Vitamin B12 Supplementation During Pregnancy on Cognitive Development (VitaPreg)

April 15, 2024 updated by: Centre For International Health

Supplementation of Vitamin B12 in Pregnancy and Postpartum on Growth and Cognitive Functioning in Early Childhood: A Randomized, Placebo Controlled Trial

Scientific basis: Globally, vitamin B12 deficiency is one of the most common micronutrient deficiencies. The only relevant source of vitamin B12 is animal-source foods and poor gut function may decrease absorption. Vitamin B12 is crucial for normal cell division and differentiation, and necessary for the development and myelination of the central nervous system. Deficiency is also associated with impaired fetal and infant growth. In the proposed study we will measure the effect of daily oral vitamin B12 supplementation to pregnant women on neurodevelopment and growth of their children. We also aim to measure the impact of B12 supplementation on several other outcomes.

Study design: Individually randomized double-blind placebo controlled trial in pregnant South Asian women at risk of poor vitamin B12 status. Participants will be randomized in a 1:1 ratio.

Study participants and site: 800 pregnant women from early pregnancy. Women will be enrolled as early as possible, but no later than in week 15 of pregnancy.

Intervention: Daily administration of 50 µg of vitamin B12 from early pregnancy until 6 months after birth.

Comparator: Placebo, identical to the vitamin B12 supplements.

Outcomes: Primary: (i) neurodevelopment in children measured at 6 and 12 months of age (ii) growth in children measured by weight and length at 12 months. Secondary: (i) neurodevelopment and cognitive functioning in children at 24 months (ii) gestational age at birth, (iii) fetal and infant growth measured by weight and length at birth, after 1 month and then at 3, 6, 9, and 24 months, (iv) hemoglobin concentration in children and mothers.

Relevance for programs and public health: The results from this study can suggest new dietary guidelines for South Asian women that again can lead to improved pregnancy outcomes and neurodevelopment and cognitive functioning in South Asian children.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Cobalamin (Vitamin B12) deficiency is common in many low- and middle-income countries. This is not surprising as the main source of vitamin B12 is animal source foods, which are expensive and for cultural and religious reasons often not eaten at all. We have in several studies in women and children demonstrated that poor vitamin B12 status is common in South Asia. There is also compelling evidence that vitamin B12 deficiency occurs frequently in many other settings including pregnant women .

Case studies have demonstrated harmful effects of severe vitamin B12 deficiency on the developing infant brain.The consequences of mild or subclinical vitamin deficiency are less clear but it has been shown to be associated with decreased cognitive performance in both elderly and children.

Three randomized controlled trials (RCT) have measured the effect of vitamin B12 supplementation on neurodevelopment in children: In a Norwegian trial, an intramuscular injection of B12 substantially improved motor development in six weeks old infants after one month. Another intervention study in low birth weight children in Norway recently confirmed these findings. The infants in these studies had evidence of suboptimal vitamin B12 status, but none were severely deficient. We found a beneficial effect of vitamin B12 supplementation for six months on neurodevelopment in young North Indian children.

During pregnancy, vitamin B12 is concentrated in the fetus and stored in the liver. Infants born to vitamin B12-replete mothers have stores of vitamin B12 that are adequate to sustain them for the first several months postpartum. Consequently, vitamin B12 deficiency rarely occurs before the infant is about four months old if the mother has adequate vitamin B12 status during pregnancy. However, many infants of vitamin B12-deficient breastfeeding mothers are vulnerable to B12 deficiency from an early age.

In this project we will randomise Nepalese women to receive a supplement containing 50µg cobalamin or a placebo from early pregnancy until 6 months postpartum.

Hypothesis to be tested

Principal hypothesis: Daily administration of vitamin B12 to pregnant women from early pregnancy until 6 months postpartum will:

  1. Increase the scores of the Bayley Scales of Infant and Toddler Development, 3rd ed. (Bayley-III) by 0.25 SD points measured at 6 and 12 months of age.
  2. Increase length for age and weight for length by 0.2 z-scores at 12 months of age.

Other hypotheses to be tested (dependent on additional funding):

  1. Daily maternal administration of vitamin B12 from the start of the early pregnancy and for 6 months postpartum improves the hemoglobin concentration in the mother and infant.
  2. Daily maternal administration of vitamin B12 from early pregnancy and for 6 months postpartum improves plasma vitamin B12 concentration and reduces plasma total homocysteine and methylmalonic acid concentration in the mother and infant.
  3. Daily maternal administration of vitamin B12 from early pregnancy and for 6 months postpartum improves insulin sensitivity in the offspring.

