TERATOLOGY
A 36-year-old woman undergoes a barium enema for rectal bleeding on
February 1, with estimated radiation dose of 4 rad. Her last menstrual
period (LMP) was January 1 and she has 35-day cycles. She was not using
any contraception. On March 15, a urine pregnancy test is positive. She
inquires about the risk to her fetus of teratogenic injury.
A teratogen is any agent that disturbs normal fetal development and affects
subsequent function. The nature of the agent, as well as its timing and duration
after conception, is critical. There are critical periods of susceptibility with each
teratogenic agent and with each organ system.
The stages of teratogenesis are as follows:
The types of agents that can result in teratogenesis or adverse outcomes are as
follows:
From conception to end of second week: embryo either survives intact or
dies because the three germ layers have not yet been formed
Postconception weeks 3–8: period of greatest teratogenic risk from formation
of the three germ layers to completion of organogenesis
After week 9 of postconception: teratogenicity is low but adverse effects
may include diminished organ hypertrophy and hyperplasia
Infectious: Agents include bacteria (e.g., chlamydia and gonorrhea cause
neonatal eye and ear infections), viruses (e.g., rubella, cytomegalovirus,
herpes virus), spirochetes (e.g., syphilis), and protozoa (e.g., toxoplasmosis).
Ionizing radiation: No single diagnostic procedure results in radiation
exposure to a degree that would threaten the developing pre-embryo, embryo,
or fetus. No increase is seen in fetal anomalies or pregnancy losses with
exposure of <5 rads. The greatest risk of exposure is between 8 and 15 weeks’
gestation with the risk of nonthreshold, linear function at doses of at least 20
rads.
Chemotherapy: Risk is predominantly a first-trimester phenomenon.
Second- and third-trimester fetuses are remarkably resistant to
chemotherapeutic agents.
Environmental: Tobacco is associated with intrauterine growth restriction
(IUGR) and preterm delivery, but no specific syndrome. Alcohol is associated
with fetal alcohol syndrome: midfacial hypoplasia, microcephaly, intellectual
disability, and IUGR.
Recreational drugs: Cocaine is associated with placental abruption, preterm
delivery, intraventricular hemorrhage, and IUGR. Marijuana is associated
with preterm delivery but not with any syndrome.
Medications (account for 1–2% of congenital malformations): The ability of
a drug to cross the placenta to the fetus depends on molecular weight, ionic
charge, lipid solubility, and protein binding. Drugs are listed by the FDA as
category A, B, C, D, or X.