Kathryn Hollowood1,2, Stepan Melnyk3, Oleksandra Pavliv3, Teresa Evans3, Ashley Sides4, Rebecca J Schmidt5, Irva Hertz-Picciotto5, William Elms5, Elizabeth Guerrero5, Uwe Kruger1, Juergen Hahn1,2,6, S Jill James3. 1. Department of Biomedical Engineering, Rensselaer Polytechnic Institute, 110 8 St, Troy, NY, 12180, USA. 2. Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 110 8 St, Troy, NY, 12180, USA. 3. Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Research Institute, 4301 W Markham St, Little Rock, AR, 72205, USA. 4. Translational Research Institute, University of Arkansas for Medical Sciences, 1301 W Markham St, Little Rock, AR, 72205, USA. 5. Department of Public Health Sciences and the MIND Institute, University of California Davis School of Medicine, 1 Shields Ave, Davis, CA, 95616, USA. 6. Department of Chemical & Biological Engineering, Rensselaer Polytechnic Institute, 110 8 St, Troy, NY, 12180, USA.
Abstract
BACKGROUND: Currently there is no test for pregnant mothers that can predict the probability of having a child that will be diagnosed with autism spectrum disorder (ASD). Recent estimates indicate that if a mother has previously had a child with ASD, the risk of having a second child with ASD is ~18.7% (High Risk) whereas the risk of ASD in the general population is ~1.7% (Low Risk). METHODS: In this study, metabolites of the folate-dependent transmethylation and transsulfuration biochemical pathways of pregnant mothers were measured to determine whether or not the risk of having a child with autism could be predicted by her metabolic profile. Pregnant mothers who have had a child with autism before were separated into two groups based on the diagnosis of their child whether the child had autism (ASD) or not (TD). Then these mothers were compared to a group of control mothers who have not had a child with autism before. A total of 107 mothers were in the High Risk category and 25 mothers in the Low Risk category. The High Risk category was further separated into 29 mothers in the ASD group and 78 mothers in the TD group. RESULTS: The metabolic results indicated that among High Risk mothers, it was not possible to predict an autism pregnancy outcome. However, the metabolic profile was able to predict with approximately 90% sensitivity and specificity whether a mother fell into the High Risk group (18.7% risk) or Low Risk group (1.7% risk). CONCLUSIONS: Based upon these measurements it is not possible to determine during a pregnancy if a child will be diagnosed with ASD by age 3. However, differences in the folate-dependent transmethylation and transsulfuration metabolites are indicative of the risk level (High Risk of 18.7% vs. Low Risk of 1.7%) of the mother for having a child with ASD.
BACKGROUND: Currently there is no test for pregnant mothers that can predict the probability of having a child that will be diagnosed with autism spectrum disorder (ASD). Recent estimates indicate that if a mother has previously had a child with ASD, the risk of having a second child with ASD is ~18.7% (High Risk) whereas the risk of ASD in the general population is ~1.7% (Low Risk). METHODS: In this study, metabolites of the folate-dependent transmethylation and transsulfuration biochemical pathways of pregnant mothers were measured to determine whether or not the risk of having a child with autism could be predicted by her metabolic profile. Pregnant mothers who have had a child with autism before were separated into two groups based on the diagnosis of their child whether the child had autism (ASD) or not (TD). Then these mothers were compared to a group of control mothers who have not had a child with autism before. A total of 107 mothers were in the High Risk category and 25 mothers in the Low Risk category. The High Risk category was further separated into 29 mothers in the ASD group and 78 mothers in the TD group. RESULTS: The metabolic results indicated that among High Risk mothers, it was not possible to predict an autism pregnancy outcome. However, the metabolic profile was able to predict with approximately 90% sensitivity and specificity whether a mother fell into the High Risk group (18.7% risk) or Low Risk group (1.7% risk). CONCLUSIONS: Based upon these measurements it is not possible to determine during a pregnancy if a child will be diagnosed with ASD by age 3. However, differences in the folate-dependent transmethylation and transsulfuration metabolites are indicative of the risk level (High Risk of 18.7% vs. Low Risk of 1.7%) of the mother for having a child with ASD.
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