hese vitamin A derivatives are among the most potent human teratogens. hree retinoids available in the United States are highly teratogenic when orally administered-isotretinoin, acitretin, and bexarotene. By inhibiting neural-crest cell migration during embryogenesis, they create a pattern of cranial neural-crest defects-termed retinoic acid embryopath-that involve the CNS, face, heart, and thymus (Fig. 12-5). Specific anomalies may include ventriculomegaly, maldevelopment of the facial bones or cranium, microtia or anotia, micrognathia, cleft palate, conotruncal heart defects, and thymic aplasia or hypoplasia.
13-cis-Retinoic acid is a vitamin A isomer that stimulates epithelial cell diferentiation and is used for dermatological disorders, especially cystic nodular acne. First-trimester exposure is associated with a high rate of pregnancy loss, and up to a third of fetuses have malformations (Lammer, 1985). he iPLEDGE program is an FDA-mandated REMS for isotretinoin and is found at: ww.ipledgeprogram.com.ihis webbased, restricted-distribution program requires participation for all patients, physicians, and pharmacies to help eliminate embryonic-fetal exposure. Although other countries have instituted similar programs, inadvertent exposure remains a global concern (Crijns, 201l).
This retinoid is used to treat severe psoriasis and was introduced to replace etretinate. he latter is a lipophilic retinoid with such a long hal-life (120 days) that birth defects resulted more than 2 years after therapy was discontinued. Although acitretin has a short half-life, it is metabolized to etretinate, and thus remains in the body for prolonged periods (Stiefel Laboratories, 2015). To obviate exposure, the manufacturer of acitretin has developed a pregnancy risk management program. Called "Do Your P.A.R.T"-Eregnancy prevention Actively Required during
FIGURE 12-5 Isotretinoin embryopathy. A. Bilateral microtia or anotia with stenosis of external (Kaplan, 2015). These results may be reassuring to pregnant women with inadvertent exposure.
Notably, the manufacturer of tazarotene cautions that application over a suicient body surface area could be comparable to oral treatment. Accordingly, its use in pregnancy is not recommended (Allergan, 2017).
There are wo natural forms of vitamin A. Beta-carotene, which is a precursor of provitamin A, is found in fruits and vegetables and has never been shown to cause birth defects (Oakley, 1995). Retinol is preformed vitamin A, ear canal. B. Flat, depressed nasal bridge and ocular hypertelorism. (Used with permission from
Dr. Edward Lammer.) and after Ireatment, this program promotes a delay of conception for at least 3 years following therapy discontinuation.
This retinoid is used to treat cutaneous T-cell lymphoma. When given to rats in doses comparable to those for human therapy, fetuses developed eye and ear abnormalities, cleft palate, and incomplete ossification. For a woman to receive this medication, the manufacturer requires two forms of contraception that are initiated 1 month before therapy and are continued for 1 month after bexarotene discontinuation. This is coupled with monthly pregnancy testing during treatment (Valeant Pharmaceuticals, 2015). Males who have partners who could become pregnant are advised to use condoms during sexual intercourse while taking bexarotene and for 1 month after discontinuing therapy.