Vitamin B12 Supplementation During Pregnancy

NCT01795131 | Completed Phase 2 DMC

• 1 other identifier: PR-09033
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Nutritional Anemia in Mothers.; Nutritional Anemia in Infants.

Keywords

Nutritional anemia; Vitamin B12; flu vaccine; immunity

Outcome Measures

Primary Outcomes (4)

• 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.)

  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.

  24 months

• Increase in influenza vaccine specific cellular and humoral responses among mothers (blastogenesis and T cell phenotyping,serum IgA, and IgG).

  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.

  24 monnths

• 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).

  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.

  24 months

• Percent reduction in nutritional anemia in infants (based on measurement of Hb, ferritin, B12 levels in plasma;

  The investigators will determine the percentage of nutritional anemia in mothers by measuring Hb, ferritin, B12 levels in plasma.

  24 months

Secondary Outcomes (2)

• Effect of B12 status on DNA methylation and one-carbon metabolism in mother-child pairs.

  24 months

• Reduce depression scores

  24 months

Study Arms (2)

Vitamin B12

ACTIVE COMPARATOR

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

PLACEBO COMPARATOR

Placebo group (N=60) that will receive placebo tablets and 60 mg of Fe and 400µg of folate daily.

Dietary Supplement: Placebo

Interventions

Vitamin B12 DIETARY_SUPPLEMENT

Vitamin B12

Placebo DIETARY_SUPPLEMENT

Placebo

Eligibility Criteria

• Age: 22 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• Women with severe anemia; hemoglobin concentration \<7.0 g/dL
• History or presence of systemic disease
• H/O of previous complicated pregnancies or of pre-term delivery, abortion
• Receipt of influenza vaccine

Sponsors & Collaborators

• International Centre for Diarrhoeal Disease Research, Bangladesh: lead

Study Sites (1)

Maternal and Child Health Training Institute

Dhaka, 1205, Bangladesh

Location

Related Publications (1)

• Siddiqua TJ, Akhtar E, Haq MA, Shahab-Ferdows S, Hampel D, Islam S, Ahmed T, Allen LH, Raqib R. Effects of vitamin B12 supplementation on oxidative stress markers and pro-inflammatory cytokines during pregnancy and postpartum among Bangladeshi mother-child pairs. BMC Nutr. 2024 Jan 3;10(1):3. doi: 10.1186/s40795-023-00785-y.

  PMID: 38172996 DERIVED

MeSH Terms

Conditions

Influenza, Human

Interventions

Vitamin B 12

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Rubhana Raqib, Ph D

  International Centre for Diarrhoeal Disease Research, Bangladesh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2013
• First Posted: February 20, 2013
• Study Start: February 1, 2010
• Primary Completion: June 1, 2012
• Study Completion: December 1, 2013
• Last Updated: April 3, 2014

Record last verified: 2009-07

Locations

BA (1)