630 Obstetrics and Gynecology Board Review •••
❍ What should you tell the patient who is thinking about starting an isotretinoin (Accutane) treatment of her
acne?
Patients who are taking oral isotretinoin treatment, even for short periods of time, have an extremely high risk of
severe birth defects. Before prescribing Accutane the patient must had a negative pregnancy test and sign the she
understands that she must not get pregnant 1 month before, during the entire time of her treatment as well as for
1 month after the end of her treatment. She must avoid sexual intercourse completely or she must use two separate
effective forms of birth control at the same time.
❍ Describe the pattern of congenital malformations caused by isotretinoin (Accutane).
Affected offspring develop severe ear defects, cardiovascular anomalies (conotruncal malformations), CNS defects,
and disturbances in development of the thymus. Another retinoid, vitamin A when ingested in quantities
10,000 IU/day has also been shown to increase the incidence of cranioneurofacial anomalies in exposed fetuses.
Beta-carotene (a vitamin A precursor) is safe in pregnancy.
❍ Is topical retinoid treatment also teratogenic?
There are no adequate and well-controlled studies in pregnant women regarding the teratogenic effect of topical
retinoid treatment; however, applied at higher doses resulted malformations in rats and rabbits (Category C). Thus,
this only should be used during pregnancy if the potential benefit justifies the potential risk to the fetus.
❍ What is the current recommendation treating epilepsy during pregnancy?
According to studies, 90% of the pregnant women on antiepileptic medication deliver normal infants.
Antiepileptic drugs (AEDs) should not be discontinued in patient in whom the drug is administered to prevent
major seizures, because of the strong possibility of precipitating status epilepticus. All commonly used AEDs have
been associated with congenital malformations, although some of the newer anticonvulsants have not been used
in large enough numbers to have meaningful data. In general, using multiple agents at higher doses is associated
with the increased incidence of birth defects. A single anticonvulsant at the lowest possible dose for efficacy is
recommended whenever possible.
❍ Is the antiepileptic phenytoin (Dilantin) safe in pregnancy?
Children of women receiving phenytoin can develop fetal hydantoin syndrome. This consists of prenatal growth
deficiency, microcephaly, mental retardation nail and digit hypoplasia, and midfacial abnormalities. Some of the
AEDs’ side effect is related to folate deficiency. Phenytoin, carbamazepine, barbiturates, and valproate are linked to
folate malabsorption or they interfere with folate metabolism. Thus, increased dose of folic acid supplementation
(4 mg daily) prior to conception and during pregnancy is recommended to patients who are using seizure
medicines such as phenytoin (Dilantin, Phenytek), carbamazepine (Tegretol, Tegretol XR, Carbatrol), and
phenobarbital. The same applies to women who take at least 1000 mg per day of Depakote (valproate).
❍ What is folate deficiency associated with pregnancy? What is the recommended folate intake during
pregnancy?
Folate deficiency is associated with neural tube defects (ie, spina bifida and anencephaly). Women of reproductive age
should ingest 400 mg of folate per day. If they have had a child with neural tube defect in the past, they should take
4 mg of folate daily periconceptionally. Ideally women should start folate supplementation prior to trying to conceive.