Major congenital anomalies are observed in about 3% of all births. Maternal exposure to drugs or environmental chemicals may be responsible for 4-6% of these anomalies, or approximately 1 in 400 liveborn infants.
Whether birth defects occur in a conceptus exposed to a potentially teratogenic agent depends in large part on two factors: 1) gestational timing of the exposure and 2) the genetic makeup of the conceptus and the mother. Morphogenetic stage of the organism’s development is a key factor in susceptibility to a potential teratogen. Exposure to a teratogenic agent during organogenesis may result in a gross defect involving the organ undergoing formation at that time. Conversely, exposure to such an agent during histogenesis may produce finer structural defects within the target organ system. Substantial evidence suggests that, second only to the gestational timing of exposure, the most important variable is difference in the genetically determined activity of the enzymes involved in the metabolism of drugs and chemicals. This difference is termed pharmacogenetic variation. An important determinant of teratogenic potential is mode of exposure. The teratogenic agent may reach the developing embryo or fetus either by direct passage through maternal tissues (eg, ionizing radiation) or by placental transfer (eg, drugs or chemicals).
Drugs and Chemicals
Epidemiologic studies have determined that most drugs commonly used during pregnancy (eg, aspirin, acetaminophen, metronidazole, caffeine, phenothiazines) are not associated with an increased risk of congenital anomalies. However, based on anecdotal evidence, maternal hyper-thermia seems to be associated with congenital anomalies when the fever persists for a protracted period of time (>24 hours) and is high (at least 101 o F). Numerous other agents have been implicated as teratogens, including chemotherapeutic agents. However, approximately 95% of the 200 most frequently prescribed drugs appear safe for use during pregnancy.
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