Abstract
Background: 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.Methods: In the Pune Rural Intervention in Young Adolescents trial (PRIYA), adolescents (N = 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.Results: 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 (n = 21) were better than the placebo (n = 27) in cognition (p = 0.044) and language (p = 0.020) domains (adjusted for maternal baseline B12 levels). There was no difference in neurodevelopmental outcomes between the B12 + MMN (n = 26) and placebo group. Cord blood Brain Derived Neurotrophic Factor (BDNF) levels were highest in the B12 alone group, though not significant.Conclusion: 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.
Highlights
The developing fetus is dependent on its mother for its nutrition
We found that pre-conceptional maternal supplementation with a near RDA dose (2 μg/day) of vitamin B12 exposed their offspring to higher vitamin B12 status peri-conceptionally and during pregnancy
This may be due to a lack of significant variation in maternal vitamin B12 status, given the low prevalence of vitamin B12 deficiency in their population [34]
Summary
Maternal nutrition before and during pregnancy affects fetal growth and development, and maternal malnutrition may predispose the offspring to undesirable outcomes in later life Maternal nutritional factors (both macro and micronutrients) influence neurodevelopmental processes in utero, such as neurogenesis, myelination, synaptogenesis, and cortical brain growth [3].Vitamins B12 and folate are of special interest due to their role in the one carbon metabolism pathway. This represents a series of biochemical reactions involving the methionine and folate cycles. We report effects of a maternal pre-conceptional vitamin B12 and multi micronutrient (MMN) supplementation on offspring neurodevelopmental performance
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