Clostridioides difficile is considered an urgent threat to human health by the US Centers for Disease Control and Prevention. In recent years, C. difficile has been reported increasingly as a cause of gastrointestinal disease in children, and the prevalence of hospital-acquired C. difficile infection and community-acquired CDI in children is increasing.

To perform a systematic review and meta-analysis of risk factors for CDI in children.

MEDLINE/PubMed, EMBASE, Web of Science, Scopus, OVID, China National Knowledge Infrastructure, Wanfang (Chinese), SinoMed (Chinese) and Weipu (Chinese) were searched from inception to 12^th January 2022. Observational studies (cohort, case–control and cross-sectional) on CDI in children were included in the analysis. Data were pooled using a fixed or random-effects model, and odds ratios (OR) were calculated.

In total, 25 observational studies were included in the analysis. Prior antibiotic exposure [OR 1.93, 95% confidence interval (CI) 1.25–2.97], prolonged hospitalization (OR 14.68, 95% CI 13.24–16.28), history of hospitalization (OR 3.67, 95% CI 1.91–7.06), gastric acid suppressants (OR 1.96, 95% CI 1.41–2.73), male gender (OR 1.18, 95% CI 1.05–1.32), neoplastic disease (OR 3.40, 95% CI, 2.85–4.07), immunodeficiency (OR 4.18, 95% CI 3.25–5.37), solid organ transplantation (OR 4.56, 95% CI 3.95–5.27) and enteral feeding (OR 2.21, 95% CI 1.05–4.62) were associated with increased risk of CDI.

This systematic review and meta-analysis provides further evidence for the susceptibility factors of CDI to improve clinicians' awareness of CDI, and prevent C. difficile-associated diarrhoea in children.