Evaluation of maternal serum folate, vitamin B12, and homocysteine levels andfactor V Leiden, factor II g.20210G>A, and MTHFR variations in prenatallydiagnosed neural tube defects.

BACKGROUND/AIM Neural tube defects (NTDs) are common congenital malformations that develop as a result of interactions between several genes and environmental factors. Many factors have been investigated in order to understand the etiology of NTDs, and many studies have identified folate intake as a common contributing factor. The exact etiology of the disease is still unknown. MATERIALS AND METHODS In this study, we compared serum folate, vitamin B12, and homocysteine levels, along with common thrombophilia-related genetic variations, including factor V Leiden, factor II g.20210G>A, MTHFR c.677C>T, and MTHFR c.1298A>C, in 35 pregnant women with fetal NTDs and 38 pregnant women with healthy fetuses. RESULTS A significant difference in serum vitamin B12 level and factor V Leiden frequency was detected between the two groups. On the other hand, serum folate, homocysteine levels, and factor II g.20210G>A, MTHFR c.677C>T, and MTHFR c.1298A>C were not significantly different in the NTD group compared to the controls. CONCLUSION These results indicate that vitamin B12 supplementation along with folate may help in lowering NTD frequency. In addition, this is the first study that provides evidence for a possible relationship between increased NTD risk and factor V Leiden.

[1]  Q. Ning,et al.  Investigations of single nucleotide polymorphisms in folate pathway genes in Chinese families with neural tube defects , 2014, Journal of the Neurological Sciences.

[2]  Jun Xie,et al.  Interaction between maternal 5,10-methylenetetrahydrofolate reductase C677T and methionine synthase A2756G gene variants to increase the risk of fetal neural tube defects in a Shanxi Han population. , 2013, Chinese medical journal.

[3]  Y. Li,et al.  Homocysteine, folate, vitamin B12 and B6 in mothers of children with neural tube defects in Xinjiang, China , 2012, Acta paediatrica.

[4]  M. R. Pepper,et al.  B12 in fetal development. , 2011, Seminars in cell & developmental biology.

[5]  H. Yaman,et al.  Serum vitamin B12 and homocysteine levels in pregnant women with neural tube defect , 2010, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[6]  I. Cetin,et al.  Maternal and Fetal Thrombophilia in Intrauterine Growth Restriction in the Presence or Absence of Maternal Hypertensive Disease , 2010, Reproductive Sciences.

[7]  A. Keshtkar,et al.  Maternal Folate and Vitamin B12 Status and Neural Tube Defects in Northern Iran: A Case Control Study , 2010, Iranian journal of pediatrics.

[8]  I. Cech,et al.  Serological Differences in Folate/Vitamin B12 in Pregnancies Affected by Neural Tube Defects , 2010, Southern medical journal.

[9]  Andrew J. Copp,et al.  Genetics of human neural tube defects , 2009, Human molecular genetics.

[10]  D. Watkins,et al.  Vitamin B(12) and birth defects. , 2009, Molecular genetics and metabolism.

[11]  M. Canfield,et al.  Maternal serum homocysteine and risk for neural tube defects in a Texas-Mexico border population. , 2009, Birth defects research. Part A, Clinical and molecular teratology.

[12]  Xue Gu,et al.  Maternal serum vitamin B12, folate and homocysteine and the risk of neural tube defects in the offspring in a high-risk area of China , 2009, Public Health Nutrition.

[13]  J. Troendle,et al.  Maternal Vitamin B12 Status and Risk of Neural Tube Defects in a Population With High Neural Tube Defect Prevalence and No Folic Acid Fortification , 2009, Pediatrics.

[14]  E. Schiff,et al.  Factor V Leiden and Antiphospholipid Antibodies in Either Mothers or Infants Increase the Risk for Perinatal Arterial Ischemic Stroke , 2009, Stroke.

[15]  E. Van Obberghen,et al.  Nutritional and genetic determinants of vitamin B and homocysteine metabolisms in neural tube defects: A multicenter case–control study , 2008, American journal of medical genetics. Part A.

[16]  N. Akar,et al.  Thrombophilia‐associated gene mutations in women with pregnancies complicated by fetal neural tube defects , 2008, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[17]  M. Thompson,et al.  Vitamin B12 and the Risk of Neural Tube Defects in a Folic-Acid-Fortified Population , 2007, Epidemiology.

[18]  Gary M. Shaw,et al.  Neural tube defects and folate: case far from closed , 2006, Nature Reviews Neuroscience.

[19]  G. Bennett,et al.  Failure of homocysteine to induce neural tube defects in a mouse model. , 2006, Birth defects research. Part B, Developmental and reproductive toxicology.

[20]  D. Reddihough,et al.  Factor V Leiden mutation: a contributory factor for cerebral palsy? , 2005, Developmental medicine and child neurology.

[21]  M. Alikaşifoğlu,et al.  Analysis of MTHFR 1298A>C in addition to MTHFR 677C>T polymorphism as a risk factor for neural tube defects in the Turkish population. , 2005, The Turkish journal of pediatrics.

[22]  S. Lynch.  Non‐multifactorial neural tube defects , 2005, American journal of medical genetics. Part C, Seminars in medical genetics.

[23]  N. Greene,et al.  Homocysteine is embryotoxic but does not cause neural tube defects in mouse embryos , 2003, Anatomy and Embryology.

[24]  G. Wells,et al.  Neonatal and fetal methylenetetrahydrofolate reductase genetic polymorphisms: an examination of C677T and A1298C mutations. , 2000, American journal of human genetics.

[25]  M. Khoury,et al.  Neural-tube defects. , 1999, The New England journal of medicine.

[26]  D. Shields,et al.  The "thermolabile" variant of methylenetetrahydrofolate reductase and neural tube defects: An evaluation of genetic risk and the relative importance of the genotypes of the embryo and the mother. , 1999, American journal of human genetics.

[27]  F. Gabreëls,et al.  A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? , 1998, American journal of human genetics.

[28]  M. den Heyer,et al.  Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida , 1995, The Lancet.

[29]  J. Mulinare,et al.  Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. , 1992, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[30]  H. El-Bassyouni,et al.  Maternal vitamin B12 and the risk of fetal neural tube defects in Egyptian patients. , 2007, Clinical laboratory.

[31]  A. Motulsky.  Nutritional ecogenetics: homocysteine-related arteriosclerotic vascular disease, neural tube defects, and folic acid. , 1996, American journal of human genetics.