Impact of Maternal SARS-CoV-2 Infection During Pregnancy on Offspring Neurodevelopment: Signature Cohort 12 Month Follow-Up. 

Abstract The COVID-19 pandemic brought unprecedented global challenges. Amid the crisis, the potential impact of SARS-CoV-2 on the neurodevelopment of offspring born to infected mothers emerged as a critical concern. This is a prospective cohort study of offspring exposed to maternal SARS-CoV-2 mild or severe infection during pregnancy. Pregnant women who acquired SARS-CoV-2 were enrolled in the SIGNATURE project at Hospital Universitario Virgen del Rocio in Seville, Spain, between 01/01/2021 and 08/31/2022. Maternal stress was assessed through the Perceived Stress Scale; offspring neurodevelopment was assessed through Ages & Stages Questionnaire, 3rd Edition (ASQ-3) at 6 months and 12 months. Association between SARS-CoV-2 illness severity and neurodevelopmental outcomes were analyzed with univariate and multivariate analysis. The cohort included 671 women categorized into three distinct groups based on maternal SARS-CoV-2 severity: non-infected mothers (N = 272), mothers with mild symptoms (N = 346), and mothers with severe symptoms (N = 53). In utero exposure to maternal SARS-CoV-2 severe infection was associated with a significant delay in the ASQ-3 personal-social subdomain at 12 months follow-up [OR = 3.00 (95% CI 1.129–7.969), p = 0.028] independently of the timing of the infection and maternal stress. This study revealed a significant association between severe maternal SARS-CoV-2 infection during pregnancy and offspring neurodevelopmental delay at the 12-month follow-up, emphasizing the importance of understanding and addressing the potential long-term consequences of maternal SARS-CoV-2 infection on offspring neurodevelopment.