Beate Ritz1,2, Qi Yan1, Karan Uppal3, Zeyan Liew4,5, Xin Cui6,7, Chenxiao Ling1, Kosuke Inoue1, Ondine von Ehrenstein1, Douglas I Walker8, Dean P Jones3. 1. Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, California, USA. 2. Department of Neurology, UCLA School of Medicine, Los Angeles, California, USA. 3. Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy, and Critical Care Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA. 4. Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USA. 5. Yale Center for Perinatal, Pediatric, and Environmental Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA. 6. Perinatal Epidemiology and Health Outcomes Research Unit, Division of Neonatology, Department of Pediatrics, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, California, USA. 7. California Perinatal Quality Care Collaborative, Palo Alto, California, USA. 8. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Abstract
Discovering pathophysiologic networks in a blood-based approach may help to generate valuable tools for early treatment or preventive measures in autism. To date targeted or untargeted metabolomics approaches to identify metabolic features and pathways affecting fetal neurodevelopment have rarely been applied to pregnancy samples, that is, an early period potentially relevant for the development of autism spectrum disorders (ASD). We conducted a population-based study relying on autism diagnoses retrieved from California Department of Developmental Services record. After linking cases to and sampling controls from birth certificates, we retrieved stored maternal mid-pregnancy serum samples collected as part of the California Prenatal Screening Program from the California Biobank for children born 2004 to 2010 in the central valley of California. We retrieved serum for 52 mothers whose children developed autism and 62 population controls originally selected from all eligible children matched by birth year and child's sex. Also, we required that these mothers were relatively low or unexposed to air pollution and select pesticides during early pregnancy. We identified differences in metabolite levels in several metabolic pathways, including glycosphingolipid biosynthesis and metabolism, N-glycan and pyrimidine metabolism, bile acid pathways and, importantly, C21-steroid hormone biosynthesis and metabolism. Disturbances in these pathways have been shown to be relevant for neurodevelopment in rare genetic syndromes or implicated in previous studies of autism. This study provides new insight into maternal mid-pregnancy metabolic features possibly related to the development of autism and an incentive to explore whether these pathways and metabolites are useful for early diagnosis, treatment, or prevention. LAY SUMMARY: This study found that in mid-pregnancy the blood of mothers who give birth to a child that develops autism has some characteristic features that are different from those of blood samples taken from control mothers. These features are related to biologic mechanisms that can affect fetal brain development. In the future, these insights may help identify biomarkers for early autism diagnosis and treatment or preventive measures. Autism Res 2020, 13: 1258-1269.
Discovering pathophysiologic networks in a blood-based approach may help to generate valuable tools for early treatment or preventive measures in autism. To date targeted or untargeted metabolomics approaches to identify metabolic features and pathways affecting fetal neurodevelopment have rarely been applied to pregnancy samples, that is, an early period potentially relevant for the development of autism spectrum disorders (ASD). We conducted a population-based study relying on autism diagnoses retrieved from California Department of Developmental Services record. After linking cases to and sampling controls from birth certificates, we retrieved stored maternal mid-pregnancy serum samples collected as part of the California Prenatal Screening Program from the California Biobank for children born 2004 to 2010 in the central valley of California. We retrieved serum for 52 mothers whose children developed autism and 62 population controls originally selected from all eligible children matched by birth year and child's sex. Also, we required that these mothers were relatively low or unexposed to air pollution and select pesticides during early pregnancy. We identified differences in metabolite levels in several metabolic pathways, including glycosphingolipid biosynthesis and metabolism, N-glycan and pyrimidine metabolism, bile acid pathways and, importantly, C21-steroid hormone biosynthesis and metabolism. Disturbances in these pathways have been shown to be relevant for neurodevelopment in rare genetic syndromes or implicated in previous studies of autism. This study provides new insight into maternal mid-pregnancy metabolic features possibly related to the development of autism and an incentive to explore whether these pathways and metabolites are useful for early diagnosis, treatment, or prevention. LAY SUMMARY: This study found that in mid-pregnancy the blood of mothers who give birth to a child that develops autism has some characteristic features that are different from those of blood samples taken from control mothers. These features are related to biologic mechanisms that can affect fetal brain development. In the future, these insights may help identify biomarkers for early autism diagnosis and treatment or preventive measures. Autism Res 2020, 13: 1258-1269.
Authors: Polina Girchenko; Marius Lahti-Pulkkinen; Jari Lipsanen; Kati Heinonen; Jari Lahti; Ville Rantalainen; Esa Hämäläinen; Hannele Laivuori; Pia M Villa; Eero Kajantie; Katri Räikkönen Journal: Mol Psychiatry Date: 2022-08-10 Impact factor: 13.437
Authors: Ja Hyeong Kim; Qi Yan; Karan Uppal; Xin Cui; Chenxiao Ling; Douglas I Walker; Julia E Heck; Ondine S von Ehrenstein; Dean P Jones; Beate Ritz Journal: Environ Res Date: 2021-02-04 Impact factor: 8.431
Authors: Kathryn Hollowood-Jones; James B Adams; Devon M Coleman; Sivapriya Ramamoorthy; Stepan Melnyk; S Jill James; Bryan K Woodruff; Elena L Pollard; Christine L Snozek; Uwe Kruger; Joshua Chuah; Juergen Hahn Journal: BMC Pediatr Date: 2020-12-14 Impact factor: 2.125