Comparative Study between the Use of Regular Folic Acid Supplement versus the Use of L-Methyl Folate in Patients with Methyl Tetrahydrofolate Reductase (MTHFR) Gene Mutation with Recurrent Pregnancy Loss
Background: Methylfolate is the active metabolite of folate
that is important for DNA repair, synthetized under the effect of
MTHFR (methyl-tetrahydro-folatereductase) enzyme. Patients with MTHFR gene
mutation have low levels of biologically active methyfolate. Those patients
have high homocysteine levels causing vasculopathy and inadequate feto-maternal
circulation. Aim of the Work: To predict the potential benefit of use of
methylfolate instead of use of the regular folic acid in patients with MTHFR
gene mutation with history of RPL(recurrent
pregnancy loss). Subjects and Methods: Study was performed on 100 women.
All women had experienced at least two consecutive miscarriages first trimester
abortion. All patients were positive of having
MTHFR gene mutation. Patients were divided into two groups in terms of 1st
trimester drug intake. The 1st group recieved a regular folic acid supplement
in a dose of 5mg per day starting from the day of positive pregnancy test till the end of the first trimester.The 2nd
group recieved L-methylfolate supplement in a dose of 1000 mcg per day starting
from the day of positive pregnancy test till the end of the first trimester.
Then both groups were compared in terms of abortion rates, pregnancy
continuation rates and the development of other major obstetric complications. Results:
References
[1]
Prevention of Neural Tube Defects (1991) Prevention of Neural Tube Defects: Results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. The Lancet, 338,131-137. https://doi.org/10.1016/0140-6736(91)90133-A
[2]
Nelen, W.L., Bulten, J., Steegers, E.A., Blom, H.J., Hanselaar, A.G. and Eskes, T.K. (2000) Maternal Homocysteine and Chorionic Vascularization in Recurrent Early Pregnancy Loss. Human Reproduction, 15, 954-960.
https://doi.org/10.1093/humrep/15.4.954
Val in the Methylene Tetrahydrofolate Reductase Gene: A Risk Factor for Arterial Disease and Venous Thrombosis. Thrombosis and Haemostasis, 77, 818-821. https://doi.org/10.1055/s-0038-1656059 -->
[3]
Arruda, V.R., von Zuben, P.M., Chiaparini, L.C., Annichino-Bizzacchi, J.M. and Costa, F.F. (1997) The Mutation Ala677-->Val in the Methylene Tetrahydrofolate Reductase Gene: A Risk Factor for Arterial Disease and Venous Thrombosis. Thrombosis and Haemostasis, 77, 818-821. https://doi.org/10.1055/s-0038-1656059
[4]
Boers, G.H. (1997) Hyperhomocysteinemia as a Risk Factor for Arterial and Venous Disease. A Review of Evidence and Relevance. Thrombosis and Haemostasis, 78, 520-522. https://doi.org/10.1055/s-0038-1657580
[5]
Yang, B., Fan, S., Zhi, X., et al. (2014) Associations of MTHFR Gene Polymorphisms with Hypertension and Hypertension in Pregnancy: A Meta-Analysis from 114 Studies with 15411 Cases and 21970 Controls. PLoS ONE, 9, e87497.
https://doi.org/10.1371/journal.pone.0087497
[6]
Greenberg, J.A., Bell, S.J., Guan, Y. and Yu, Y.H. (2011) Folic Acid Supplementation and Pregnancy: More than Just Neural Tube Defect Prevention. Reviews in Obstetrics and Gynecology, 4, 52-59.
[7]
Rieder, M.J. (1994) Prevention of Neural Tube Defects with Periconceptional Folic Acid. Clinics in Perinatology, 21, 483-503.
https://doi.org/10.1016/S0095-5108(18)30328-2
[8]
Pitkin, R.M. (2007) Folate and Neural tube Defects. The American Journal of Clinical Nutrition, 85, 285s-288s. https://doi.org/10.1093/ajcn/85.1.285S
[9]
De Wals, P., Tairou, F., Van Allen, M.I., et al. (2007) Reduction in Neural-Tube Defects after Folic Acid Fortification in Canada. The New England Journal of Medicine, 357, 135-142. https://doi.org/10.1056/NEJMoa067103
[10]
Pietrzik, K., Bailey, L. and Shane, B. (2010) Folic acid and L-5-Methyltetrahydrofolate: Comparison of Clinical Pharmacokinetics and Pharmacodynamics. Clinical Pharmacokinetics, 49, 535-548. https://doi.org/10.2165/11532990-000000000-00000
[11]
Chaithra, P.T., Malini, S. and Kumar, C. (2011) An Overview of Genetic and Molecular Factors Responsible for Recurrent Pregnancy Loss. International Journal of Human Genetics, 11, 217-225. https://doi.org/10.1080/09723757.2011.11886145
[12]
Zhu, L. (2015) Polymorphisms in the Methylene Tetrahydrofolate Reductase and Methionine Synthase Reductase Genes and Their Correlation with Unexplained Recurrent Spontaneous Abortion Susceptibility. Genetics and Molecular Research, 14, 8500-8508. https://doi.org/10.4238/2015.July.28.19
[13]
Rady, H.A. (2018) Maternal Methyltetrahydrofolate Reductase Gene Mutation in Patients with Missed Abortions. Journal of Taibah University Medical Sciences, 13, 93-96. https://doi.org/10.1016/j.jtumed.2017.04.004
[14]
Miller, A.L. (2008) The Methylation, Neurotransmitter, and Antioxidant Connections between Folate and Depression. Alternative Medicine Review, 13, 216-226.
[15]
Malinow, M.R., Rajkovic, A., Duell, P.B., Hess, D.L. and Upson, B.M. (1998) The Relationship between Maternal and Neonatal Umbilical Cord Plasma Homocyst(e)ine Suggests a Potential Role for Maternal Homocyst(e)ine in Fetal Metabolism. American Journal of Obstetrics and Gynecology, 178, 228-233.
https://doi.org/10.1016/S0002-9378(98)80005-7
[16]
Keen, C.L., Clegg, M.S., Hanna, L.A., et al. (2003) The Plausibility of Micronutrient Deficiencies Being a Significant Contributing Factor to the Occurrence of Pregnancy Complications. Journal of Nutrition, 133, 1597s-1605s.
https://doi.org/10.1093/jn/133.5.1597S
