Teratogenicity

Question 1

TERATOGENICITY - define

Answer 1

ability of the drug to cause adverse fetal effects

Question 2

TERATOGENICITY degree to exposure to drug causes

Answer 2

drug causes adverse effects
dependent on
 Dose
 Route of administration
 Exposure to other agents
 Timing (2-10 weeks)

Question 3

TERATOGENICITY - defects

Answer 3

Gross malformations

 Neurobehavioral and metabolic anomalies

Question 4

Development occurs in three stages:

Answer 4

 Conception through week 2
 Embryonic period: Weeks 3 through 8
 Gross malformations produced by teratogens
 Fetal period: Week 9 through delivery
 Functions disrupted with teratogen exposure

Question 5

Category A:

Answer 5

no evidence of fetal risk in controlled human studies. (Only potassium, thyroid hormone, and
multiple vitamins are in this category)

Question 6

Category B:

Answer 6

either animal studies show no risk but there are no human studies or animal studies show risk
that is not confirmed in human studies. (penicillin, magnesium, prednisone, narcotics, acetaminophen,
ritodrine, terbutaline, cephalosporins, erythromycin, meclizine, insulin, caffeine)

Question 7

Category C:

Answer 7

either animal studies show risk and there are no human studies or there are no animal or
human studies (phenergan, all laxatives, heparin, albuterol)

Question 8

Category D:

Answer 8

Positive evidence of human fetal risk, but the benefits may be acceptable despite the risk
(streptomycin, iodine, sulfonamides, reserpine, Phenobarbital, amitriptyline, nalorphine, Seconal)

Question 9

Category X: p

Answer 9

\: positive risk to the human fetus. Drug use contraindicated in women who are or may
become pregnant (Estrogen, Coumadin, Accutane)

Question 10

KNOWN TERATOGENS

Answer 10

Chemotherapeutic agents (methotrexate, cyclophosphamide)
 folic acid antagonist (intrauterine growth retardation, low set ears, hypoplastic
mandible)

Anticonvulsants
 phenytoin: fetal hydantoin syndrome ( hypoplastic facies, prenatal and postnatal growth
restrictions, mental retardation, hypoplastic digits, facial clefts, and/or cardiac
anomalies; rare. 90-95% of offspring of women treated with Dilantin have NO
anomalies. Anomalies more common in offspring of untreated epileptic women. If use, use
low dose, try phenobarbital
 valproic acid: neural tube defects, heart, head and neck, urogenital tract anomalies,
limb/skeletal, skin and muscle anomalies. Incidence: 1-2%

Question 11

KNOWN TERATOGENS

two more

Answer 11

Sex hormones
 androgens
 masculinization of female fetus
 diethylstilbetstrol
 male: anomalies of testicles and epididymus; infertility
 female: anomalies of uterine fusion, cervical development, vaginal adenosis;
adult problems with menstrual abnormalities, pregnancy, wastage, and vaginal
carcinoma

Question 12

KNOWN TERATOGENS

3 -5

Answer 12

Warfarin
 Fetal bleed/death, fetal warfarin syndrome (nasal hypoplasia, epiphyseal stippling,
cerebral and cardiac malformations)
ACE inhibitors
 Fetal renal aplasia/dysplasia secondary to decreased fetal hypotension and renal
fetal blood flow; neonatal renal failure
Anticholinergic drugs
 Meconium ileu

Question 13

KNOWN TERATOGENS - 6 and 7

Answer 13

Oral hypoglycemic drugs
 Neonatal hypoglycemia
 Use early in pregnancy might cause increased risk of abnormalities
Lithium Carbonate
 First trimester: increased incidence of Epstein’s anomaly of the fetal heart
 Late pregnancy: neonatal electrolyte imbalance or goiter

Question 14

KNOWN TERATOGENS - 8-10

Answer 14

Misoprostol (prostaglandin E1 analog)
 Given orally causes termination of pregnancy
 Unlabeled intravaginal use for cervical ripening)
NSAIDs
 Constriction of ductus arteriosis
Psychoactive drugs
 Withdrawal symptoms

Question 15

KNOWN TERATOGENS - 11 - 13

Answer 15

Retinoids (Accutane)
 anomalies of CNS, craniofacial, cardiovascular, and limbs
Thalidimides
 limb defects/absent limbs
Tetracyclines
 impaired calcium deposition in long bone epiphysis (transient, no long term effect)
and damage to teeth enamel forming cells causing staining and inadequate calcium
content to prevent later tooth decay)
 Maternal fatty metamorphosis of liver

Question 16

KNOWN TERATOGENS - 14-15

Answer 16

Antithyroid drugs (radioactive iodine)
 Fetal hypothyroidism, athyroitic cretenism
Alcohol
 Fetal Alcohol Syndrome, fetal alcohol effect)
 spectrum of fetal effects including prenatal and postnatal growth restriction,
mental retardation, characteristic facies, malformation of brain, eyes, heart,
palate, kidney, or long bones

Question 17

SUSPECTED TERATOGENS

Answer 17

Oral contraceptives (refuted)
 Incidence of 0.7% of exposed pregnancies
 95-99% of women who took OCPs in the first trimester had NO birth defects
 Associated with VACTERL syndrome: vertebral, anal, cardiac, tracheal,
esophageal, renal, radial, limb abnormalities
 2016 report: no increase in birth defects among women on OCP during
early pregnancy 1977-20

Question 18

ENVIRONMENTAL AGENTS

Answer 18

industrial solvents
lead
organic mercury
polychlorinated biphenyls

Question 19

Lead

Answer 19

(reproductive effects: irregular menses, abnormal spermatogenesis,
increased rate of spontaneous abortion, preterm labor, and stillbirths

Question 20

Organic mercury

Answer 20

(neurological abnormalities similar to cerebral palsy:
mercury concentrates in the fetal brain; the US produces 5 million pounds
of mercury per year for use in pesticides and plants)

Question 21

Polychlorinated Biphenyls

Answer 21

(Yusho Syndrome: cola-colored pigment of
skin, low birth weight, pigmented gums, nails and groin; hypoplastic
deformed nails, conjunctivitis, abnormal skull calcifications, and rocker
bottom feet)

Question 22

PREVENTION AND RESPONSE TO EXPOSURE

Answer 22

Minimizing the risk for teratogenesis
 Pregnant patients should avoid unnecessary drug use (e.g., alcohol, cocaine)
Responding to teratogen exposure
 Identifying details of exposure
 Ultrasound scans