Maternal vitamin B₁₂, folate during pregnancy and neurocognitive outcomes in young adults of the Pune Maternal Nutrition Study (PMNS) prospective birth cohort: study protocol

Introduction: The Developmental Origins of Health and Disease (DOHaD) hypothesis proposes that intrauterine and early life exposures significantly influence fetal development and risk for disease in later life. Evidence from prospective birth cohorts suggests a role for maternal B₁₂ and folate in influencing neurocognitive outcomes in the offspring. In the Indian setting, B₁₂ deficiency is common during the pregnancy while rates of folate deficiency are lower. The long-term influences of maternal nutrition during the pregnancy on adult neurocognitive outcomes have not been examined. The Pune Maternal Nutrition Study (PMNS) is a preconceptional birth cohort into its 24th year and is considered a unique resource to study the DOHaD hypothesis. We found an association between maternal B₁₂ status in pregnancy and child's neurocognitive status at 9 years of age. We now plan to assess neurocognitive function and MRI measurements of brain structural-functional connectivity at young adult age to study its association with maternal nutritional exposures during the pregnancy.

Methods and analysis: As part of ongoing prospective follow-up in young adults of the PMNS at the Diabetes Unit, KEM Hospital Research Center, Pune India, the following measurements will be done: neurocognitive performance (Standardised Tests of Intelligence, Verbal and Visual Memory, Attention and Executive Functions), temperament (Adult Temperament Questionnaire), psychopathology (Brief Symptom Inventory and Clinical Interview on Mini Neuropsychiatric Interview 7.0). Brain MRI for structural T1, resting-state functional connectivity and diffusion tensor imaging will be performed on a subset of the cohort (selected based on exposure to a lower or higher maternal B₁₂ status at 18 weeks of pregnancy).

Ethics and dissemination: The study is approved by Institutional ethics committee of KEM Hospital Research Center, Pune. The results will be shared at national and international scientific conferences and published in peer-reviewed scientific journals.

Trial registration number: NCT03096028.