A Comparison of Two Different Doses of Maternal B12 Supplementation in Improving Infant B12 Deficiency and Neurodevelopment (MATCOBIND)

Supplementation with Iron and folate have been part of a worldwide strategy targeting anaemia and neural tube defects for many years. However, vitamin B12 deficiency has received much less attention. High prevalence of deficiency in mothers in the antenatal period and in their infants, has been documented. Multiple case series document the neurological consequences of severe deficiency and their reversal with B-12. Trials on the subject are limited and those available have either used an ineffective dose or for a short duration.

Therefore, we propose this randomised controlled trial to compare the efficacy of two different doses (pharmacological and preventive) of maternal Vitamin B-12 supplementation in improving infant B12 deficiency and neurodevelopment. We propose to undertake a multi-centric trial in India and Nepal given the high prevalence of deficiency reported from these countries and to allow a wider socio-demographic spectrum (Pay-for-service hospital catering to middle income populace from India and a free-care public hospital catering to lower income groups from Nepal). We will recruit 720 vegetarian, pregnant women from the antenatal clinics of the Indian and Nepalese centres at their first antenatal visit. Elderly primi mothers, taking B12 supplementation, multiple gestations, chronic medical conditions, anticipating moving out of the city, treated for infertility or with known psychological illnesses will be excluded. In Stage 1, recruited mothers will be randomized into 2 equal groups (360 each). Group 1-Daily 250 μg Vitamin B12 supplementation. Group 2-Daily 50 μg Vitamin B12 supplementation. B-12 will be started in 1st trimester and continue up to 6 months post-partum. In Stage 2, the birth and post-delivery course of the new-born will be monitored and documented for any morbidity. At 9 months, the neurodevelopmental, complementary feeding and home environment will be assessed and infant B12 status will be determined.

The two groups will be compared for the primary (neurodevelopment) and secondary outcomes (biochemical parameters in mother and infant). The results of this study will be used to generate scientific evidence on whether B-12 should be supplemented in vegetarian pregnant women with a view to preventing B-12 deficiency and its neurodevelopmental consequences in the infant.

Study Overview

• Status: Completed
• Conditions: Vitamin B 12 Deficiency
• Intervention / Treatment: Drug: Vit B12

• Study Type: Interventional
• Enrollment (Actual): 708
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110016
      • Sitaram Bhartia Institute of Science and Research
• Nepal
  • Kathmandu, Nepal
    • Rajendra Pant

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• <12 weeks gestation

Vegetarian mothers

Exclusion Criteria:

1. Mothers already on B12 supplementation
2. 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, IUGR and other neonatal morbidities which could influence neurodevelopment)
3. Women who anticipate moving out of the city before/ after delivery
4. Women treated for infertility
5. Women with known psychological illnesses including depression

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intervention group; Group A Intervention: 360 pregnant women will receive 250 mcg of B-12 daily orally from 1st trimester to 6 months postpartum	Drug: Vit B12; Vitamin B12 250mcg
ACTIVE_COMPARATOR: Control group; Group B- Control: 360 pregnant women will receive 50 mcg of B-12 daily orally from 1st trimester to 6 months post partum	Drug: Vit B12; Vitamin B12 250mcg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infant neurodevelopment	Developmental Assessment Scale for Indian Infant (modified Bayleys scale) measured as average of motor and mental scores	9 Month of infant age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical B12 status of mother	Change in B12 status of mother between first and third trimester	At recruitment
Biochemical B12 status of infant	Biochemical B12 status of infant at nine months postpartum	9 months of infant age

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Haemoglobin of infants	Haemoglobin of infants in grams per deciliter	9 months of infant age
Infant weight	Infant weight in kilograms	9 months of infant age
Infant length	Infant Length in cms	9 months of infant age
Infant head circumference	Infant Head circumference in cms	9 months of infant age

Collaborators and Investigators

• Sponsor: Sitaram Bhartia Institute of Science and Research
• Collaborators: University College, London; Public Health Foundation of India; Paropakar Matenity and Women's Hospital, Kathmandu, Nepal

Publications and helpful links

General Publications

• Nagpal J, Mathur MR, Rawat S, Nagrath D, Lee C, Singhal A, Heys M, Cortina Borja M, Augustin K, Gautam J, Pant R, Swabey L, Lakhanpaul M. Efficacy of maternal B12 supplementation in vegetarian women for improving infant neurodevelopment: protocol for the MATCOBIND multicentre, double-blind, randomised controlled trial. BMJ Open. 2020 May 25;10(5):e034987. doi: 10.1136/bmjopen-2019-034987.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 26, 2018
• Primary Completion (ACTUAL): September 25, 2022
• Study Completion (ACTUAL): September 25, 2022

Study Registration Dates

• First Submitted: September 2, 2019
• First Submitted That Met QC Criteria: September 5, 2019
• First Posted (ACTUAL): September 10, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 26, 2022
• Last Update Submitted That Met QC Criteria: October 24, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Vitamin B Deficiency; Vitamin B 12 Deficiency; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Hematinics; Vitamin B 12; Hydroxocobalamin
• Other Study ID Numbers: MATCOBIND 2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No