Departments of Neuroscience and Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Departments of Pediatrics and Psychiatry, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian Morgan Stanley Children’s Hospital, New York, NY 10032, USA
Elena Baldwin
Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Roozie J.J. Coenen
Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Luke A. Hammond
Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA
Darcy S. Peterka
Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA
Lynne Heilbrun
Family and Community Medicine, School of Medicine, University of Texas Health Sciences Center, San Antonio, TX 78229, USA
Richard E. Frye
Department of Neurology, Barrow Neurological Institute, Phoenix Children’s Hospital, Phoenix, AZ 85016, USA
Raymond Palmer
Family and Community Medicine, School of Medicine, University of Texas Health Sciences Center, San Antonio, TX 78229, USA
Hjalmar Nobel Norrman
Center of Neurodevelopmental Disorder (KIND), Division of Neuropsychiatry, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm 171 77, Sweden
Anna Fridell
Center of Neurodevelopmental Disorder (KIND), Division of Neuropsychiatry, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm 171 77, Sweden; Child and Adolescent Psychiatry Research Center, Center for Psychiatry Research, Region Stockholm, Stockholm 104 31, Sweden
Karl Lundin Remnelius
Center of Neurodevelopmental Disorder (KIND), Division of Neuropsychiatry, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm 171 77, Sweden
Johan Isaksson
Center of Neurodevelopmental Disorder (KIND), Division of Neuropsychiatry, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm 171 77, Sweden; Department of Medical Sciences, Child and Adolescent Psychiatry Unit, Uppsala University, Uppsala 751 85, Sweden
Christine Austin
Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Linus Biotechnology Inc., New York, NY 10013, USA
Paul Curtin
Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Linus Biotechnology Inc., New York, NY 10013, USA
Sven Bölte
Center of Neurodevelopmental Disorder (KIND), Division of Neuropsychiatry, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm 171 77, Sweden; Child and Adolescent Psychiatry Research Center, Center for Psychiatry Research, Region Stockholm, Stockholm 104 31, Sweden; Curtin Autism Research Group, Curtin School of Allied Health, Curtin University, Perth, WA 6102, Australia
Manish Arora
Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Linus Biotechnology Inc., New York, NY 10013, USA; Corresponding author
Summary: Atypical regulation of inflammation has been proposed in the etiology of autism spectrum disorder (ASD); however, measuring the temporal profile of fetal inflammation associated with future ASD diagnosis has not been possible. Here, we present a method to generate approximately daily profiles of prenatal and early childhood inflammation as measured by developmentally archived C-reactive protein (CRP) in incremental layers of deciduous tooth dentin. In our discovery population, a group of Swedish twins, we found heightened inflammation in the third trimester in children with future ASD diagnosis relative to controls (n = 66; 14 ASD cases; critical window: −90 to −50 days before birth). In our replication study, in the US, we observed a similar increase in CRP in ASD cases during the third trimester (n = 47; 23 ASD cases; −128 to −21 days before birth). Our results indicate that the third trimester is a critical period of atypical fetal inflammatory regulation in ASD.
