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Neuroimaging assessment of pediatric cerebral changes associated with SARS-CoV-2 infection during pregnancy
David Alves de Araujo Junior1,2,3,4, Felipe Motta1,2,3, Geraldo Magela Fernandes1,2,3
1Department of Medicine, University of Brasilia (UnB), Brasilia, Brazil.
Insights
Maternal SARS-CoV-2 infection is linked to white matter changes in newborns, affecting myelin and brain elasticity. Advanced ultrasound techniques like elastography can help identify infants at risk for neurologic damage.
Area of Science:
- Neonatal Neurology
- Neuroimaging
- Infectious Diseases
Background:
- Maternal SARS-CoV-2 infection's impact on perinatal neurologic outcomes remains unclear.
- Evidence suggests white matter disease and impaired neurodevelopment in newborns exposed to maternal SARS-CoV-2.
- These effects may stem from direct viral impact and systemic inflammation, affecting glial cells, myelin, and cerebral blood flow.
Purpose of the Study:
- To characterize central nervous system consequences in newborns following maternal SARS-CoV-2 infection.
- To investigate the role of maternal and fetal inflammatory states on neonatal brain development.
Main Methods:
- Longitudinal prospective cohort study (June 2020 - December 2021) of newborns born to mothers with and without SARS-CoV-2 exposure.
- Neuroimaging included cranial ultrasound scans (CUS) with grayscale, Doppler studies, and ultrasound-based brain elastography.
- Brain elastography measured parenchymal stiffness as an indicator of cerebral myelin content in specific brain regions.
Main Results:
- 219 infants enrolled (201 exposed, 18 controls); neuroimaging at 6 months adjusted age.
- 18 grayscale and 21 Doppler abnormalities noted, primarily deep white matter/basal ganglia hyperechogenicity and reduced intracranial arterial flow indices.
- Shear-wave US elastography revealed significantly reduced stiffness in SARS-CoV-2 exposed infants, particularly in deep white matter (p < 0.001).
Conclusions:
- Maternal SARS-CoV-2 infection is associated with pediatric structural brain changes, predominantly affecting deep white matter.
- Findings suggest impaired myelin content due to regional hyperechogenicity and reduced elasticity.
- Doppler and elastography are valuable functional tools for identifying infants at risk of neurologic damage.
Background:
SARS-CoV-2 infection and perinatal neurologic outcomes are still not fully understood. However, there is recent evidence of white matter disease and impaired neurodevelopment in newborns following maternal SARS-CoV-2 infection. These appear to occur as a consequence of both direct viral effects and a systemic inflammatory response, with glial cell/myelin involvement and regional hypoxia/microvascular dysfunction. We sought to characterize the consequences of maternal and fetal inflammatory states in the central nervous system of newborns following maternal SARS-CoV-2 infection.
Methods:
We conducted a longitudinal prospective cohort study from June 2020 to December 2021, with follow-up of newborns born to mothers exposed or not exposed to SARS-CoV-2 infection during pregnancy. Brain analysis included data from cranial ultrasound scans (CUS) with grayscale, Doppler studies (color and spectral), and ultrasound-based brain elastography (shear-wave mode) in specific regions of interest (ROIs): deep white matter, superficial white matter, corpus callosum, basal ganglia, and cortical gray matter. Brain elastography was used to estimate brain parenchymal stiffness, which is an indirect quantifier of cerebral myelin tissue content.
Results:
A total of 219 single-pregnancy children were enrolled, including 201 born to mothers exposed to SARS-CoV-2 infection and 18 from unexposed controls. A neuroimaging evaluation was performed at 6 months of adjusted chronological age and revealed 18 grayscale and 21 Doppler abnormalities. Predominant findings were hyperechogenicity of deep brain white matter and basal ganglia (caudate nuclei/thalamus) and a reduction in the resistance and pulsatility indices of intracranial arterial flow. The anterior brain circulation (middle cerebral and pericallosal arteries) displayed a wider range of flow variation than the posterior circulation (basilar artery). Shear-wave US elastography analysis showed a reduction in stiffness values in the SARS-CoV-2 exposed group in all analyzed regions of interest, especially in the deep white matter elasticity coefficients (3.98 ± 0.62) compared to the control group (7.76 ± 0.77); p-value < 0.001.
Conclusion:
This study further characterizes pediatric structural encephalic changes associated with SARS-CoV-2 infection during pregnancy. The maternal infection has been shown to be related to cerebral deep white matter predominant involvement, with regional hyperechogenicity and reduction of elasticity coefficients, suggesting zonal impairment of myelin content. Morphologic findings may be subtle, and functional studies such as Doppler and elastography may be valuable tools to more accurately identify infants at risk of neurologic damage.
