634 Obstetrics and Gynecology Board Review •••
❍ Is varicella infection during pregnancy innocuous?
No. Varicella (chicken pox) is a known teratogen. Maternal infection in the first half of pregnancy results in
congenital varicella syndrome in 1% to 5% of cases. This syndrome consists of CNS and skeletal abnormalities
and mental retardation. Maternal varicella infection late in pregnancy (within 5 days before and after delivery) may
result in chicken pox skin lesions, pneumonia, and other complications. Approximately 30% of infected children
develop disseminated disease.
❍ What factors affect the ability of a drug or a chemical to cross the placenta and reach the embryo?
These include molecular weight, lipid solubility, degree of ionization, and protein binding. Compounds with
low molecular weight, high lipid affinity, low degree of ionization, and low protein binding affinity will cross the
placenta easily and rapidly. Also placental blood flow, pH gradient between the maternal and fetal serum and
tissues, and placental metabolism of the chemical significantly affect drug transport.
❍ How does pregnancy affect an individual’s susceptibility to toxins?
Increased ventilation enhances absorption of toxic gasses.
Progesterone decreases gut motility and may enhance absorption of certain agents.
Hypoalbuminuria results in decreased serum protein binding and thus increased bioavailability of protein-bound
toxins.
Increased GFR may increase clearance of some agents.
Increased blood volume and body fat results in increased distribution and sequestration
❍ What criteria are necessary to establish that a drug or chemical exposure causes congenital abnormalities?
Epidemiologic studies should consistently display an adverse association in exposed individuals.
Secular trends consistently display a relationship between the incidence of a particular malformation and human
exposures. An animal model mimics the human malformation at clinically comparable exposures. The
teratogenic effects should increase in relation to the dose.
The observed teratogenic effect should be consistent with biologic and scientific principles of occurrence.
❍ In general, during which time during pregnancy is the fetus most susceptible to teratogens?
During the embryonic period, this lasts from 2 to 12 weeks postconception. This is the time of organogenesis.
❍ What are the fetal toxic effects of the agents listed in the left hand column?
- Benzodiazepines A. Orofacial clefting
- Lithium B. Epstein anomaly
- Valproic acid C. Neural tube defects
- DES D. Vaginal adenosis, uterine malformations
- ACE inhibitors E. Renal dysplasia
❍ What are the categories of fetal development defects?
There are malformations, disruptions, and deformations.