Risk factors for the occurrence and progression of diabetic retinopathy in children and adolescents: a systematic review and meta-analysis

Background: Diabetic retinopathy (DR) is a severe microvascular complication in children and adolescents with diabetes, causing irreversible visual impairment. Despite increasing pediatric diabetes prevalence, evidence on DR risk factors in this population remains limited. This study aimed to systematically evaluate risk factors for DR onset and progression to support early screening and stratified management. Methods: Systematic review and meta-analysis was registered with PROSPERO (CRD420261330671). Databases including PubMed, Web of Science, Embase, and Scopus were searched from inception to March 2026. Eligible studies were cohort studies involving patients aged ≤ 20 years. Study quality was assessed using the Newcastle-Ottawa Scale. Analyses were performed in R 4.2.3 with random-effects model; meta-regression, subgroup analyses, and trim-and-fill method were used to explore heterogeneity and publication bias. Results: Twenty-eight cohort studies with 71,697 participants (93.84% T1DM) were included. Meta-analysis demonstrated that elevated glycated hemoglobin (HbA1c) was the strongest predictor of DR onset and progression. In the random-effects model, each 1% increase in HbA1c was associated with a 78% higher risk of DR onset (HR = 1.76, 95% CI: 1.45-2.14) and a 65% higher risk of DR progression (HR = 1.65, 95% CI: 1.15-2.37). Elevated systolic blood pressure (HR = 1.17), longer diabetes duration (HR = 1.38), and younger age at diabetes onset (HR = 0.84) were associated with DR onset, although these associations did not reach statistical significance in random-effects models. Meta-regression revealed that exposure metric and sample size were the main sources of heterogeneity, with small-sample studies systematically overestimating effect sizes. The trim-and-fill method indicated significant publication bias for the association between HbA1c and DR, and the pooled effect became statistically nonsignificant after bias correction. Conclusions: HbA1c is a key associated factor for pediatric DR, but its estimated effect is significantly affected by publication bias and high heterogeneity, and the pooled effect became non-significant after bias correction. Therefore, conclusions should be drawn cautiously. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261330671, identifier: CRD420261330671.