TERATOLOGY, TERATOGENS AND FETOTOXIC AGENTS

2-3% of all newborns have major congenital anomaly detectable at birth

All women have an approximate 3% chance of having an infant with birth defect
3% diagnosed by age 5
8-10% by age 18 have one or more apparent functional or developmental abnormalities
<1% of all birth defects are caused by medications
70% of birth defects do not have obvious etiology, identified cause, far more likely to be genetic
than teratogenic

Teratology
Study of birth defects and their etiology
Teratogen
A drug or other chemical substance, a physical or environmental factor such as heat or radiation,
a maternal metabolite such as phenylketonuria or diabetes, a genetic abnormality or an infection
Teratogen causes structural abnormalities
Hadegen agent that interferes with normal maturation and function of an organ
Trophogen agent that alters growth
How do they affect?
Disturb specific physiological processes which in turn lead to abnormal cellular differentiation,
altered tissue growth or cell death
Different teratogens may disturb similar processes that may produce similar phenotypic
abnormalities
Even the most potent teratogen induces birth defects in only a fraction of exposed embryos
The reason why some infants are affected and others are not remains largely unknown

FDA CATEGORIES FOR DRUGS AND MEDICATIONS

Drug Category
A

Description
(-) pregnant women

(-) animals or
(+) animals but (-) well controlled pregnant
women
Teratogenic in animals, or no studies available

Causes fetal harm

Contraindicated in pregnant women

Example
Levothyroxine, K+
supplement, prenatal vitamins
Penicillins, cephalosporins, macrolides

Albuterol, Zidovudine, Ca++ channel

blockers
Corticosteroids, azathioprine,
carbamazepine, lithium
Rubella Vaccine

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Gee, 2014 FDA New System for Labeling Drugs

1.
2.
3.
4.

A fetal risk summary

A section on clinical considerations
Section on prescribing decisions for pregnant and lactating women
Detailed discussion of human and animal data

TERATOGENS
1. Alcohol
Fetal Alcohol Syndrome
Dysmorphic features: small palpebral fissures, thin vermilion
border, and smooth philtrum
Prenatal and/or postnatal growth impairment
th
CNS abnormalities: head size <10 percentile, significant brain
abnormality on imaging, neurological and functional

2. Anticonvulsants
Orofacial clefts, cardiac malformation and neural tube defects
3% risk major malformation in pregnancies treated with single anticonvulsant
4% risk for major malformation in pregnancies untreated
3. Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin-Receptor Blocking Agents
(ARBs)
Fetal hypotension and renal hypoperfusion with subsequent ischemia and anuria
Cardiac and CNS abnormalities
4. Antifungal Medications
Oral clefts, abnormal fascies, cardiac, skull, long bone and joint abnormalities
400-800 mg/day
5. Anti-inflammatories
NSAIDs (ASA, Ibuprofen, and Indomethacin)
Constriction of the fetal ductus arteriosus
Reduced amniotic fluid volume
6. Leflunomide
Hydrocephalus, eye anomalies, skeletal abnormalities and embryo death
7. Antimicrobials
a. Nitrofurantoin
Hypoplastic left heart syndrome, microphthalmia/anophthalmia, clefts, ASDs
b. Sulfonamides
Anencephaly, left ventricular outflow tract obstruction, choanal atresia, diaphragmatic hernia
8. Antineoplastics
a. Cyclophosphamide
Pregnancy loss, skeletal abnormalities, limb defects, cleft palate, eye abnormalities
b. Methotrexate
Craniosynostosis with cover leaf skull, wide nasal bridge, low set ears, micrognathia, limb
abnormalities
c. Tamoxifen
DES-like syndrome
d. Trastuzumab
Oligohydramnios, anhydramnios, fetal renal failure, pulmonary hypoplasia, skeletal
abnormalities, and neonatal death

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9. Antiviral Agents
a. Ribavirin
Skull, palate, eye, skeleton and GI abnormalities
b. Efavirenz
CNS abnormality
10. Sex Hormones
a. Testosterone and anabolic steroids
Labioscrotal fusion, and phallic enlargement
b. Danazol
Clitoromegaly, fused labia and urogenital sinus malformation

DERMATOLOGICAL DISORDERS

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