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Research article
Juergen Hahn
Corresponding Author
ORCiD: https://orcid.org/0000-0002-1078-4203
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Background: Previous research studies have demonstrated abnormalities in the metabolism of mothers of young children with autism.
Method: Metabolic analysis was performed on blood samples from 30 mothers of young children with Autism Spectrum Disorder (ASD-M) and from 29 mothers of young typically-developing children (TD-M). Targeted metabolic analysis focusing on the folate one-carbon metabolism (FOCM) and the transsulfuration pathway (TS) as well as broad metabolic analysis were performed. Statistical analysis of the data involved both univariate and multivariate statistical methods.
Results: Univariate analysis revealed significant differences in 5 metabolites from the folate one-carbon metabolism and the transsulfuration pathway and differences in an additional 48 metabolites identified by broad metabolic analysis, including lower levels of many carnitine-conjugated molecules.
Multivariate analysis with leave-one-out cross-validation allowed classification of samples as belonging to one of the two groups of mothers with 93% sensitivity and 97% specificity with five metabolites. Furthermore, each of these five metabolites correlated with 8-15 other metabolites indicating that there are five clusters of correlated metabolites. In fact, all but 5 of the 50 metabolites with the highest area under the receiver operating characteristic curve were associated with the five identified groups. Many of the abnormalities appear linked to low levels of folate, vitamin B12, and carnitine-conjugated molecules.
Conclusions: Mothers of children with ASD have many significantly different metabolite levels compared to mothers of typically developing children at 2-5 years after birth.
Keywords
Autism, metabolic profile, Fisher Discriminant Analysis, Logistic Regression, metabolomics, mothers
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CURRENT STATUS: Published
View the published article at BMC Pediatrics.
No community comments so far
Editorial decision: Accept
On 18 Nov, 2020
Editor assigned
On 17 Nov, 2020
Submission checks complete
On 17 Nov, 2020
Editor invited
On 17 Nov, 2020
No comments provided
Editor assigned
On 29 Oct, 2020
Submission checks complete
On 28 Oct, 2020
Editor invited
On 28 Oct, 2020
No comments provided
Editorial decision: Minor revision
On 27 Oct, 2020
Review #2 received
Received 26 Oct, 2020
Review #1 received
Received 24 Oct, 2020
Reviewer #2 agreed
On 12 Oct, 2020
Editor assigned
On 09 Oct, 2020
Reviewers invited
Invitations sent on 09 Oct, 2020
Reviewer #1 agreed
On 09 Oct, 2020
Submission checks complete
On 08 Oct, 2020
Editor invited
On 08 Oct, 2020
Version 2
Posted 04 Sep, 2020
No comments provided
Review #2 received
Received 20 Sep, 2020
Editorial decision: Minor revision
On 20 Sep, 2020
Review #1 received
Received 18 Sep, 2020
Reviewer #2 agreed
On 07 Sep, 2020
Reviewers invited
Invitations sent on 03 Sep, 2020
Reviewer #1 agreed
On 03 Sep, 2020
Editor assigned
On 02 Sep, 2020
Submission checks complete
On 01 Sep, 2020
Editor invited
On 01 Sep, 2020
No comments provided
Review #3 received
Received 02 Aug, 2020
Editorial decision: Major revision
On 02 Aug, 2020
Review #2 received
Received 23 Jul, 2020
Review #1 received
Received 16 Jul, 2020
Reviewer #3 agreed
On 12 Jul, 2020
Reviewer #2 agreed
On 06 Jul, 2020
Reviewer #1 agreed
On 28 Jun, 2020
Reviewers invited
Invitations sent on 26 Jun, 2020
Editor assigned
On 18 Jun, 2020
First submitted
On 17 Jun, 2020
Submission checks complete
On 17 Jun, 2020
Editor invited
On 17 Jun, 2020
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Subject Areas
Pediatrics
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A new preprint design is coming!
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See the published version of this preprint at BMC Pediatrics.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Juergen Hahn
Corresponding Author
ORCiD: https://orcid.org/0000-0002-1078-4203
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Pediatrics.
No community comments so far
Editorial decision: Accept
On 18 Nov, 2020
Editor assigned
On 17 Nov, 2020
Submission checks complete
On 17 Nov, 2020
Editor invited
On 17 Nov, 2020
No comments provided
Editor assigned
On 29 Oct, 2020
Submission checks complete
On 28 Oct, 2020
Editor invited
On 28 Oct, 2020
No comments provided
Editorial decision: Minor revision
On 27 Oct, 2020
Review #2 received
Received 26 Oct, 2020
Review #1 received
Received 24 Oct, 2020
Reviewer #2 agreed
On 12 Oct, 2020
Editor assigned
On 09 Oct, 2020
Reviewers invited
Invitations sent on 09 Oct, 2020
Reviewer #1 agreed
On 09 Oct, 2020
Submission checks complete
On 08 Oct, 2020
Editor invited
On 08 Oct, 2020
Version 2
Posted 04 Sep, 2020
No comments provided
Review #2 received
Received 20 Sep, 2020
Editorial decision: Minor revision
On 20 Sep, 2020
Review #1 received
Received 18 Sep, 2020
Reviewer #2 agreed
On 07 Sep, 2020
Reviewers invited
Invitations sent on 03 Sep, 2020
Reviewer #1 agreed
On 03 Sep, 2020
Editor assigned
On 02 Sep, 2020
Submission checks complete
On 01 Sep, 2020
Editor invited
On 01 Sep, 2020
No comments provided
Review #3 received
Received 02 Aug, 2020
Editorial decision: Major revision
On 02 Aug, 2020
Review #2 received
Received 23 Jul, 2020
Review #1 received
Received 16 Jul, 2020
Reviewer #3 agreed
On 12 Jul, 2020
Reviewer #2 agreed
On 06 Jul, 2020
Reviewer #1 agreed
On 28 Jun, 2020
Reviewers invited
Invitations sent on 26 Jun, 2020
Editor assigned
On 18 Jun, 2020
First submitted
On 17 Jun, 2020
Submission checks complete
On 17 Jun, 2020
Editor invited
On 17 Jun, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Pediatrics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Pediatrics.
Background: Previous research studies have demonstrated abnormalities in the metabolism of mothers of young children with autism.
Method: Metabolic analysis was performed on blood samples from 30 mothers of young children with Autism Spectrum Disorder (ASD-M) and from 29 mothers of young typically-developing children (TD-M). Targeted metabolic analysis focusing on the folate one-carbon metabolism (FOCM) and the transsulfuration pathway (TS) as well as broad metabolic analysis were performed. Statistical analysis of the data involved both univariate and multivariate statistical methods.
Results: Univariate analysis revealed significant differences in 5 metabolites from the folate one-carbon metabolism and the transsulfuration pathway and differences in an additional 48 metabolites identified by broad metabolic analysis, including lower levels of many carnitine-conjugated molecules.
Multivariate analysis with leave-one-out cross-validation allowed classification of samples as belonging to one of the two groups of mothers with 93% sensitivity and 97% specificity with five metabolites. Furthermore, each of these five metabolites correlated with 8-15 other metabolites indicating that there are five clusters of correlated metabolites. In fact, all but 5 of the 50 metabolites with the highest area under the receiver operating characteristic curve were associated with the five identified groups. Many of the abnormalities appear linked to low levels of folate, vitamin B12, and carnitine-conjugated molecules.
Conclusions: Mothers of children with ASD have many significantly different metabolite levels compared to mothers of typically developing children at 2-5 years after birth.
Figure 1
Figure 2
Figure 3
Figure 4
The full text of this article is available to read as a PDF.
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