Teratology Lecture

Question 1

What is the background risk of having a pregnancy with a birth defect?

Answer 1

3-5%

Question 2

What is a teratogen?

Answer 2

Any agent that interferes with normal or embryonic development to cause pregnancy loss, a birth defect, or a complication

Question 3

What are some caveats to the all or none period theory?

Answer 3

Medication may remain in the system even after it has been stopped (half-life is important to know), some animal data suggests there can still be a possible effect on development, there is no clear endpoint

Question 4

What does specificity of effect refer to?

Answer 4

May be species specificity in which placental structure and function vary between species and animal studies may not always be telling
May refer to a specific defect or constellation of effects and a pattern that is more consistent across studies are more likely a true teratogenic effect

Question 5

What are some mechanisms through which a teratogen can have an effect?

Answer 5

Mutations in genes critical for development; chromosomal damage; receptor-ligand interactions; enzyme inhibition; interference with cell-cell interactions

Question 6

What are some factors that affect placental transport?

Answer 6

Molecular weight, molecular size, lipophilic/hydrophilic quality, molecular charge

Question 7

Tell me about thalidomide

Answer 7

Medication used to treat NVP and as a sedative that led to a 20% chance of malformations including short/missing limbs, anomalies of internal and external ears, facial hemangiomas/paralysis, heart defects, renal agenesis

Question 8

What are the risks associated with isotretinoin? (accutane)

Answer 8

• 50% chance of miscarriage
• 30-35% chance of major birth defects with any exposure 4-7 weeks post LMP
• cognitive impairment with exposure even after critical period

Question 9

What are risks associated with valproic acid?

Answer 9

first trimester exposure:
-10-20% chance of major anomalies
Fetal Valproate Syndrome: craniofacial anomalies (similar to FAS), cardiovascular anomalies, NTDs, oral clefts, hypospadias, craniosynostosis
-effects on cognitive function

Question 10

What are the risks associated with phenytoin (dilantin)?

Answer 10

First trimester exposure:

• 10% chance of fetal hydrantoin syndrome: growth deficiency, craniofacial anomalies, hypoplastic digits and nails, cardiac defects, abnormal cognitive and motor development
• 30% chance of any effect (kidney anomalies, clefting, hydrocephalus)

Question 11

What are risks associated with carbamazepine (tegretol)?

Answer 11

First trimester exposure:

• 1% chance of neural tube defects
• increased chance of craniofacial defects and developmental delay

Question 12

What are risk factors in pregnancy for antiepileptics in general?

Answer 12

polytherapy (many medications) and high doses

Question 13

What are risks associated with untreated seizure disorders in pregnancy?

Answer 13

• maternal death 10x population
• maternal and fetal hypoxia and acidosis
• increasing fetal heart rate
• stillbirth (5%)

Question 14

What are risks associated with warfarin?

Answer 14

• structural and CNS defects with exposure in first trimester (specifically 8-9 weeks post LMP)
• optic, CNS effects possible later in pregnancy

Question 15

What are risks associated with methotrexate?

Answer 15

• clover-leaf skull with large head, low-set ears, prominent eyes, wide nasal bridge, limb and skeletal defects, intellectual disability
• it is a folic acid antagonist so body cannot make use of folic acid

Question 16

What level of ionizing radiation is considered concerning in pregnancy?

Answer 16

5-10 rads: potential for concern

>10 rads: serious fetal risk

Question 17

What are risks associated with ionizing radiation?

Answer 17

Microcephaly, growth retardation, intellectual disability and other CNS effects, possible increase in carcinogenesis

Question 18

What are risks associated with lead in pregnancy?

Answer 18

• can cross the placenta at around 12 weeks of pregnancy
• IUGR, preterm delivery, preeclampsia
• impaired neurobehavioral development

Question 19

What are risks associated with methylmercury in pregnancy?

Answer 19

Neurologic disorders like CP, cognitive deficits, and brain atrophy and hypoplasia

Question 20

What factors influence the incidence/clinical outcomes of congenital infections?

Answer 20

• timing of infection during pregnancy
• order of infection
• genetics
• socio-economic conditions
• presentation of infected neonate

Question 21

What does TORCH stand for?

Answer 21

Toxoplasmosis, Other, Rubella, CMV, Herpes

Question 22

What are risks associated with TORCH infections?

Answer 22

Functional consequences/disruptions like microcephaly, cardiac defects, cataracts/glaucoma

Question 23

What are risks associated with congenital syphilis?

Answer 23

• stillbirth, early infant death
• neurologic effects
• blindness, deafness
• bone malformations

Question 24

What are risks associated with Congenital Zika Syndrome?

Answer 24

• microcephaly and brain calcification
• join contractures, movement problems
• eye anomalies
• hearing problems
• seizures
• developmental delay

Question 25

What are risks associated with maternal diabetes?

Answer 25

• cardiac anomalies
• neural tube defects
• CNS anomalies
• GI anomalies
• GU anomalies
• Situs inversus
• Caudal regression/sacral agenesis

Question 26

What are risks associated with alcohol in pregnancy?

Answer 26

• challenges in learning and behavior
• growth restriction
• heart defects
• specific facial features

Question 27

What are the risks associated with cigarette-use in pregnancy?

Answer 27

• miscarriage
• oral clefts
• prematurity
• low birth weight
• placental problems
• newborn withdrawal
• SIDS
• childhood asthma/infections
• learning and behavioral issues

Question 28

What are some concerns about supplement use in pregnancy?

Answer 28

• lack of FDA oversight for safety, purity, efficacy
• risk of contamination, mislabeling
• strength of plant-derived ingredients can vary
• generally no data on use in pregnancy, breastfeeding