Review on Fetal Alcohol Spectrum Disorders

What Is It?

The term “fetal alcohol spectrum disorders” (FASDs) indicates several pathologies that affect children born of mothers who drank alcohol during pregnancy. Disorders vary from mild to severe, and affect many systems. The most severe is fetal alcohol syndrome (FAS), causing permanent deficits affecting vision, hearing, attention span, memory and all cognitive abilities. Embryos are subjected to both ethanol and acetaldehyde toxicity. Alcohol increases oxidative stress, and results in subsequent general effects (e.g., epigenetic imprinting, gene expression and metabolite levels). In addition, studies indicate that genetic factors and epigenetic mechanisms, such as DNA methylation, histone post-translational modifications and noncoding RNAs, contribute to the gene expression changes caused by ethanol.^1,2

In essence, both maternal and paternal genetic factors may contribute to the sensitivity, resistance or vulnerability of the fetus to alcohol. The period of alcohol teratogenicity is around the time of conception. The placenta allows free transfer of acetaldehyde to the fetus. Although ethanol and acetaldehyde are normally metabolized in the adult liver, the fetal liver is too underdeveloped to achieve this function.

Incidence

The CDC estimates that one of 1,000 live-born infants in the United States has FAS. Despite the warning mandated by the FDA almost three decades ago, the use of alcohol during pregnancy has continued worldwide. U.S. surveys indicate that 20% to 30% of women drink alcohol at some point during their pregnancy.³ However, not all embryos exposed to alcohol exhibit symptoms after birth. Nevertheless, there is no known safe limit for alcohol consumption. The lifetime cost for patients with FAS has been estimated at $2 million.⁴

Diagnosis

Diagnosis depends on maternal history, which may be inaccurate. Presentation at birth is variable from normal to very low birth weight. However, most babies with FASDs are born below the 10th percentile in height and weight, with a small head size. The growth rate is slower, often falling below the third percentile. Structural, neurologic and functional impairments occur in the central nervous system, especially delayed development, intellectual disability, neural tube defects, hyperactivity and seizure disorders. Facial dysmorphism includes malformations of the eyes (up to 90% have difficulty with vision), strabismus, micrognathia, low-set ears, a high arched or cleft palate, and abnormal dentition. Heart murmurs are common and often resolve after one to two years. Findings in neonates include ventricular septal defects and atrial septal defects. Abnormal position and function of joints; altered palmar creases; hepatic dysfunction; and horseshoe, aplastic, dysplastic or hypoplastic kidneys also are common.

Treatment

Clearly, prevention of alcohol intake with education during pregnancy would be curative. Otherwise, treatment is symptom dependent.

Anesthetic Precautions

Preanesthetic assessment must evaluate neurologic (visual and auditory) and cardiac anomalies as well as renal and hepatic function.⁵ Care of the premature infant requires selection of appropriate drug doses, maintenance of temperature and postoperative vigilance for apnea. Intellectual disability may make cooperation difficult. Seizures should be under control, including laboratory assurance of adequate blood levels of antiseizure medications. Although external examination of the airway may appear normal, a high arched or cleft palate may make intubation difficult.

References

1. Liyanage VR, Curtis K, Zachariah RM, et al. Overview of the genetic basis and epigenetic mechanisms that contribute to FASD pathobiology. Curr Top Med Chem. 2017;17(7):808-828.
2. Ehrhart F, Roozen S, Verbeek J, et al. Review and gap analysis: molecular pathways leading to fetal alcohol spectrum disorders. Mol Psychiatry. 2018 Jun 11. doi: 10.1038/s41380-018-0095-4
3. National Institute on Alcohol Abuse and Alcoholism. Fetal alcohol exposure. www.niaaa.nih.gov/ alcohol-health/ fetal-alcohol-exposure. Accessed October 1, 2018.
4. CDC. Data & statistics: prevalence of FASDs. www.cdc.gov/ ncbddd/ fasd/ data.html. Accessed October 1, 2018.
5. Frost EA, Gist RS, Adriano E. Drugs, alcohol, pregnancy, and the fetal alcohol syndrome. Int Anesthesiol Clin. 2011;49(1):119-133.