fetal alcohol syndrome

Fetal alcohol spectrum disorder (FASD) describes a spectrum of permanent and often devastating birth-defect syndromes caused by maternal consumption of alcohol during pregnancy. The main effect of fetal alcohol exposure is brain damage. This can be caused during any trimester, because the fetus's brain continues to develop throughout the entire pregnancy. The brain damage is often accompanied by, and reflected in, distinctive facial stigmata, as seen in the photograph on the right.

There are a number of subtypes, including full-blown fetal alcohol syndrome (FAS), and the less noticeable, but sometimes equally serious, possible fetal alcohol effects (PFAE). The latter is also known as prenatal exposure to alcohol (PEA) or alcohol-related neurodevelopmental disorder (ARND).

Features of FASD may include facial deformities, stunted physical and emotional development, memory and attention deficits, a tendency to impulsive behavior, inability to reason from cause to effect, a failure to comprehend the concept of time, difficulty telling fantasy from reality, inability to control sexual impulses, and an apparent lack of remorse. Secondary disabilities such as mental illness and drug addiction are also likely to develop. Unlike the primary disabilities, these do not reflect the central nervous system damage, but instead develop because the child has difficulty adapting to his environment.

Fetal alcohol exposure is regarded by researchers as the leading known cause of mental retardation in the Western world. ^[1] In the United States alone, it is estimated that, every year, one in 750 babies born suffers from FAS, and 40,000 from PFAE. ^[2] The lifetime medical and welfare costs of each child are estimated by some to be as high as US$5 million.^[3]

Naming of the syndrome

Fetal alcohol syndrome was named in 1973 by two dysmorphologists, Kenneth Lyons Jones and David W. Smith of the University of Washington Medical School in Seattle. They identified a pattern of "craniofacial, limb, and cardiovascular defects associated with prenatal onset growth deficiency and developmental delay" in eight unrelated children of three ethnic groups, all born to mothers who were alcoholics. ^[4] The pattern of malformations indicated that the damage was prenatal. News of the discovery was "shocking, and met at first with disbelief." ^[5]

Dr. Paul Lemoine of Nantes, France had already published a study in a French medical journal in 1968 about children with distinctive features whose mothers were alcoholics, ^[6] and in the U.S., Christy Ulleland and colleagues at the University of Washington Medical School ^[7] had conducted an 18-month study in 1968-1969 documenting the risk of maternal alcohol consumption among the offspring of 11 alcoholic mothers. The Washington and Nantes findings were confirmed by a research group in Gothenburg, Sweden in 1979. ^[8]

Researchers in France, Sweden, and the United States were struck by how similar these children looked, though they were not related, and how they behaved in the same unfocused and hyperactive manner. ^[8]

Within four years of the Washington discovery, animal studies, including non-human primate studies carried out at the University of Washington Primate Center by Dr Sterling Clarren, had confirmed that alcohol was a teratogen. By 1978, 245 cases of FAS had been reported by medical researchers, and the syndrome began to be described as the most frequent known cause of mental retardation.

Brain damage and facial defects

Craniofacial abnormalities are visible in children with FAS, though not in children with FAE. Generally, children with FAS have a smaller head circumference and low birth weight, and they may fail to thrive. Their facial features are distinctive and diagnostically significant, in that they are a sign of brain damage, although there may be brain damage without the visible facial effects.

Common findings are mild to moderate microcephaly; small palpebral fissure lengths (palpebral fissures are the opening of the eyelids, measured from between the exocanthion and endocanthion of each eye); a thin upper lip; smooth philtrum (the vertical "divot" or groove between the nose and upper lip); flattened cheekbones; and a short nose. ^[9]

Sterling Clarren of the University of Washington's Fetal Alcohol and Drug Unit told a conference in 2002:

I have never seen anybody with this whole face who doesn't have some brain damage. In fact in studies, as the face is more FAS-like, the brain is more likely to be abnormal. The only face that you would want to counsel people or predict the future about is the full FAS face. But the risk of brain damage increases as the eyes get smaller, as the philtrum gets flatter, and the lip gets thinner. The risk goes up but not the diagnosis.

At one-month gestation, the top end of your body is a brain, and at the very front end of that early brain, there is tissue that has been brain tissue. It stops being brain and gets ready to be your face ... Your eyeball is also brain tissue. It's an extension of the second part of the brain. It started as brain and "popped out." So if you are going to look at parts of the brain from alcohol damage, or any kind of damage during pregnancy, eye malformations and midline facial malformations are going to be very actively related to the brain across syndromes ... and they certainly are with FAS. [4]

As of 2002, there were 25 reports of autopsies on babies known to have been suffering from FASD. The first was in 1973 on a baby who died shortly after birth. ^[4] The examination revealed extensive brain damage, including microcephaly, migration anomalies, callosal dysgenesis, and a massive neuroglial, leptomeningeal heterotopia covering the left hemisphere. ^[10]

Sterling Clarren described a second baby born in 1977, whose mother was a binge drinker. The baby died ten days after birth. The autopsy showed severe hydrocephalus, abnormal neuronal migration, and a small corpus callosum (which connects the two hemispheres) and cerebellum (ibid).

