Fetal Alcohol Spectrum Disorder

Raja A S Mukherjee (UK), Sheila Hollins (UK), Jeremy Turk (UK)

What are Fetal Alcohol Spectrum Disorders?
Fetal alcohol spectrum disorders is an umbrella term for a set of disorders caused by the consumption of alcohol by a mother whilst pregnant. These conditions range in diversity from the full presentation of fetal alcohol syndrome (FAS), involving a characteristic set of facial features combined with growth and neuro-cognitive deficits, to a range of conditions affecting the neuro-behavioural presentations of the condition without all these features.

Hogarth 1751: Gin Lane depicting early alcohol abuse and reported to
depict a baby possibly affected with Fetal Alcohol Spectrum Disorders

Box 1 summarises the different clinical criteria used, based on the Institute of Medicine diagnoses (USA), as well as the common diagnostic methods used. (1,2).O'Leary (3) recently summarised the epidemiological research in to fetal alcohol spectrumdisorders concluding that the estimated worldwide prevalence is around 1 per 100 for fetal alcohol spectrum disorders, making it the most common cause of intellectual difficulties.

Box 1
Summary of diagnostic categories and methods. (Hoyme 2005).
1. Fetal Alcohol Syndrome : Confirmed alcohol exposure
 a.Alcohol Exposure.
 b.Facial pattern of Short palpebral fissures < / = 10 percentile, Thin upper lip vermillion, Smooth philtrum.
 c.Evidence of pre / postnatal growth retardation.
 d.Evidence of Neurocognitive deficits.
2. Fetal Alcohol Syndrome: No confirmed alcohol exposure.
 a.As above but no alcohol exposure found.
3. Partial Fetal Alcohol syndrome: Confirmed Alcohol Exposure
 a.Not all of the above features are present but neurocognitive and some facial features needed.
4. Alcohol Related Birth Defect (ARBD)
 a.Confirmed maternal alcohol consumption as well as some but not all of the facial features are present however the behavioral features or structural abnormalities are more pronounced.
5. Alcohol Related Neurodevelopmental Disorder (ARND)
 a.Confirmed maternal alcohol consumption with the absence of growth retardation or facial features and with the neurocognitive features being prominent.

Knowledge of Fetal Alcohol Spectrum Disorders

Knowledge levels about fetal alcohol spectrum disorders by the general public and health professionals in the UK are not accurately known. Most relevant studies have taken place in the USA and Canada where there is greater general awareness of the disorder. Nanson et al (4) surveyed a group of paediatricians and general practitioners. She showed that whilst most people had heard of fetal alcohol spectrum disorders, less than 50 % knew much about how to recognise it. 10% of those that did recognise the condition did nothing about it. Stohler (5) studied 40 high risk pregnancies to see if fetal alcohol syndrome was detected in the offspring. A specially trained research assistant identified 16 cases resulting from these pregnancies. None had been identified by routine paediatric screening. Further, 73% of the case notes made no record of maternal alcohol consumption despite the mothers being known to be in a high risk group.


Kesmodel et al (6) studied a group of pregnant Danish women. A majority 74% felt that drinking in pregnancy was acceptable and 65% reported they had received little or no information from their midwife about possible dangers. This is consistent with data collected by the UK government in their alcohol reduction strategy, where it was found that 61% of women drank during pregnancy to some level (7). MacKinnion (8) studied a group of teenagers in America. Although 97% had heard of alcohol causing problems during pregnancy, 48% thought that the condition related to the baby being addicted to alcohol and just over 50% felt the condition could be cured. Similar information needs to be collected in the UK urgently in order to inform health promotion strategies.

Diagram Highlighting the Number of Units in a Glass
Glass letterVolume
Alcohol content (%)No of units in glassNumber of glasses needed to have a binge
(6 units in one sitting)

Pathology in Fetal Alcohol Spectrum Disorders

Picture of extreme damage in an alcohol exposed brain taken by Sterling Clarren. FAS brain on Right.

