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Vitamins and plant ingredients

Vitamin B12 status in pregnant women and their infants in South India

Abstract

Background/Objectives:

Vitamin B12 deficiency during pregnancy has been associated with increased risk of adverse perinatal outcomes. However, few studies have investigated the burden and determinants of vitamin B12 status in young infants. This study was conducted to determine the associations between maternal and infant vitamin B12 status.

Subjects/Methods:

Pregnant women participating in a vitamin B12 supplementation trial in Bangalore, India, were randomized to receive vitamin B12 (50 μg) or placebo supplementation daily during pregnancy through 6 weeks postpartum. All women received 60 mg of iron and 500 μg of folic acid daily during pregnancy, as per standard of care. This prospective analysis was conducted to determine the associations between maternal vitamin B12 biomarkers (that is, plasma vitamin B12, methylmalonic acid (MMA) and tHcy) during each trimester with infant vitamin B12 status (n=77) at 6 weeks of age.

Results:

At baseline (14 weeks of gestation), 51% of mothers were vitamin B12 deficient (vitamin B12<150 pmol/l) and 43% had impaired vitamin B12 status (vitamin B12<150 pmol/l and MMA>0.26 μmol/l); 44% of infants were vitamin B12 deficient at 6 weeks of age. After adjusting for vitamin B12 supplementation, higher vitamin B12 concentrations in each trimester were associated with increased infant vitamin B12 concentrations and lower risk of vitamin B12 deficiency in infants (P<0.05). After adjusting for vitamin B12 supplementation, infants born to women with vitamin B12 deficiency had a twofold greater risk of vitamin B12 deficiency (P<0.01). Higher maternal folate concentrations also predicted lower risk of vitamin B12 deficiency in infants (P<0.05). Impaired maternal vitamin B12 status, which combined both circulating and functional biomarkers, was the single best predictor of infant vitamin B12 status.

Conclusions:

Impaired maternal vitamin B12 status throughout pregnancy predicted higher risk of vitamin B12 deficiency in infants, after adjusting for vitamin B12 supplementation. Future interventions are needed to improve vitamin B12 status periconceptionally, and to ensure optimal vitamin B12 status and health outcomes in pregnant women and their children.

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References

  1. Allen LH . How common is vitamin B-12 deficiency? Am J Clin Nutr 2009; 89: 693S–696S.

    Article  CAS  Google Scholar 

  2. McLean E, de Benoist B, Allen LH . Review of the magnitude of folate and vitamin B12 deficiencies worldwide. Food Nutr Bull 2008; 29: S38–S51.

    Article  Google Scholar 

  3. Allen LH . Folate and vitamin B12 status in the Americas. Nutr Rev 2004; 62: S29–S33, discussion S34.

    Article  Google Scholar 

  4. Brito A, Mujica-Coopman MF, Lopez de Romana D, Cori H, Allen LH . Folate and vitamin B12 status in Latin America and the Caribbean: an ppdate. Food Nutr Bull 2015; 36: S109–S118.

    Article  Google Scholar 

  5. Siekmann JH, Allen LH, Bwibo NO, Demment MW, Murphy SP, Neumann CG . Kenyan school children have multiple micronutrient deficiencies, but increased plasma vitamin B-12 is the only detectable micronutrient response to meat or milk supplementation. J Nutr 2003; 133: 3972S–3980S.

    Article  CAS  Google Scholar 

  6. McLean ED, Allen LH, Neumann CG, Peerson JM, Siekmann JH, Murphy SP et al. Low plasma vitamin B-12 in Kenyan school children is highly prevalent and improved by supplemental animal source foods. J Nutr 2007; 137: 676–682.

    Article  CAS  Google Scholar 

  7. Refsum H, Yajnik CS, Gadkari M, Schneede J, Vollset SE, Orning L et al. Hyperhomocysteinemia and elevated methylmalonic acid indicate a high prevalence of cobalamin deficiency in Asian Indians. Am J Clin Nutrition 2001; 74: 233–241.

    Article  CAS  Google Scholar 

  8. Taneja S, Bhandari N, Strand TA, Sommerfelt H, Refsum H, Ueland PM et al. Cobalamin and folate status in infants and young children in a low-to-middle income community in India. Am J Clin Nutr 2007; 86: 1302–1309.

    Article  CAS  Google Scholar 

  9. Allen LH . Causes of vitamin B12 and folate deficiency. Food Nutr Bull 2008; 29: S20–S34, discussion S35-27.

    Article  Google Scholar 

  10. Dror DK, Allen LH . Dairy product intake in children and adolescents in developed countries: trends, nutritional contribution, and a review of association with health outcomes. Nutr Rev 2014; 72: 68–81.

    Article  Google Scholar 

  11. Finkelstein JL, Layden AJ, Stover PJ . Vitamin B-12 and perinatal health. Adv Nutr 2015; 6: 1–12.

    Article  Google Scholar 

  12. Black MM . Effects of vitamin B12 and folate deficiency on brain development in children. Food Nutr Bull 2008; 29: S126–S131.

    Article  Google Scholar 

  13. Pepper MR, Black MM . B12 in fetal development. Semin Cell Dev Biol 2011; 22: 619–623.

    Article  CAS  Google Scholar 

  14. Venkatramanan S, Armata IE, Strupp BJ, Finkelstein JL . Vitamin B-12 and cognition in children. Adv Nutr 2016; 7: 879–888.

