The number of drugs used to treat viral infections has increased rapidly during the past 20 years. For most, experience in pregnant women is limited.
This nucleoside analogue is a component of therapy for hepatitis C infection, discussed in Chapter 55 (p. 1065). Ribavirin causes birth defects in multiple animal species at doses signiicantly lower than those recommended for human use. Reported malformations include skull, palate, eye, skeleton, and gastrointestinal abnormalities. he drug has a half-life of 12 days and persists in extravascular compartments following therapy discontinuation. Treated women must use two forms of contraception and have monthly pregnancy tests while on therapy and for 6 months following drug discontinuation (Genentech, 2015). Ribavirin use is also contraindicated in men whose partners are pregnant.
This is a nonnucleoside reverse transcriptase inhibitor used to treat HIV infection (Chap. 65, p. 1249). CNS and ocular abnormalities have been reported in cynomolgus monkeys treated with doses comparable to those used in humans. Several case reports also describe neural-tube defects following human exposure to efavirenz. Reassuringly, the Antiretroviral Pregnancy Registry has identiied no increased birth defect rates in more than 800 pregnancies with irst-trimester exposure (Bristol-Meyers Squibb, 2017b).
Bosentan, ambrisentan, and macitentan are three endothelinreceptor antagonists used to treat pulmonary arterial hypertension (Chap. 49, p. 962). he endothelin-receptor signaling pathway is important for neural-crest development. Mice deicient in endothelin receptors develop neural-crest cell defects that include craniofacial and cardiac outflow tract abnormalities (de Raaf, 2015). Each of these three agents has been found to cause similar birth defects in multiple animal species (Actelion, 2017). No human data are available. Endothelin-receptor antagonists may be obtained only through restricted access programs, each of which has stringent requirements that include contraception and monthly pregnancy testing (Actelion, 2016, 2017; Gilead, 2015).
Some of the functions and efects of male and female hormones on the developing fetus are discussed in Chapter 3 (p. 38). It is intuitive that exposure of female fetuses to excessive male sex hormones-and vice versa-might be detrimental.
Androgen exposure in reproductive-aged women typically stems from anabolic steroid use to accrue lean body mass and muscular strength. Exposure of a female fetus may cause varying degrees of virilization and may result in ambiguous genitalia similar to that encountered in congenital adrenal hyperplasia . Findings can include labioscrotal fusion with irst-trimester exposure and phallic enlargement from later fetal exposure (Grumbach, 1960; Schardein, 1980).
This ethinyl testosterone derivative has weak androgenic activity. It is used to treat endometriosis, immune thrombocytopenic purpura, migraine headaches, premenstrual syndrome, and fibrocystic breast disease. In a review of inadvertent exposure during early pregnancy, Brunskill (1992) reported that 40 percent of exposed female fetuses were virilized. There was a doserelated pattern of clitoromegaly, fused labia, and urogenital sinus malformation.