Providers are encouraged to enroll pregnant women treated with antiepileptic medication in the NAAED Pregnancy Reg istry. Management of epilepsy in pregnancy is discussed in
Chapter 60 (p. 1159).
These medications may result in ACE-inhibitor etopathy. Normal renal development depends on the fetal renin-angiotensin system. ACE-inhibitor medication may cause fetal hypotension and renal hypoperfusion, with subsequent ischemia and anuria (Guron, 2000; Pryde, 1993). Reduced perfusion can result in fetal-growth restriction and calvarium maldevelopment, and oligohydramnios may lead to pulmonary hypoplasia and limb contractures (Barr, 1991). Because angiotensin-receptor blockers have a similar mechanism of action, concerns regarding fetotoxicity have been generalized to include this entire medication class.
Concerns were also raised about ACE-inhibitor embryotoxiciy, although these have largely been disproven. In 2006, a review of 29,000 infants from the Tennessee Medicaid database identified a two-to threefold greater risk for neonatal cardiac and CNS abnormalities among the 209 that had prenatal ACE-inhibitor exposure (Cooper, 2006). Subsequent larger studies have not corroborated these observations. First, in a retrospective cohort study of more than 460,000 pregnancies, risks for birth defects were not greater with ACE inhibitors than with other antihypertensive medications (Li, 201i1). Similarly, Bateman and coworkers (2017) reviewed 1.3 million pregnancies from the Medicaid Analytic eXtract and found no higher risk for any malformation with ACE-inhibitor exposure after adjusting for confounding factors such as diabetes. hus, women with inadvertent irst-trimester exposure to these medications can be reassured. However, given the many therapeutic options for treating hypertension during pregnancy, discussed in Chapter 50 (p. 980), it is recommended that ACE inhibitors and angiotensin receptor-blocking drugs be avoided in pregnancy.
From this class of drugs, fluconazole has been associated with a pattern of congenital malformations resembling the autosomal recessiveAntly-Bixler syndrome. Abnormalities include oral clets, abnormal facies, and cardiac, skull, long-bone, and joint abnormalities. Such indings have been reported only with chronic, irsttrimester, high-dose treatment at doses of 400 to 800 mg daily.
Regarding low-dose treatment of vulvovaginal candidiasis, the Motherisk Program recently conducted a systematic review of pregnancies with first-trimester fluconazole exposure of 150
Teratology, Teratogens, and Fetotoxic Agents 241 or 300 mg in total (Alsaad, 2015). The overall risk for birth defects was not greater, although a small increase in rates of cardiac malformations could not be excluded. A populationbased cohort study from Denmark identified a threefold greater risk for tetralogy of FaIlor following exposure to low-dose fluconazole (M0Igaard-Nielsen, 2013). The birth prevalence of tetralogy of Fallot rose from 3 to 10 cases per 10,000. This is a risk so low that we would not endorse specialized sonography for this indication. Notably, investigators did not identiy increased risks for 14 other birth defects previously associated with exposure to high-dose azole antifungal agents (M0IgaardNielsen,i20l3).
such as ibuprofen and indomethacin. They exert their efects by inhibiting prostaglandin synthesis. In a report from the