Association of hypomineralized second primary molars (HSPM) and hypomineralized primary canines (HPC) with molar-incisor hypomineralization (MIH): a systematic review and meta-analysis

Molar-incisor hypomineralization is a common developmental enamel defect associated with pain, functional limitations, and restorative challenges in children. Because of overlapping risk factors of HSPM and MIH, and shared formation period of the first permanent molar, second molar, and deciduous canine, an association is plausible. Several studies have shown that HSPM and/or HPC have an association with MIH; however, the results regarding the strength of these studies are conflicting. This systematic review and meta-analysis aimed to investigate the association of HSPM and HPC with MIH, and to update the existing evidence by including newly published studies. A comprehensive search was performed in PubMed, Scopus, Web of Science, Embase, ProQuest, and Google Scholar up to July 2025. Citation tracking was also applied to identify additional eligible studies. The methodological risk of bias was assessed using the Joanna Briggs Institute (JBI) checklists for cross-sectional, cohort, and case–control studies. The certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Random-effects meta-analysis was conducted with odds ratios (ORs) and 95% confidence intervals (CIs), using STATA version 18. Heterogeneity, sensitivity analyses, and publication bias were also examined. A total of 28 studies were qualitatively and 24 quantitatively analyzed (22,678 participants). The pooled crude OR for the MIH–HSPM association was 8.55 (95% CI: 4.72–15.50; I2 = 96.97%, p < 0.001), showing a strong and consistent association. Additionally, subgroup analyses were performed and study design and type of OR (crude vs adjusted) were the only factors showing a statistically significant difference across groups. No strong evidence of publication bias was detected (Begg’s p = 0.60; Egger’s p = 0.61). Only one study assessed the HPC–MIH association, reporting a significant but limited relationship (OR = 6.02; 95% CI: 1.46–24.75). Children with HSPM are approximately nine times more likely to present MIH. The evidence supports an association rather than a confirmed predictive relationship, mainly due to the predominance of cross-sectional studies and high heterogeneity. Further longitudinal studies are needed to clarify causality.