Maternal Methyl-Nutrient Status and Infant Neurodevelopment Study

Evidence regarding the association between maternal methyl-nutrient status during pregnancy and offspring neurodevelopment remains inconsistent. To address this gap, the present study is designed to comprehensively evaluate maternal methyl-nutrient status-specifically dietary intake and concentrations of choline, folate, betaine, and vitamin B12-at different gestational stages, and to examine their associations with infant and early childhood neurodevelopmental outcomes. This prospective mother-child cohort will recruit pregnant women aged 20-45 years from the Department of Obstetrics and Gynecology at Far Eastern Memorial Hospital who are receiving routine prenatal care and intend to deliver at the study site. At each trimester, maternal dietary intake will be assessed using a semi-quantitative food frequency questionnaire and three-day dietary records, accompanied by the collection of blood and stool specimens. These samples will be analyzed for metabolic biomarkers (e.g., homocysteine, trimethylamine N-oxide [TMAO], and gut microbiota composition). Furthermore, genetic polymorphisms in one-carbon metabolism-related genes (e.g., MTHFR, PEMT), maternal DNA methylation status, and the expression of neurodevelopment-related genes will be measured to investigate potential mechanistic pathways. Infant outcomes will include neonatal anthropometrics (gestational age, birth weight, length, and head circumference) and longitudinal neurodevelopmental assessments at 6 months, 12 months, and 24 months using the Bayley Scales of Infant and Toddler Development. In addition, meconium and cord blood samples at birth and stool samples during infancy will be collected for analysis. By integrating multi-dimensional data on maternal nutrition, genetics, metabolism, and the gut microbiome, this study seeks to construct a comprehensive model linking maternal methyl-nutrient status during pregnancy with offspring neurodevelopment. The findings are expected to inform evidence-based recommendations for optimal methyl-nutrient intake during pregnancy in Taiwan, thereby contributing to prenatal nutrition guidelines and early preventive strategies against developmental delays.