Since the naming of fetal alcohol syndrome (FAS) in 1973 there has been some controversy as to its actual existence. Further uncertainty persists regarding the level of maternal alcohol consumption that can cause damage. Evidence for pathogenic mechanisms comes from mainly animal studies. These have been corroborated by some human investigations. The difficulty with human research lies in the ethics of the methodology and the subsequent biases inherent in available approaches. It is the combination of all the evidence that has given most insight into the condition's pathogenesis.

Maier and West (9) suggest that it is the rise in alcohol levels, as well as the subsequent withdrawal, which cause damage. Both raised acetaldehyde levels as well as subsequent apoptotic damage from excess glutamate activity following GABA (gamma amino butyric acid) withdrawal are implicated. Ikonomidou et al (10) report that exposure of rat brain to ethanol for a period of hours during a specific developmental stage induces an apoptotic neurodegenerative reaction that deletes large neurones from several developing sites. This process is further complicated by individual genetic differences, diet, and hormonal interactions as some of the multifaceted risk factors. Thus prediction of individual risk is particularly difficult if not impossible. The UK binge drinking culture and lack of awareness of true drink size by the general public are additional risks (7,11).

Diagram showing developmental periods during pregnancy

Reports have shown increasingly that there are vulnerable periods of neonatal development that can be affected by teratogenic ingestion. In terms of neural development, which occurs throughout pregnancy, it is often the inter-neuron connections that are damaged. This is especially the case at lower levels of consumption. Charness et al (12) report that even at low concentrations of ethanol exposure, cell adhesion molecules are inhibited. These have subsequent effects on neuronal migration, fasciculation and synaptogenesis, which are all vital to the developing brain. These risk factors, as well as protective factors, need further clarification.

More recently work by Hepper et al(13) using ultrasound monitoring of fetal behaviour where mothers consumed alcohol at levels within current UK government guidance showed effects on fetal startle which did not habituate to a level achieved by those that consumed no alcohol. They suggest that this is a sign that even at the low levels of alcohol consumption (an average of 4.3 units per week +/- 1.9) permanent damage to the developing fetal brains is occurring.

Neurocognitive deficits & secondary disabilities
Jacobson (14) summarised the cognitive deficits associated classically with fetal alcohol spectrum disorders. These deficits tend to be life long, and are evident in the absence of facial pathology. Box 2 summarises the core deficits witnessed. Rasmussen (15) recently published a systematic review of the executive and working memory deficits associated with fetal alcohol spectrum disorders. Further, it was reported that the severity of these long term core deficits is independent of the presence of facial features, meaning a diagnosis of ARND (Alcohol Related Neurodevelopmental Disorder) can be as debilitating as full fetal alcohol syndrome. In many cases it can be more because the person may appear superficially not to have a disability and will be expected to perform to a level of sophistication and ability they simply cannot manage. Clinical evidence suggests that this makes individuals more vulnerable to avoidable serious secondary disabilities.

Streissguth et al (16) have highlighted ongoing secondary difficulties. Intellectual tests show that average IQ is 85.9 for fetal alcohol spectrum disorders. This group has an uneven profile of abilities and disabilities that means their average level of intellectual functioning is not truly reflective or predictive of their pattern of cognitive strengths and needs.


IQ Score

WRAT Arithmetic

Vineland Adaptive Behaviour Scale Score





















They further show this group are vulnerable to life events. 90% have some form of diagnosable mental disorder. These can be as diverse as ADHD (attention deficit hyperactivity disorder), social and communicatory impairments, personality disorder, schizophrenia, addiction and depression. 50% have some form of confinement in mental health or criminal justice situations and 50% some form of sexually inappropriate behaviour. Much of this can be related to their inability to control and maintain their behaviour attributable to damage caused to their executive function abilities combined with difficulties in receptive language and inability to consolidate memories because of temporal / hippocampal damage.

