires 1 and 2 and at least one other):

1. Confirmed or unconfirmed maternal alcohol exposure.

2. Facial features - 2 or more of:

  • Philtrum rank 4 or 5

  • Upper lip rank 4 or 5

  • Palpebral fissure length ≤10th percentile.

3. Growth retardation: antenatal or postnatal weight or height ≤10th percentile.

4. CNS - at least one of:

  • Structural brain abnormalities

  • Head circumference ≤10th percentile

  • Evidence of a complex pattern of behavioural or cognitive abnormalities inconsistent with developmental level that cannot be explained by genetic predisposition, family background, or environment alone. The pattern includes marked impairment in the performance of complex tasks (e.g., complex problem solving, planning, judgement, abstraction, metacognition, and arithmetic tasks), higher-level receptive and expressive language deficits, and disordered behaviour (e.g., difficulties in personal manner, emotional lability, motor dysfunction, poor academic performance, and deficient social interaction).

ARND (diagnosis requires 1 and 2):

1. Confirmed maternal alcohol exposure

2. CNS - at least one of:

  • Structural brain abnormalities

  • Head circumference ≤10th percentile

  • Evidence of a complex pattern of behavioural or cognitive abnormalities inconsistent with developmental level that cannot be explained by genetic predisposition, family background, or environment alone. The pattern includes marked impairment in the performance of complex tasks (e.g., complex problem solving, planning, judgement, abstraction, metacognition, and arithmetic tasks), higher-level receptive and expressive language deficits, and disordered behaviour (e.g., difficulties in personal manner, emotional lability, motor dysfunction, poor academic performance, and deficient social interaction).

ARBD (diagnosis requires all 3 criteria):

1. Confirmed maternal alcohol exposure.

2. Facial features - 2 or more of:

  • Philtrum rank 4 or 5

  • Upper lip rank 4 or 5

  • Palpebral fissure length ≤10th percentile.

3. Congenital structural defects in one or more categories (≥2 required if patient has only minor abnormalities):

  • Cardiac anomalies:

    • Atrial septal defects

    • Ventricular septal defects

    • Aberrant great vessels

    • Conotruncal defects.

  • Skeletal anomalies:

    • Radioulnar synostosis

    • Vertebral segmentation defects

    • Large joint contractures

    • Scoliosis.

  • Renal anomalies:

    • Aplastic, dysplastic, or hypoplastic kidneys

    • Ureteral duplication

    • Horseshoe kidneys.

  • Ocular anomalies:

    • Strabismus

    • Ptosis

    • Retinal vascular anomalies

    • Optic nerve hypoplasia.

  • Ears:

    • Conductive hearing loss

    • Sensorineural hearing loss.

  • Minor abnormalities:

    • Hypoplastic nails

    • Short fifth fingers

    • Camptodactyly

    • Clinodactyly of fifth fingers

    • Pectus carinatum or excavatum

    • Hockey-stick palmar creases

    • Refractive errors

    • Railroad-track ears.

Fetal alcohol spectrum disorder: Canadian guidelines for diagnosis

The previous Canadian guidelines[59] included elements of both the IOM criteria and the 4-digit diagnostic code and provide specific cut-off values for growth parameters. The criteria for CNS involvement are more stringent than other classifications, requiring evidence of involvement of 3 or more CNS domains.

FAS (diagnosis requires all 4 criteria):

1. Confirmed or unconfirmed maternal alcohol exposure

2. Facial features - all 3 of:

  • Philtrum rank 4 or 5

  • Upper lip rank 4 or 5

  • Palpebral fissure length ≤3rd percentile.

3. Growth retardation - at least one of:

  • Birth weight or birth length ≤10th percentile for gestational age

  • Height or weight ≤10th percentile

  • Disproportionately low weight-to-height ratio (≤10th percentile).

4. CNS - evidence of impairment in 3 or more of the following CNS domains with impairment indicated by function ≥2 standard deviations from the mean:

  • Hard or soft neurological signs

  • Brain structure

  • Cognition

  • Communication

  • Academic achievement

  • Memory

  • Executive functioning and abstract reasoning

  • Attention deficit/hyperactivity

  • Adaptive behaviour

  • Social skills

  • Social communication.

Partial FAS (diagnosis requires all 3 criteria):

1. Confirmed maternal fetal alcohol exposure.

2. Facial features - 2 or more of:

  • Philtrum rank 4 or 5

  • Upper lip rank 4 or 5

  • Palpebral fissure length <3rd percentile.

3. CNS - evidence of impairment in 3 or more of the following CNS domains:

  • Hard or soft neurological signs

  • Brain structure

  • Cognition

  • Communication

  • Academic achievement

  • Memory

  • Executive functioning and abstract reasoning

  • Attention deficit/hyperactivity

  • Adaptive behaviour

  • Social skills

  • Social communication.

ARND (diagnosis requires 1 and 2):

1. Confirmed maternal alcohol exposure.

2. CNS - evidence of impairment in 3 or more of the following CNS domains:

  • Hard or soft neurological signs

  • Brain structure

  • Cognition

  • Communication

  • Academic achievement

  • Memory

  • Executive functioning and abstract reasoning

  • Attention deficit/hyperactivity

  • Adaptive behaviour

  • Social skills

  • Social communication.

An updated version of the Canadian guidelines has been published.[36] Key to the updated guidelines is the use of the term FASD (with or without 3 sentinel facial features) as a diagnosis rather than an umbrella term that encompasses FAS, partial FAS, and ARND. Less emphasis is placed on growth as a criterion for diagnosis and the domains of neurodevelopmental impairment have been modified. An Australian guide to the diagnosis of FASD adopts most elements of the Canadian guideline.[47] A Scottish guideline on children and young people exposed prenatally to alcohol was published in early 2019.[60] This document is based mostly on the updated Canadian guidelines but elements of the Australian guide to the diagnosis of FASD have also been incorporated. Minor changes have been made to align the guidance with practice in Scotland.

The use of different criteria internationally must urgently be addressed to enhance clarity for clinicians and enable accurate diagnosis and early intervention.

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