Understanding the potential impact of trimester-specific maternal immune activation due to SARS-CoV-2 on early human neurodevelopment and the role of cytokine balance

Abstract

Purpose: The COVID-19 pandemic presents significant future health challenges. Its impact on pregnant women and their newborn is a particular area of concern. This study aims to examine the potential role of maternal immune activation (MIA), due to SARS-CoV-2 infection, on early neurodevelopment. Methods: We analysed 107 mother-infant dyads from the COGESTCOV-19 study in Cantabria, Spain, which included 59 SARS-CoV-2 exposed (cases) and 48 unexposed (controls) mothers, recruited between December 2020 and February 2022. Cytokine levels (IL-6 and IL-10) were obtained from maternal blood and cord blood. Neurodevelopment was assessed using the Neonatal Behavioral Assessment Scale (NBAS) at six weeks of age. Trimester of infection was considered in the main analyses. Results: Results showed no significant overall delays in early neurodevelopment due to maternal SARS-CoV-2 infection. Control infants performed better in some NBAS items. However, cases infants showed trimester-specific differences. First-trimester exposure was related to motor and reflex delays, second-trimester to poorer performances in motor tasks and autonomic stability, and third-trimester to weaker state organization, regulation, and reflexes. Some correlations between cytokine levels and NBAS performance showed moderate associations. Conclusions: These findings highlight the need for ongoing neurodevelopmental monitoring of infants born during the COVID-19 pandemic. The study enhances our understanding of MIA's impact on early development, emphasizing the importance of addressing homeostatic mechanisms in mothers and newborns.

Keywords

• Maternal immune activation (MIA)
• SARS-CoV-2
• Neurodevelopment
• Cytokines
• Homeostasis
• Neonatal behavioral assessment scale (NBAS)