Porth's Essentials of Pathophysiology, 4e

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Genetic and Congenital Disorders

C h a p t e r 6

individuals more difficult. Each of these defects can vary in severity, probably reflecting the timing of alcohol con- sumption in terms of the period of fetal development, amount of alcohol consumed, and hereditary and envi- ronmental influences. In 2004, the National Task Force on Fetal Alcohol Syndrome and Fetal Alcohol Effects published guidelines for the referral and diagnosis of FAS. 52 The criteria for FAS diagnosis require the documented presence of three of the following findings: (1) three facial abnormalities (smooth philtrum, thin vermillion, and small palpe- bral fissures), (2) growth deficits (prenatal or postnatal height or weight, or both, below the 10th percentile), and (3) CNS abnormalities (e.g., head circumference below 10th percentile, global cognitive or intellectual deficits, motor functioning delays, problems with atten- tion or hyperactivity). The amount of alcohol that can be safely consumed during pregnancy is unknown. Even small amounts of alcohol consumed during critical periods of fetal devel- opment may be teratogenic. For example, if alcohol is consumed during the period of organogenesis, a vari- ety of skeletal and organ defects may result. When alcohol is consumed later in gestation, when the brain is undergoing rapid development, there may be behav- ioral and cognitive disorders in the absence of physical abnormalities. Chronic alcohol consumption through- out pregnancy may result in a variety of effects, ranging from physical abnormalities to growth retardation and compromised CNS functioning. Evidence suggests that short-lived high concentrations of alcohol such as those that occur with binge drinking may be particularly sig- nificant, with abnormalities being unique to the period of exposure. Because of the possible effect on the fetus, it is recommended that women abstain from alcohol during pregnancy. Infectious Agents Many microorganisms cross the placenta and enter the fetal circulation, often producing multiple malformations. The acronym TORCH stands for t oxoplasmosis, o ther, r ubella (i.e., German measles), c ytomegalovirus, and h er- pes, which are the agents most frequently implicated in fetal anomalies. 2 Other infections include varicella-zoster virus infection, listeriosis, leptospirosis, Epstein-Barr virus infection, and syphilis. Human immunodeficiency virus (HIV) and human parvovirus (B19) have been suggested as additions to the list. The TORCH screening test exam- ines the infant’s serum for the presence of antibodies to these agents. These infections tend to cause similar clini- cal manifestations, including microcephaly, hydrocepha- lus, defects of the eye, and hearing problems. Toxoplasmosis is a protozoal infection caused by Toxoplasma gondii . The infection can be contracted by eating raw or inadequately cooked meat or food that has come in contact with infected meat. 57 The domes- tic cat can carry the organism, excreting the protozoa in its feces. It has been suggested that pregnant women should avoid contact with excrement from the family cat. Although the introduction of the rubella vaccine has

virtually eliminated congenital rubella syndrome in most developed countries, it remains endemic in many devel- oping countries, where it is the major preventable cause of hearing impairment, blindness, and adverse neurode- velopmental outcome. The epidemiology of cytomega- lovirus infection is largely unknown. Some infants are severely affected at birth, and others, although having evidence of the infection, have no symptoms. In some symptom-free infants, brain damage becomes evident over a span of several years. There also is evidence that some infants contract the infection during the first year of life, and in some of them the infection leads to retar- dation a year or two later. Herpes simplex virus type 2 infection is considered to be a genital infection and usu- ally is transmitted through sexual contact. The infant acquires this infection in utero or in passage through the birth canal. Nutrient Deficiencies Although most birth defects are related to exposure to a teratogenic agent, deficiencies of nutrients and vita- mins also may be a factor. Folic acid deficiency has been implicated in the development of neural tube defects (e.g., anencephaly, spina bifida, encephalocele). Studies have shown a reduction in neural tube defects when folic acid was taken before conception and continued during the first trimester of pregnancy. 58,59 The Public Health Service recommends that all women of childbearing age should receive 400 micrograms ( μ g) of folic acid daily. These recommendations are particularly important for women who have previously had an affected pregnancy, for couples with a close relative with the disorder, and for women with diabetes mellitus and those taking anti- convulsant drugs who are at increased risk for having infants with birth defects. Since 1998, all enriched cereal grain products in the United States have been fortified with folic acid. To achieve an adequate intake of folic acid, pregnant women should couple a diet that contains folate-rich foods (e.g., orange juice; dark, leafy green vegetables; and legumes) with sources of synthetic folic acid, such as fortified food products. 58

SUMMARY CONCEPTS

■■ Teratogenic agents such as radiation, chemicals and drugs, and infectious organisms produce abnormalities in the developing embryo. ■■ The stage of development of the embryo determines the susceptibility to teratogens. The period during which the embryo is most susceptible to teratogenic agents is the time during which rapid differentiation and development of body organs and tissues are taking place, usually from days 15 to 60 postconception.

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