TERATOLOGY

Yeshiwas A.
• Teratology
– Derived from the Greek noun teras, meaning
monster.
– Historically, the study of malformations early in life
that result from exposure to chemicals such as
mercury, lead, …
 Early history
• Early Hebrews
– Deformed person’s association with the devil.
• Aristotle, the 4th century B.C.,
– Disturbance in reproduction rather than
supernatural occurrence
• Aristotle and Hippocrates, a physician in Greece 5th
century B.C.,

– A pregnant woman’s experience or emotions called

maternal impressions, can affect the formation of the
fetus.

– The theory of maternal impressions persisted until the

early 1900s, despite evidences to the contrary by John
Hunter, a surgeon in Scotland in the late 18th century.
 Teratogenic effects
• Teratogens may affect the embryo in a number of ways:

– Causing physical malformations

– Problems in the behavioral or emotional development of the

child

– Decreased intellectual quotient (IQ) in the child

– Preterm labor, spontaneous abortions, or miscarriages.

 Four types of teratogens
• Physical agents,
– Ionizing radiation, hyperthermia (saunas, hot tubs, infections)
 microcephaly, NTD

• Metabolic conditions,
– Malnutrition, diabetes, thyroid disorders

• Infections,
– Rubella, HSV, syphilis, CMV

• Drugs and chemicals,

– Alcohol, cocaine, thalidomide
 Principles of teratology
• In considering the effects of drugs on pregnancy
– Genetic susceptibility
– Developmental stage
– Mechanisms
– End points
• Death, malformation, growth restriction, or functional
defect
– Access and
– Dose response
• The most common malformations
– Craniofacial dysmorphisms
– Cleft palate
– Thymic aplasia
– Neural tube defects

• The tranquilizer thalidomide

– One of the most famous and notorious teratogens.
• The two most important teratogens today
– Alcohol and smoking
– Among the leading preventable causes of birth defects and developmental
disabilities.

• Infectious agents:
– Rubella, Cytomegalovirus
– Varicella, Herpes simplex
– Toxoplasma, Syphylis

• Physical agents:
– Radiation
– Hyperthermia
• What drugs cause teratogenic effects?

– ACE (angiotensin converting enzyme) inhibitors

– Angiotensin II antagonists
– Isotretinoin (an acne drug)
– Alcohol
– Cocaine
– High dose of vitamin A
– Lithium
– Androgens (male hormons)
 Pregnancy risk classifications

A Drugs taken by large number of No proven increase risk

pregnant women
B Drugs taken by only limited number of Human data lacking
pregnant women
B1 Animal study Not shown any increased
risk
B2 Animal studies are limited There does not seem to be
any increase risk
B3 Animal studies show increase risk Not clear if this risk applies
to humans
C May cause harm to the fetus without Effects may be revesible
causing birth defects
D Drugs that have caused or may cause The health benefit may
birth defects outweigh the risk
X High risk of birth defects Should not be used during
pregnancy
Some women must take medications
• Existing health problems
– Epilepsy
– High blood pressure
– Diabetes
– Thyroid conditions
– Asthma

• Acute illness or pregnancy complications

– Pneumonia
– Preeclampsia
 Developmental stage
• What stage of pregnancy are teratogens most
harmful?
– Most teratogens are harmful during a critical
window of development
• Eg thalidomide is teratogenic only between days 28 and
50 of pregnancy (4th – 7th weeks of gestation).
• Period of organogenesis (3rd – 8th weeks of gestation)
–Embryonic period
 Mechanism
• Teratogenic agents
– Inhibit specific receptors or enzymes or
– Disrupt specific developmental pathways
• Eg some agents show neurotropism or cardiotropism.
• How can teratigens be avoided during
pregnancy?
– No drug policy
– Do not use chemicals that may harm
• Pesticides, funficides, or harsh cleaning products
– Do not smoke
– Do not consume alcohol
Good day