1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Effects of vitamin B 12 supplementation on neurodevelopment and growth in Nepalese Infants: A randomized controlled trial

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Vitamin B 12 deficiency is common and affects cell division and differentiation, erythropoiesis, and the central nervous system. Several observational studies have demonstrated associations between biomarkers of vitamin B 12 status with growth, neurodevelopment, and anemia. The objective of this study was to measure the effects of daily supplementation of vitamin B 12 for 1 year on neurodevelopment, growth, and hemoglobin concentration in infants at risk of deficiency.

          Methods and findings

          This is a community-based, individually randomized, double-blind placebo-controlled trial conducted in low- to middle-income neighborhoods in Bhaktapur, Nepal. We enrolled 600 marginally stunted, 6- to 11-month-old infants between April 2015 and February 2017. Children were randomized in a 1:1 ratio to 2 μg of vitamin B 12, corresponding to approximately 2 to 3 recommended daily allowances (RDAs) or a placebo daily for 12 months. Both groups were also given 15 other vitamins and minerals at around 1 RDA. The primary outcomes were neurodevelopment measured by the Bayley Scales of Infant and Toddler Development 3rd ed. (Bayley-III), attained growth, and hemoglobin concentration. Secondary outcomes included the metabolic response measured by plasma total homocysteine (tHcy) and methylmalonic acid (MMA). A total of 16 children (2.7%) in the vitamin B 12 group and 10 children (1.7%) in the placebo group were lost to follow-up. Of note, 94% of the scheduled daily doses of vitamin B 12 or placebo were reported to have been consumed (in part or completely). In this study, we observed that there were no effects of the intervention on the Bayley-III scores, growth, or hemoglobin concentration. Children in both groups grew on an average 12.5 cm (SD: 1.8), and the mean difference was 0.20 cm (95% confidence interval (CI): −0.23 to 0.63, P = 0.354). Furthermore, at the end of the study, the mean difference in hemoglobin concentration was 0.02 g/dL (95% CI: −1.33 to 1.37, P = 0.978), and the difference in the cognitive scaled scores was 0.16 (95% CI: −0.54 to 0.87, P = 0.648). The tHcy and MMA concentrations were 23% (95% CI: 17 to 30, P < 0.001) and 30% (95% CI: 15 to 46, P < 0.001) higher in the placebo group than in the vitamin B 12 group, respectively. We observed 43 adverse events in 36 children, and these events were not associated with the intervention. In addition, 20 in the vitamin B 12 group and 16 in the placebo group were hospitalized during the supplementation period. Important limitations of the study are that the strict inclusion criteria could limit the external validity and that the period of vitamin B 12 supplementation might not have covered a critical window for infant growth or brain development.

          Conclusions

          In this study, we observed that vitamin B 12 supplementation in young children at risk of vitamin B 12 deficiency resulted in an improved metabolic response but did not affect neurodevelopment, growth, or hemoglobin concentration. Our results do not support widespread vitamin B 12 supplementation in marginalized infants from low-income countries.

          Trial registration

          ClinicalTrials.gov NCT02272842

          Universal Trial Number: U1111-1161-5187 (September 8, 2014)

          Trial Protocol: Original trial protocol: PMID: 28431557 (reference [ 18]; study protocols and plan of analysis included as Supporting information).

          Abstract

          Tor A. Strand and colleagues measure the effects of daily supplementation of vitamin B12 for one year on neurodevelopment, growth, and hemoglobin concentration in infants at risk of deficiency.

          Author summary

          Why was this study done?
          • Many marginalized children fail to reach their cognitive and growth potential.

          • Subclinical vitamin B 12 deficiency, which is poor vitamin B 12 status without overt clinical symptoms, is common in this population in Nepal.

          • Vitamin B 12 deficiency in children is associated with anemia (low hemoglobin concentration), stunted growth, and poor neurodevelopment.

          What did the researchers do and find?
          • In this population-based, double-blind, randomized controlled trial (RCT), we measured the effects of daily supplementation of vitamin B 12 for 1 year in 600 infants.

          • The primary outcomes were neurodevelopment, growth, and hemoglobin concentration.

          • We targeted stunted infants as these children are at risk of vitamin B 12 deficiency.

          • Daily supplementation of vitamin B 12 for a year resulted in a metabolic profile reflecting substantially improved B 12 status (lower total homocysteine (tHcy) and methylmalonic acid (MMA) concentrations) but did not affect neurodevelopment, growth, or hemoglobin concentration.

          What do these findings mean?
          • In spite of the improved metabolic profile following vitamin B 12 supplementation, the findings do not support widespread vitamin B 12 supplementation to improve short-term growth, neurodevelopment, or hemoglobin concentration in infants.

          Related collections

          Most cited references30

          • Record: found
          • Abstract: found
          • Article: not found

          WHO Child Growth Standards based on length/height, weight and age

          To describe the methods used to construct the WHO Child Growth Standards based on length/height, weight and age, and to present resulting growth charts.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Vitamin B12 deficiency as a worldwide problem.

