From CRONOS to CRONOS-Kids: Investigating Neurological Development in Toddlers After Maternal SARS-CoV-2 Infection During Pregnancy – A Study Protocol For A Prospective Cohort Study

Abstract Infection with SARS-CoV-2 during pregnancy increases the risk for adverse events in mothers and newborns. Research is increasingly exploring potential consequences of intrauterine exposure to the developing nervous system. However, there is still a lack of high-quality studies on long-term outcomes. The CRONOS-Kids study aims to investigate the global development of children after exposure to SARS-CoV-2 in utero in comparison to an unexposed control group. This paper outlines the CRONOS-Kids study protocol. The study is designed as a prospective population-based cohort study and will recruit children aged 36–60 months at the time of assessment. The exposed cohort will be recruited from the German CRONOS registry and will include only children who have been exposed to the Alpha and Delta variants of SARS-CoV-2. The unexposed cohort will be recruited by local pediatricians and via social media. For clinical evaluations, the Movement Assessment Battery for Children, 2nd Edition will be used. Parental self-reports on development will use the Ages and Stages Questionnaire, 3rd Edition. Additional questionnaires cover information about maternal and child health, vaccinations, healthcare usage, media consumption, and maternal quality of life. Until April 2026, we aim to recruit 125 exposed and 125 unexposed children across five study sites. The CRONOS-Kids study will explore the impact of intrauterine SARS-CoV-2 exposure to specific virus variants on long-term neurologic outcomes in children as well as broader consequences of the pandemic.