AUTHOR=D'souza Naomi , Behere Rishikesh V. , Patni Bindu , Deshpande Madhavi , Bhat Dattatray , Bhalerao Aboli , Sonawane Swapnali , Shah Rohan , Ladkat Rasika , Yajnik Pallavi , Bandyopadhyay Souvik K. , Kumaran Kalyanaraman , Fall Caroline , Yajnik Chittaranjan S. 

TITLE=Pre-conceptional Maternal Vitamin B12 Supplementation Improves Offspring Neurodevelopment at 2 Years of Age: PRIYA Trial

JOURNAL=Frontiers in Pediatrics

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2021.755977

DOI=10.3389/fped.2021.755977

ISSN=2296-2360

ABSTRACT=<p><bold>Background:</bold> The first thousand days window does not include the pre-conceptional period. Maternal pre-conceptional health has a profound influence on early embryonic development (implantation, gastrulation, placentation etc). Nutrition provided by B-complex vitamins is important for fetal growth, especially neural development. We report effects of a maternal pre-conceptional vitamin B12 and multi micronutrient (MMN) supplementation on offspring neurodevelopmental performance.</p><p><bold>Methods:</bold> In the Pune Rural Intervention in Young Adolescents trial (PRIYA), adolescents (<italic>N</italic> = 557, 266 females) were provided with vitamin B12 (2 μg/day) with or without multiple micronutrients, or a placebo, from preconception until delivery. All groups received mandatory iron and folic acid. We used the Bayley's Scale of Infant Development (BSID-III) at 24–42 months of age to investigate effects on offspring neurodevelopment.</p><p><bold>Results:</bold> Participants had similar baseline B12 levels. The levels improved in the B12 supplemented groups during pre-conception and pregnancy (28 weeks gestation), and were reflected in higher cord blood holotranscobalamin (holo-TC) levels compared to the placebo group. Neurodevelopmental outcomes in the B12 alone group (<italic>n</italic> = 21) were better than the placebo (<italic>n</italic> = 27) in cognition (<italic>p</italic> = 0.044) and language (<italic>p</italic> = 0.020) domains (adjusted for maternal baseline B12 levels). There was no difference in neurodevelopmental outcomes between the B12 + MMN (<italic>n</italic> = 26) and placebo group. Cord blood Brain Derived Neurotrophic Factor (BDNF) levels were highest in the B12 alone group, though not significant.</p><p><bold>Conclusion:</bold> Pre-conceptional vitamin B12 supplementation improved maternal B12 status and offspring neurodevelopment at 2 years of age. The usefulness of cord BDNF as a marker of brain development needs further investigation. Our results highlight the importance of intervening during pre-conception.</p>