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IATROGENIC AGENTS

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 drugs, chemicals, birth defects, congenital malformations, causes 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 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 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.

Epidemiologic studies have determined that most 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 hyperthermia 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 F). Numerous other chemotherapeutic agents. However, approximately 95% of the 200 most frequently prescribed appear safe for use during.

HORMONAL AGENTS

Danazol and other androgenic hormone agents may produce clitoral enlargement or labioscrotal fusion in the female fetus when they are given before 13 weeks of gestation. Recent studies, however, have failed to demonstrate a significant relationship between anomalies and first-trimester use of oral contraceptive agents or medroxyprogesterone acetate.

ANTICOAGULANTS

Warfarin and other coumarin-derived anticoagulants inhibit the synthesis of vitamin K-dependent coagulation factors, and use during gestation can produce major and minor anomalies in as many as 25% of fetuses exposed during the first trimester. Abnormalities characteristic of warfarin include hypoplastic nose, epiphyseal stippling, optic atrophy, microcephaly, IUGR, and other central nervous system anomalies. Heparin and low-molecular-weight heparin are not associated with an increased frequency of anomalies.