Plasma vitamin values and antiepileptic therapy: Case reports of pregnancy outcomes affected by a neural tube defect

Abstract

BACKGROUND: Folic acid supplementation reduces the occurrence of neural tube defects (NTDs); however, it is not clear whether it protects against teratogenic effects of antiepileptic drugs. METHODS: We report the cases of four pregnant women receiving valproic acid therapy, who all had NTD-affected offspring, despite periconceptional 5 mg/day of folic acid supplementation (cases), and investigated homocysteine metabolism, linked with folate metabolism. Their plasma homocysteine, folates, and vitamin B6 and B12 results were compared with values of two other women, who were also receiving valproic acid and folic acid complement, but who had normal pregnancies (valproic acid controls), and values of 40 pregnant women who had normal pregnancies and were not receiving any therapy (controls without therapy). Because of the possible existence of a genetic susceptibility, polymorphisms in homocysteine metabolism were sought. RESULTS: Two cases showed a decreased phosphopyridoxal level, compared with levels in the controls not receiving therapy. The genotype TT (C677T) is an NTD genetic susceptibility, but it was observed in only one valproic acid control. Various polymorphisms were observed in the cases, but were also common in the controls. Several studies have reported that valproic acid therapy lowers vitamin B6 levels. Our case with the greatest decrease in plasma phosphopyridoxal, who was taking periconceptional folic acid plus pyridoxine therapy, had a normal second pregnancy outcome. CONCLUSIONS: In addition to folates, other vitamins, such as vitamin B6, may have played a role in NTDs in our patients taking an antiepileptic drug. Birth Defects Research (Part A) 79: 62-64, 2007.

Maternal and Fetal Outcomes of Women with Epilepsy: Study from a Tertiary Care Center in India

“…However recent evidence fails to support the same. Many reports [18][19][20] demonstrated no decrease in the risk of NTD of valproate by supplementation of folatets.…”

Antiepileptic drugs and pregnancy outcomes

“…However, a growing literature has consistently been reporting the lack of any benefit in terms of protection from NTDs derived from folic acid supplementation in women receiving VPA therapy during pregnancy [Candito et al, 2007; Craig et al, 1999; Pittschieleret al, 2008]. As recently reviewed by Ornoy and colleagues [2009], there is no evidence to demonstrate that the risk of NTDs can be further reduced by folic acid supplementation in women taking VPA, a position previously articulated by Yerby and co-workers [2003].…”

Valproic acid effect on neural tube defects is not prevented by concomitant folic acid supplementation: Early chick embryo model pilot study

“…Valproic acid does not reduce serum folate levels contrary to some antiepileptics as carbamazepine (Jentink et al, 2010; Apeland et al, 2001; Kishi et al, 1997; Schwaninger et al, 1999). However, cases of NTDs have been described in mothers on VA use despite FA supplement (Jentink et al, 2010; Craig et al, 1999; Candito et al, 2007; Duncan et al, 2001). Specifically, lower level of NTDs had been described for those cases.…”