This article is written in collaboration with Dr. Mike Stadler, an obstetrician with a passion for his patients and a preventative bend to his care. Like his partner, Dr. Grey, he is always looking for ways to enhance health with small actionable changes.

Since the early 1990s, the American medical community has recommended prenatal vitamins with folic acid as a supplement for mothers-to-be prior to and during the first 3 months of pregnancy. The thought was that this synthetic vitamin would be specifically targeting a group of congenital disorders called neural tube defects, disorders where the spinal cord does not form correctly and causes much childhood morbidity. Later, in the 90s, the government went a little further by adding folic acid to shelf stable foods like breads and cereals with the goal of increasing young women’s exposure to the synthetic micronutrient.

The initial effect of this program was a significant reduction in neural tube defects from 25-50 percent in different studies in different countries. This was a resounding success, from a public health perspective. However, as with how cholesterol reduction has not answered the question of coronary artery disease, folic acid supplementation has not completely resolved the problem.

What are we missing? Where is the piece that completes the puzzle?

It is clear from the literature that the neural tube and many other embryological pathways are established and completed very early in pregnancy. Therefore, it is critical that we provide a mother-to-be with all of the necessary macro- and micro-nutrients to allow for these embryological pathways to proceed as nature intended them to.

As we performed a deep dive into the literature, it became clear that the pathways involved in neural tube development are complicated and well beyond just vitamin B9 or folate. The neural tube closes before the first month of pregnancy is complete, well before most mothers are aware of the pregnancy. Thus, it is critical to prepare for pregnancy and not be reactionary. It appears that adequate and functional levels of vitamin B12, choline and betaine are also necessary for pathways to process and proceed with normal fetal development.

Some specifics

There are cassettes of genes that, when altered over time, are putting mothers and their offspring at increased risk. These genes have SNPs, single nucleotide polymorphisms, that make the metabolism of folate, B12 and choline less functional. This puts extra pressure on the mother to increase her intake to meet the needs of her body based on her gene makeup. For example, a gene called MTHFR, methyl tetrahydrofolate reductase, is involved in folate metabolism. If it has a SNP that changes its function, then a mother would need significantly more folate to effect the same change in pathway development. This means that she is at higher risk for a child with a neural tube defect or other poor offspring outcome if she does not consume enough folate. The genes MTRR, MTR, MTHFD1, DHFR, CHKA, CUBN, and others are candidates for further study in this realm.

This is the critical part of the story. Most of us have no clue what our folate, B12, choline metabolic pathway genes are and cannot make an educated decision without this knowledge. Therefore, we must make best guess decisions for the population as a whole based on the unknowns.