Management of Fetal Alcohol Spectrum Disorders

From Vol. 18, No. 1, 1994 of the Journal Alcohol Health & Research World

Management of fetal alcohol spectrum disorders classically is divided into two main areas. Firstly, recognition of the dangers of alcohol consumption in pregnancy and the prevention of damage to the fetus. The second area is less well researched but relates to the management of people who have the condition. The emphasis on prevention has been the most highly publicised of the two with numerous authors stressing the level of risk that is harmful, early detection of at risk mothers, the need for information sharing between professionals and public as paramount priorities (17,18). Emerging methods such as the use of routine screening tools such as TWEAK, hair sampling, or meconium testing have been suggested (19,20), however the ethical debate around their use is in its infancy thus clarification is required before they can be recommended routinely. Research into protective factors during pregnancy has been inconclusive and contradictory. The use of vitamin E as a potential antioxidant has been shown beneficial in some studies and ineffective in others (21,22). Clearly much has still to be done before conclusive information can be given to mothers contemplating pregnancy. For this reason we continue to emphasise the general abstinence message (17).

With regard to children and adults who have fetal alcohol spectrum disorders, much work has been undertaken to categorise difficulties and establish diagnoses. Less research has been undertaken relating to clinical management. This work has mainly involved children in the United States and Canada. Chudley et al (1) recently reviewed the Canadian guidance on diagnosing and managing fetal alcohol spectrum disorders. . They emphasise early recognition and psychometric testing combined with multidisciplinary intervention approaches.

Much of what can be implemented depends on local resources and vision. Preconception prevention aspects involve Government and general practitioners in terms of health promotion and advice, whilst later general practitioners, obstetricians and others are needed during the pregnancy in addition to routine antenatal care to monitor alcohol use and to provide health advice. It is here that suspected cases can be highlighted and information passed to colleagues in order to maximise early pickup of problems. Simple, regular recording of information about alcohol consumption will facilitate this process and inform future diagnoses. Failure to do so leads to avoidable difficulties and impairments later.

Further management involves a wide range of health professionals, many of whom may not be aware of the issues facing them. Clinical genetics services ( equivalent to clinical dysmorphology services in other parts of the world) and access to clinical psychology and speech and language therapy may in some areas be limited. The provision of specialist schools, whilst useful, is not available in the UK specifically for fetal alcohol spectrum disorders. Those children in the general special needs school set-up in the UK anecdotally seem to do better than those who remain in the mainstream. Unfortunately this remains the minority.

Unlike the situation in America and Canada, where specific, dedicated fetal alcohol spectrum disorder centres exist, there are very few fetal alcohol spectrum disorder experts in the UK. Thus obtaining specialist advice is restricted to the lucky few. As is the case for many, clinical service funding streams mean that for people with fetal alcohol syndrome it is not always possible to obtain what they need. Nonetheless, recognising the condition, obtaining sufficient early evidence and using resources locally available in collaboration with multi-professional colleagues can reap important rewards. By combining these multi-professional agencies in a single setting, as is the case in other parts of the world, has the outcome of potentially facilitating a seamless approach to the condition and the experience for the patient.

The estimated extra cost of fetal alcohol spectrum disorders in USA in has been estimated at $500,000 per individual over a 20 year period (23). For a condition that can be prevented, increasing awareness, education and UK based research will help to allow access to local provisions and could be expected to reduce the prevalence of the condition as well as the human cost in the future.

