Analysis of Metabolites from Blood Samples of Pregnant Mothers and Probability of Autism Diagnosis of the Child

Autism Spectrum Disorder (ASD) is estimated to affect approximately one out every 68 children in the United States, leading to a high annual economic burden. Yet despite this prevalence, relatively little is known about the mechanism underlying ASD.

One promising approach is based upon that it has been shown that there are significant differences in measurements of the metabolites and the metabolite ratios between ASD and typically developing (TD) patients in the Folate One-Carbon Metabolism (FOCM) and Transsulfuration (TS) pathways. These differences have the potential for the development of a test supporting an ASD diagnosis. However, the key question is how early differences could be detected that point towards an ASD diagnosis in the future. In this work, we focus on metabolites of the mothers during pregnancy as the earliest possible timepoint of detection.

Blood samples were taken at different time-points throughout the pregnancy: 1st trimester, 2nd trimester, and 3rd trimester from two groups of pregnant mothers: mothers who have already had a child with ASD (High Risk) and those who have not (Control). It is important to point out that the risk of having a child with ASD increases after a mother has already had a child with ASD (18.7% as compared to the 1.5% across the general population). The High Risk group is further divided into two subgroups: ASD or Typically Developing (TD) based on a diagnosis after three years of age. Measurements from the FOCM and TS pathways were recorded for all groups. Fisher Discriminant Analysis (FDA) is used to separate the different groups of data. The results of this study show that it is not possible to predict if a child will be diagnosed with ASD from the FOCM/TS metabolites of the mother during pregnancy. However, the results indicate that it is possible to predict with reasonably high probability (misclassification errors of approximately 10%) if a mother falls into the High Risk group or the Control group. While these findings will need to be replicated in additional studies, they show promising results that the probability of having a child with ASD can be predicted during pregnancy based on multivariate analysis of the FOCM/TS metabolites.