Fetal alcohol spectrum disorder

Fetal alcohol spectrum disorder (FASD) is caused by damage to the fetal brain by antenatal alcohol exposure.[8]Chambers CD. Fetal alcohol spectrum disorder. In: Preedy V, Watson R, eds. Comprehensive handbook of alcohol related pathology. London: Elsevier; 2005:349-60.[9]Jones KL, Smith DW. Recognition of the fetal alcohol syndrome in early infancy. Lancet. 1973;302:999-1001. http://www.ncbi.nlm.nih.gov/pubmed/4127281?tool=bestpractice.com [10]Jones KL, Smith DW, Ulleland CN, et al. Pattern of malformation in offspring of chronic alcoholic mothers. Lancet. 1973;1:1267-1271. http://www.ncbi.nlm.nih.gov/pubmed/4126070?tool=bestpractice.com [11]Jones KL. From recognition to responsibility: Josef Warkany, David Smith, and the fetal alcohol syndrome in the 21st century. Birth Defects Res A Clin Mol Teratol. 2003;67:13-20. http://www.ncbi.nlm.nih.gov/pubmed/12749380?tool=bestpractice.com [12]Lemoine P, Harousseau H, Borteyru JP, et al. Children of alcoholic parents - observed anomalies: discussion of 127 cases. Ther Drug Monit. 2003;25:132-136. http://www.ncbi.nlm.nih.gov/pubmed/12657907?tool=bestpractice.com ​ Alcohol is teratogenic, readily crosses the placenta, and may cause a wide range of structural birth defects involving the central nervous system, face, and other organs and functional neurodevelopmental problems.[11]Jones KL. From recognition to responsibility: Josef Warkany, David Smith, and the fetal alcohol syndrome in the 21st century. Birth Defects Res A Clin Mol Teratol. 2003;67:13-20. http://www.ncbi.nlm.nih.gov/pubmed/12749380?tool=bestpractice.com Alcohol use is one of the few modifiable risk factors for poor pregnancy and child outcomes.

Not all fetuses exposed to alcohol are harmed, and the risk to the fetus depends on the amount, frequency, and pattern of maternal alcohol consumption and its timing during pregnancy.[8]Chambers CD. Fetal alcohol spectrum disorder. In: Preedy V, Watson R, eds. Comprehensive handbook of alcohol related pathology. London: Elsevier; 2005:349-60. A 'safe' level of alcohol consumption during pregnancy has not been established.[8]Chambers CD. Fetal alcohol spectrum disorder. In: Preedy V, Watson R, eds. Comprehensive handbook of alcohol related pathology. London: Elsevier; 2005:349-60. The peak fetal blood alcohol level is thought to determine fetal damage. Fetal blood alcohol levels are similar to maternal blood alcohol levels, which in turn are determined by the amount and pattern of alcohol intake and by other maternal factors, including alcohol dehydrogenase genotype. The timing of exposure during the first trimester of gestation is critical in determining the pattern of birth defects. Damage to the brain resulting in neurological dysfunction may occur with exposure at any stage of pregnancy.[13]Coles C. Critical periods for prenatal alcohol exposure. Alcohol Health Res World. 1994;18:22-29.[14]Pearson MA, Hoyme HE, Seaver LH, et al. Toluene embryopathy: delineation of the phenotype and comparison with fetal alcohol syndrome. Pediatrics. 1994;93:211-215. http://www.ncbi.nlm.nih.gov/pubmed/7510061?tool=bestpractice.com

Risk to the individual fetus may be modified by fetal and maternal factors, including maternal age, nutritional status, health, parity, body composition, alcohol dehydrogenase genotype, and previous alcohol use.[15]May PA, Gossage JP, Brooke LE, et al. Maternal risk factors for fetal alcohol syndrome in the Western cape province of South Africa: a population-based study. Am J Public Health 2005;95:1190-1199. http://www.ncbi.nlm.nih.gov/pubmed/15933241?tool=bestpractice.com

