Maternal Methyl-Nutrient Status and Infant Neurodevelopment Study

Maternal Methyl-Nutrient Status During Pregnancy and Its Association With Infant Neurodevelopment: Exploring Potential Mechanisms

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Pregnancy; Nutrition; Methylation; Birth Outcomes; Homocysteine; Trimethylamine N-oxide (TMAO); Dietary Intake Assessment; Dietary Quality; Infant Neurodevelopment

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.

• Study Type: Observational
• Enrollment (Estimated): 240

Contacts and Locations

• Study Contact: Name: CHI MAN KUOK; Phone Number: (+886) 952289592; Email: carmentoe@hotmail.com

Study Locations

• Taiwan
  • New Taipei City, Taiwan
    • Far Eastern Memorial Hospital
    • Contact: Far Eastern Memorial Hospital; Phone Number: +886 2 8966 7000

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

120 pregnant women and their 120 newborns/infants

Description

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

Exclusion Criteria for Newborns

• Diagnosed with congenital anomalies, epilepsy, or severe brain injury
• Inability to complete neurodevelopmental assessments at 6 months, 1 year, and 2 years of age at the study site
• Infants whose mothers are diagnosed with eating disorders or psychiatric conditions that may impair the assessment of nutritional status

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
FEMHPregnancy cohort; Throughout pregnancy, delivery, and infant follow-up at FEMH

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ｍaternal 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	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).	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	At 6, 12, and 24 months of age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma homocysteine concentration	Plasma homocysteine levels (µmol/L) will be measured using standard enzymatic assays.	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.	During pregnancy (each trimester) and at birth (cord blood)
Global DNA methylation levels	DNA methylation status (%) will be assessed using LINE-1 methylation analysis	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	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 (%)	During pregnancy
Expression levels of neurodevelopment-related genes	Gene expression levels will be measured using RT-qPCR and report as relative expression levels	During pregnancy (each trimester) and at birth (cord blood)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dietary intake and diet quality	Dietary intake will be assessed using a Food Frequency Questionnaire (FFQ) and 3-day dietary records, including assessment of nutrient intake (grams/day ,mg/day)and dietary patterns. Diet quality will be derived from these data	From enrollment through pregnancy to 4 months postpartum

Collaborators and Investigators

• Sponsor: Far Eastern Memorial Hospital
• Collaborators: Fu Jen Catholic University

Study record dates

Study Major Dates

• Study Start (Estimated): May 6, 2026
• Primary Completion (Estimated): January 18, 2029
• Study Completion (Estimated): January 18, 2029

Study Registration Dates

• First Submitted: April 20, 2026
• First Submitted That Met QC Criteria: April 28, 2026
• First Posted (Actual): May 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: 114224-F

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No