Maternal B12 Supplementation to Improve Infant B12 Deficiency and Neurodevelopment

NCT03783104 | Unknown

• 1 other identifier: 13795/001
• Study Type: interventional
• Target: 720
• Locations: 2 countries
• Sites: 2

Brief Summary

Vitamin B12 plays a key role in the development and normal functioning of the brain and nervous system. Unborn and new-born infants derive their vitamin B12 stores almost entirely from maternal B12 stores. As such, infants who are born to vegetarian mothers and exclusively breast fed are at a high-risk of B12 deficiency. This is because the best sources of vitamin B12 are found in animal based or fortified foods (e.g. cheese, milk and eggs). Vitamin B12 deficiency is widely reported among antenatal mothers and children, particularly in Low and Middle Income Countries (LMICs) where these food sources are uncommon. So far, studies have shown that antenatal vitamin B12 deficiency in mothers may be associated with poorer neurodevelopment in their children. Furthermore, vitamin B12 supplementation during pregnancy and early lactation has been shown to increase maternal, breast milk, and infant levels of vitamin B12. Although existing literature documents several studies on maternal vitamin B12 supplementation, there is a lack of research on the causative effect of maternal vitamin B12 supplementation on infant development. This project, funded by the Medical Research Council (MRC), will undertake a multi-centric nutritional trial in Nepal and India, as these are two LMICs where high incidence of vitamin B12 deficiency is reported.

Conditions

Child Developmental Delay; Child Malnutrition; Maternal Exposure; Vitamin B 12 Deficiency

Keywords

Vitamin B12; Maternal nutrition; Neurodevelopment; Supplementation

Outcome Measures

Primary Outcomes (1)

• Infant neurodevelopment

  The effect of higher dose oral maternal vitamin B12 supplementation on infant neurodevelopment as measured by Developmental Assessment Scales for Indian Infants (DASII) at age 9 months, as compared to low dose

  9 months in all infant subjects

Secondary Outcomes (5)

• Maternal B12 status

  First trimester (<12 weeks gestation) and third trimester (≥ 27 weeks)

• Infant B12 status

  9 months (± 2 weeks) of age after birth

• Hemoglobin levels and infant anthropometry

  Between first and third trimester

• Hemoglobin levels and infant anthropometry

  At 9 months after birth

• Hemoglobin levels and infant anthropometry

  At 1, 2, 3, 4, 6 and 9 months after birth

Other Outcomes (8)

• Socio-economic mediators of the relationship between maternal B12 status, supplementation and infant neurodevelopment

  At study enrolment

• Effect of maternal diet

  During the third trimester (27 weeks of gestation)

• Effect of type of milk feeding on infant vitamin B12 status

  At 9 months (± 2 weeks) infant age

Study Arms (2)

250μg of vitamin B12 supplementation

EXPERIMENTAL

Group 1 (Intervention) will receive 250μg of vitamin B12 supplementation delivered daily to the mother from 12 weeks gestation up to 6 months post-partum.

Dietary Supplement: B12 Supplement

50μg of vitamin B12 supplementation

ACTIVE COMPARATOR

Group 2 (Control) will receive 50μg of vitamin B12 supplementation delivered daily to the mother from 12 weeks gestation up to 6 months post-partum.

Dietary Supplement: B12 Supplement

Interventions

B12 Supplement DIETARY_SUPPLEMENT

Differential doses of vitamin B 12 supplementation in a two-armed randomised controlled trial

250μg of vitamin B12 supplementation; 50μg of vitamin B12 supplementation

Eligibility Criteria

• Age: 18 Years - 35 Years
• Gender Eligibility Details: Only pregnant women are eligible.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Able and willing to give full consent (record if verbal consent is being used)
• First presentation of the mother to the antenatal clinic \<12 weeks of gestation (mothers presenting later not included as the investigators may miss a proportion of the brain growth period)
• Vegetarian mothers (higher risk of deficiency; defined as self-reported dietary pattern that includes vegans and/or people who do eat egg and/or people who do consume milk and/or meat/fish \< once a month)
• Mother is expecting singleton birth
• Living within an a-priori defined geographical area (to enhance efficiency of follow-up): Delhi - National Capital Region; Nepal - 10km radius of Paropakar Maternity \& Women's Hospital, Kathmandu valley including the three districts of Kathmandu, Bhaktapur and Lalitpur.
• Is familiar with English, Hindi, or Nepalese

You may not qualify if:

• Younger mothers (\<18 years; higher risk of neonatal morbidity)
• Maternal Age\>35 years ( higher risk of neonatal morbidity)
• Mothers already on medicinal B12 supplementation including as B-complex or multivitamins (confounder)
• Women with multiple gestation, those diagnosed with chronic medical conditions (diabetes mellitus, hypertension, heart disease, neurological disease or thyroid disease), and those who tested positive for hepatitis B, HIV or syphilis (associated with prematurity, intrauterine growth restriction (IUGR) and other neonatal morbidities which could influence neurodevelopment)
• Women who anticipate moving out of the city before/ after delivery (follow-up difficult/not possible, 16% delivered outside Sitaram Bhartia Institute of Science \& Research (SBISR) in earlier work done by Principle Investigator) (3)
• Women treated for infertility (higher risk of prematurity and neonatal complications
• Women with known pre-diagnosed mental health disorder including depression, drug or alcohol abuse likely to affect participation in the study
• Participation in another study within 4 weeks prior to trial start
• Allergy to B12 or another supplement constituent

Sponsors & Collaborators

• University College, London: lead
• Sitaram Bhartia Institute of Science and Research: collaborator
• Paropakar Maternity and Women's Hospital: collaborator

Study Sites (2)

Sitaram Bhartia Institute for Science and Research

New Delhi, 110016, India

RECRUITING

Paropakar Maternity and Women's Hospital

Kathmandu, 44600, Nepal

RECRUITING

MeSH Terms

Conditions

Learning Disabilities; Child Nutrition Disorders; Vitamin B 12 Deficiency

Condition Hierarchy (Ancestors)

Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurodevelopmental Disorders; Mental Disorders; Nutrition Disorders; Nutritional and Metabolic Diseases; Vitamin B Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition

Study Officials

• Monica Lakhanpaul

  University College, London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Monica Lakhanpaul

CONTACT

+442079052259; m.lakhanpaul@ucl.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double-blinded
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A total of 720 recruited mothers across India and Nepal will be randomly allocated to 2 equal groups (360 each). Group 1 (Intervention) will receive 250μg of vitamin B12 supplementation delivered daily to the mother from 12 weeks gestation up to 6 months post-partum. Group 2 (Control) will receive 50μg of vitamin B12 supplementation delivered daily to the mother from 12 weeks gestation up to 6 months post-partum.

Study Record Dates

• First Submitted: December 17, 2018
• First Posted: December 20, 2018
• Study Start: April 27, 2019
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: July 22, 2019

Record last verified: 2019-07

Locations

IN (1); NE (1)