Hx and Principles
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| Background risk for a congenital anomaly | 3%
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| Causes of Malformations | 1) Genetic (28%) 2. Toxicants (3%) 3. Uterine factors and twinning (3%) 4. Multifactorial (23%) 5. Unknown (43%)
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| Teratogen definition | Any environmental agent such as a drug, chemical, infection, or pollutant which potentially harms the developing fetus
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| Wilsons Principles of Teratology | biologic explanation for the mechanism of action of the teratogen
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| There are 4 basic manifestations of abnormal development | 1. Pregnancy loss 2. Malformations 3. Growth retardation 4. Functional deficits
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| Types of reproductive toxiticity | 1. Alterations in libido, fertility, menstruation 2. Gene mutations or chromosome breaks 3. Pregnancy Loss 4. Fetal malformations 5. Fetal growth retardation 6. Behaviorial teratogenesis 7. Transplacental carcinogenesis
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| Paternal exposures | 1. Sperm develop over a 90 day period 2. Possible effects include: DNA mutations or chromosome breaks 3. Alterations to fertility 4. Excreted in semen, absorbed by woman, directly affects fetus, may affect methylation; Poorly studied
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| With this genetic basis, phenytoin will lead to embryopathy | Deficient epoxide hydrolase
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| Which this genetic basis, alcohol will lead to FAS | Alleles of ADH and ALDH
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| With this genetic basis, smoking can cause oral clefts | TGF alpha alleles
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| With this genetic basis, retinoic acid may lead to embryopathy | Distribution of cell receptor
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| Nature of damage depends on timing of exposure | 1. Period when a structure is sensitive to insult...leads to permanent damage 2. Generally just prior to or during appearance of the structure in the embryo 3. Functional maturation may take longer than structural development
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| Gestational age and teratogenic exposure: days 0 to 15 | Miscarriage, fetal death
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| Gestational age and teratogenic exposure: days 15 to 60 | Fetal death, major malformations, growth retardation, impaired IQ
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| Gestational age and teratogenic exposure: days 60 to 80 | Fetal death, vascular disruption caused by hypocia, hemorrhage and tissue loss
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| Gestational age and teratogenic exposure: second and third trimester | Stillbirth, growth retardation, impaired IQ
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| Syndrome of outcomes is specific to the toxicant | Likely due to access of chemical to susceptible tissues, metabolic pathways, receptors in particular structures
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| Thalidomide | Phocomelia
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| Alcohol | Characteristic facies, growth retardation, functional deficits
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| Shepard's Criteria for Teratogenicity (3) | 1. The agent must be present during the critical periods of development 2. The agent should produce congenital defects in an experimental animal 3. Proof should be obtained that the agent acts in an unaltered state on the embryo-fetus
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| Karnofsky's Law | Anything at the right time of pregnancy, at the right dosage, in the right species of animal can be teratogenic
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Created by:
KChatham
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