Educational only — not medical advice.

Early Study Find Connection Between Low B12 Levels and Birth Defects

The connection between folate deficiency and neural tube defects (NTDs) has been understood for decades. Folic acid supplementation before and during early pregnancy is known to reduce the risk of spina bifida and help support normal fetal development. Newer research suggests that vitamin B12 — another methyl-donating nutrient that works closely with folate — may also play a meaningful role.

Early findings from Dutch researchers reported that mothers with low B12 levels had a significantly higher risk of having a child with spina bifida. Vitamin B12 and folate interact in several shared metabolic pathways, especially in methylation and DNA synthesis, which may explain their overlapping importance in neural tube development.

A study published in the American Journal of Obstetrics and Gynecology (July 2004) measured serum B12 in 45 mothers of infants with spina bifida and 83 mothers of healthy infants. Mothers of affected infants had B12 levels more than 20% lower than controls. Those in the lowest B12 range showed an estimated 300% increase in risk.

The authors suggested that women with low B12 levels may benefit from a multivitamin containing adequate B12 and folate. Because the neural tube closes very early — often before a woman knows she is pregnant — optimization of B12 and folate status ideally occurs before conception. More research is needed, but the data consistently show that low B12 may be a modifiable risk factor.

Newer Research Supports the Need for B12 During Pregnancy

1. Low maternal B12 is consistently linked with higher neural tube defect risk (2021–2024 reviews) [1].

• Several updated meta-analyses report that low maternal B12 correlates with increased risk of NTDs, especially when combined with low folate.
• Combination deficiencies (low folate + low B12) appear to carry the highest risk.
• Methylation pathway disruption is the suspected mechanism.

2. High homocysteine levels remain a strong predictor of NTD risk [2].

• Homocysteine rises when either folate or B12 is low.
• Multiple 2020–2023 reviews confirm that elevated maternal homocysteine is strongly associated with NTDs.
• This further supports the B12 connection.

3. Vegan and vegetarian mothers show higher rates of B12 insufficiency in pregnancy [3].

• Several cohort studies (2020–2024) consistently show lower B12 status in plant-based eaters and increased risk of low birthweight, preterm birth, and possible higher NTD risk if not supplemented.

4. Preconception B12 status matters more than previously understood [4,5].

• Recent studies emphasize that B12 levels at conception — not just during pregnancy — are predictive of fetal neural tube health.

  1. Behere R.V., Yajnik C.S., and colleagues. “Maternal Vitamin B12 Status During Pregnancy and Its Association with Outcomes of Pregnancy and Early Child Development.” Frontiers in Endocrinology. 2021;12:619176. https://doi.org/10.3389/fendo.2021.61917
  2. Kucha W., Seifu D., Tirsit A., et al. “Folate, Vitamin B12, and Homocysteine Levels in Women with Neural Tube Defect-Affected Pregnancy in Addis Ababa, Ethiopia.” Frontiers in Nutrition. 2022;9:873900. https://doi.org/10.3389/fnut.2022.873900
  3. McNulty H., et al. “Beyond folic acid: can optimizing maternal status of other methyl donors contribute to further reducing the risk of neural tube defects?” The American Journal of Clinical Nutrition. 2023; [E-pub ahead of print]. https://doi.org/10.1016/j.ajcnut.2023.166026-5
  4. Tirsit A., et al. “Risk Factors for Neural-Tube Defects Detected in Utero.” Early Human Development. 2024; (in press). https://doi.org/10.1016/j.earlhumdev.2024.104989
  5. Nie L., et al. “The Emerging Role of Maternal Vitamin B12 in Neural Tube Development: A Systematic Review and Meta-Analysis.” Nutrients. 2025; Jun 19;17(12):2040.  doi: 10.3390/nu17122040