Blood sample analysis showed that, two to five years after they gave birth, mothers of children with autism spectrum disorder (ASD) had several significantly different metabolite levels compared to mothers of typically developing children.
That’s according to new research recently published in BMC Pediatrics by a multidisciplinary team from Rensselaer Polytechnic Institute, Arizona State University, and the Mayo Clinic.
Researchers analyzed blood samples from 30 mothers whose young children had been diagnosed with ASD and 29 mothers of typically developing children. At the time that the samples were taken, the women’s children were between 2 and 5 years old. The team found differences in several metabolite levels between the two groups of mothers.
When examined further, researchers were able to group those differences into five subgroups of correlated metabolites. While the samples analyzed were taken several years after pregnancy, these research findings raise the question of whether or not the differences in metabolites may have been present during pregnancy as well, suggesting further research is needed in this area.
Many of the variances, the researchers said, were linked to low levels of folate, vitamin B12, and carnitine-conjugated molecules. Carnitine can be produced by the body and can come from meat sources like pork or beef, but there wasn’t a correlation between mothers who ate more meat and mothers who had higher levels of carnitine.
According to Juergen Hahn, the head of the Department of Biomedical Engineering at Rensselaer and co-author on this paper, this finding suggests that the differences may be related to how carnitine is metabolized in some mothers’ bodies.
“We had multiple metabolites that were associated with the carnitine metabolism,” said Hahn, who is also a member of the Center for Biotechnology and Interdisciplinary Studies at Rensselaer.
“This suggests that carnitine and mothers is something that should be looked at.”
The team’s big data approach proved to be highly accurate in using a blood sample analysis to predict which group a mother belonged to, which suggests that the development of a blood test to screen for mothers who are at a higher risk of having a child with ASD may be possible.
“A blood test would not be able to tell if your child has autism or not, but it could tell if you’re at a higher risk,” Hahn said. “And the classification of higher risk, in this case, can actually be significant.”
“Based on these results, we are now conducting a new study of stored blood samples collected during pregnancy, to determine if those metabolites are also different during pregnancy,” said James Adams, a President’s Professor in the School of Engineering of Matter, Transport and Energy, and director of the Autism/Asperger’s Research Program, both at Arizona State University. Adams co-authored this paper with Hahn.
This research builds upon Hahn’s other work. He previously discovered patterns with certain metabolites in the blood of children with autism that can be used to successfully predict diagnosis.
He has used this same method to investigate a mother’s risk for having a child with ASD. He and Adams have also done similar work studying children with autism who have chronic gastrointestinal issues.
Autism spectrum disorder (ASD) involves a combination of abnormal social communication, stereotyped behaviors, and restricted interests [1]. ASD is assumed to be caused by complex interactions between genetic and environmental factors, both of which can affect metabolism.
Previous studies have revealed significant abnormalities in the folate-one carbon metabolism and the transsulfuration pathways of children with ASD [2–5] and their mothers [6–8], resulting in decreased methylation capability, decreased glutathione levels, and increased oxidative stress.
Furthermore, the presence of mutations in the MTHFR gene (A1298C and C667T) was found to be associated with increased risk of ASD [9].
The MTHFR gene makes an enzyme, Methylenetetrahydrofolate reductase, which converts 5,10-methylenetetrahydrofolate, a form of folate, to 5-methyltetrahydrofolate, a different form of folate.
This latter form of folate is crucial in the conversion of homocysteine to methionine [10]. Additionally, levels of prenatal vitamins taken during pregnancy that include B12 and folate are associated with a decreased ASD risk [11], suggesting an association of metabolite levels of the folate one-carbon metabolism (FOCM) and the transsulfuration (TS) pathways with ASD.
Studies have also found that too much folic acid supplementation can potentially lead to an increased risk of ASD [11, 12]. One of these studies suggests that folic acid and B12 supplements are associated with ASD risk by a u-shaped curve, showing that too little and too much folic acid or B12 supplementation can both lead to an increased risk of ASD [11].
Other studies found that maternal gene variants in the one-carbon metabolism pathway were associated with increased ASD risk when there was no or only low levels of periconceptional prenatal vitamin intake [13, 14].
Additional metabolic differences may also be present in mothers of children with ASD, but there has been relatively little investigation of their metabolic state. A more comprehensive understanding of metabolites and metabolic pathways of mothers of children with ASD may lead to a better understanding of the etiology of ASD and provide some insights for evaluating pre-conception risk and/or risk during pregnancy.
For example, currently, the general risk of having a child with ASD in the US is approximately 1.9% [15], however, the recurrence risk increases to approximately 19% if the mother already has a child diagnosed with ASD [16].
This paper focuses on analyzing the metabolic profile of mothers of young children with ASD and mothers of typically developing children, 2–5 years after birth. Measurements were conducted with whole blood to provide information on both intra-cellular and extra-cellular metabolism.
This study was limited to women who were not taking folate, B12, or multi-vitamin/ mineral supplements during the 2 months prior to sample collection, in order to minimize the effect of supplements on metabolism. The study includes assessments of many different aspects of metabolism, including analysis of amino acids, peptides, carbohydrates, lipids, nucleotides, Kreb’s cycle, vitamins/co-factors, and xenobiotics.
This work is part of a larger study, the ASU-Mayo Pilot Study of Young Children with ASD and their Mothers (AMPSYCAM). Although it would be ideal to have biological samples obtained during conception, pregnancy, lactation, and infancy, this would represent a significant hurdle for study design.
Instead, this pilot study focuses on 2–5 years after birth to provide preliminary insight into metabolic differences that currently exist. Results from this study provide the motivation for larger future studies to validate the findings and potentially to expand the time horizon to include the time during conception/pregnancy/lactation.
reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734806/
More information: Kathryn Hollowood-Jones et al, Altered metabolism of mothers of young children with Autism Spectrum Disorder: a case control study, BMC Pediatrics (2020). DOI: 10.1186/s12887-020-02437-7
