Investigating the impact of severe maternal SARS-CoV-2 infection on infant DNA methylation and neurodevelopment.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
30 Oct 2024
30 Oct 2024
Historique:
received:
11
06
2024
accepted:
21
10
2024
revised:
17
10
2024
medline:
31
10
2024
pubmed:
31
10
2024
entrez:
31
10
2024
Statut:
aheadofprint
Résumé
Maternal infections during pregnancy can increase the risk to offspring of developing a neurodevelopmental disorder. Given the global prevalence and severity of infection with Severe Acute Respiratory Syndrome related Coronavirus 2 (SARS-CoV-2), the objective of this study was to determine if in utero exposure to severe maternal SARS-CoV-2 infection alters infant neurodevelopmental outcomes at 12 months and to identify potential biological markers of adverse infant outcomes. Mother-infant dyads exposed to severe SARS-CoV-2 infection (requiring hospitalization) during pregnancy and age and sociodemographic matched control dyads were recruited from Monash Medical Centre, Australia in 2021/22 and prospectively assessed over 12 months. Maternal serum cytokine levels and Edinburgh Postnatal Depression Scale (EPDS) scores were assessed at birth. DNA methylation was assessed from infant buccal swabs at birth (Illumina EPIC BeadChip). Infant neurodevelopmental outcomes at 12 months were assessed using the Ages and Stages Questionnaire (ASQ-3). Mothers exposed to severe SARS-CoV-2 exhibited elevated serum IL-6 and IL-17A and higher EPDS scores than controls at birth. Infants exposed to severe SARS-CoV-2 in utero demonstrated over 3000 significant differentially methylated sites within their genomes compared to non-exposed (adjusted p-value < 0.05), including genes highly relevant to ASD and synaptic pathways. At 12 months, severe SARS-CoV-2 exposed infants scored lower on the ASQ-3 than non-exposed infants, and communication and problem-solving scores negatively correlated with maternal IL-6 levels at birth. DNA methylation changes therefore unveil potential mechanisms linking infection exposure to delayed neurodevelopment and maternal serum IL-6 levels may be a potential biomarker of child developmental delay. Mothers exposed to severe SARS-CoV-2 infections show elevated pro-inflammatory cytokines. Infants exposed in utero to severe SARS-CoV-2 infection show altered DNA methylation at birth and delayed development at 12 months of age. Created in Biorender.com.
Identifiants
pubmed: 39478169
doi: 10.1038/s41380-024-02808-x
pii: 10.1038/s41380-024-02808-x
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : GNT2000893
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : GNT20001907
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature Limited.
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