Teratogens and Congenital Defects Flashcards
Define congenital abnormality/malformation
Abnormality present at birth
What are the 4 broad types of congenital abnormality?
Malformation: misformed (e.g. heart septum)
Deformation: formed then affected (e.g. limb and umbilical bodies)
Dysplasia: expansion of immature cells
Disruption: of a normal process, e.g. cell migration
Name some causes of birth defects
Multifactorial inheritance
Chromosomal abnormalities
Mutant genes
Environmental agents, drugs and viruses
Define teratogenesis
Define teratogen
The process whereby an abnormality is induced in a developing organism during uterine life caused by a teratogen
Teratogen= foreign agent capable of causing teratogenesis.
Give some examples of teratogens and the defects they can cause
Alcohol: fetal alcohol syndrome
Vitamin A: cleft palate, mandibular hypoplasia, cardiac defects
Valproate: neural tube defects, facial and limb defects
Rubella/HSV - deafness, cataracts, retina dysplasia, microcephaly
X-ray: microcephaly, spina bifida, cleft palate
How can teratogen exposure occur?
Medication used prior to knowledge of pregnancy
Medication necessary for conditions independent of pregnancy (e.g. epilepsy)
Medication used for pregnancy specific conditions (e.g. HTN)
Environmental agents that are impossible to avoid
Which dietary teratogens can be avoided/supplemented
Folate deficiency
Zinc: too high or too low
Glucose or ketone bodies: diabetic control
Retinoids: avoid
In which period of gestation do the majority of structural congenital defects occur?
Main embryonic period (3-8 weeks)
Weeks 9-14 still susceptible but lower risk
In which period of gestation do the majority of functional defects and m inor abnormalities occur?
Foetal period (14 - 38 weeks)
How is embryonic damage controlled in the pre-differentiation stage? (1-2 weeks)
All sub-lethal damage repaired
In which weeks of gestation is the developing embryo most susceptible to damage? Why?
Weeks 3-8, majority of core systems develop within this phase.
What is the highest risk of developmental abnormality in the foetal period?
Functional abnormality
Some (low) risk of structural abnormality
What influences teratogenicity?
- The ability of the teratogen to access the developing embryo/foetus
- The genome of the embryo/foetus
- Timing and dosage
- Stage of development at exposure to teratogen
Of neural tube defects and mental retardation, which is likely to occur earlier in pregnancy and which is more likely to occur later?
Neural tube defects more likely to occur earlier in pregnancy (embryonic period)
Mental retardation most likely to occur later on in pregnancy (later embryonic period and foetal period)
How can a substance be teratogenic?
By causing:
- DNA sequence mutations
- Interruption of DNA or RNA synthesis
- Failure of normal cell - cell interactions
- Interference with cell differentiation
- Chromosomal abnormalities leading to structural/quantitative DNA changes
