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Effect of Maternal Vitamin B12 Supplementation on Cognitive Outcomes in South Indian Children: A Randomized Controlled Clinical Trial

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Abstract

Objectives To examine the effects of oral maternal vitamin B12 supplementation during pregnancy and early lactation on cognitive development in children. Method We studied 218 children born to mothers enrolled in a placebo-controlled, randomized trial of vitamin B12 supplementation during pregnancy through 6 weeks post-partum. Cognitive functions were assessed at 30 months using the Bayley Scales of Infant Development- 3rd edition (BSID III). The association of maternal sociodemographic characteristics, maternal biochemical status during pregnancy, birth weight and home environment with each sub-domain of BSID-III was examined using linear regression analysis. Separate multiple linear regression analyses for each of the BSID-III sub-domains with maternal trimester specific nutritional biomarker status was conducted. Results Children of mothers who received oral vitamin B12 supplementation had significantly higher scores on expressive language compared to children of mothers who received placebo (β = 0.14, P = 0.03). Children of mothers with elevated serum total homocysteine (tHcy) in the second and third trimesters of pregnancy had significantly lower scores on expressive language (β = − 0.18, P = 0.03 and β = − 0.19, P = 0.02, respectively) and gross motor domains (β = − 0.23, P = 0.008 and β = − 0.30, P = 0.001, respectively) of BSID-III adjusted for treatment arm and multiple confounders, compared with children whose mothers did not have elevated tHcy. Conclusions for practice Maternal B12 supplementation during pregnancy was associated with higher expressive language scores in children at 30 months. Elevated maternal tHcy levels during pregnancy had negative associations with expressive language and gross motor domains of BSID-III. Larger trials of maternal B12 supplementation are needed to confirm these findings.

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Acknowledgements

The present study was supported by Indian Council of Medical Research Grant 5/7/900/12-RCH Grant. The parent trial was supported by the Indian Council of Medical Research Grant 5/7/192/06-RHN and the US National Institutes of Health Grant R03 HD054123. CD was supported in part by NIH Grants K24DK104676 and 2P30 DK040561. The ongoing follow up study is being supported by the Norwegian Research Council (Grant No. 234495). There are no conflicts of interest. We thank Dr Nirmala for helping us obtain permission to conduct the study at Hosahalli Hospital. We thank Ms Vijaya P. and Ms Surekha S. for technical assistance. We are grateful to Ms Sarita Chowdhary for conducting the analyses of total homocysteine and methylmalonic acid and Ms Beena Bose for conducting the analyses of vitamin B12. Finally we thank all the participating women and their children.

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Authors and Affiliations

  1. Division of Mental Health & Neurosciences, St John’s National Academy of Health Sciences, St John’s Research Institute, Bengaluru, Karnataka, 560034, India

    Susan Thomas, Asha Ramthal & Krishnamachari Srinivasan

  2. Department of Psychiatry, St John’s Medical College, Bengaluru, Karnataka, India

    Krishnamachari Srinivasan

  3. Division of Epidemiology, Biostatistics and Population Health, St John’s Research Institute, Bengaluru, Karnataka, India

    Tinku Thomas

  4. Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, MA, USA

    Ronald J. Bosch

  5. Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

    David C. Bellinger

  6. Division of Nutrition, St John’s Research Institute, Bengaluru, Karnataka, India

    Anura V. Kurpad & Christopher P. Duggan

  7. Department of Physiology, St Johns Medical College, Bengaluru, Karnataka, India

    Anura V. Kurpad

  8. Division of Gastroenterology, Hepatology and Nutrition, Center for Nutrition, Boston Children’s Hospital, Boston, MA, USA

    Christopher P. Duggan

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  1. Susan Thomas
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  8. Krishnamachari Srinivasan
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Correspondence to Krishnamachari Srinivasan.

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Thomas, S., Thomas, T., Bosch, R.J. et al. Effect of Maternal Vitamin B12 Supplementation on Cognitive Outcomes in South Indian Children: A Randomized Controlled Clinical Trial. Matern Child Health J 23, 155–163 (2019). https://doi.org/10.1007/s10995-018-2605-z

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