Neonatal Levels of Acute Phase Proteins and Risk of Autism Spectrum Disorder.
Acute phase protein
Autism spectrum disorder
C-reactive protein
Ferritin
Infection
Inflammation
Innate immunity
Journal
Biological psychiatry
ISSN: 1873-2402
Titre abrégé: Biol Psychiatry
Pays: United States
ID NLM: 0213264
Informations de publication
Date de publication:
01 03 2021
01 03 2021
Historique:
received:
13
02
2020
revised:
03
09
2020
accepted:
03
09
2020
pubmed:
15
11
2020
medline:
24
4
2021
entrez:
14
11
2020
Statut:
ppublish
Résumé
Immune signaling pathways influence neurodevelopment and are hypothesized to contribute to the etiology of autism spectrum disorder (ASD). We aimed to assess risk of ASD in relation to levels of neonatal acute phase proteins (APPs), key components of innate immune function, measured in neonatal dried blood spots. We included 924 ASD cases, 1092 unaffected population-based controls, and 203 unaffected siblings of ASD cases in this case-control study nested within the register-based Stockholm Youth Cohort. Concentrations of 9 different APPs were measured in eluates from neonatal dried blood spots from cases, controls, and siblings using a bead-based multiplex assay. Neonatal C-reactive protein was consistently associated with odds of ASD in case-control comparisons, with higher odds associated with the highest quintile compared with the middle quintile (odds ratio [OR] = 1.50, 95% confidence interval [CI] = 1.10-2.04) in adjusted analyses. In contrast, the lowest quintiles of α-2-macroglobulin (OR = 3.71, CI = 1.21-11.33), ferritin (OR = 4.20, CI = 1.40-12.65), and serum amyloid P (OR = 3.05, CI = 1.16-8.01) were associated with odds of ASD in the matched sibling comparison. Neonatal APPs varied with perinatal environmental factors and maternal/fetal phenotypes. Significant interactions in terms of risk for ASD were observed between neonatal APPs and maternal infection during late pregnancy, maternal anemia, and maternal psychiatric history. Indicators of the neonatal innate immune response are associated with risk of ASD, although the nature of these associations varies considerably with factors in the perinatal environment and the genetic background of the comparison group.
Sections du résumé
BACKGROUND
Immune signaling pathways influence neurodevelopment and are hypothesized to contribute to the etiology of autism spectrum disorder (ASD). We aimed to assess risk of ASD in relation to levels of neonatal acute phase proteins (APPs), key components of innate immune function, measured in neonatal dried blood spots.
METHODS
We included 924 ASD cases, 1092 unaffected population-based controls, and 203 unaffected siblings of ASD cases in this case-control study nested within the register-based Stockholm Youth Cohort. Concentrations of 9 different APPs were measured in eluates from neonatal dried blood spots from cases, controls, and siblings using a bead-based multiplex assay.
RESULTS
Neonatal C-reactive protein was consistently associated with odds of ASD in case-control comparisons, with higher odds associated with the highest quintile compared with the middle quintile (odds ratio [OR] = 1.50, 95% confidence interval [CI] = 1.10-2.04) in adjusted analyses. In contrast, the lowest quintiles of α-2-macroglobulin (OR = 3.71, CI = 1.21-11.33), ferritin (OR = 4.20, CI = 1.40-12.65), and serum amyloid P (OR = 3.05, CI = 1.16-8.01) were associated with odds of ASD in the matched sibling comparison. Neonatal APPs varied with perinatal environmental factors and maternal/fetal phenotypes. Significant interactions in terms of risk for ASD were observed between neonatal APPs and maternal infection during late pregnancy, maternal anemia, and maternal psychiatric history.
CONCLUSIONS
Indicators of the neonatal innate immune response are associated with risk of ASD, although the nature of these associations varies considerably with factors in the perinatal environment and the genetic background of the comparison group.
Identifiants
pubmed: 33187600
pii: S0006-3223(20)31908-9
doi: 10.1016/j.biopsych.2020.09.005
pii:
doi:
Substances chimiques
Acute-Phase Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
463-475Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.