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

Purpose Infection with SARS-CoV-2 during pregnancy increases the risk for adverse events in mothers and their newborns. Research is increasingly exploring the 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. Methods 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 only include participants who have been exposed to the Alpha and Delta variants of SARS-CoV-2. The unexposed cohort will be recruited by local paediatricians 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 general information about maternal and child health, vaccinations, healthcare usage, media consumption, maternal quality of life, and social status. Results Until December 2025, we aim to recruit 125 exposed and 125 unexposed children across five study sites. Conclusion The CRONOS-Kids study will explore the impact of intrauterine SARS-CoV-2 exposure of specific virus variants on long-term neurologic outcomes in children, as well as the broader consequences of the pandemic. Trial registration The study was registered at clinicaltrials.gov in April 2025 (NCT06968897).