This medication is included for historical context. From 1940 until 1971, between 2 and 10 million pregnant women were given this synthetic estrogen for ill-advised indications. It was removed from the market after Herbst and associates (1971) reported a series of eight women exposed to DES in utero who developed an otherwise rare neoplasm, vaginal clear-cell adenocarcinoma. With no relationship to drug dosage, the absolute cancer risk approximates 1 case per 1000 DES-exposed fetuses. Twofold greater rates of vaginal and cervical intraepithelial neoplasia were also described (Vessey, 1989).
DES exposure has further been associated with genital tract abnormalities in exposed fetuses of both genders. Women may have a hypoplastic, T-shaped uterine cavity; cervical collars, hoods, septa, and coxcombs; and "withered" fallopian tubes (Goldberg, 1999; Salle, 1996). Some are described and illustrated in Chapter 3 (p. 45). Later in life, women exposed in utero have slightly higher rates of earlier menopause and breast cancer (Hoover, 2011). Men may develop epididymal cysts, microphallus, hypospadias, cryptorchidism, and testicular hypoplasia (Klip, 2002; Stillman, 1982).
Some of the immune functions necessary for pregnancy maintenance are discussed in Chapter 5 (p. 95). Given these important interactions, immunosuppressant drugs logically might afect pregnancy.
hese medications include glucocorticoids and mineralocorticoids, which have antiinflammatory and immunosuppressive actions. They are frequently used to treat serious disorders such as asthma and autoimmune disease. Corticosteroids have been associated with clefts in animal studies. In one metaanalysis of case-control studies by the Motherisk Program, systemic corticosteroid exposure was associated with a threefold increase in the rate of clefts. his is an absolute risk of 3 cases per 1000 exposed fetuses (Park-Wyllie, 2000). A 10-year prospective cohort study by the same group, however, did not identiy higher risks for major malformations. Based on these findings, corticosteroids are not considered to represent a major teratogenic risk.
Unlike other corticosteroids, the active metabolite of prednisone, which is prednisolone, is inactivated by the placental enzyme 11�-hydroxysteroid dehydrogenase 2. Thus, it may not efectively reach the fetus.
This inosine monophosphate dehydrogenase inhibitor, and a related agent, mycophenolic acid, are immunosuppressants. They are used to prevent rejection in organ-transplant recipients and to treat autoimmune disease (Chap. 59, p. 1142). Mycophenolate is a potent teratogen. From the National Transplantation Pregnancy Registry, of pregnancies in which mycophenolate was not discontinued until after the first trimester, birth defects complicated 30 percent, and another 30 percent spontaneously aborted (ing, 2017). One prospective review by the European Network of Teratology Information Services similarly identified a spontaneous loss rate of nearly 30 percent in exposed pregnancies. More than 20 percent of liveborn infants had major anomalies (Hoeltzenbein, 2012).