Fetal Alcohol Spectrum Disorders
In 1973, researchers began to recognize the harmful effects alcohol had on a developing fetus. Jones and colleagues, of the University of Washington–Seattle, published a report in the Lancet describing both the dysmorphic and developmental effects alcohol had on eight children born to women affected by alcoholism. A later report by Jones and Smith first coined the term “fetal alcohol syndrome” (FAS).
The reports initiated further research on the syndrome, under the National Institute on Alcohol Abuse and Alcoholism (NIAAA), who looked to further confirm the harmful effects and characterize it. The Seattle 500 Study, an active 30-year research project headed by Dr. Ann Streissguth, examined the full spectrum of effects of alcohol on developing fetuses, specifically targeting the relationship between drinking levels and neurodevelopment.3 However, it was the result of animal research that solidified the relationship between alcohol and dysmorphic and developmental effects on fetuses. As many were skeptical of alcohol’s effects given the substance’s long history of use and the medical field’s late recognition, scientists were able to perform controlled tests to pinpoint whether or not alcohol was the cause.3 The studies of alcohol on pregnant rats, mice, and dogs all produced similar fetus effects as the substance did with humans. Alcohol did, in fact, have harmful effects on a developing fetus.
The Institute of Medicine estimate that, in the United States, the prevalence of FAS is between 0.5 and 2.0 of 1,000 live births.3 However, because children with FASD are often diagnosed with disorders such as attention deficit hyperactivity disorder, oppositional defiant disorder, or conduct disorder, the neurodevelopmental deficits are frequently ignored and a proper diagnosis is not made; therefore, the prevalence is thought to be higher.3 Concerning FASD, Sampson and colleagues estimate the prevalence to be one percent of live births in the United States.3
There are three diagnostic criteria for FAS: facial dysmorphology, pre- and postnatal growth deficiencies, and central nervous system dysfunction.3 However, FAS can produce a wide spectrum of effects, some more apparent than others; therefore, within FAS, the Institute of Medicine describes a number of diagnoses under the term fetal alcohol spectrum disorders (FASD), including partial FAS, fetal alcohol effects, alcohol-related birth defects, and alcohol-related neurodevelopmental disorders.3 Dose, pattern, and timing of alcohol exposure all influence the harmful effects to the fetus, and because the effects vary widely, no amount of alcohol is safe for consumption while pregnant.3 Factors such as prenatal care, nutrition, and genetics all influence the effect the alcohol will have on the fetus.
The facial deformations that may result from FASDs are as follows: skin folds at the corner of the eyes; smaller eye openings, mid-face, and head circumference; a thin upper lip; a lower nasal bridge; a shorter nose; and an indistinct groove between the nose and the upper lip.3 However, it was found that fetuses could suffer from brain abnormalities without showing facial abnormalities.3 In the 1990s, Riley and colleagues conducted structural imaging studies that found alcohol is linked to smaller brain size, abnormal brain shape, difference in cortical thickness (the combined thickness of the cerebral cortex, or outermost tissue layers, of the brain), and alterations of the hippocampus (which translates short-term memories into long-term and controls spatial navigation). Behaviorally, alcohol has been linked to impaired intelligence and reflex development, motor coordination deficits, and hyperactivity.3 Kodituwakku found that deficits in learning, memory, and attention, as well as the inability to regulate emotions are also caused by FASDs. Fetal alcohol spectrum disorders may also contribute to psychiatric disorders and addiction vulnerability.3
Identifying those with prenatal alcohol exposure is difficult, as some individuals with FASDs do not fully meet the classifying factors. Therefore, the NIAAA is currently funding research to develop effective methods of diagnosing individuals so correct treatment may be provided.3 Scientists are exploring three-dimensional camera imaging for the detection of facial deformations, and trying to link the deformations with certain brain functions in order to identify a “unique signature” of FASDs.3 Current methods of diagnosis include questionnaire screenings of the mother, as better identifying women who drink during pregnancy will aid in the diagnosis of FASDs. The TACE, TWEAK, AUDIT, and AUDIT-C are all used to screen for alcohol use.
