Background: Developmental enamel hypomineralisation is characterised by qualitative defects in enamel mineralisation that affect both primary and permanent dentitions. Proteomic studies have provided novel insights into the molecular mechanisms underlying these conditions; however, an updated critical appraisal integrating the available evidence across both Molar–Incisor Hypomineralisation (MIH) and Hypomineralised Second Primary Molars (HSPM) is needed. Methods: A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA 2020 guidelines. PubMed/MEDLINE, Embase, Scopus, and Web of Science were searched from inception until 30 July 2026. Observational and laboratory studies examining proteomic changes in enamel, saliva, or other oral biological samples from individuals diagnosed with MIH or HSPM were included. Risk of bias was assessed using the revised Joanna Briggs Institute (JBI) tool and the Quality Assessment Tool for In Vitro Studies (QUIN). Results: Ten reports satisfied the inclusion criteria, representing nine independent primary datasets. Consistent findings included increased retention of serum-derived proteins, particularly albumin, alongside enrichment of protease inhibitors and inflammatory proteins within hypomineralised enamel. Additionally, alterations in proteins involved in enamel matrix processing and maturation, including matrix metalloproteinase-20 (MMP20) and kallikrein-related peptidase 4 (KLK4), were identified. Salivary analyses revealed quantitative differences in proteins involved in immune, inflammatory and mineralisation-related pathways. Both shared and distinct proteomic features were observed across hypomineralised enamel in the primary and permanent dentitions. Conclusions: Current evidence indicates recurrent proteomic alterations in developmental enamel hypomineralisation, particularly impaired enamel maturation, abnormal retention of serum-derived proteins, and alterations in inflammatory pathways. Further standardised proteomic studies are needed to validate these findings and assess their potential as biomarkers.

Background: Molar–incisor hypomineralization (MIH) is a common developmental enamel defect that presents important diagnostic and therapeutic challenges in pediatric dentistry. Differences in dental professionals’ knowledge and clinical confidence may affect patient care. Aim: To evaluate dental professionals’ awareness, diagnostic confidence, clinical management, referral practices, and training related to MIH. Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Random-effects meta-analyses were performed to calculate pooled estimates, with subgroup analyses by geographic region, dental specialty, and risk of bias. Results: Thirty-six observational studies including over 10,000 dental professionals were included. Awareness of MIH diagnostic criteria was moderate (72.1%) and higher among pediatric dentists than general dental practitioners. Diagnostic confidence (67.5%) and comfort in providing treatment (64.1%) were suboptimal, particularly among non-specialists. Most respondents perceived a distinct caries pattern in MIH-affected teeth (84.8%), while referral to pediatric dentists was inconsistent (52.5%). Approximately 80% of participants reported a need for additional MIH-related training. Substantial heterogeneity was observed across analyses. Conclusions: Despite moderate awareness of MIH, important gaps persist in diagnostic confidence, clinical management, and referral practices. Strengthening undergraduate education, continuing professional development, and structured referral pathways is essential to improve early diagnosis, appropriate management, and outcomes for children affected by MIH, highlighting the pivotal role of paediatric dentists in interdisciplinary care.