Related Experiment Video
Updated: Dec 10, 2025
Rapid Detection of Neurodevelopmental Phenotypes in Human Neural Precursor Cells NPCs
Published on: March 2, 2018
A prospective birth cohort study on cord blood folate subtypes and risk of autism spectrum disorder
Ramkripa Raghavan1, Jacob Selhub2, Ligi Paul2
1Center on Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Insights
High levels of unmetabolized folic acid (UMFA) in cord blood were linked to increased autism spectrum disorder (ASD) risk, particularly in Black children. Further research is needed to understand UMFA
Area of Science:
- Environmental Health
- Neurodevelopmental Disorders
- Nutritional Biochemistry
Background:
- Previous research indicated a link between high maternal plasma folate and increased autism spectrum disorder (ASD) risk.
- This study investigates specific folate forms in cord blood and their association with ASD risk.
Purpose of the Study:
- To assess the association between cord blood unmetabolized folic acid (UMFA), 5-methyl tetrahydrofolate (THF), and total folate with ASD risk.
- To explore potential modifying factors like DHFR genotype and cord plasma creatinine on the UMFA-ASD association.
- To examine prenatal factors associated with cord UMFA concentrations.
Main Methods:
- The Boston Birth Cohort (BBC) included 567 children, prospectively followed from birth.
- ASD diagnosis was determined using International Classification of Diseases (ICD)-9 and ICD-10 codes.
- Cord blood folate levels (UMFA, 5-methyl THF, total folate) were measured and associated with ASD risk, with subgroup analyses by race/ethnicity and adjustments for creatinine and genotype.
Main Results:
- Higher cord blood UMFA concentrations were associated with increased ASD risk (aORquartile4: 2.26).
- This association was significant in Black children (aORquartile4: 9.85) and influenced by race/ethnicity (P=0.007).
- Cord plasma creatinine showed a slight attenuating effect on the UMFA-ASD association in Black children (P=0.05). No significant associations were found for 5-methyl THF, total folate, or DHFR genotype with ASD risk.
Conclusions:
- Elevated cord blood UMFA, not 5-methyl THF or total folate, is associated with higher ASD risk in Black children.
- The findings highlight the need for further investigation into the role and sources of UMFA in neurodevelopmental outcomes.
- This study underscores the complexity of folate metabolism and its potential impact on child neurodevelopment.
Background:
We previously reported that extremely high concentrations of maternal plasma folate were associated with increased risk of autism spectrum disorder (ASD) in children. This study explored whether specific types of folate in cord blood have differential association with ASD.
Objectives:
In the Boston Birth Cohort (BBC), we assessed the association between cord blood unmetabolized folic acid (UMFA), 5-methyl tetrahydrofolate (THF), and total folate and a child's ASD risk. In a subset, we explored whether the association between UMFA and ASD risk can be affected by the dihydrofolate reductase (DHFR) genotype and cord plasma creatinine. We also examined prenatal correlates of cord UMFA concentrations.
Methods:
This report included 567 BBC children (92 ASD, 475 neurotypical), who were recruited at birth and prospectively followed at the Boston Medical Center. ASD was defined from International Classification of Diseases (ICD)-9 and ICD-10 codes documented in electronic medical records.
Results:
Children with cord UMFA in the highest, versus lowest quartile, had a greater ASD risk (adjusted OR, aORquartile4: 2.26; 95% CI: 1.08, 4.75). When stratified by race/ethnicity, the association was limited to 311 (45 ASD) Black children (aORquartile4: 9.85; 95% CI: 2.53, 38.31); a test of interaction between race/ethnicity and cord UMFA concentrations was significant (P = 0.007). The UMFA-ASD association in Black children slightly attenuated after adjusting for cord plasma creatinine (P = 0.05). There was no significant association between cord 5-methyl THF, total folate, DHFR genotype, and ASD risk. Cord total folate and maternal supplement intake during second trimester were associated with higher cord UMFA.
Conclusions:
Higher concentrations of cord UMFA, but not 5-methyl THF or total folate, were associated with a greater risk of ASD in Black children. This study in a preterm-birth-enriched cohort raises more questions than it could answer and underscores the need for additional investigations on the sources and role of cord UMFA in children's neurodevelopmental outcomes and underlying mechanisms.
More Related Videos
05:44Author Spotlight: Collecting the Brain and Serum from the Same Mice Fetus to Study Brain Tumor Development
Published on: May 17, 2024
11:14A Novel Experimental and Analytical Approach to the Multimodal Neural Decoding of Intent During Social Interaction in Freely-behaving Human Infants
Published on: October 4, 2015
Related Concept Videos
01:19Autism Spectrum Disorder
These core symptoms manifest differently among individuals, ranging from mild to severe. The disorder's complexity extends beyond its clinical presentation, encompassing a diverse range of biological, cognitive, and sociocultural influences.
01:35Pedigree Analysis