Teratogens

Question 1

6 Principles of Teratogenicity

Answer 1

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)

Question 2

Hydantoin

Answer 2

• 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)

Question 3

Ionizing Radiation

Answer 3

• Example of a physical teratogen

- directly acts on proteins and DNA or indirectly makes free radicals that alter proteins and DNA

Question 4

Valproic Acid

Answer 4

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

Question 5

Amniotic Band Syndrome

Answer 5

• 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

Question 6

Isotretinoin

Answer 6

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

Question 7

Warfarin

Answer 7

• 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

Question 8

CMV

Answer 8

• 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

Question 9

Rubella

Answer 9

• Most common manifestation = deafness
• Also… cataracts, micropthalmia, cardiac, intellectual disability and inc risk Type I DM
• Mechanism - apoptosis and inhibition of mitosis

Question 10

Fetal Alcohol Syndrome

Answer 10

• 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

Question 11

DES

Answer 11

• 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)

Question 12

Abx

Answer 12

• CAN TAKE PCN
• Tetracycline - discolored teeth
• Streptomycin derivatives - CN VII damage –> hearing problems

Question 13

Zika Virus

Answer 13

• Flavivirus transmitted by Aedes mosquito
• In adults –> fever, maculopapular rash, arthralgia and non-purulent conjunctiva
• If infected in pregnancy –> microcephaly, brain malformation

Question 14

TORCH

Answer 14

• T - toxoplasmosis
• O - other (syphilis, VZV, parovirus B19)
• R - rubella
• C - CMV
• H - Herpes