The Neurodevelopmental Consequences of Prenatal Alcohol Exposure

Elizabeth Welch-Carre, RN, MSN, NNP


Adv Neonatal Care. 2005;5(4):217-229. 

In This Article

Alcohol: A Potent Teratogen

Alcohol is a potent teratogen, capable of causing serious harm to the fetus. Because alcohol causes central nervous system (CNS) damage, it is also classified as a neurobehavioral teratogen.[1,21] Persistent CNS damage is the most debilitating feature of PAE across the lifespan.[18]

The embryo and fetus are dependent on the maternal liver to metabolize alcohol.[22] Alcohol crosses the placenta readily; the embryo and later the fetus are exposed to the same levels of alcohol as in the maternal bloodstream.[22] The timing of exposure determines how and which cells are affected.[23]

Alcohol can cause cell death by both necrosis and apoptosis in the developing embryo and fetus.[23,24,25,26,27,28] Death of a cell line can affect production, migration, and differentiation of future cell lines.[26] Cells in the CNS have a lower threshold for alcohol and, hence, experience more rapid cell death than other cells in the developing embryo.[26] Consequently some individuals may not have the facial characteristics of FAS, yet have significant CNS damage attributable to alcohol exposure.[24,25]

Another probable contributing factor to FAS is oxidative stress.[29,30,31] Oxidative stress occurs when the rate of free-radical production exceeds the ability of the cells to detoxify or eliminate them.[32] There are 2 mechanisms by which this stress may occur. First, a byproduct of the metabolism of alcohol is free radicals; in particular, oxygen-containing free radicals referred to as reactive oxygen species.[32] Second, alcohol consumption suppresses antioxidants that are necessary for free-radical elimination.[33] The combination of increased free-radical production and decreased free-radical elimination can cause toxic levels of free-radical exposure, leading to mitochondrial dysfunction, cell damage, and cell death.[34] Some animal and in vivo studies have shown that treatment with antioxidants can reduce the degree of cell damage and death.[33,34,35,36,37]

Alcohol may further interfere with growth factors necessary for normal CNS development. This has been shown in several studies on insulin-like growth factors (IGF) I and II.[38,39,40] Ordinarily, IGF I and II bind with an IGF receptor on the neuron and a message is sent to stimulate cell division. In the presence of alcohol, the receptor site becomes dysfunctional and the message is never sent.[41] Furthermore, for nondividing nerve cells, IGF I and II receptors are important for maintenance of cell life. Their function is impaired in the presence of alcohol.[42]

Glial cells, important to guide the migration of neurons to their final destination in the brain, are adversely affected by alcohol.[43] In the normal brain, glial cells become astrocytes after all neuronal migration is complete. However, glial cells exposed to alcohol become astrocytes prematurely and remaining neurons are unable to migrate to their proper locations.[44] This explains why some neurons in the alcoholexposed brain are not in their usual location.[44,45]

The neurotransmitters serotonin and glutamate, both important for fetal brain development, are adversely affected by alcohol exposure. Alcohol appears to delay the development of the serotonin system. Without serotonin, growth-factor–releasing astrocytes are not stimulated and normal brain development does not occur.[46,47] Glutamate is an important excitatory neurotransmitter that interacts with several receptors to control brain function. One of these receptors is N-methyl-D-aspartate (NMDA).[23] Alcohol exposure can reduce the number and functionality of the NMDA receptors, further affecting other neurotransmitter systems.[23] These reductions may cause some of the CNS disorganization commonly seen in FAS.[23]

Exposure of fetal cells to alcohol affects glucose uptake. In cell culture studies, the glucose transporter protein GLUT1, found in the brain, was decreased after alcohol exposure.[48] Because glucose metabolism is imperative to brain development and growth, the reduction in glucose uptake may be a major contributor to CNS deficiencies.[48]

The regions of the brain that are affected by alcohol exposure are the basal ganglia, corpus callosum, cerebellum, and, to some degree, the hippocampus.[49,50,51,52] These areas of the brain affect motor and cognitive skills, learning, memory, and executive functioning.[53] Deficiencies in the area of executive functioning are often the most devastating during adulthood; the ability to solve problems, plan for the future, and understand abstract concepts such as time and money can all be affected.[53,54,55] An individual's intelligence quotient is not a direct correlate of executive functioning.[53,54]

The causes of FAS, ARND, and ARBD seem to be multifactorial. Individual genetic makeup plays a part in how alcohol exposure manifests.[1] Dizygotic twins are often affected differently.[56] Furthermore, the frequency, amount, and type of maternal drinking (binge versus frequent low-dose) affect the fetus differently.[57,58] Finally, advanced maternal age, poor maternal health, and comorbid behaviors such as smoking and/or drug use may make the effects of alcohol more potent.[17,57] No studies have determined if there is a safe threshold of alcohol that can be consumed during pregnancy. Current recommendations strongly suggest that pregnant women abstain from alcohol consumption.[10]


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