Birth Outcomes, Dietary Intake Assessment, Dietary Quality, Homocysteine, Infant Neurodevelopment, Methylation, Nutrition, Pregnancy, Trimethylamine N-oxide (TMAO)
Conditions
Brief summary
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.
Detailed description
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.
Interventions
None listed
Sponsors
Far Eastern Memorial Hospital
Fu Jen Catholic University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
0 Days to 45 Years
Healthy volunteers
Yes
Inclusion criteria
for Pregnant Women * Aged 20-45 years * Singleton pregnancy * Receiving routine prenatal care at the study site and planning to deliver at Far Eastern Memorial Hospital
Exclusion criteria
for Pregnant Women * Diagnosed with major chronic diseases, including renal disease (defined as chronic kidney disease stage 3 or above or history of renal transplantation), liver disease (defined as liver cirrhosis or history of liver transplantation), or malignancy * Alcohol consumption during pregnancy * Diagnosed with eating disorders or psychiatric conditions that may impair the assessment of nutritional status Inclusion Criteria for Newborns ● Newborns delivered by mothers who participate in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ｍaternal methyl-nutrient and other nutrition status | From enrollment to delivery (approximately 9 months) | 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 |
| Birth anthropometric measurements of the newborn | At birth | 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). |
| Infant neurodevelopmental outcomes | At 6, 12, and 24 months of age | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma homocysteine concentration | During pregnancy (each trimester) and at birth (cord blood) | Plasma homocysteine levels (µmol/L) will be measured using standard enzymatic assays. |
| Plasma trimethylamine N-oxide (TMAO) concentration | During pregnancy (each trimester) and at birth (cord blood) | Plasma TMAO levels (ng/mL, µmol/L)will be measured using enzyme-linked immunosorbent assay (ELISA) kit. |
| Global DNA methylation levels | During pregnancy (each trimester) and at birth (cord blood) | DNA methylation status (%) will be assessed using LINE-1 methylation analysis |
| Gut microbiota composition | During pregnancy (each trimester), at birth (meconium), and at 4, 6, 12, and 24 months of age | Gut microbiota composition will be analyzed using 16S rRNA gene sequencing and reported as relative abundance and diversity indices |
| Genetic polymorphisms related to methyl metabolism | During pregnancy | Genetic polymorphisms (e.g., MTHFR, PEMT) will be assessed using genotyping methods and reported as genotype frequencies (%) |
| Expression levels of neurodevelopment-related genes | During pregnancy (each trimester) and at birth (cord blood) | Gene expression levels will be measured using RT-qPCR and report as relative expression levels |
Countries
Taiwan
Contacts
CONTACTCHI MAN KUOK
Outcome results
None listed