Clinical trial NCT04083560: A Comparison of Two Different Doses of Maternal B12 Supplementation in Improving Infant B12 Deficiency and Neurodevelopment
Official title: A Comparison of Two Different Doses of Maternal B12 Supplementation in Improving Infant B12 Deficiency and Neurodevelopment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Vitamin B 12 Deficiency
Lead sponsor: Sitaram Bhartia Institute of Science and Research
Sponsor class: OTHER
Collaborators: name: Public Health Foundation of India
name: Paropakar Matenity and Women's Hospital, Kathmandu, Nepal
name: University College, London
First posted: 2019-09-10
Enrollment: 708
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Infant neurodevelopment
timeFrame: 9 Month of infant age
Secondary outcomes:
measure: Biochemical B12 status of mother
timeFrame: At recruitment
measure: Biochemical B12 status of infant
timeFrame: 9 months of infant age
Other outcomes:
measure: Mean Haemoglobin of infants
timeFrame: 9 months of infant age
measure: Infant weight
timeFrame: 9 months of infant age
measure: Infant length
timeFrame: 9 months of infant age
measure: Infant head circumference
timeFrame: 9 months of infant age
Locations:
city: New Delhi
country: India
facility: Sitaram Bhartia Institute of Science and Research
state: Delhi
city: Kathmandu
country: Nepal
facility: Rajendra Pant
Study officials:
References:
citation: 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.