Clinical Effectiveness of Resin Infiltration and Fluoride Varnish for Managing White Spot Lesions (International Caries Detection and Assessment System (ICDAS) ≤ 2) During Multibracket Orthodontic Treatment: A Systematic Review and Meta-Analysis

White spot lesions (WSLs) are a common adverse effect of fixed orthodontic treatment, caused by enamel demineralization associated with biofilm accumulation around brackets. These lesions are typically non-cavitated. Conventional treatments such as fluoride varnish enhance remineralization but often provide limited esthetic improvement. Resin infiltration has emerged as a minimally invasive alternative that improves the appearance of lesions by infiltrating porous enamel and altering its optical properties. This systematic review and meta-analysis evaluated the clinical effectiveness of resin infiltration compared with fluoride varnish in the management of WSLs (International Caries Detection and Assessment System (ICDAS) ≤ 2) in orthodontic patients. A systematic search was conducted across five electronic databases from November 2020 to December 2025. Randomized controlled trials comparing resin infiltration with fluoride varnish or placebo were included. The primary outcome was esthetic improvement assessed by color change (ΔE). Secondary outcomes included lesion regression, changes in ICDAS scores, and caries activity. A random-effects meta-analysis was performed using IBM SPSS 30.0 (IBM Corp., Armonk, NY, USA), and results were expressed as mean differences (MDs) with 95% confidence intervals (CIs). Three randomized controlled trials were included, of which two were eligible for meta-analysis. Meta-analysis showed a statistically significant reduction in color difference favoring resin infiltration (MD = −3.43; 95% CI: −4.20 to −2.66; I² = 0%). Narrative synthesis indicated greater lesion regression and caries arrest in the resin infiltration group, reflected by reductions in ICDAS scores and caries activity measures, including quantitative light-induced fluorescence (QLF) and DIAGNOdent values. Follow-up periods ranged from one week to 12 months. This review is subject to several limitations, including a restriction to English-language publications, a limited publication timeframe (2020-2025), and the inclusion of only full-text studies, which may have introduced selection bias and limited the comprehensiveness of the evidence. Furthermore, gray literature sources and trial registries were not systematically searched, which may have resulted in the omission of relevant unpublished or ongoing studies. The small number of included studies and relatively short follow-up periods may limit the generalizability of the findings. Resin infiltration appears to be more effective than fluoride varnish in improving esthetic outcomes and promoting regression of ICDAS ≤ 2 WSLs. It represents a valuable minimally invasive treatment option; however, further well-designed randomized controlled trials with longer follow-up are required to confirm long-term effectiveness.