Study Type

Interventional

Enrollment (Actual)

800

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Nepal
      • Bhaktapur, Nepal, P.O.Box 40
        • Manjeswori Ulak

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Pregnant mother in early pregnancy and not later than 15 weeks of pregnancy.
  • Current resident and plan to reside in Bhaktapur district for at least the next 2 years.
  • Age of mother between 18 and 40 years.
  • Consent to participate in the study.

Exclusion Criteria:

  • Taking or plan to take dietary or multivitamin supplements containing vitamin B12.
  • Known case of chronic disease like asthma, tuberculosis, diabetes, hypertension, hypo or hyperthyroidism or others
  • Known case of current high risk pregnancy
  • Severe anemia (hemoglobin concentration <7 g/dL).
  • Where the study doctor finds it necessary to treat the woman with vitamin B12 or vitamin B12 containing supplements

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Vitamin B12
cobalamin, 50 µg per day throughout pregnancy and during the first 6 months postpartum.
Dietary supplement: cobalamin
Vitamin supplment tablet containing 50µg cobalamin
Other Names:
  • Vitamin B12
Placebo Comparator: Placebo
Identical taste and appearance with the Experimental arm. Contains no cobalamin
Dietary supplement: placebo
A tablet identical to the vitamin supplement but containing no vitamin B12

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Length
Time Frame: 12 months of age
Length measured in centimeters and expressed as z-scores
12 months of age
Neurodevelopment
Time Frame: measured 6 and 12 months of age
Cognitive composite score of the Bayley Scales of Infant and Toddler Development, 3rd ed. (Bayley-III)
measured 6 and 12 months of age

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Child hemoglobin concentration
Time Frame: measured 6 and 12 months of age
Hemoglobin measured by hemocue in full blood
measured 6 and 12 months of age
Child development ASQ
Time Frame: 12 first months of life
Total and subscale scores of the Ages and Stages Questionnaire - 3rd ed.
12 first months of life
Child development Bayley
Time Frame: measured 6 and 12 months of age
Subscale scores of the Bayley Scales of Infant and Toddler Development, 3rd ed. (Bayley-III)
measured 6 and 12 months of age
Heart rate variability
Time Frame: 12 first months of life
Heart rate variability or vagal tone
12 first months of life
Sleep and activity
Time Frame: 12 first months of life
Sleep and activity measured by Actigraph (Actiwatch)
12 first months of life
The Infant Motor Performance
Time Frame: 2 months after birth
Screening tool to assess motor development
2 months after birth
Still births
Time Frame: Birth.
Number of still births
Birth.
Maternal hemoglobin concentration
Time Frame: at end of pregnancy and 6 and 12 months post party.
Hemoglobin measured by hemocue in full blood
at end of pregnancy and 6 and 12 months post party.
Number of complicated births
Time Frame: Birth.
Number of births that were complicated
Birth.
Children born at small for gestational age
Time Frame: Birth
Number of children born at small for gestational age
Birth
Birth weight
Time Frame: Birth
weight in g
Birth
Low birth weight
Time Frame: Birth
Birthweight < 2,500 g
Birth
Very low birth weight
Time Frame: Birth
Birthweight < 2,000 g
Birth
High birth weight
Time Frame: Birth
Birthweight > 4,000 g
Birth

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre For International Health

Collaborators

Sykehuset Innlandet HF
Tribhuvan University Teaching Hospital, Institute Of Medicine.
NORCE Norwegian Research Centre AS

Investigators

  • Principal Investigator: Tor A Strand, MD/PhD, University of Bergen
  • Principal Investigator: Laxman Shestha, MD, Tribhuvan University
  • Principal Investigator: Ram K Chandyo, MD/PhD, Kathmandu University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 27, 2017

Primary Completion (Actual)

June 28, 2022

Study Completion (Estimated)

December 31, 2029

Study Registration Dates

First Submitted

February 23, 2017

First Submitted That Met QC Criteria

March 1, 2017

First Posted (Actual)

March 7, 2017

Study Record Updates

Last Update Posted (Actual)

April 16, 2024

Last Update Submitted That Met QC Criteria

April 15, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CISMAC-B12
  • Universal Trial Number (Registry Identifier: U1111-1183-4093)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data will be shared with other researchers upon request after completion of the study (data collection) and after publication of the main outcomes. And if the ethical review boards approve the use of the data for other purposes that what is described in the proposal.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Anemia

Clinical Trials on cobalamin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Latvia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe