Plasma vitamin values and antiepileptic therapy: case reports of pregnancy outcomes affected by a neural tube defect.
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.
Candito
Mirande
M
Inserm UI 145 and Biochemistry, Hôpital Pasteur, 30 Avenue de la Voie Romaine, 06002 Nice cedex 1, and Inserm 724, University Center of Nancy, France. candito.m@chu-nice.fr
Naimi
Mourad
M
Boisson
Catherine
C
Rudigoz
Jean-Charles
JC
Gaucherand
Pascal
P
Guéant
Jean-Louis
JL
Luton
Dominique
D
Van Obberghen
Emmanuel
E
D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000627:therapeutic use; D020022:Genetic Predisposition to Disease; D006710:Homocysteine / Q000097:blood; D006801:Humans; D009436:Neural Tube Defects / Q000209:etiology* / Q000235:genetics; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011256:Pregnancy Outcome; D014635:Valproic Acid / Q000009:adverse effects* / Q000627:therapeutic use; D014805:Vitamin B 12 / Q000097:blood*; D025101:Vitamin B 6 / Q000097:blood*
D000927:Anticonvulsants; D006710:Homocysteine; D014635:Valproic Acid; D025101:Vitamin B 6; D005492:Folic Acid; D014805:Vitamin B 12