Teratogens Flashcards
6 Principles of Teratogenicity
1- Susceptibility dep on genotype of conceptus and how it interacts w environment
2- Susceptibility varies by developmental stage when exposed
- Wks 3-8 = embryopathies - After 8 wks = fetopathies
3- Affect developing cells (mechanism) –> abnormal embryogenesis (pathogenesis)
4- Final result is death, malformation, growth retardation and functional disorders
5- The specific teratogenic agent determines how it accesses embryo
6- Higher dose = higher degree of deviation (dose-response relationship)
Hydantoin
- anti-sz med
- 10% of fetuses exposed to hydantoin have syndrome (craniofacial and digital abnormalities; nail hypoplasia; mental disability)
- Those that were affected appeared to have lower baseline epoxide hydroxylase enzyme (genetic susceptibility)
Ionizing Radiation
- Example of a physical teratogen
- directly acts on proteins and DNA or indirectly makes free radicals that alter proteins and DNA
Valproic Acid
fetal valproate syndrome
-inc risk of spina bifida, cleft palate/lip, cardio or GU anomalies, developmental delay, limb defects, endocrine disorders and autism if used in 1st trimester
Amniotic Band Syndrome
- baby entangled in fibrous amniotic bands which restricts blood flow
- If wrap around limbs or toes –> amputation
- If wrap around face –> cleft lip or palate
- If wrap around umbilical cord –> miscarriage
Isotretinoin
ACCUTANE
- 40% exposed embryos are spontaneously aborted and
- if used in first trimester, those that survive can have … external ear malformations, cleft palates, undersized jaw, heart defects, hydrocephalus, microcephaly and intellectual disability
Warfarin
- crosses placenta (unlike heparin)
- nasal hypoplasia, depressed nasal bridges, stippling of un-calcified epiphyses in first yr; nail hypoplasia and shorter fingers; low birth wt, intellectual disability, sz, dec muscle tone, widely spaced nipples, feeding difficulties, deafness
CMV
- Primary maternal infection –> transmission to child 25-75% of the time
- Majority are asymptomatic (hard to dx) but then may have sequalae later (sensorineural hearing loss, delayed psychomotor development, visual impairment)
- 10-15% do have symptoms at birth (growth restriction, microcephaly, hepatosplenomegaly, jaundice, choriorentinitis, thrombocytopenia, anemia)
- 20-30% die in utero likely from DIC, liver problems OR bacterial superinfection
- Risk of congenital symptoms is highest in first trimester BUT risk of transmission is highest in 3rd trimester
Rubella
- Most common manifestation = deafness
- Also… cataracts, micropthalmia, cardiac, intellectual disability and inc risk Type I DM
- Mechanism - apoptosis and inhibition of mitosis
Fetal Alcohol Syndrome
- Manifestations are very variable b/n children exposed
- Facial - small eyes, thin upper lip, upturned nose, smooth skin b/n nose and upper lip
- Slow growth before and after birth
- Microcephaly / cog disability
- Vision and hearing problems
DES
- Synthetic estrogen given b/c ppl thought it would prevent pregnancy complications and losses (diethylstilboestrol)
- Manifestations …
- 1- Clear cell carcinoma of vagina in women exposed in utero
- 2- Physical anomalies (vaginal adenosis, erosions of cervix, T-shaped uterus, transverse cleavage of vagina)
Abx
- CAN TAKE PCN
- Tetracycline - discolored teeth
- Streptomycin derivatives - CN VII damage –> hearing problems
Zika Virus
- Flavivirus transmitted by Aedes mosquito
- In adults –> fever, maculopapular rash, arthralgia and non-purulent conjunctiva
- If infected in pregnancy –> microcephaly, brain malformation
TORCH
- T - toxoplasmosis
- O - other (syphilis, VZV, parovirus B19)
- R - rubella
- C - CMV
- H - Herpes
