Teratogens II Flashcards
What is a teratogen?
an agent that can cause abnormalities of form or function in a fetus exposed to the agent
What is the general population risk for structural anomalies in pregnancies?
~2-5%
Teratogenic agents cause approximately ____% of congenital malformations.
7
What are possible teratogenic exposures?
drugs, infectious agents, physical agents, maternal health factors/disease, environmental agents
List prescription medications that are potential teratogenic exposures.
valproic acid, carbamazepine, phenobarbital, lithium, Coumadin
List infectious agents that are potential teratogenic exposures.
rubella, cytomegalovirus, varicella, herpes simplex, toxoplasma, syphilis
What are the three kinds of bias that could invalidate epidemiology data.
ascertainment bias
observer bias
recall bias
What is ascertainment bias?
increased likelihood to report adverse outcomes over normal outcomes
What is recall bias?
more likely to recall exposures if adverse outcomes happened
amount of time since exposure affects recall
List environmental agents that are considered potential teratogenic exposures.
organic mercury compounds, lead, radiation, polychlorinated biphenyl, herbicides, industrial solvents
List examples of possible teratogenic effects.
miscarriage/fetal demise intrauterine growth restriction microcephaly major/minor structural anomalies (1+) metabolic dysfunction cognitive dysfunction and/or intellectual disability neurological dysfunction altered behavior increased risk for malignancy
What is teratogenic effect related to?
type of agent dose gestational age at time of exposure duration/mode of exposure genetic susceptibilities carried by the woman and fetus interactions of agents
What were the FDA Pregnancy Risk Categories prior to 2015?
A B C D X
Describe a Category A drug.
adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters)
Describe a Category B drug.
animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women
Describe a Category C drug.
animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of this in pregnant women despite risk
Describe a Category D drug.
there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite risk
Describe a Category X drug.
studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits
What replaced the risk letter categories for defining teratogen risk in 2015?
narrative sections and subsections including:
pregnancy (including labor and delivery)
lactation (including nursing mothers)
females and males of reproductive potential
What were Shepart’s Criteria for Teratogenicity?
- proven exposure to agent at critical time(s) in prenatal development
- consistent findings by 2 or more epidemiologic studies of high quality
- careful deliniation of the clinical cases
- rare environmental exposure associated with rare defect
- teratogenicity in experimental animals important but not essential
- the association should make biological sense
- proof in an experimental system that the agent acts in an unaltered state
Implantation takes place within _____ post-fertilization in the _____ period.
~1-2 weeks
all or none
When is the fetal period?
3-9 months
