Trial record 13 of 141 for:    folic acid AND pregnancy NOT (male OR men)

Vitamin B12 Supplementation During Pregnancy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
International Centre for Diarrhoeal Disease Research, Bangladesh
ClinicalTrials.gov Identifier:
NCT01795131
First received: February 9, 2013
Last updated: April 2, 2014
Last verified: July 2009
  Purpose

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 Intervention Phase
Nutritional Anemia in Mothers.
Nutritional Anemia in Infants.
Dietary Supplement: Vitamin B12
Dietary Supplement: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by International Centre for Diarrhoeal Disease Research, Bangladesh:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    The investigators will determine the percentage of nutritional anemia in mothers by measuring Hb, ferritin, B12 levels in plasma.


Secondary Outcome Measures:
  • Effect of B12 status on DNA methylation and one-carbon metabolism in mother-child pairs. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 120
Study Start Date: February 2010
Study Completion Date: December 2013
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   22 Years to 35 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Hb level in the range of 7.0-11 g/dL
  2. Age: 22-35 years
  3. Mothers at the beginning of second trimester (i.e. at 11-14 weeks of gestation)
  4. Willing to stay in Dhaka during pregnancy and willing to get admitted in the clinic for delivery
  5. Self-reported Last Menstrual Period (LMP) and urine pregnancy test will be used to determine the gestational age.

Exclusion Criteria:

  1. Women with severe anemia; hemoglobin concentration <7.0 g/dL
  2. History or presence of systemic disease
  3. H/O of previous complicated pregnancies or of pre-term delivery, abortion
  4. Receipt of influenza vaccine
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01795131

Locations
Bangladesh
Maternal and Child Health Training Institute
Dhaka, Bangladesh, 1205
Sponsors and Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh
Investigators
Principal Investigator: Rubhana Raqib, Ph D International Centre for Diarrhoeal Disease Research, Bangladesh
  More Information

No publications provided

Responsible Party: International Centre for Diarrhoeal Disease Research, Bangladesh
ClinicalTrials.gov Identifier: NCT01795131     History of Changes
Other Study ID Numbers: PR-09033
Study First Received: February 9, 2013
Last Updated: April 2, 2014
Health Authority: Bangladesh: Ethical Review Committee

Keywords provided by International Centre for Diarrhoeal Disease Research, Bangladesh:
Nutritional anemia
Vitamin B12
flu vaccine
immunity

Additional relevant MeSH terms:
Vitamin B Complex
Anemia
Hematologic Diseases
Vitamin B 12
Hydroxocobalamin
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Hematinics
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 23, 2014