Alcohol interferes with all developmental stages of the central nervous system (CNS) in the embryo and fetus, and the functional problems seen in children later in life may be due to a combination of alcohol-induced anomalies at any, or all, stages of CNS development. The neocortex, hippocampus, and cerebellum are particularly susceptible. Alcohol has adverse effects on glial development, which may be the origin of neuroglial heterotopies, agenesis of the corpus callosum and anterior commissure, and abnormal neuronal migration.[16]Guerri C. Neuroanatomical and neurophysiological mechanisms involved in central nervous system dysfunctions induced by prenatal alcohol exposure. Alcohol Clin Exp Res. 1998;22:304-312. http://www.ncbi.nlm.nih.gov/pubmed/9581633?tool=bestpractice.com

Several neurotransmitter systems that influence CNS development are impaired by antenatal alcohol exposure, leading to reduced numbers of neurons; decreased levels of serotonin, dopamine, norepinephrine (noradrenaline), glycine, and histamine; and decreases in the number of neurotransmitter-uptake sites and certain neurotransmitter receptors. Antenatal alcohol exposure also alters hormones that influence CNS development, including thyroxine, and regulation of the hypothalamic-pituitary-gonadal axis.

Alcohol may cause damage directly via alterations in glial cell function, decreased neurotrophic factors and receptors, and decreased cell adhesion molecules. Decreased neurotrophic support alters neuron survival and differentiation. High blood alcohol concentration may also cause hypoxia and ischaemia in areas such as the hippocampus and lead to structural brain damage.[16]Guerri C. Neuroanatomical and neurophysiological mechanisms involved in central nervous system dysfunctions induced by prenatal alcohol exposure. Alcohol Clin Exp Res. 1998;22:304-312. http://www.ncbi.nlm.nih.gov/pubmed/9581633?tool=bestpractice.com

Alcohol may cause damage indirectly via poor maternal nutrition, resulting in decreased availability of essential nutrients, antioxidants, and trophic factors. Alcohol may also induce cell and membrane damage via free-radical generation and lipid peroxidation.[16]Guerri C. Neuroanatomical and neurophysiological mechanisms involved in central nervous system dysfunctions induced by prenatal alcohol exposure. Alcohol Clin Exp Res. 1998;22:304-312. http://www.ncbi.nlm.nih.gov/pubmed/9581633?tool=bestpractice.com

Alteration to frontal brain development affects the development of the optic vesicles, which affects the size and/or placement of the palpebral fissures and the placement of the olfactory placodes. Underdevelopment of the medial nasal processes results in a long, smooth philtrum and thin vermillion border of the upper lip. The skeletal anomalies seen may reflect impaired brain development (i.e., normal joint development depends on fetal activity).[11]Jones KL. From recognition to responsibility: Josef Warkany, David Smith, and the fetal alcohol syndrome in the 21st century. Birth Defects Res A Clin Mol Teratol. 2003;67:13-20. http://www.ncbi.nlm.nih.gov/pubmed/12749380?tool=bestpractice.com

Changes in placental structure (decreased placental weight, villous infarction) and function (changes in hormones and other important regulatory endogenous influences, cytokines, and nutritional supply) mediated by placental vasoconstriction, changes in the thromboxane/prostacyclin ratio, and oxidative stress may impair antenatal growth and contribute to CNS damage.[17]Burd L, Roberts D, Olson M, et al. Ethanol and the placenta: a review. J Matern Fetal Neonatal Med. 2007;20:361-375. http://www.ncbi.nlm.nih.gov/pubmed/17674239?tool=bestpractice.com

International classification of diseases (ICD)-11[2]World Health Organization. International classification of diseases (ICD)-11. Geneva: WHO; 2022. https://www.who.int/standards/classifications/classification-of-diseases ​​

LDF.0: toxic or drug-related embryofetopathies

LD2F.00: fetal alcohol syndrome.

Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR)[3]American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed, text revision (DSM-5-TR). Washington, DC: American Psychiatric Publishing; 2022.

Neurodevelopmental Disorder Associated with Prenatal Alcohol Exposure (ND-PAE) is included in the appendix of the fifth edition of the American Psychiatric Association’s DSM-5-TR.[3]American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed, text revision (DSM-5-TR). Washington, DC: American Psychiatric Publishing; 2022. ND-PAE is used as an example for 'Other Specified Neurodevelopmental Disorder' and is listed as a condition requiring further study and includes proposed criteria. The DSM-5-TR determined that there was insufficient evidence to warrant inclusion of these proposals as official mental disorder diagnoses in Section II of DSM-5.