Exposição pré-natal ao SARS-CoV-2, ativação imune materno-fetal e desfechos do neurodesenvolvimento infantil

Abstract

This thesis investigates the relationship between maternal SARS-CoV-2 infection and the expression of pro-inflammatory markers in children up to 18 months of age. The research bases itself on the theory that the activation of the maternal immune system during pregnancy (MIA), due to exposure to pathogens such as SARS-CoV-2, can lead to the release of pro-inflammatory cytokines that remodel fetal brain connections, increasing the risk of neurodevelopmental disorders. In terms of methodology, the investigation uses the PLACOVGEN-BR cohort from the Neuropsychopharmacology Laboratory (LABNEURO/NPDM/UFC) in collaboration with the Assis Chateaubriand School Maternity (MEAC/UFC) and the Nucleus for Early Treatment and Stimulation (NUTEP), collecting data from pregnant women and their children between 2021 and 2023, involving the measurement of cytokines and chemokines in biospecimens via multiplex assay and the clinical evaluation of offspring neurodevelopment using gold-standard scales, such as the Bayley scale, to analyze cognitive, motor, and communication domains. The findings showed that prenatal exposure to SARS-CoV-2 was associated with a high frequency of neurodevelopmental delays at 24 months, particularly in the communication and motor domains. An increasing frequency of delays was observed between 6 and 24 months, especially in communication. Additionally, elevated levels of cytokines and chemokines in umbilical cord blood were associated with the observed outcomes, suggesting that perinatal inflammatory mediators, such as IFN-γ, TNF-α, IL-6, IL-8, IL-17, IL-1β, and CXCL10, may serve as early risk biomarkers for neurodevelopmental alterations in children exposed in utero to SARS-CoV-2. Taken together, these findings indicate that prenatal exposure to SARS-CoV-2 may adversely affect infant neurodevelopment, possibly through mechanisms involving maternal-fetal immune activation. These results reinforce the importance of longitudinal follow-up of children exposed during pregnancy and suggest the potential of perinatal inflammatory biomarkers for early risk identification.