These compounds, initially used to treat acne, have become so popular for the treatment of sun damage that they are called cosmeceuticals (Panchaud, 2012). The most commonly used topical agents are tretinoin, isotretinoin, and adapalene. Systemic absorption is low, and this argues against plausible teratogenicity.
Isolated case reports have described malformations following topical tretinoin, and it is unknown whether this is due to variability in absorption or perhaps potential individual susceptibility (Kaplan, 2015). A prospective study by the European Network of Teratology Information Services found no higher rates of birth defects or spontaneous losses, and no case of retinoid embryopathy (Panchaud, 2012). One systematic review by the Motherisk Program included 635 pregnancies with exposure to topical retinoids. Investigators similarly identified no higher risk for congenital malformations, spontaneous abortion, stillbirth, low birthweight, or preterm delivery cranial neural-crest defects when more than 10,000 IU per day is consumed in the first trimester (Rothman, 1995). It seems reasonable to avoid doses of preformed preparations that exceed the recommended 3000 IU daily allowance (American Academy of Pediatrics, 2017).
Possibly the most notorious human teratogen, thalidomide causes malformations in 20 percent of fetuses exposed between 34 and 50 days menstrual age. The characteristic malformation is phocomelia-an absence of one or more long bones. As a result, hands or feet are attached to the trunk, occasionally by a small rudimentary bone. Cardiac malformations, gastrointestinal abnormalities, external ear malformations, eye anomalies, and other limb-reduction defects are also common following thalidomide exposure. The manufacturer reports that up to 40 percent of afected newborns do not survive the neonatal period (Celgene, 2017 a).
Thalidomide was marketed outside the United States from 1956 to 1960, before its teratogenicity was appreciated. The ensuing disaster, with thousands of afected children, was instructive of several important teratological principles. First, the placenta is not an efective barrier to the transfer of toxic substances from mother to embryo (Dally, 1998). Second, diferent species show extreme variability in their susceptibility to drugs and chemicals. Namely, thalidomide produced no defects in multiple rodent species and was assumed to be safe for humans. Last, exposure timing and defect type are often closely related (Vargesson, 2015). For example, upper-limb amelia may develop with thalidomide exposure during days 24 to 30 postconception, upper-limb phocomelia with exposure during days 24 to 33, and lower-limb phocomelia with exposure during days 27 to 33.
halidomide was irst approved in the United States in 1999 and currently is used to treat erythema leprosum nodosum and multiple myeloma (Celgene, 2017a). The FDA has mandated a web-based, restricted-distribu tion program for thalidomide, called THALOMID REMS, which is required before patients, physicians, and pharmacies can access the medication.
Lenalidomide is an analogue of thalidomide that is used to treat some types of myelodys myeloma. It crosses the placenta in multiple animal species, and gene, 2017b). Because of obvi ous teratogenicity concerns, a similar to that used for thalido mide has been developed.