Drugs in Pregnancy

Question 1

Why are the embryo and fetus uniquely susceptible to exogenous compounds?

Answer 1

Rapid cellular growth and division

Many tissues are in the process of differentiation

Question 2

What are the 6 principles of teratology?

Answer 2

1. Susceptibility depends on the genotype and how it interacts with the environment
2. Susceptibility varies with the developmental stage at the time of exposure
3. Teratogenic agents act in specific mechanisms on developing cells and tissues
4. Access of AEs to tissues depends on the nature of the agent
5. 4 manifestations of deviant development are: death, malformation, growth retardation and functional deficit
6. Manifestations of deviant development increase in frequency and degree as dosage increases

Question 3

Define teratogen

Answer 3

A teratogen:

1. results in a characteristic set of malformations and is organ selective
2. exerts its effects at a specific stage
3. is dose dependent

Question 4

What does preclinical drug testing involve with regards to fetal health?`

Answer 4

Fertility evaluation including effects on estrous cycles and spermatogenesis
Teratogenicity tests to identify gross malformation
perinatal studies to evaluate behavioural effects after birth
longer term behavioural studies
Multi-generational studies

Question 5

What does an FDA risk category of A mean?

Answer 5

Controlled studies in women fail to demonstrate a risk in the first trimester, and no evidence of risk in late trimesters

Question 6

What does an FDA risk category of B mean?

Answer 6

Animal studies have not represented a risk, and no studies in pregnant women or
Animal studies have shown a risk, but was not shown in controlled studies in women

Question 7

What does an FDA risk category of C mean?

Answer 7

Animal studies show a risk, but no controlled studies in women, or studies in women and animals are not available. Should only be given if the potential benefit justifies the risk

Question 8

What does an FDA risk category of D mean?

Answer 8

Positive evidence of fetal risk, but may be acceptable despite the risk

Question 9

What does an FDA risk category of X mean?

Answer 9

Significant evidence of fetal risk, unlikely that benefit will outweigh this risk.

Question 10

Describe the case of diethylstilbestrol

Answer 10

Estrogen used to prevent miscarriage, was linked to vaginal cancer cases and poor semen in men

Question 11

Describe the case of retinoids in pregnancy

Answer 11

Several pieces of evidence for the role of retinoic acid signaling in embryogenesis

Question 12

Describe the case of anticonvulsants in pregnancy

Answer 12

Several drugs linked to fetal malformations and other AEs

Ex. phenytoin can result in fetal hydantoin syndrome in 10% of exposed infants

Question 13

What is the base rate of gross fetal abnormalities?

Answer 13

1%

1% of abnormalities occur even in the absence of a drug, and may be incorrectly attributed to a srug

Question 14

What effects does cannabis use have on birth?

Answer 14

Low birth weights, numerous unknown potential adverse effects related to cannabinoids