Vitamin B12 Supplementation During Pregnancy
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|ClinicalTrials.gov Identifier: NCT01795131|
Recruitment Status : Completed
First Posted : February 20, 2013
Last Update Posted : April 3, 2014
Nutritional anemia is a major public health problem among children and women in developing countries. Despite ongoing national program of supplementing pregnant women with iron-folate, prevalence of anemia is 39% among pregnant women and 78% among infants in Bangladesh. Vitamin B12 deficiency is a more prevalent cause of megaloblastic anemia than folate in many developing countries. This data raises the interest to address the role of vitamin B12 deficiency in nutritional anemia. Low dietary intake of animal products, a predominant source of vitamin B12 may cause anemia. Besides maintaining normal erythropoiesis, B12 is essential for immune function. However, no studies have evaluated the effect of maternal B12 supplementation on reduction of anemia and improving immunity of their infants. The investigators hypothesize that vitamin B12 supplementation plus iron-folate during pregnancy and 3-mo postpartum would: (a) Decrease anemia among mothers and infants; (b) Improve vaccine specific cellular and humoral immune responses among mothers; (c) Improve vaccine specific immunity in infants by passive transfer; (d) Improve DNA methylation and one-carbon metabolism in mother-child pairs; (e) Reduce antenatal/postnatal depression. Results from this study will guide and provide support to the policy makers to identify effective strategies to reduce nutritional anemia in population at risk.
The investigators aim to conduct a double-masked placebo controlled trial to investigate the added effect of vitamin B12 on the iron-folate supplementation among pregnant women. Anemic (Hb level <11.0 g/dl) mothers at 11-14 weeks of gestation will be randomized into two groups: supplement group will receive 250 ug vitamin B12 plus 400 ug folate and 60 mg iron; placebo group will receive folate and iron only. This daily supplementation will continue up to 3-mo postpartum. At 26-28 wk of gestation mothers will be given inactivated influenza vaccine. Data on anthropometric indices of mothers and children, birth size, infant growth and morbidity (mothers and children) throughout the study period will be recorded. 24-h dietary recall data will be collected from the mothers bimonthly throughout the study. Biochemical indicators of anemia including Hb, vitamin B12, ferritin, folate and α-glycoprotein (AGP) will be assessed in plasma of mothers (pre- and post-supplementation) and infants (cord blood and 3-months). Additional measurements include serum transferrin receptor (sTfR) in plasma and methyl malonic acid (MMA) and total homocysteine (tHcy) in the urine of mothers. Plasma vaccine specific antibody responses will be measured in mothers (pre- and post supplementation) and in infants (cord blood and 3-months). In breast milk, B12, folate and s-IgA will be determined. Genetic polymorphism (one-carbon metabolism) and DNA methylation will be studied in mothers and in cord blood.
|Condition or disease||Intervention/treatment||Phase|
|Nutritional Anemia in Mothers. Nutritional Anemia in Infants.||Dietary Supplement: Vitamin B12 Dietary Supplement: Placebo||Phase 2 Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||120 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Primary Purpose:||Health Services Research|
|Official Title:||Role of Vitamin B12 Supplementation During Pregnancy and Postpartum to Reduce Nutritional Anemia and Improve Immunity in Bangladeshi Women and Their Infants|
|Study Start Date :||February 2010|
|Actual Primary Completion Date :||June 2012|
|Actual Study Completion Date :||December 2013|
Active Comparator: Vitamin B12
Supplementation group (N=60) that will receive 250 µg of vitamin B12 in addition to 60 mg of Fe and 400µg of folate.
Dietary Supplement: Vitamin B12
Placebo Comparator: Placebo
Placebo group (N=60) that will receive placebo tablets and 60 mg of Fe and 400µg of folate daily.
Dietary Supplement: Placebo
- a) Percent reduction in nutritional anemia among mothers (based on measurement of Hb, ferritin, sTfR, folate, B12 levels in plasma; urinary MMA and tHcy; B12 levels in breast milk.) [ Time Frame: 24 months ]The investigators will determine the percentage of nutritional anemia in mothers by measuring Hb, ferritin, sTfR, B12 levels in plasma. They will also measure urinary MMA and tHcy and B12 levels in breast milk.
- Increase in influenza vaccine specific cellular and humoral responses among mothers (blastogenesis and T cell phenotyping,serum IgA, and IgG). [ Time Frame: 24 monnths ]Influenza vaccine-specific antibody responses (IgA, IgG) in plasma and colostrum/ breast milk [secretory IgA (s-IgA)] will be measured by ELISA. PBMC will be stimulated with Flu vaccine for blastogensis response.
- Increase in influenza vaccine specific immunity in infants by passive transfer (vaccine specific IgG in cord blood and breast milk and IgA in children at 3 mo). [ Time Frame: 24 months ]Influenza vaccine-specific antibody responses (IgA, IgG) in plasma and colostrum/ breast milk [secretory IgA (s-IgA)] will be measured by ELISA. PBMC will be stimulated with Flu vaccine for blastogensis response.
- Percent reduction in nutritional anemia in infants (based on measurement of Hb, ferritin, B12 levels in plasma; [ Time Frame: 24 months ]The investigators will determine the percentage of nutritional anemia in mothers by measuring Hb, ferritin, B12 levels in plasma.
- Effect of B12 status on DNA methylation and one-carbon metabolism in mother-child pairs. [ Time Frame: 24 months ]Genomic DNA methylation will be measured by the methyl acceptance assay . Total homocysteine (tHcy) will be measured in urine samples by using HPLC with fluorimetric detection. Mutations in the ALPL, MTHFR C677T and FUT2 genes will be determined by PCR- RFLP assay and DNA sequencing.
- Reduce depression scores [ Time Frame: 24 months ]Participants will be interviewed on their mental status using the Centre for Epidemiological Studies-Depression questionnaire. The questionnaire contains 20 items comprising six major aspects of depression: depressed mood, hopelessness, worthlessness, fatigue, appetite and sleep disturbances. It has been previously used in rural and urban Bangladeshi women (J Hamadani) and found to correlate sensibly to children's growth and development. The interview will be conducted twice at the homes of the women first at baseline and at 3 mo postpartum.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01795131
|Maternal and Child Health Training Institute|
|Dhaka, Bangladesh, 1205|
|Principal Investigator:||Rubhana Raqib, Ph D||International Centre for Diarrhoeal Disease Research, Bangladesh|