Vitamin B12 in addition to Foliate is needed to reduce neural tube defects – July 2018

Association between biomarkers of vitamin B12 status and the risk of neural tube defects

Journal of Obstetrics and Gynaecology Research, 25 July 2018 https://doi.org/10.1111/jog.13751
Sameh M. Senousy Mona K. Farag Amr S. Gouda Mohamed A. El Noury Ola A. Dabbous Khaled R. Gaber

PDF is available free at Sci-Hub   10.1111/jog.13751

Aim
The aim of this study was to evaluate the association between vitamin B12 and its biomarkers and the risk of neural tube defects.

Methods
A total of 120 pregnant Egyptian women were included in the study. They were classified into two groups. Group A consisted of 50 women with neural tube defects in current pregnancy or with a history in previous pregnancies, and Group B consisted of 70 women with no history of neural tube defects in previous pregnancies or in the current pregnancy. All women were subjected to ultrasound anomaly scan and serum analysis of vitamin B12, homocysteine (Hcy), methyl malonic acid (MMA) and active vitamin B12 concentrations. Receiver operating characteristic curve analysis was used to determine the best cut‐off values of vitamin B12.

Results
Serum levels of vitamin B12 were decreased in Neural tube defects (NTDs) cases compared to controls (2.736 vs 3.091 ng/mL; P = 0.0015), while Hcy and MMA concentrations were elevated (18.39 vs 13.95 μmol/L; P = 0.0008 and 263 vs 229.7 μmol/L; P = 0.003, respectively). Active vitamin B12 reduction was not statistically significant (96.8 vs 99.36 pmol/L; P = 0.8013). The optimal cut‐off value of vitamin B12, 2.9 ng/mL, is the best threshold to expect neural tube defects, with a sensitivity of 60% and specificity of 74.29%.

Conclusion
Low vitamin B12 is a risk factor for having a fetus with neural tube defects. The monitoring of MMA and Hcy levels might be important in understanding and following cases with neural tube defects. Adding vitamin B12 to folic acid may help to decrease the incidence of neural tube defects in the Egyptian population.

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Paragraphs from Discussion

• It has been established that folic acid supplementation decreases the incidence of NTD by three fourths.15 It is generally agreed that not all NTD are preventable by folic acid, and until now, studies have not clearly explained the metabolic mechanism(s) underlying human folic acid responsiveness in NTD.
• Tang et al.,24 performed a meta-analysis of 32 studies to understand the relationship between maternal biomarkers and NTD and revealed that NTD-affected mothers had a significant increase in Hcy levels and lower levels of folic acid and vitamin B12. So, Tang et al. suggested that periconception supplementation of vitamin B12 and folic acid may be more effective in NTD prevention.38 These results are in concordance with our results as we found a significant deficiency in vitamin B12 level and high levels of Hcy in the case group when compared to the control group.
• In case-control studies conducted on Chinese women, a low vitamin B12 level was found, and a recommendation was made that vitamin B12 supplementation is needed to prevent NTD in China.28,29
• In a Turkish study, a statistical significant difference in serum vitamin B12 level was detected in the NTD group compared to the controls. On the other hand, serum folic acid and Hcy levels were not significantly different in the two groups. These results showed that vitamin B12 supplementation may help in lowering NTDs.30
• Many women do not take folic acid and vitamin B12 supplement until they are pregnant, which is too late for the effective prevention of NTD. So, intake of folic acid-fortified foods and preconceptional folic acid and vitamin B12 supplementation should be applied.31
• Ceyhan et al.,21 said that vitamin B12 deficiency does not play a causative role in the development of fetal NTD, and monitoring maternal Hcy levels might be important in understanding the causes of fetal NTD.
• This study confirmed that low maternal vitamin B12 status is an important risk factor for having a fetus with NTD. Introducing the monitoring of MMA and Hcy levels might be important in understanding and following cases with NTD.
• Finally, we recommend that dietary supplementation by adding vitamin B12 to folic acid may help to decrease the incidence of NTD in the Egyptian population.