Dr. Senturias of Atrium Health/Levine Children’s Hospital has no relevant financial relationships to disclose.)
Mr. Bonthius of Wartburg College has no relevant financial relationships to disclose.)
Dr. Bonthius of the University of Iowa has no relevant financial relationships to disclose.)
Dr. Maria of Thomas Jefferson University has no relevant financial relationships to disclose.)
Fetal alcohol syndrome is the most common preventable cause of intellectual disability in the Western world. In addition to inducing developmental delay, gestational alcohol exposure can lead to a variety of neurodevelopmental abnormalities, including epilepsy, attention deficit hyperactivity disorder, and academic difficulties. Many of these behavioral deficits in children with fetal alcohol syndrome are due to alcohol-induced neuronal death. In this updated article, the authors discuss the various clinical presentations of fetal alcohol spectrum disorders, the way in which binge drinking increases the risk of alcohol-induced fetal brain injury, and the purported mechanisms of alcohol-induced neuronal death. In addition, the authors discuss the importance of genetics in determining the risk of fetal alcohol spectrum disorder in the offspring of alcohol-consuming pregnant women.
• Fetal alcohol syndrome is the constellation of developmental defects that results from maternal alcohol abuse during pregnancy.
• Although the syndrome includes prenatal and postnatal growth disturbances and abnormalities of midface development, brain dysfunction is the most clinically important component of the syndrome.
• Impairments in learning and attention constitute the most common neurologic problems of fetal alcohol syndrome.
• Neuronal death plays a central role in the pathogenesis and outcome of fetal alcohol syndrome.
• Fetal alcohol spectrum disorder is an umbrella term that covers all of the adverse effects of alcohol on the developing fetus.
Historical note and terminology
It has been known for centuries that the children of alcoholic women are often intellectually impaired. In Problemata (322 BCE), Aristotle observed that “foolish, drunken or hare-brained women for the most part bring forth children like unto themselves, difficult and listless.” The Babylonian Talmud (200 CE to 500 CE) warns that “one who drinks intoxicating liquor will have ungainly children.”
Through most of history, alcoholism has been seen not as a medical problem but as a moral failure. It was assumed that the flawed children of alcoholic women acquired their defects, not from alcohol, but from the constitutional weaknesses of their mothers. Only recently has it been recognized that the fetus is directly and adversely affected by alcohol and that the ill effects are similar enough from 1 affected child to the next to constitute an identifiable syndrome.
In 1968, an article by Lemoine and coworkers was published in a French medical journal describing a combination of physical defects and neuropsychological abnormalities affecting the children of alcoholic mothers (Lemoine et al 1968). The reported physical defects included abnormal facies, heart anomalies, and limb deformities. The neuropsychological manifestations included delayed psychomotor and language development and lowered intelligence quotient. The article received little attention. During the subsequent 5 years, few follow up clinical or experimental studies were published examining the possibility of alcohol-induced birth defects.
In 1973, unaware of Lemoine's report, Smith and coworkers at the University of Washington described a constellation of developmental defects attributed to maternal alcohol abuse during pregnancy (Jones and Smith 1973; Jones et al 1973). The constellation, which closely resembled the signs described by Lemoine, included facial abnormalities, pre- and postnatal growth deficiencies, defects in major organ systems, limb anomalies, microcephaly, and developmental delay. The authors named this constellation of developmental defects the “fetal alcohol syndrome,” and their work received immediate international attention. Since 1973, hundreds of clinical and experimental studies have been published exploring the effect of alcohol on fetal development.
Within several years of the original description of fetal alcohol syndrome, it was discovered that not all of the characteristic features of the syndrome are always expressed following intrauterine alcohol exposure. Children whose mothers abused alcohol during pregnancy and who exhibit some, but not all, of the clinical signs of fetal alcohol syndrome have been described as having alcohol-related birth defects, fetal alcohol effects, or alcohol-related neurodevelopmental disorders (Hoyme et al 2016; Wozniak et al 2019).
In 1996, the Institute of Medicine described fetal alcohol spectrum disorder as an umbrella term for the effects of prenatal alcohol exposure and defined criteria for diagnostic entities under the fetal alcohol spectrum disorder umbrella (Stratton et al 1996). Since then, the diagnostic entities under this umbrella have been updated and include fetal alcohol syndrome, alcohol-related neurodevelopmental disorder, partial fetal alcohol syndrome, and alcohol-related birth defects (Hoyme et al 2005).
Today, “fetal alcohol syndrome” is defined by a triad of developmental abnormalities that include the following: (1) prenatal and postnatal growth retardation, (2) a characteristic set of midface abnormalities, and (3) central nervous system dysfunction. All 3 components must be present to make the diagnosis of fetal alcohol syndrome.
Educators, advocates, and federal agencies (including the National Institute on Alcohol Abuse and Alcoholism and the Centers for Disease Control and Prevention) have adopted “fetal alcohol spectrum disorder” as an umbrella term to promote a better understanding and description of alcohol's wide-ranging teratogenic effects. Unlike “fetal alcohol syndrome,” which is a defined syndrome whose features are clearly linked to alcohol, fetal alcohol spectrum disorder does not have defined features. Instead, “fetal alcohol spectrum disorder” is a term used to describe an adverse outcome suspected, but not necessarily proven, to have been due to prenatal alcohol exposure (Mattson et al 2019).
For most children with fetal alcohol spectrum disorder, neurobehavioral issues will be the presenting concern. Neurobehavioral disorder associated with prenatal alcohol exposure is the latest diagnostic entity that has been proposed in the APA Diagnostic and Statistical Manual – 5th edition and is also found as an example of a DSM diagnostic category called other specified neurodevelopmental disorder 315.8 (American Psychiatric Association 2013). In addition to prenatal exposure to alcohol, criteria for neurobehavioral disorder associated with prenatal alcohol exposure include impairments in neurocognition, self-regulation, and 2 areas of adaptive functioning (Hagan et al 2016).
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