Lipids are critical to healthy neurodevelopment, are variably enriched across regions of the brain, and are integral to human metabolism. Meconium, the first bowel movements of a newborn, begin accumulation in approximately the 12th week of gestation, and contains high lipid content. Thus, meconium may provide a window into the abnormal neurodevelopment that occurs in the early etiology of autism spectrum disorder. This proposal will quantify and compare the lipid content of meconium in typically developing versus neurodevelopmentally delayed children from a prospective enriched risk cohort of early events in autism spectrum disorder. To extend the relevance of the putatively identified lipid biomarkers, the structures of the biomarkers will be elucidated, and the lipid content of the samples derived from the cohort will be compared to meconium from healthy newborns as well as other biospecimens from newborns. Finally, targeted methods will be developed in suitable matrices for future validation of the biomarkers. We will conduct this research in three specific aims as follows;
Aim 1. Identify unknown chromatographic features with differential abundance between ASD and controls in a prospective enriched risk cohort.
Aim 2. Structurally elucidate the putative biomarkers of ASD and compare the lipid content of meconium, placenta, and cord blood.
Aim 3. Develop and validate a targeted method for the quantitation of putative biomarkers of ASD.

Public Health Relevance

This research will use cutting edge analytical technology to quantify the lipid composition of meconium in relation to development of autism spectrum disorder. Since meconium begins accumulation around the 12th week of gestation and is passed as the first bowel movements of a newborn, meconium will provide a window into the early origins of autism. This will facilitate understanding of the causes of autism and other developmental disorders of prenatal origin.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HD087866-02
Application #
9265899
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Kau, Alice S
Project Start
2016-04-22
Project End
2019-03-31
Budget Start
2017-04-01
Budget End
2019-03-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Drexel University
Department
Type
Schools of Medicine
DUNS #
002604817
City
Philadelphia
State
PA
Country
United States
Zip Code
19102
O'Connor, Roddy S; Guo, Lili; Ghassemi, Saba et al. (2018) The CPT1a inhibitor, etomoxir induces severe oxidative stress at commonly used concentrations. Sci Rep 8:6289
Carrer, Alessandro; Parris, Joshua L D; Trefely, Sophie et al. (2017) Impact of a High-fat Diet on Tissue Acyl-CoA and Histone Acetylation Levels. J Biol Chem 292:3312-3322
Frey, Alexander J; Park, Bo Y; Schriver, Emily R et al. (2017) Differences in testosterone and its precursors by sex of the offspring in meconium. J Steroid Biochem Mol Biol 167:78-85
Mesaros, Clementina; Arroyo, Alejandro D; Blair, Ian A et al. (2017) Coenzyme A thioester formation of 11- and 15-oxo-eicosatetraenoic acid. Prostaglandins Other Lipid Mediat 130:1-7
Simithy, Johayra; Sidoli, Simone; Yuan, Zuo-Fei et al. (2017) Characterization of histone acylations links chromatin modifications with metabolism. Nat Commun 8:1141
Lyall, Kristen; Croen, Lisa; Daniels, Julie et al. (2017) The Changing Epidemiology of Autism Spectrum Disorders. Annu Rev Public Health 38:81-102
Zhao, Steven; Torres, AnnMarie; Henry, Ryan A et al. (2016) ATP-Citrate Lyase Controls a Glucose-to-Acetate Metabolic Switch. Cell Rep 17:1037-1052
Frey, Alexander J; Wang, Qingqing; Busch, Christine et al. (2016) Validation of highly sensitive simultaneous targeted and untargeted analysis of keto-steroids by Girard P derivatization and stable isotope dilution-liquid chromatography-high resolution mass spectrometry. Steroids 116:60-66