Part 17 (1/2)

Yes (2) Bologa et al. (1991) Primidone 14.1040 PO.

No Nau et al. (1982a) Primidone 7.1640 PO.

Yes (2) Dam et al. (1979) Vaproic acid 1.28.PO.

No Nau et al. (1982b) Source: Little BB. Obstet Gynecol 1999; 93 93: 858.

167.

EGA, estimated gestational age; AUC, area under the curve; V , volume of distribution; C , peak plasma concentration; C , steady-state concentration; t , half-life; Cl, d max SS.

1/2.

clearance; PPB, plasma protein binding; PO, by mouth; denotes a decrease during pregnancy compared with nonpregnant values; denotes an increase during pregnancy compared with nonpregnant values; = denotes no difference between pregnant and nonpregnant values; IV, intravenous, IM, intramuscular.

aControl groups: 1, nonpregnant women; 2, same individuals studied postpartum; 3, historic adult controls (s.e.x not given); 4, adult male controls; 5, adult male and female controls combined.

168.

Anticonvulsant drugs during pregnancy Janz, 1975, 1982; Kelly, 1984). A review of approximately 750 000 pregnancies (13 separate cohort studies) indicated that the birth defect rate for newborns of epileptic mothers was 7 percent compared to 3 percent for controls (Kelly, 1984).

ETIOLOGY OF MALFORMATIONS.

The pathophysiology of congenital malformations a.s.sociated with epilepsy is unknown.

Evidence suggests that it is a combination of exposure to anticonvulsant medication in an individual with epilepsy who may be 'genetically' susceptible to poor metabolism of the drugs. It is thought that teratogenic effects of certain anticonvulsant drugs may be secondary to a genetic 'defect' (lowered or no activity) in the epoxide hydrolase enzyme system, resulting in an inability to completely metabolize 'toxic' intermediary oxidative metabolites (Bielec et al et al., 1995; Buehler et al et al., 1990; Finnell et al et al., 1992; Jones et al et al., 1989; Stickler et al et al., 1985; Van d.y.k.e et al et al., 2000).

Some anticonvulsants, especially of the phenytoin type, may be a.s.sociated with folic acid anemia and may also depress vitamin D (Lane and Hathaway, 1985). Therefore, vitamin (D and K) and folic acid supplements have been recommended for the pregnant woman with epilepsy who is taking anticonvulsant medications (Yerby, 2003).

Phenytoin and other anticonvulsants may be a.s.sociated with hemorrhagic disease in the neonate, which may progress to be severe or fatal if it occurs in the first 24 h following delivery (Allen et al et al., 1980; Lane and Hathaway, 1985). Other than avoiding salicylates during pregnancy, vitamin K supplementation during the last 2 months of pregnancy (10 mg PO) or in the last 2 weeks (20 mg PO) was recommended (Lane and Hathaway, 1985).