Congenital birth defects and teratology Flashcards
What is congenital abnormality?
Abnormalities present at birth - can be malformation, deformation, dysplasia or disruption
What are teratogens?
Foreign agents inducing abnormalities in a developing organism during uterine life (incl. alcohol, drugs, viruses, dietary intake, radiation, chemicals etc.)
What congenital abnormalities can be caused by vitamin A?
Cleft palate
Mandibular hypoplasia
Heart defects
What congenital abnormalities can be caused by rubella or HSV?
Deafness
Cataracts
Retinal dysplasia
Microcephaly
What congenital abnormalities can be caused by X-ray exposure?
Microcephaly
Spina Bifida
Cleft palate
What congenital abnormalities can be caused by Sodium Valproate?
Neural tube defects
Facial or limb defects
What congenital abnormalities can be caused by alcohol?
Fetal alcohol syndrome - abnormalities include heart defects, short palpebral fissure, midline facial abnormalities (incl. flattened nose, thin top lip), neural problems (e.g. behavioural or developmental)
What nutritional causes could result in congenital malformation?
Folate deficiency
Zinc (too high or too low)
Glucose or ketone bodies (e.g. due to diabetic condition)
Retinoid excess
When is the embryo most at risk of damage?
Structural abnormality - risk highest between 3-8 weeks gestation [Nb. many women don’t know they are pregnant throughout this period!]
Functional abnormality - risk increases after 8 weeks gestation
What factors can influence the teratogenicity of a substance?
- Teratogen must be in contact with developing embryo/ foetus
- Period of development at exposure
- Exposure timing or dosage
- Genotype influences susceptibility
What are the 6 general principles of teratology (Wilson, 1973)?
- Abnormal development = death, growth retardation, malformation or functional disorder
- Susceptibility varies with the developmental stage at the time of exposure
- Teratogenic agents act in specific ways on developing cells and tissues in initiating abnormal embryogenesis
- Degree of abnormal development increases as dose increases
- Access of environmental influences to developing tissues depends on the nature of the agent
- Susceptibility of a teratogen depends on the genotype and interaction with environmental factors
What are the potential mechanisms of teratogenesis?
Mutational changes in DNA sequence Interruption of DNA or RNA synthesis Failure of normal cell migration Chromosomal abnormalities leading to structural or quantitative changes in DNA Interference with cell differentiation Failure of normal cell interactions
What is amelia?
Congenital abnormality in which individual is lacking one or more limb
What is meromelia?
Congenital abnormality resulting in lacking of a part of one or more limb with hand or foot present
What is phocomelia?
Congenital abnormality resulting in hand or foot that is closely attached to the trunk with the rest of the limb being grossly underdeveloped or absent
What is polydactyly?
Congenital abnormality resulting in the presence of extra digit(s)
What is syndactyly?
Congenital abnormality resulting in wholly or partly united digits (“webbing”)
What teratogens can cause limb abnormalities?
Thalidomide (anti-nauseant, sleeping pill)
Retinoids (vitamin A derivative)
Mechanically induced via amniotic bands cutting off tissue
What can be done to avoid teratogen exposure during pregnancy?
Nutritional and lifestyle advice pre-conception
Avoid prescribing where possible - safest and minimal therapeutic doses where necessary
How are medications classified in terms of teratogenicity?
A (not shown to increase risk)
B (no risk in animal studies where there are no human studies or risk found in animals but not in humans)
C (adverse effects seen in animals but studies not available in humans, or no studies available in animals or humans)
D (medications that are associated with human birth defects but benefit may potentially outweigh risks e.g. ACEi, ARBs)
X (medications contraindicated in human pregnancy e.g. warfarin, statins, benzodiazepines)
