Vitamin B12 in Pregnancy
Concern with a Systematic Review’s Conclusions
A concern about vitamin B12 deficiency causing adverse outcomes in pregnant women, particularly of South Asian descent, prompted us to look more closely at this hot topic. We identified a systematic review (SR) that focused on the vitamin B12 status of women and infants living in India (1). The review concluded that low maternal vitamin B12 status is associated with adverse maternal and child health outcomes and the review authors noted: "Based on the quality of evidence reviewed, we recommend the addition of vitamin B12 to various nutritional programs in India for children, adolescents, women in the reproductive age group, pregnant and lactating women. This public health measure would help in reduction in risk of NTD and improving birth weight in the offspring” (1). After reviewing the SR, the PEN® Team has concerns about its quality and question the accuracy of the authors’ conclusions.
More Details on the Findings
What potentially brings the SR’s conclusions into question is that the SR’s authors did not follow the SR guidelines that they stated they followed in the preparation of their summary statements. The authors rated evidence for birth weight and neural tube defects as “high quality evidence” despite the fact that some of the evidence they found was from indirect studies (1):
- A food supplementation in a pregnancy study did not mention vitamin B12 or cobalamin (2).
- Some included studies evaluated the effects of various foods supplemented in pregnancy that differed in other nutrients without much difference in vitamin B12 intakes (3,4).
- Some of the cited studies’ results contradict their conclusion about higher birth weight after vitamin B12 (3-5).
- The evidence for neural tube defects (NTD) was rated as high (1) despite the lack of temporal evidence of vitamin B 12 deficiency data from the same point in pregnancy that the NTD occurred. Their strongest evidence for an association between vitamin B12 deficiency and NTD was the indirect association between a gene polymorphism that produces lower intracellular vitamin B12 concentrations (1) was not direct evidence that NTD can be prevented by adequate vitamin B12 status.
While it is important for the SR authors to include studies even if the results do not agree with other studies, it is not appropriate in these cases to rate the summary conclusions as “high quality evidence”. The SR authors should also consider evidence that is not direct, which they did; however, this indirect evidence needs to be considered weak support for the topic under study. Overall, with these identified weaknesses, the PEN Team does not have confidence in the findings or conclusions from this SR.
However, the authors raise the concern about women of South Asian descent being more vulnerable to vitamin B12 deficiency in pregnancy. There are studies that offer support to this concern, including:
- A Canadian study that addressed the question of whether some pregnant women are at higher risk of vitamin B12 deficiency found that some women (18%) were deficient based on their blood levels, and those who were deficient were from an ethnic group that was more likely to be vegetarian (6). They examined the vitamin B12 status among a convenience sample of 320 pregnant women living in Vancouver using both plasma vitamin B12 and methylmalonic acid (a marker for vitamin B12 status). They found 18% and 33% of the women had plasma B12 levels in the deficient and suboptimal ranges and 2% had methylmalonic acid levels suggestive of deficiency. The odds of being B12 deficient were about 10-times higher for those women who self-identified as South Asian (noted to frequently be vegetarian) compared to the other ethnicities, likely due to vegetarian eating patterns. Those taking vitamin B12 supplements had 69% lower odds of having vitamin B12 deficiency.
For pregnant women who consume animal products including meat, poultry and fish, meeting recommended B12 levels can be easily met. For pregnant women who follow a vegan diet, sources of B12 from fermented foods, including nori, chlorella, spirulina and algae and unfortified nutritional yeast cannot be relied on as adequate sources of vitamin B12. As per PEN recommendations, dietitians should encourage pregnant women who follow vegetarian diet patterns to regularly consume foods fortified with vitamin B12 or to take a vitamin B12 supplement (7).
The Institute of Medicine International Dietary Reference Values are 2.6 for pregnancy and 2.8 ug/day in lactation (8).
See Additional Content:
- Behere RV, Deshmukh AS, Otiv S, Gupte MD, Yajnik CS. Maternal vitamin b12 status during pregnancy and its association with outcomes of pregnancy and health of the offspring: a systematic review and implications for policy in India. Front Endocrinol (Lausanne). 2021 Apr 12;12:619176. doi: 10.3389/fendo.2021.619176. eCollection 2021. Abstract available from: https://pubmed.ncbi.nlm.nih.gov/33912132/
- Rao S, Yajnik CS, Kanade A, Fall CH, Margetts BM, Jackson AA, et al. Intake of micronutrient-rich foods in rural Indian mothers is associated with the size of their babies at birth: Pune Maternal Nutrition Study. J Nutr. 2001 Apr;131(4):1217-24. doi: 10.1093/jn/131.4.1217. Abstract available from: https://pubmed.ncbi.nlm.nih.gov/11285330/
- Potdar RD, Sahariah SA, Gandhi M, Kehoe SH, Brown N, Sane H, et al. Improving women's diet quality preconceptionally and during gestation: effects on birth weight and prevalence of low birth weight--a randomized controlled efficacy trial in India (Mumbai Maternal Nutrition Project). Am J Clin Nutr. 2014 Nov;100(5):1257-68. doi: 10.3945/ajcn.114.084921. Epub 2014 Sep 17. Abstract available from: https://pubmed.ncbi.nlm.nih.gov/25332324/
- Lawande A, Gravio CD, Potdar RD, Sahariah SA, Gandhi M, Chopr H, et al. Effect of a micronutrient-rich snack taken preconceptionally and throughout pregnancy on ultrasound measures of fetal growth: The Mumbai Maternal Nutrition Project (MMNP). Matern Child Nutr. 2018 Jan;14(1):e12441. doi: 10.1111/mcn.12441. Epub 2017 Mar 2. Abstract available from: https://pubmed.ncbi.nlm.nih.gov/28251804/
- Duggan C, Srinivasan K, Thomas T, Samuel T, Rajendran R, Muthayya S, et al. Vitamin B-12 supplementation during pregnancy and early lactation increases maternal, breast milk, and infant measures of vitamin B-12 status. J Nutr. 2014 May;144(5):758-64. doi: 10.3945/jn.113.187278. Epub 2014 Mar 5. Abstract available from: https://pubmed.ncbi.nlm.nih.gov/24598885/
- Jeruszka-Bielak M, Isman C, Schroder TH, Li W, Green TJ, Lamers Y. South Asian ethnicity is related to the highest risk of vitamin b12 deficiency in pregnant Canadian women. Nutrients. 2017 Mar 23;9(4):317. doi: 10.3390/nu9040317. Abstract available from: https://pubmed.ncbi.nlm.nih.gov/28333089/
- Dietitians of Canada. How can vitamin B12 requirements be met on a vegetarian diet throughout the life cycle? In: Practice-Based Evidence in Nutrition [PEN]. 2021 Apr 26. Available from: https://www.pennutrition.com/KnowledgePathway.aspx?kpid=2709&pqcatid=145&pqid=28832. Access only by subscription.
- Institute of Medicine. Dietary reference intakes: the essential guide to nutrient requirements. Vitamin B12. Washington, DC: The National Academies Press; 2006. Available from: https://www.nap.edu/read/11537/chapter/19.