Impact of vitamin B12 on neurodevelopment and cognitive function from early life into school age.

Lack of vitamin B12 and other vitamins and minerals in young children can impair cognitive development and is more common than many are aware of. In this project, scientists from India, Tanzania, USA, and Norway have estimated the long-term impact of vitamin B12 nutrition during pregnancy and in infancy on neurodevelopment and growth. The data we have collected is from long-term follow-ups of experimental studies in Tanzania, and North and South India. In these studies, we gathered information on several factors that can influence early child development. We also measured various neurodevelopmental domains using state-of-the-art neuropsychological tests. The different instruments were translated, adapted, and validated at the individual sites. We found that the contribution of vitamin B12 nutrition in early life on neurodevelopment and child growth is limited from a public health perspective. There may, however, be several subpopulations that are severely affected by inadequate vitamin B12 status and that face detrimental consequences because of this. We did not specifically target such groups but focused on populations that were characterized by sub-optimal status. Our studies have also quantified the importance of other critical factors related to development during early life, such as responsive stimulation, infections, and other nutrients. The results from these analyses show that efforts to optimize children's cognitive potential need a broad approach. Our collaborative activities have also expanded to include scientists and students from other countries such as Nepal and Pakistan. Thus, our project has not only provided novel insights into the role of vitamin B12 on child development. It has also consolidated an international interdisciplinary network of scientists working on improving early child development in marginalized populations. Data from this project is being used in two Norwegian Ph.D. projects: Ranadip Chowdhry from India submits his thesis in February 2020. He is funded from the partner institution in India and his thesis is based on data from the Indian component of the project. Beate Solvik, who is a Ph.D. student funded by the Innlandet Hospital Trust, will visit Harvard School of Public health for 6 months. From this partner institution, she will work on data from the Tanzanian site (with the partner institution Muhimbili University of Health and Allied Sciences). Other collaborations and research questions from this project will continue into other, new projects. For example, The South Eastern Health Authority recently granted a project on vitamin B12 supplementation in pregnant women. Also, in collaboration with the Society for Applied Studies in New Delhi, we have started randomized controlled trials on nutrition and early child development. And we are about to submit new grant proposals with our partners from the Harvard School of Public Health (USA) and St Johns Research Institute (India).

Results i. Increased understanding of the role of vitamin B12 nutrition in early life. This information is crucial to inform policy. ii. Increased awareness regarding factors that may impair early child development in marginalized populations. Platforms for ongoing and future research i. Enhanced the expertise of the different multidisciplinary trial teams: a. Translating and adapting neuropsychological tests b. Analysing and interpretation of neuropsychological tests ii. Strengthened clinical research capacity in the participating institutions by training future clinical scientists and public health researchers iii. Conducted focused science meetings that can be used as a tool for developing new research iv. Foster collaborations with other groups nationally and globally to augment our skills and the ongoing research v. Developed a platform for sub-studies to answer additional questions within these RCT cohorts.

As many as 200 million children under the age of five from developing countries may fail to reach their full cognitive potential partly because of poor nutrition during pregnancy and the first 2 years of life. Many children in South Asia and Africa suffer from subtle deficiencies of several nutrients including vitamin B12, which is important for brain development. If improving vitamin B12 status in early life has an impact on brain function later in life, learning and work performance may improve, which c an lift individuals from the vicious cycle of poverty and malnutrition, and potentially lead to sustainable improvements in health and equity. We have studied the effects of malnutrition and micronutrient deficiencies on child health and development for m any years. In the studies described in this proposal, we will follow up findings from our previous studies and further investigate the role of poor nutrition in general and poor vitamin B12 status in particular on neurodevelopment. The current proposal ta kes advantage of an exceptional situation as we are able to build on strong existing partnerships and ongoing and recently completed cohort studies and randomized-placebo controlled trials (RCT) with scientists from Tanzania, India, Norway and USA. These studies enables us to fexplore the long term effects of malnutrition, micronutrient deficiencies and vitamin B12 supplementation on neurodevelopmental outcomes. The project fits well within the aims of the GLOBVAC call with potential for sustainable impro vements for the most vulnerable, strong national and international partnerships and the possibility for significant public health implications.