Suggestions for further reading

1.Chudley AE, Conry J, Cook JL, Loock C, Rosales T, LeBlanc N. Fetal alcohol spectrum disorder: Canadian guidelines for diagnosis. Canadian Medical Association Journal 2005; 172 :S1 – S21
2.Hoyme HE, May PA, Kalberg WO, Kodutuwakku P, Gossage JP, Trujillo PM, et al. A practical clinical approach to the diagnosis of fetal alcohol spectrum disorder : clarification of the 1996 institute of medicine criteria. Paediatrics 2005; 115(1): 39 – 47
3.O'Learey CM. Foetal Alcohol Syndrome; Diagnosis, epidemiology and developmental outcomes.  Journal of Paediatrics and Child Health 2004; 40: 2-7
4.Nanson JL, Bolaria R, Snyder RE, Morse BA, Weiner L, Physician awareness of FAS ; survey of paediatricians and GP. Canadian Medical Association Journal 1995 ;152(7) :1071- 1076
5.Stoler JM, Holmes LB. Under recognition of prenatal alcohol effects of infants of known alcohol abusing women. Journal of Paediatrics 1999 ;135(4): 430 – 436
6.Kesmodel U, Kesmodel PS. Drinking during pregnancy: attitudes and knowledge among pregnant Danish women in 1998. Alcoholism Clinical and Experimental Research 2002 ;26(10): 1553-60
7.Department of Health Strategy Unit.  Alcohol harm reduction project: Interim analytical report  DOH London 2003
8.Mackinnon DP, William- Avery RM, Pentz MA. Youth belief and knowledge about the risks of drinking while pregnant.  PublicHealth Reports 1995; 110(6) :754 – 763
9.Maier SE, West JR. Drinking patterns and alcohol related birth defects. Alcohol Research and Health 2001; 25(3) :168 –174
10.Ikonomidou C, Bittagau P, Ishimaru MJ, Woznaik DF, Koch C et al. Ethanol induced apoptic neurodegeneration and fetal alcohol syndrome.  Science 2000; 287: 1056-1060
11.Kaskutas LA, Graves K. Pre pregnancy drinking: how drink size affects risk assessment. Addiction 2001;96: 1199-1209
12.Charness ME, Safran RM, Perides G. Ethanol inhibits neural cell- cell adhesion. Journal of Biological Chemistry 1994; 269(12) :9304-9
13.Hepper PG, Dornan JC, Little JF,  Maternal alcohol consumption may delay the development of spontaneous fetal startle behaviour.  Physiology and Behaviour 2005; 83 : 711- 714
14.Jacobson JL, Jacobson SW. Effects of prenatal alcohol exposure on child development.  Alcohol Research and Health 2002; 26(4): 282-286
15.Rasmussen C. Executive functioning and working memory in fetal alcohol spectrum disorder.  Alcoholism: Clinical and Experimental Research 2005;29 (8) :1359 – 1367
16.Streithguth AP, O'Malley K. Neuropsychiatric implications and long term consequences of fetal alcohol spectrum disorders Seminars in Clinical Neuropsychiatry 2000 ;5(3): 177 – 190
17.Mukherjee RAS, Hollins S, Abou Saleh MT, Turk JT. Low level alcohol consumption and the fetus. British Medical Journal 2005; 330: 375-6
18.Valborg KL, Leonardson GR, Borzelleca J, Brock E, Neff-Smith M,  Welty TK. Characteristics of mothers who have children with fetal alcohol syndrome or some characteristics of fetal alcohol syndrome.  Journal American Board of Family Practitioners 2003;16(4): 296-303
19.Russel M. New assessment tools for risk assessment during pregnancy T-ACE TWEAK and others. Alcohol Research and Health 1994; 18(1): 55-61
20.Chan D. Meconium fatty acid ethyl esters: an emerging marker. Journal of Fetal Alcohol Syndrome International 2003;1:c9
21.Marino MD, Aksenov MY, Kelly JS. Vitamin E protects against alcohol induced cell loss oxidative stress in the neonatal rat hippocampus. International Journal of Developmental Neuroscience 2004;22( 5-6): 363-377
22.Tran TD, Jackson HD, Horn, KH, Goodlett CR. Vitamin E does not protect against neonatal ethanol induced cerebellar damage or deficits in eyeblink classically conditioned rats.  Alcoholism: Clinical and Experimental Research 2005; 29(1) :117 – 129
23.Klug MG, Burd L. Foetal alcohol syndrome prevention: annual and cumulative cost savings Neurotoxicol Teratol 2001: 25; 763 - 65

Reproduced from the JRSM, volume 99. 2006 pg 298-302, with permission from the Royal Society of Medicine Press, London.

The article has been edited by the authors and some illustrations have been added.

Published on this website in March 2007.