Should vitamin B₁₂ status be considered in assessing risk of neural tube defects?

Abstract

There is a strong biological premise for including vitamin B12 with folic acid in strategies to prevent neural tube defects (NTDs), due to the closely interlinked metabolism of these two vitamins. For example, reduction of B12 deficiency among women of reproductive age could enhance the capacity of folic acid to prevent NTDs by optimizing the cellular uptake and utilization of natural folate cofactors. Vitamin B12 might also have an independent role in NTD prevention, such that adding it in fortification programs might be more effective than fortifying with folic acid alone. Globally, there is ample evidence of widespread vitamin B12 deficiency in low‐ and middle‐income countries, but there is also considerable divergence of vitamin B12 status across regions, likely due to genetic as well as nutritional factors. Here, I consider the evidence that low vitamin B12 status may be an independent factor associated with risk of NTDs, and whether a fortification strategy to improve B12 status would help reduce the prevalence of NTDs. I seek to identify knowledge gaps in this respect and specify research goals that would address these gaps.

Folic acid and vitamin B 12 fortification of food for preventing neural tube defects in Europe

“…This supports the case for mandatory food fortification with both vitamins to optimise prevention of neural tube defects, particularly when low vitamin B 12 is independently associated with increased risk 6. Even if governments agree to mandatory fortification with both vitamins, consensus has yet to be developed on how to implement it.…”

Improving maternal folate status to prevent infant neural tube defects: working group conclusions and a framework for action

“…This is based on the closely interlinked biochemical pathways involving these two vitamins. The report for this section considered two possibilities in the scope of this review: (1) that B 12 might have an independent or synergistic role in NTD prevention, such that adding B 12 in fortification programs might reduce NTDs further than fortifying with folic acid alone; and (2) that reduction of B 12 deficiency among WRA might have an important function in enhancing the capacity of folic acid to prevent NTDs . Two issues concerning the relationship of B 12 relative to NTD prevention were considered: (1) whether B 12 should be delivered routinely along with folic acid to avoid possible masking of B 12 deficiency and (2) whether B 12 deficiency is an independent contributor to NTD risk.…”

Prevalence rates of spina bifida in Alberta, Canada: 2001–2015. Can we achieve more prevention?

“…In Canada, low maternal B12 was associated with an almost tripling in the risk for NTD (Ray et al, ). Similarly, in Ireland, lower vitamin B12 status was associated with a higher risk for NTD (Molloy, ; Molloy et al, ). In the general Canadian population, approximately 5% and 20% of women of childbearing age have vitamin B12 deficiency or marginal status.…”