Since then, FASD has also been linked to brainstem and cerebellar changes, agenesis of the corpus callosum and anterior commissure, migration errors, absent olfactory bulbs, meningomyelocele, and porencephaly (ibid, p. 11).

Diagnostic criteria

Although clinicians agree on the definition of full-blown fetal alcohol syndrome, there is no agreement on the clinical criteria or names for lesser forms of it. This has led to some confusion for clinicians and patients. The following definitions are used in the clinic of Dr. Sterling Clarren (Clarren in Streissguth and Kanter 2002, p. 46):

• FAS with a confirmed history of fetal alcohol exposure

The definition of FAS is much the same as when the syndrome was first named. Diagnostic criteria include growth deficiency, the characteristic set of facial anomalies described above, and evidence of organic brain damage including structural, neurological, or functional stigmata.

• FAS without a confirmed history of fetal alcohol exposure

Clarren writes that he has never seen a patient with the same findings as above who has confirmed negative for prenatal alcohol exposure. However, his clinic does see patients who fit the diagnosis for whom no early history is available. Prenatal exposure is therefore not regarded as part of the diagnostic criteria, but will tend only to confirm it.

• Atypical FAS or Possible FAS (PFAS)

These patients have almost all the findings, and a confirmed history of alcohol exposure, but may lack growth deficiency or the full facial stigmata.

• Fetal alcohol effect (FAE), possible fetal alcohol effect (PFAE)

This term was used in research studies to describe humans and animals in whom teratogenic effects were seen after confirmed fetal alcohol exposure, but without obvious physical anomalies (Clarren and Smith 1978). Because alcohol could not be regarded with certainty as the only cause of the effects, the term "possible fetal alcohol effects" was proposed for clinical use. This term has fallen out of favor with clinicians because it was being regarded by the public as a final diagnosis rather than a tentative one, and because it seemed to overstate the relationship between the possible cause and the perceived effects.

• Alcohol-related birth defect

This was proposed as an alternative to FAE and PFAE, but it has fallen out of favor, according to Clarren.

• Alcohol-related neurodevelopmental disorder

This was suggested by Stratton, Howe, and Battaglia in 1996 to replace FAE and PFAE, but Clarren regards the term as begging the question regarding the extent to which alcohol may have played a role, when the damage in some patients is minimal and hard to evaluate in terms of causation.

When the brain damage occurs

During the first trimester, according to Sterling Clarren and Ann Streissguth of the University of Washington, alcohol interferes with the migration and organization of brain cells (Journal of Pediatrics, 92(1):64-67).

Most of the clinical features of FAS (the facial and other visible deformities) are believed to be caused mainly during the 10th and 20th week (Early Human Development; 1983 Jul Vol. 8(2) 99-111).

During the third trimester, damage can be caused to the hippocampus, which plays a role in memory, learning, and emotion, leading to difficulty encoding visual and auditory information (Neurotoxicology and Teratology, 13:357-367, 1991). [5]

Other physical effects

• Growth — Pre- and postnatal onset growth retardation.
• Performance — The I.Q. may be in the region of 63, though this depends on the severity of the condition. Poor eye-hand coordination. Fine motor dysfunction manifested by a weak grasp.
• Skeletal — Joint anomalies including abnormal position and function, altered palmar crease patterns. Small distal phalanges and small fifth fingernails.
• Cardiac — A heart murmur that frequently disappears by one year of age. Ventricular septal defect most commonly seen, followed by an atrial septal defect.
• Occasional abnormalities — Ptosis of the eyelid. Microophthalmia, cleft lip with or without a cleft palate, webbed neck, short neck, Tetralogy of Fallot, coarctation of the aorta, Spina bifida, and hydrocephalus.

Prevention

Alcohol is a teratogen, and the only certain way to prevent FASD is to avoid drinking alcohol during pregnancy. Some studies have shown that small amounts of alcohol during pregnancy might not pose a risk to the fetus (for example, Abel, 1996; Day, 1992; du Florey et al., 1992; Forrest and du Florey, 1991; Goodlett and Peterson, 1995; Polygenis et al., 1998; Streissguth et al., 1994; Wilkie, 1997), although no amount of alcohol during pregnancy can be guaranteed to be absolutely safe. In the United States, the Surgeon General recommended in 1981 that women not drink while pregnant or while planning a pregnancy, the latter to avoid damage in the earliest stages of a pregnancy while the woman may not be aware that she has conceived. Congress passed legislation in 1989 that requires warning labels be placed on all alcoholic beverage containers.

Notes

References

Further reading

• Singer, Songwriter, Actor Paul Williams has set up a page with information and links about Fetal Alcohol Syndrome