Prenatal exposure to maternal immune activation with SARS-Cov-2 alters the developing human brain.
Poster No:
318
Submission Type:
Abstract Submission
Authors:
Julie Sigurdardottir1, Dafnis Batalle2, Ayesha Javed2, Abi Gartner2, Molly Eddison2, J-Donald Tournier3, Mary Rutherford2, Carolyn Gill4, Deena Gibbons5, Katie Doores5, Lucilla Poston4, A. David Edwards2, Grainne McAlonan1
Institutions:
1Dep of Forensic & Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, 2Early Life Imaging Research Department, School of Biomedical Engineering & Imaging Sciences, King's College London, London, 3Early Life Imaging Research Department, School of Biomedical Engineering & Imaging Sciences, King's College London, London9, 4Dep Of Women & Children’s Health, School of Life Course & Population Sciences., King's College London, London, 5Dep Of Immunobiology, School of Immunology & Microbial Sciences,, King's College London, London
First Author:
Julie Sigurdardottir
Dep of Forensic & Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience
King's College London, London
Dep of Forensic & Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience
King's College London, London
Co-Author(s):
Dafnis Batalle
Early Life Imaging Research Department, School of Biomedical Engineering & Imaging Sciences
King's College London, London
Early Life Imaging Research Department, School of Biomedical Engineering & Imaging Sciences
King's College London, London
Ayesha Javed
Early Life Imaging Research Department, School of Biomedical Engineering & Imaging Sciences
King's College London, London
Early Life Imaging Research Department, School of Biomedical Engineering & Imaging Sciences
King's College London, London
Abi Gartner
Early Life Imaging Research Department, School of Biomedical Engineering & Imaging Sciences
King's College London, London
Early Life Imaging Research Department, School of Biomedical Engineering & Imaging Sciences
King's College London, London
Molly Eddison
Early Life Imaging Research Department, School of Biomedical Engineering & Imaging Sciences
King's College London, London
Early Life Imaging Research Department, School of Biomedical Engineering & Imaging Sciences
King's College London, London
J-Donald Tournier
Early Life Imaging Research Department, School of Biomedical Engineering & Imaging Sciences
King's College London, London9
Early Life Imaging Research Department, School of Biomedical Engineering & Imaging Sciences
King's College London, London9
Mary Rutherford
Early Life Imaging Research Department, School of Biomedical Engineering & Imaging Sciences
King's College London, London
Early Life Imaging Research Department, School of Biomedical Engineering & Imaging Sciences
King's College London, London
Carolyn Gill
Dep Of Women & Children’s Health, School of Life Course & Population Sciences.
King's College London, London
Dep Of Women & Children’s Health, School of Life Course & Population Sciences.
King's College London, London
Deena Gibbons
Dep Of Immunobiology, School of Immunology & Microbial Sciences,
King's College London, London
Dep Of Immunobiology, School of Immunology & Microbial Sciences,
King's College London, London
Katie Doores
Dep Of Immunobiology, School of Immunology & Microbial Sciences,
King's College London, London
Dep Of Immunobiology, School of Immunology & Microbial Sciences,
King's College London, London
Lucilla Poston
Dep Of Women & Children’s Health, School of Life Course & Population Sciences.
King's College London, London
Dep Of Women & Children’s Health, School of Life Course & Population Sciences.
King's College London, London
A. David Edwards
Early Life Imaging Research Department, School of Biomedical Engineering & Imaging Sciences
King's College London, London
Early Life Imaging Research Department, School of Biomedical Engineering & Imaging Sciences
King's College London, London
Grainne McAlonan
Dep of Forensic & Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience
King's College London, London
Dep of Forensic & Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience
King's College London, London
Introduction:
Inflammatory molecules are essential to normal brain development and regulate synaptic pruning, plasticity and signalling. This immunological balance can be disrupted in contexts such as maternal immune activation (MIA) during pregnancy. MIA can alter placental function and, further downstream, fetal brain growth trajectories and increase likelihood of neurodivergent and psychiatric diagnoses (Atladottir, 2010). The coronavirus disease 2019 (COVID-19) pandemic may have posed a threat to maternal and fetal health outcomes but the specific effects of antenatal infection over a general "pandemic" effect potentially linked to stress also needs to be established. Here, we took a whole-brain approach to study these effects among neonates using tensor-based morphometry [TBM] and normative modelling as a first step to understanding health trajectories in this generation of children.