    Article  CAS  Google Scholar 

  15. 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; 144: 758–764.

    Article  CAS  Google Scholar 

  16. Shobha V, Tarey SD, Singh RG, Shetty P, Unni US, Srinivasan K et al. Vitamin B(1)(2) deficiency and levels of metabolites in an apparently normal urban south Indian elderly population. Indian J Med Res 2011; 134: 432–439.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Polito A, Intorre F, Andriollo-Sanchez M, Azzini E, Raguzzini A, Meunier N et al. Estimation of intake and status of vitamin A, vitamin E and folate in older European adults: the ZENITH. Eur J Clin Nutr 2005; 59: S42–S47.

    Article  CAS  Google Scholar 

  18. Obeid R, Morkbak AL, Munz W, Nexo E, Herrmann W . The cobalamin-binding proteins transcobalamin and haptocorrin in maternal and cord blood sera at birth. Clin Chem 2006; 52: 263–269.

    Article  CAS  Google Scholar 

  19. Yetley EA, Pfeiffer CM, Phinney KW, Bailey RL, Blackmore S, Bock JL et al. Biomarkers of vitamin B-12 status in NHANES: a roundtable summary. Am J Clin Nutr 2011; 94: 313S–321S.

    Article  CAS  Google Scholar 

  20. Fedosov SN, Brito A, Miller JW, Green R, Allen LH . Combined indicator of vitamin B12 status: modification for missing biomarkers and folate status and recommendations for revised cut-points. Clin Chem Lab Med 2015; 53: 1215–1225.

    Article  CAS  Google Scholar 

  21. Spiegelman D, Hertzmark E . Easy SAS calculations for risk or prevalence ratios and differences. Am J Epidemiol 2005; 162: 199–200.

    Article  Google Scholar 

  22. Wacholder S . Binomial regression in GLIM: estimating risk ratios and risk differences. Am J Epidemiol 1986; 123: 174–184.

    Article  CAS  Google Scholar 

  23. Zou G . A modified poisson regression approach to prospective studies with binary data. Am J Epidemiol 2004; 159: 702–706.

    Article  Google Scholar 

  24. Greenland S . Modeling and variable selection in epidemiologic analysis. Am J Public Health 1989; 79: 340–349.

    Article  CAS  Google Scholar 

  25. Miettinen O . Theoretical Epidemiology vol. 107, John Wiley & Sons: New York, 1985.

    Google Scholar 

  26. Bjorke Monsen AL, Ueland PM, Vollset SE, Guttormsen AB, Markestad T, Solheim E et al. Determinants of cobalamin status in newborns. Pediatrics 2001; 108: 624–630.

    Article  CAS  Google Scholar 

  27. Guerra-Shinohara EM, Paiva AA, Rondo PH, Yamasaki K, Terzi CA, D'Almeida V . Relationship between total homocysteine and folate levels in pregnant women and their newborn babies according to maternal serum levels of vitamin B12. BJOG 2002; 109: 784–791.

    Article  CAS  Google Scholar 

  28. Koc A, Kocyigit A, Soran M, Demir N, Sevinc E, Erel O et al. High frequency of maternal vitamin B12 deficiency as an important cause of infantile vitamin B12 deficiency in Sanliurfa province of Turkey. Eur J Nutr 2006; 45: 291–297.

    Article  CAS  Google Scholar 

  29. Muthayya S, Dwarkanath P, Mhaskar M, Mhaskar R, Thomas A, Duggan C et al. The relationship of neonatal serum vitamin B12 status with birth weight. Asia Pac J Clin Nutr 2006; 15: 538–543.

    CAS  Google Scholar 

  30. Deegan KL, Jones KM, Zuleta C, Ramirez-Zea M, Lildballe DL, Nexo E et al. Breast milk vitamin B-12 concentrations in Guatemalan women are correlated with maternal but not infant vitamin B-12 status at 12 months postpartum. J Nutr 2012; 142: 112–116.

    Article  CAS  Google Scholar 

  31. Lindblad B, Zaman S, Malik A, Martin H, Ekstrom AM, Amu S et al. Folate, vitamin B12, and homocysteine levels in South Asian women with growth-retarded fetuses. Acta Obstet Gynecol Scand 2005; 84: 1055–1061.

    Google Scholar 

  32. Schneider H, Miller RK . Receptor-mediated uptake and transport of macromolecules in the human placenta. Int J Dev Biol 2010; 54: 367–375.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the mothers and children, and field teams, including physicians, nurses, midwives, research, laboratory and administrative staff, who made this study possible; and St. John’s Medical College, Bangalore, India for its institutional support. This study was supported by grants from the National Institutes of Health (NICHD R03HD054123 and K24DK104676); and the Indian Council of Medical Research (ICMR: 5/7/192/06-RHN).

Author contributions

The authors’ responsibilities were as follows: CD, KS, AVK and JLF designed the research; all the authors conducted the research; JLF conducted the data analysis and wrote the initial draft of the manuscript; and CD had the primary responsibility for the final content. All authors contributed to the interpretation of the data and in the development of this manuscript, and read and approved the final version.

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Correspondence to C Duggan.

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Finkelstein, J., Kurpad, A., Thomas, T. et al. Vitamin B12 status in pregnant women and their infants in South India. Eur J Clin Nutr 71, 1046–1053 (2017). https://doi.org/10.1038/ejcn.2017.29

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