Teratogens Flashcards
Define Teratogenesis
Process whereby an abnormality is induced in a developing organism during uterine life by foreign agents (teratogens)
What are some common teratogens and their defects?
Alcohol = foetal alcohol syndrome
Vitamin A = cleft palate, heart defects, mandibular hypoplasia
Rubella/HSV = deafness, cataracts, retinal dysphasia, microcephaly
X-ray = microcephaly, spina bifida, clef palate
Valproate = neural tube defects, facial defects, limbs
What nutritional/supplements can be used to avoid birth defects?
Folate
Zinc (too high or low can cause problems)
Glucose and ketone bodies (diabetic conditions)
Retinoids excess
What’s going on in the foetus when it’s at most risk of teratogens?
Cell division
Organogenesis
Midline union
How do the risks of functional and structural abnormality differ?
Risk of structural abnormality greatest in weeks 3-8
Risk of functional abnormality from week 8 onwards
What part of pregnancy are we not susceptible to teratogenesis?
Weeks 1-2 where zygote is developing, implanting and bilaminar embryo formed
What are some major congenital anomalies and when do they occur?
Neural tube defects and mental retardation week 3 - 16 are most sensitive periods
Truncus arteriosus, atrial septal defect and ventricular septal defect week 3.5-7
What can influence the teratogenicity of a substance?
Teratogens must contact developing embryo/foetus
Period of development at exposure
Exposure timing and dosage
Foetus genotype influences susceptibility
What are Wilson’s 6 general principles of teratology?
- The final manifestations of an abnormal development are death, malformation, growth retardation and functional disorder
- Susceptibility to the conceptus to teratogenic agents varies with the developmental stage at time of exposure
- Teratogenic agents act in specific ways on developing cells initiating abnormal embryogenesis
- Manifestations of abnormal development increase in degree from the no-effect to the totally lethal level as dosage increases
- The access of adverse environmental influences to developing tissues depends on the nature of the agent
- Susceptibility to a teratogen depends on the genotype of the conceptus and on the manner in which the genotype interacts with environmental factors
How can a substance be teratogenic?
Mutational changes in DNA sequences Interruption of DNA or RNA synthesis Failure of normal cell migrations Failure of normal cell-cell interactions Interference with cell differentiation Chromosomal abnormalities leading to structural or quantitative changes in DNA
What can be signs of feral alcohol syndrome?
Heart defects Short palpebral fissure Midline facial abnormalities Flattened nose Neural problems - behavioural and developmental
What are some developmental limb abnormalities?
Meromelia (part limb) Phocomelia (seal limb) Polydactyly Syndactyly Amelia (no limb)
How can limb abnormalities arise?
Teratogens/genetic mutation induced
Thalidomide (anti-nausea sleeping pill)
Retinoids (vitamin A derivatives)
Mechanical vs amniotic bands strangling tissue
What are common cardiac defects?
Septal defects - neural crest cell associated
Tetralogy of fallow - transposition of great vessels
Alcohol can cause
What are neural tube defects? What deficiency are they associated with?
Meningocoele Anencephaly Sensory system defects of the ear/eye Associated with multiple teratogens Associated with deficiency of folic acid
What are facial abnormalities associated with?
Anti seizure drugs
Retinoids
Corticosteroids
Usually accompanied by other defects: reduced brain size, cardiac problems
Why are cardiac and facial defects often seen together?
Both involve neural crest cells - abnormal neural crest cell migration
What are some examples of facial abnormalities? What are their features?
Treacher-Collins
Pierre Robin syndrome
Autosomal dominant or teratogen-induced (alcohol, retinoids, maternal diabetes)
Mandibulofacial maldevelopment (zygomatic, mandible, maxilla)
Downsplanting palpebral fissure
Malformed ears and possible conductive deafness
What weeks are the most susceptible period for teratogenesis?
3-14
How can clinicians prevent teratogenesis?
Avoid prescribing where possible
Choose safest minimal therapeutic doses
Give nutritional/lifestyle pre-conception advice
How are teratogens classified?
A-D X
A = medication not shown for increased risk in birth defects
B = animal studies haven’t demonstrated risk
C = animal studies have shown adverse effects but no studies are available in humans
D = medications that are associated with birth defects in humans, but potential benefits may outweigh risks
X = medications are contraindicated in human pregnancy because of clear foetal abnormalities
What drugs are classified as category D?
ACE inhibitors Angiotensin II receptor antagonists Aminoglycosides Aspirin Atenolol Benzodiazepines Carbamazepine Methotrexate Phenytoin Phenobarbital Tamoxifen Tetracycline Medications that affect iodine levels
What infectious teratogens CHEAP TORCHES stand for?
Chickenpox and shingles Hepatitis Enteroviruses AIDS Parvovirus
Toxoplasmosis Other infections: group B strep, listeria, candida Rubella Cytomegalovirus HSV Everything else sexually transmitted Syphillis
When is it advised to take folic acid supplements and why?
During first 12 weeks of pregnancy and while planning to get pregnant - while neural tube is developing
Higher dose required for those with history of neural tube defects
