This prospective cohort study examines the relationship between maternal methyl-nutrient status during pregnancy and offspring neurodevelopment. It integrates maternal dietary, biomarker, genetic, and microbiome data and follows children up to 24 months.
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.
Study Type
OBSERVATIONAL
Enrollment
240
Far Eastern Memorial Hospital
New Taipei City, Taiwan
NOT_YET_RECRUITINGFar Eastern Memorial Hospital
New Taipei City, Taiwan
RECRUITINGMaternal methyl-nutrient and other nutrition status
Maternal methyl-nutrient status will be assessed using the following measurements: * Blood biomarkers: plasma or serum concentrations of choline(µmol/L), betaine(µmol/L), RBC and serum folate(ng/mL), vitamin B12 (pg/mL) measured using by standard laboratory assays * Dietary intake: assessed using a validated Food Frequency Questionnaire (FFQ) and 3-day dietary records
Time frame: From enrollment to delivery (approximately 9 months)
Birth anthropometric measurements of the newborn
This outcome will be assessed using medical records, including birth weight (grams), birth length (centimeters) , birth head circumference (centimeters), and gestational age at birth (weeks).
Time frame: At birth
Infant neurodevelopmental outcomes
Infant neurodevelopment will be assessed using the Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-IV), including composite scores for cognitive, language, motor and social-emotional domains
Time frame: At 6, 12, and 24 months of age
Plasma homocysteine concentration
Plasma homocysteine levels (µmol/L) will be measured using standard enzymatic assays.
Time frame: During pregnancy (each trimester) and at birth (cord blood)
Plasma trimethylamine N-oxide (TMAO) concentration
Plasma TMAO levels (ng/mL, µmol/L)will be measured using enzyme-linked immunosorbent assay (ELISA) kit.
Time frame: During pregnancy (each trimester) and at birth (cord blood)
Global DNA methylation levels
DNA methylation status (%) will be assessed using LINE-1 methylation analysis
Time frame: During pregnancy (each trimester) and at birth (cord blood)
Gut microbiota composition
Gut microbiota composition will be analyzed using 16S rRNA gene sequencing and reported as relative abundance and diversity indices
Time frame: During pregnancy (each trimester), at birth (meconium), and at 4, 6, 12, and 24 months of age
Genetic polymorphisms related to methyl metabolism
Genetic polymorphisms (e.g., MTHFR, PEMT) will be assessed using genotyping methods and reported as genotype frequencies (%)
Time frame: During pregnancy
Expression levels of neurodevelopment-related genes
Gene expression levels will be measured using RT-qPCR and report as relative expression levels
Time frame: During pregnancy (each trimester) and at birth (cord blood)
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