Methods:
A UK sample of n=145 (75 males) neonates participated in the Brain Imaging in Babies. 88 were enrolled from March 2020 ("pandemic" cohort) and 57 prior. T2-weighted MRI of the neonatal brain was acquired on a 3T Philips scanner at mean (SD) 41.4 ±2.1 postmenstrual (PMA) weeks, following the Developing Human Connectome Project (dhcp) acquisition protocol and reconstructed to a 0.5mm3 resolution (Edwards, 2022). Imaging data was excluded if of poor quality, if neonates showed incidental findings or had a family history of neurodevelopmental conditions. Antenatal COVID-19 exposure was defined from blood of infants and their mothers collected at scan as antibody response to SARS-CoV-2 Nucleocapsid protein, and/or to Spike protein > 4 fold over background (Gee,2021). Using the dhcp structural processing pipeline, brains were automatically segmented using the DRAWEM algorithm to retrieve volumes for 87 regions and 9 tissues. Normative z-scores adjusted for PMA at scan, at birth and infant sex were calculated using a reference sample of 434 healthy neonates from the dhcp 3rd data release scanned before the pandemic. TBM: T2 images were downsampled to 1mm isotropic resolution, registered to a dHCP 40-week template using ANTs (SyN), the log-Jacobian determinants calculated and a 3-voxel kernel smoothing applied. TBM analysis was performed using Mrtrix3 mrclusterstats with cluster free enhancement and 10 000 permutations. A generalised linear model included COVID-19 exposure, infant sex, postmenstrual age at scan and birth. To compare volumes between pandemic groups, normative z-scores were entered in a regression model including the COVID-19 seropositivity as the exposure, adjusted or unadjusted for a "pandemic" effect. Results are shown with p<0.05 corrected and fdr-corrected.
Results:
33/88 (37.5%) neonates were likely exposed in utero. We found a higher representation of white maternal ethnicity in the unexposed group (73.3% vs 36.7%, p<0.001) but no differences in maternal education, age or household income. Descriptives of data collections (MRI and blood) are presented in Figure 1. The TBM maps show, among exposed neonates, an expansion of CSF (e.g. 4th ventricle, quadrigeminal and interpeduncular a cisterns), bilateral hypothalami and subthalamic nuclei. They show a retraction in GM in the cuneus of the occipital lobe, right hippocampus and amygdala and bilateral inferior temporal gyrus (GM/WM), in the bilateral lateral orbital gyrus in the frontal lobe (GM,WM) and left inferior frontal gyrus (GM/WM). Small clusters survived FWE corrections. The normative z-scores show that, accounting for the pandemic effect, maternal COVID-19 infection was associated with smaller volumes in bilateral occipital GM and in the right medial and inferior temporal gyrus (GM/WM) (Figure 2) but this did not survive FDR correction.
·Fig 1. Chronology and results of blood antibodies for baby and mother (A,C) and infant age at neonatal scan (B)
·Fig 2. Whole brain analyses between neonates exposed and not exposed to antenatal maternal COVID-19 infection using TBM (A-C) and normative modeling (D).
Conclusions:
MIA through COVID-19 infection and a global pandemic effect may have elicited changes in prenatal structural neurodevelopment and CSF which will require long-term follow-up to understand their clinical relevance.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Lifespan Development:
Early life, Adolescence, Aging
Modeling and Analysis Methods:
Segmentation and Parcellation 2
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Anatomy and Functional Systems
Keywords:
Blood
Congenital
Development
Infections
Plasticity
Segmentation
STRUCTURAL MRI
1|2Indicates the priority used for review
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Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
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Provide references using APA citation style.
Edwards, A. D.(2022). The developing human connectome project neonatal data release. Frontiers in neuroscience, 16, 886772.
Gee, S. (2021). The legacy of maternal SARS CoV-2 infection on the immunology of the neonate. Nature Immunology 22 (12): 1490–1502.