Abstract
Background: Molar-incisor hypomineralization (MIH) is an enamel defect affecting molars and incisors, often leading to hypersensitivity, enamel breakdown, and increased caries risk. Non-invasive treatments, such as casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and fluoride varnish, show potential in remineralizing affected enamel and reducing sensitivity, but their efficacy is still debated. This study systematically reviews and analyzes the effectiveness of CPP-ACP and other non-invasive agents in improving remineralization and reducing hypersensitivity in MIH-affected teeth. Methods: A systematic search was conducted on PubMed, Embase, and Central in July 2024, including interventional and observational studies on remineralization and hypersensitivity in pediatric MIH patients (<18 years). A total of 1566 studies were found, with 15 included in the meta-analysis. A random-effects model was applied, including subgroup analysis by lesion severity. Results: CPP-ACP showed no statistically significant advantage over fluoride in remineralization (MD -3.80, 95% CI: -8.57; 0.98), but it significantly reduced hypersensitivity compared to fluoride varnish (MD -2.36, 95% CI: -3.83; -0.89). Although this reduction in hypersensitivity may be clinically relevant, the high heterogeneity (I² = 83%) and wide confidence intervals limit the reliability of these findings. Conclusions: CPP-ACP has a moderate effect in reducing hypersensitivity but does not outperform fluoride in remineralization. Other agents, such as calcium glycerophosphate and silver diamine fluoride, showed mild benefits. The current evidence base is limited and heterogeneous, highlighting the need for high-quality, long-term studies to confirm these findings and guide MIH management.