A randomised controlled trial to compare two different doses of maternal B12 supplementation in improving infant B12 deficiency and neurodevelopment

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Vitamin B12, also called cobalamin, is a water-soluble vitamin that has a key role in the normal functioning of the brain and nervous system. Up to 74% women are reported deficient during antenatal period in some populations. Deficiency of B12 in newborns is problematic given the role Vitamin B12 plays in neuronal health (brain and nerve cells health) and in the development of foetal and infant brain. We propose this research to compare two different doses (a treatment dose in comparison with a dose known to just prevent further deficiency) of maternal Vitamin B12 supplementation in terms of their effectiveness in removing infant B12 deficiency and neurodevelopment.We propose to undertake a multi-centric trial in India and Nepal as these are countries where high incidence of deficiency is reported. We will recruit 720 pregnant women from the antenatal clinics of the department of Gynaecology and Obstetrics at Sitaram Bhartia institute of Science and Research, New Delhi and Paropakar Indrarajayalaxmi Maternity Hospital, Kathmandu, Nepal. The subjects will be recruited at their first presentation to the antenatal clinic and should be vegetarian as they are at high-risk of B12 deficiency. Mothers who are >35 years of age, are already on B12 supplementation, have multiple gestation, chronic medical conditions, known psychological illnesses or those who anticipate moving out of the city before/after delivery will be excluded from the study. Recruited mothers will be randomly allocated to 2 equal groups (360 each). Group 1 (Intervention) will receive daily 250 micrograms Vitamin B12 supplementation to the mother through pregnancy and up to 6 months post-partum. Group 2 (Control) will receive 50 micrograms Vitamin B12 supplementation to the mother through pregnancy and up to 6 months post-partum. The profile information of the mother including age, height, weight, ethnicity, education, socioeconomic status, maternal dietary assessment (by Food Frequency Questionnaire), intake of any supplements (iron, folate, Vitamin-D) etc. will be recorded. Vitamin B12 dosage will be provided at enrolment and then monthly to mothers. Mother's blood levels for Vitamin B12 status and other deficiencies will be drawn. Sampling for these biochemical tests will be combined with other routine tests at these stages to avoid any additional discomfort for the mother. At childbirth, the delivery and post-delivery course of the new-born will be monitored and documented for any problems potentially influencing neurodevelopment. After discharge, all neonates will be routinely followed with preventive and vaccination care as per standard protocols. During routine visits, anthropometric measurements including weight, length and head circumference will be recorded and signs of micronutrient deficiency (especially anaemia and rickets) will be noted. Any illnesses suffered by the child in the intervening period will be recorded. Supplementation of the mother in both groups will be stopped at 6 months after childbirth followed by evaluation at 9 months. The neurodevelopmental assessment and home environment assessment will be done by a developmental therapist and complementary feeding assessment by a nutritionist. Along with routine sampling for Hb screening at 9 months, infant B12 levels status will be determined. The assessment of the infant neurodevelopment scores, the biochemical measures of B12 status of the infant and those of the mother will then be compared between the two groups to see if the neurodevelopment and/or B12 status in the group receiving the higher dose (250 mcg) is better and safe. A positive or a negative result will generate scientific evidence on whether B12 should be supplemented in vegetarian pregnant women with a view to preventing B12 deficiency and its neurodevelopmental consequences in the infant. This will also allow the development of policies and frameworks for routine/wider usage of this supplement in high-risk populations