Teratogenesis Flashcards
What is teratogenesis?
the process by which congenital malformations are produced in an embryo or fetus
What are the five principles of teratogenesis?
-Susceptibility to teratogens is variable
-susceptibility is specific for stage of development of embryo or fetus
-the mechanism of teratogenesisis specific for each teratogen
-teratogenesis is dose-dependent
-teratogens produce death, growth, retardation, malformation, or functional impairment
Approximately 31% of fertilizations end in what?
spontaneous abortions
About 3% of infants are born with what?
structural anomalies
What is the critical fetal period for teratogenesis and why?
3-16 weeks due to impairment of organogenesis
What are the potential adverse effect(s) of fetotoxic exposure at pre-implantation stage?
spontaneous abortions
What are the potential adverse effect(s) of fetotoxic exposure at the embryonic (2-8 weeks) stage?
-spontaneous abortions
-structural malformations
What are the potential adverse effect(s) of fetotoxic exposure at the fetal (8-40 weeks) stage?
-central nervous system function
-growth restriction
-neurobehavioral effects
-fetal demise
When do most birth defects occur and why is this an issue?
occur prior to 8 weeks which is usually before the first prenatal appointment
What should you do whenever you are prescribing medications to a patient who is of child-bearing age?
ensure you know the pregnancy status by asking when their last menstrual period was and if they could be pregnant
What is the description of category A medications?
well-controlled studies in humans show no risk to the fetus
What is the description of category B medications?
no well-controlled studies have been conducted in humans; animal studies show no risk to the fetus
What is the description of category C medications?
no well-controlled studies have been conducted in humans; animal studies have demonstrated an adverse effect on the fetus
What is the description of category D medications?
evidence of human risk to the fetus exists; however, benefits may outweigh risks in certain situations
What is the description of category X medications?
controlled studies in animals or humans demonstrate fetal abnormalities; the risk in pregnant women clearly outweighs any possible benefit
Drugs in the mother’s blood can pass through what structure to get to the fetus?
the umbilical cord
What was a medication marketed in the 1950s for nausea in pregnancy and was widely used in Europe, Australia, and Japan?
thalidomide
Why was approval of the use of thalidomide in the US withheld?
Dr. Frances Kelsey was concerned over the safety and side effects of thalidomide such as peripheral neuropathy
What is peripheral neuropathy?
weakness, numbness, and pain in your extremities
What did the tragedy of thalidomide lead to?
the development of testing of pharmaceuticals for adverse effects on fetal development
What are these deformities associated with?
-amelia
-meromelia
-phocomelia
thalidomine use
What is amelia?
complete absence of a limb or limbs
What is meromelia?
partial absence of a limb
What is phocomelia?
form of meromelia where there is an absence of long bones with hands and feet attached to trunk with small rudimentary bones
What are other deformities associated with?
ENT system:
-malformations of inner and outer ear
-hearing loss
-visual impairment
-cleft palate
Other:
-intellectual disability and autism
-congenital heart disease
-urogenital and gastrointestinal defects
thalidomide use
What is thalidomide still used for today?
treatment of:
-leprosy
-HIV
-multiple myeloma
What act was created due to the outcomes of the thalidomide tragedy?
Kefauver-Harris Drug Amendments Act
Prior to the Kefauver-Harris Drug Amendments Act, medications could be sold for how long after application filed with the FDA?
60 days
What did the Kefauver-Harris Drug Amendments Act enforce after the thalidomide tragedy?
-FDA requires manufacturers prove safety and efficacy prior to approval
-FDA is given 180 days to review new medications
-Adverse events must be recorded
-Process of drug approval can now take 8-10 years
What is diethystilbestrol (DES)?
a potent estrogen used to prevent spontaneous abortion and premature labor (used between 1940 and 1971)
By 1953, where there any beneficial effects of DES?
No, but it was still used and came in many forms/combinations with other hormones
An estimated 2-10 million _____ and _____ were exposed to DES during the first decade of its use
women and their fetuses
What were the effects of DES for women who took DES, “DES mothers”?
modest increase in the relative risk of breast cancer only (counseling on potential small increase in risk, breast self-examination and regular mammograms encouraged to these patients)
What were the effects of DES for females exposed to DES in utero, “DES daughters”?
-early onset and increased risk of vaginal cancer
-increased risk of cervical cancer
-structural defects in cervix, uterus, and fallopian tubes
-infertility or poor pregnancy outcomes
What were the effects of DES for males exposed to DES in utero, “DES sons”?
-increased risk for cysts of epididymis, microphallus, undescended testicle or testicular hypoplasia, decreased sperm count
-no decrease in fertility
-no increase in cancer risk
What is another term for undescended testicle?
cryptorchidism
What is testicular hypoplasia?
one testicle is significantly smaller than the other
Excessive amounts of what vitamin has been associated with teratogenicity?
Vitamin A
What teratogenic medication are these deformities associated with?
-cleft lip
-cleft palate
-hydrocephalus (water in ventricles of brain)
-cardiac deformities
vitamin A
What teratogenic medication is a vitamin A isomer (13-cis-retinoic acid)?
isotretinoin (Accutane)
What is isotretinoin (Accutane) used in?
treatment of cystic acne
What are the adverse effects of using isotretinoin (Accutane) while pregnant?
-increased risk of spontaneous abortion
-20-30% of exposed neonates have evidence of abnormalities such as thalidomide-like malformations and malformation in multiple organs
What program was started to reduce prenatal exposure to isotretinoin (Accutane)?
iPLEDGE
Isotretinoin prescribers must be what?
-registered with the iPLEDGE program
-demonstrate awareness of its potential effects