Congenital birth defects and teratology

Question 1

What is congenital abnormality?

Answer 1

Abnormalities present at birth - can be malformation, deformation, dysplasia or disruption

Question 2

What are teratogens?

Answer 2

Foreign agents inducing abnormalities in a developing organism during uterine life (incl. alcohol, drugs, viruses, dietary intake, radiation, chemicals etc.)

Question 3

What congenital abnormalities can be caused by vitamin A?

Answer 3

Cleft palate
Mandibular hypoplasia
Heart defects

Question 4

What congenital abnormalities can be caused by rubella or HSV?

Answer 4

Deafness
Cataracts
Retinal dysplasia
Microcephaly

Question 5

What congenital abnormalities can be caused by X-ray exposure?

Answer 5

Microcephaly
Spina Bifida
Cleft palate

Question 6

What congenital abnormalities can be caused by Sodium Valproate?

Answer 6

Neural tube defects

Facial or limb defects

Question 7

What congenital abnormalities can be caused by alcohol?

Answer 7

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)

Question 8

What nutritional causes could result in congenital malformation?

Answer 8

Folate deficiency
Zinc (too high or too low)
Glucose or ketone bodies (e.g. due to diabetic condition)
Retinoid excess

Question 9

When is the embryo most at risk of damage?

Answer 9

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

Question 10

What factors can influence the teratogenicity of a substance?

Answer 10

1. Teratogen must be in contact with developing embryo/ foetus
2. Period of development at exposure
3. Exposure timing or dosage
4. Genotype influences susceptibility

Question 11

What are the 6 general principles of teratology (Wilson, 1973)?

Answer 11

1. Abnormal development = death, growth retardation, malformation or functional disorder
2. Susceptibility varies with the developmental stage at the time of exposure
3. Teratogenic agents act in specific ways on developing cells and tissues in initiating abnormal embryogenesis
4. Degree of abnormal development increases as dose increases
5. Access of environmental influences to developing tissues depends on the nature of the agent
6. Susceptibility of a teratogen depends on the genotype and interaction with environmental factors

Question 12

What are the potential mechanisms of teratogenesis?

Answer 12

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

Question 13

What is amelia?

Answer 13

Congenital abnormality in which individual is lacking one or more limb

Question 14

What is meromelia?

Answer 14

Congenital abnormality resulting in lacking of a part of one or more limb with hand or foot present

Question 15

What is phocomelia?

Answer 15

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

Question 16

What is polydactyly?

Answer 16

Congenital abnormality resulting in the presence of extra digit(s)

Question 17

What is syndactyly?

Answer 17

Congenital abnormality resulting in wholly or partly united digits (“webbing”)

Question 18

What teratogens can cause limb abnormalities?

Answer 18

Thalidomide (anti-nauseant, sleeping pill)
Retinoids (vitamin A derivative)
Mechanically induced via amniotic bands cutting off tissue

Question 19

What can be done to avoid teratogen exposure during pregnancy?

Answer 19

Nutritional and lifestyle advice pre-conception

Avoid prescribing where possible - safest and minimal therapeutic doses where necessary

Question 20

How are medications classified in terms of teratogenicity?

Answer 20

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)