However, information regarding alcohol use may not always be available, and in that case, identifying biomarkers that reflect fetal alcohol exposure may aid in early recognition and even intervention.3 Unfortunately, alcohol’s main biomarkers are carbon dioxide and water, which are both naturally abundant in humans.3 Therefore, using less prominent ones would have to be used, such as fatty acid ethyl esters (FAEEs) which build up in hair and a newborn’s first fecal excretion. FAEEs can detect alcohol use within the last few weeks of pregnancy.
While the means of preventing FASDs is for the mother to abstain from drinking during pregnancy, it does not always happen. Therefore, the Institute of Medicine has created a three-level model for prevention. One level targets the general population, a second targets high-risk communities, and a third targets specific individuals.3 It has been found that targeting the general population is not an effective approach; however, targeting high-risk communities and specific individuals has shown success. For high-risk communities, screening has shown to be successful in recognizing and intervening with risky drinking habits; however, it is not always utilized so scientists have begun researching methods of reducing the severity of FASD effects, such as vitamin use.3 In animal studies, vitamins C and E have shown to reduce the potential effects. Scientists are also looking at serotonin agonists and nutrients such as choline, folate, zinc, and nicotinamide.3
The study of FASDs has come far within the past 40 years, and although there is still research to be done, much has been learned about its causes and preventions.
 Jones, K.L.; Smith, D.W.; Ulleland, C.N.; and Streissguth, A.P. Pattem of malformation in offspring of chronic alcoholic mothers. Lancet 1(7815):1267-1271, 1973. PMID: 4126070
 Jones, KL., and Smith, D.W. Recognition of the fetal alcohol syndrome in early infancy. Lancet 302(7836):999-1001,1973. PMID: 4127281
 Thomas, J.D. PH.D; Warren, K.R., PH.D.; and Hewitt, B.G. (2010). Fetal Alcohol Spectrum Disorders. Alcohol Research & Health, 33(1 and 2), 118-125.
 Abel, E.L., and Dintcheff, B.A. Effects of prenatal alcohol exposure on growth and development in rats. Journal of Pharmacology and Experimental Therapeutics 207(3):916-921, 1978. PMID: 731439
 Mattson, S.N.; Riley, E.P.; Jernigan, T.L.; et al. Fetal alcohol syndrome: A case report of neuropsychological, MRI and EEG assessment of two children. Alcoholism: Clinical and Experimental Research 16(5):1001-1003, 1992. PMID: 1443415
 Norman, A.L.; Crocker, N.; Mattson, S.N.; and Riley, E.P. Neuroimaging and fetal alcohol spectrum disorders. Developmental Disabilities Research Reviews 15(3):209-217, 2009. PMID: 19731391
 Kodituwakku, P.W. Defining the behavioral phenotype in children with fetal alcohol spectrum disorders: A review. Neuroscience and Biobehavioral Reviews 31(2):192-201, 2007. PMID: 16930704
 Chasnoff, I.J.; Wells, A.M.; McGourri, R.F. and Bailey, L.K Validation of the 4P’s Plus screen for substance use in pregnancy. Journal of Perinatology 27(12):744-748, 2007. PMID: 17805340
 Kulaga, V.; Pragst, F.; Fulga, n.; and Koren, G. Hair analysis of fatty acid ethyl esters in the detection of excessive drinking in the context of fetal alcohol spectrum disorders. Therapeutic Drug Monitoring 31(2):261-266, 2009. PMID: 19258930
 Bearer, C.F.; Jacobson, J.L.; Jacobson, S.W. et al. Validation of a new biomarker of fetal exposure to alcohol. Journal of Pediatrics 143(4):463-469, 2003. PMID: 14571221
 May, PA; Miller, J.H.; Goodhart, KA.; et al. Enhanced case management to prevent fetal alcohol spectrum disorders in Northern Plains communities. Maternal and Child Health Journal 12(6):747-759, 2008b. PMID: 18026824
 Druse, M.J.; Tajuddin, N.F.; Gillespie, RA; and Le, P. The effects of ethanol and the serotonin(1A) agonist ipsapirone on the expression of the serotonin(1A) receptor and several antiapoptotic proteins in fetal rhombencephalic neurons. Brain Research 1092(1); 79-86,2006. PMID: 16687129