Teratogenic effects of antiepileptic drugs.

Many antiepileptic drugs (AEDs) have therapeutic applications that extend beyond epilepsy to include neuropathic pain, migraine headaches and psychiatric disorders. The risk of some AEDs has been clearly established, but for newer drugs, small sample sizes and polytherapy exposures preclude a conclusive determination of their teratogenic potential. Most women with epilepsy will require AED therapy throughout their entire pregnancy to control seizures; the vast majority of pregnancies in women with epilepsy have positive outcomes. A conservative estimate suggests that AED monotherapy doubles, and polytherapy triples, the risk for major congenital malformations. Furthermore, while evidence is still accruing, recent investigations suggest that exposure to select AEDs results in altered cognitive function later in development. There is no evidence to suggest that additional folic acid supplementation ameliorates the increased risk of congenital malformations conferred by in utero AED exposure.

Investigations into the etiology of neural tube defects.

Neural tube defects (NTDs) are serious malformations affecting approximately 1 per 1000 births, yet the mechanisms by which they arise are unknown. There have been consistent efforts in many fields of research to elucidate the etiology of this multifactorial condition. While no single gene has been identified as a major independent risk factor for NTDs, candidate genes have been proposed that may modify the effects of maternal and/or embryonic exposures. Folate supplementation effectively reduces the occurrence of NTDs and, consequently, has focused much research on metabolism of folate-related pathways during pregnancy and development. Further understanding of normal development and how teratogens can perturb these orchestrated processes also remains at the fore of modern scientific endeavors. The composite of these factors remains fragmented; the aim of this review is to provide the reader with a summary of sentinel and current works in the body of literature addressing NTD disease etiology.