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

Study Overview
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Brief Summary
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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.

Official Title
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A Comparison of Two Different Doses of Maternal B12 Supplementation in Improving Infant B12 Deficiency and Neurodevelopment

Conditions
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Vitamin B 12 Deficiency

Intervention / Treatment
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* Drug: Vit B12


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: <12 weeks gestation Vegetarian mothers Exclusion Criteria: Mothers already on B12 supplementation 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) Women who anticipate moving out of the city before/ after delivery Women treated for infertility Women with known psychological illnesses including depression

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>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<br>* Vitamin B12 250mcg<br>|
| Active Comparator: Control group<br>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<br>* Vitamin B12 250mcg<br>|

What is the study measuring?
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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 |