            Pernicious anemia is a common cause of megaloblastic anemia throughout the world and especially in persons of European or African descent. Dietary deficiency of vitamin B12 due to vegetarianism is increasing and causes hyperhomocysteinemia. The breast-fed infant of a vitamin B12-deficient mother is at risk for severe developmental abnormalities, growth failure, and anemia. Elevated methylmalonic acid and/or total homocysteine are sensitive indicators of vitamin B12-deficient diets and correlate with clinical abnormalities. Dietary vitamin B12 deficiency is a severe problem in the Indian subcontinent, Mexico, Central and South America, and selected areas in Africa. Dietary vitamin B12 deficiency is not prevalent in Asia, except in vegetarians. Areas for research include intermittent vitamin B12 supplement dosing and better measurements of the bioavailability of B12 in fermented vegetarian foods and algae.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Causes of vitamin B12 and folate deficiency.

              This review describes current knowledge of the main causes of vitamin B12 and folate deficiency. The most common explanations for poor vitamin B12 status are a low dietary intake of the vitamin (i.e., a low intake of animal-source foods) and malabsorption. Although it has long been known that strict vegetarians (vegans) are at risk for vitamin B12 deficiency, evidence now indicates that low intakes of animal-source foods, such as occur in some lacto-ovo vegetarians and many less-industrialized countries, cause vitamin B12 depletion. Malabsorption of the vitamin is most commonly observed as food-bound cobalamin malabsorption due to gastric atrophy in the elderly, and probably as a result of Helicobacter pylori infection. There is growing evidence that gene polymorphisms in transcobalamins affect plasma vitamin B12 concentrations. The primary cause of folate deficiency is low intake of sources rich in the vitamin, such as legumes and green leafy vegetables, and the consumption of these foods may explain why folate status can be adequate in relatively poor populations. Other situations in which the risk of folate deficiency increases include lactation and alcoholism.
                Bookmark

                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: Project administrationRole: SupervisionRole: Writing – original draft
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: Writing – review & editing
                Role: InvestigationRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Academic Editor
                Journal
                PLoS Med
                PLoS Med
                plos
                plosmed
                PLoS Medicine
                Public Library of Science (San Francisco, CA USA )
                1549-1277
                1549-1676
                1 December 2020
                December 2020
                : 17
                : 12
                Affiliations
                [1 ] Innlandet Hospital Trust, Department of Research, Lillehammer, Norway
                [2 ] Centre for International Health, University of Bergen, Bergen, Norway
                [3 ] Department of Pediatrics, Child Health Research Project, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal
                [4 ] Department of Psychosocial Science, University of Bergen, Bergen, Norway
                [5 ] Regional Center for Child and Youth Mental Health and Child Welfare, NORCE Norwegian Research Centre, Bergen, Norway
                [6 ] Bevital AS, Bergen, Norway
                [7 ] Department of Community Medicine, Kathmandu Medical College, Kathmandu, Nepal
                London School of Hygiene and Tropical Medicine, UNITED KINGDOM
                Author notes

                I have read the journal's policy and the authors of this manuscript have the following competing interests: AMC and PMU are paid employees at Bevital AS.

                Article
                PMEDICINE-D-20-00074
                10.1371/journal.pmed.1003430
                7707571
                33259482
                1153ca4b-9a15-47a0-80b2-9c7a9108f56e
                © 2020 Strand et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Figures: 2, Tables: 3, Pages: 15
                Product
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100005627, Thrasher Research Fund;
                Award ID: 11512
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100006095, Helse Sør-Øst RHF;
                Award ID: 2012090
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100005416, Norges Forskningsråd;
                Award ID: 234495
                Award Recipient :
                This study was funded by grants from the Thrasher Research Fund (award # 11512), and the South-Eastern Norway Regional Health Authority (grant # 2012090). TAS reports funding from the South-Eastern Norway Regional Health Authority (grant # 2012090), IK from the Research Council of Norway (grant # 234495), and MU from Thrasher Research Fund (award # 11512) for conducting this research. AMC and PMU are paid employees at Bevital AS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Physical Sciences
                Chemistry
                Chemical Compounds
                Organic Compounds
                Vitamins
                B Vitamins
                Cobalamins
                Physical Sciences
                Chemistry
                Organic Chemistry
                Organic Compounds
                Vitamins
                B Vitamins
                Cobalamins
                People and Places
                Population Groupings
                Age Groups
                Children
                Infants
                People and Places
                Population Groupings
                Families
                Children
                Infants
                Biology and Life Sciences
                Biochemistry
                Proteins
                Hemoglobin
                Biology and Life Sciences
                Developmental Biology
                Morphogenesis
                Neurodevelopment
                Medicine and health sciences
                Hematology
                Anemia
                Megaloblastic anemia
                Vitamin B12 deficiency
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Medicine and Health Sciences
                Clinical Medicine
                Clinical Trials
                Randomized Controlled Trials
                Medicine and Health Sciences
                Pharmacology
                Drug Research and Development
                Clinical Trials
                Randomized Controlled Trials
                Research and Analysis Methods
                Clinical Trials
                Randomized Controlled Trials
                Biology and Life Sciences
                Biochemistry
                Biomarkers
                Custom metadata
                Data available on request. In order to meet ethical requirements for the use of confidential patient data, requests must be approved by the Nepal Health Research Council (NHRC) and the Regional Committee for Medical and Health Research Ethics in Norway. Requests for data should be sent to the authors, by contacting NHRC ( http://nhrc.gov.np), or by contacting the Department of Global Health and Primary Care at the University of Bergen ( post@ 123456igs.uib.no ).

                Medicine
                Medicine

                Comments

                Comment on this article