30817
Autism and Metabolomics in Maternal Pregnancy Serum
The exposures and biologic mechanism that may contribute to autism during fetal development are still largely unknown. Interrogating maternal metabolic features during pregnancy may help identify pathways relevant for the development of autism in the offspring.
Objectives:
The aim of this study is to comprehensively profile the blood metabolome during mid-pregnancy using untargeted high-resolution metabolomics (HRM) in order to identify maternal metabolic features and pathways associated with autism in offspring.
Methods:
We retrieved stored serum samples from 114 mothers sampled in mid-pregnancy. All subjects lived in the Central Valley of California which is a largely immigrant Hispanic community. Of these, 52 had given birth to a child diagnosed with autism in childhood according to the California Department of Developmental Services records and they were matched (by birth year and gender) to 62 controls randomly selected from the California Birth Records. Using liquid chromatography-high resolution mass spectrometry, we obtained metabolic profiles in an untargeted approach and used partial least squares discriminant analysis (PLS-DA) to select metabolic features that were statistically significantly different in case and control mothers while controlling for potential confounders selected a prior. Pathway and network analyses were employed using the mummichog approach.
Results:
In total we extracted 4030 and 4994 metabolic features from maternal serum samples in the HILIC column (positive ion mode) and the C18 column (negative ion mode), respectively. Controlling for confounders, 90 and 68 discriminatory metabolic features (HILIC and C18, respectively) were selected according to the criterion Variable Importance In projection (VIP) greater than 2. Pathway enrichment analysis for discriminatory features indicated that the steroid hormone pathway was upregulated in case mothers and we also found alterations in inflammatory and oxidative stress related pathways that distinguished case from control mothers.
Conclusions:
Profiling metabolomic features and generating pathways from maternal serum in mid-pregnancy, we found that differences in steroid hormones, inflammatory and oxidative stress pathway may contribute to the development of autism in the offspring.