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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.

Authors+Show Affiliations

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.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17120234

Citation

Candito, Mirande, et al. "Plasma Vitamin Values and Antiepileptic Therapy: Case Reports of Pregnancy Outcomes Affected By a Neural Tube Defect." Birth Defects Research. Part A, Clinical and Molecular Teratology, vol. 79, no. 1, 2007, pp. 62-4.
Candito M, Naimi M, Boisson C, et al. Plasma vitamin values and antiepileptic therapy: case reports of pregnancy outcomes affected by a neural tube defect. Birth Defects Res Part A Clin Mol Teratol. 2007;79(1):62-4.
Candito, M., Naimi, M., Boisson, C., Rudigoz, J. C., Gaucherand, P., Guéant, J. L., ... Van Obberghen, E. (2007). Plasma vitamin values and antiepileptic therapy: case reports of pregnancy outcomes affected by a neural tube defect. Birth Defects Research. Part A, Clinical and Molecular Teratology, 79(1), pp. 62-4.
Candito M, et al. Plasma Vitamin Values and Antiepileptic Therapy: Case Reports of Pregnancy Outcomes Affected By a Neural Tube Defect. Birth Defects Res Part A Clin Mol Teratol. 2007;79(1):62-4. PubMed PMID: 17120234.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Plasma vitamin values and antiepileptic therapy: case reports of pregnancy outcomes affected by a neural tube defect. AU - Candito,Mirande, AU - Naimi,Mourad, AU - Boisson,Catherine, AU - Rudigoz,Jean-Charles, AU - Gaucherand,Pascal, AU - Guéant,Jean-Louis, AU - Luton,Dominique, AU - Van Obberghen,Emmanuel, PY - 2006/11/23/pubmed PY - 2007/4/10/medline PY - 2006/11/23/entrez SP - 62 EP - 4 JF - Birth defects research. Part A, Clinical and molecular teratology JO - Birth Defects Res. Part A Clin. Mol. Teratol. VL - 79 IS - 1 N2 - 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. SN - 1542-0752 UR - https://www.unboundmedicine.com/medline/citation/17120234/Plasma_vitamin_values_and_antiepileptic_therapy:_case_reports_of_pregnancy_outcomes_affected_by_a_neural_tube_defect_ L2 - https://doi.org/10.1002/bdra.20318 DB - PRIME DP - Unbound Medicine ER -