The qualitative synthesis of systematic review indicates that there is no observed association between MIH and specific malocclusion patterns. Furthermore, the relationship between MIH and orthodontic treatment is predominantly therapeutic in nature, rather than aetiological. Management of severely affected FPMs through extraction creates orthodontic considerations that can be successfully addressed through appropriate timing, patient selection, and interdisciplinary collaboration. Maxillary extractions yield superior outcomes to mandibular extractions in terms of spontaneous space closure. The optimal timing for extraction remains unclear; however, the included studies have indicated an age range of 6–10 years as ideal. Since it is generally not possible at this age to accurately verify the presence and angulation of third permanent molars, their premature extraction warrants careful consideration of potential long-term consequences. There exists a possibility that children may have a shortened dental arch or require complex and costly surgical and prosthetic interventions in the future (Radlanski 2002).

The current evidence base examining the relationship between MIH and orthodontic treatment has advanced over the past two decades, yet significant knowledge gaps persist.

A fundamental limitation across existing literature is the relatively restricted follow-up period (3–6 years). Most contemporary investigations, including the recent Gothenburg University (GuREx-MIH) trial (Hajdarevic et al. 2025b), achieve limited years of observational data. This pattern captures initial eruption patterns and early space closure, but fails to provide definitive information regarding long-term occlusal stability and the complete orthodontic implications extending into late adolescence and adulthood. Future prospective cohort studies should incorporate extended follow-up protocols extending minimum ten to fifteen years post-extraction to comprehensively evaluate final occlusal relationships, third molar integration, temporomandibular joint function, and periodontal health. Such longitudinal designs would establish whether early space closure patterns persist unchanged or require subsequent orthodontic intervention. Another limitation was the lack of control group in the included studies. Baseline data (before orthodontic treatment) or space closure outcomes with and without orthodontics could be implemented in future studies.

The specific finding that mandibular extractions yield less favourable spontaneous space closure compared to maxillary procedures warrants particular attention in long-term investigations (Brusevold et al. 2022). Understanding whether suboptimal mandibular space closure observed at five years stabilises naturally or progressively worsens would substantially inform clinical decision-making. Additionally, extended follow-up protocols could elucidate whether third molars that appear favourably positioned after early FPM extraction maintain optimal positioning into adulthood or become compromised by ongoing alveolar remodelling.

Research consistently demonstrates that maxillary extractions achieve nearly total space closure without orthodontic intervention, while mandibular outcomes prove substantially less predictable (Stabilini et al. 2025; Jälevik & Möller 2007; Brusevold et al. 2022). However, the biological mechanisms underlying this differential response remain inadequately understood. Future investigations might examine whether mandible-specific factors—including tongue factors, masticatory muscle condition and dynamics, or differences in cortical plate thickness—influence dentoalveolar remodelling patterns following extraction.

Development and validation of predictive models

In the frame of the present review, it was noticed that the currently available evidence has not adequately reported on several proposed predictive factors, including root developmental stage, presence of third molars, suggested age for extraction within studied ranges; yet clinicians lack reliable prognostic tools to anticipate individual outcomes. Future research should employ contemporary statistical approaches including machine learning algorithms and artificial intelligence applications to develop and validate predictive models integrating multiple variables simultaneously. These analyses should incorporate novel radiographic parameters including three-dimensional bone density measurements, trabecular bone patterns, alveolar height-to-width ratios, and precise angulation measurements obtainable through cone-beam computed tomography. Prospective multi-centre studies with standardized data collection protocols would provide the large datasets necessary for algorithm development. Once developed and validated, such models could enable clinicians to identify mandibular cases at particular risk for inadequate spontaneous space closure, facilitating earlier orthodontic referral and potentially improving outcomes through timely intervention.

Advanced radiographic methodology and three-dimensional imaging research

The GuREx-MIH study (Hajdarevic et al. 2025b) identified substantial radiographic positioning errors in 75% of panoramic radiographs, despite measurement reliability remaining satisfactory through ratio calculations. This finding raises important methodological questions regarding the optimal imaging approach for longitudinal eruption studies. Future investigations could systematically evaluate cone-beam computed tomography (CBCT) protocols that eliminate projection geometry concerns and provide volumetric analysis of alveolar bone changes, precise measurement of tooth displacement vectors, and assessment of root proximity relationships. While radiation dose considerations justify limited CBCT use in clinical practice, research-focused studies with appropriate ethical oversight could establish three-dimensional baseline data against which subsequent radiographic intervals are evaluated. Importantly, research should address the specific challenge of accurate angulation measurement on panoramic radiographs, examining whether software-based correction algorithms can compensate for positioning variability. Comparison studies between traditional panoramic radiography and contemporary three-dimensional reconstruction methods could establish consensus regarding optimal imaging methodology for future eruption studies.

Investigation of MIH severity progression and adult outcomes

Longitudinal studies comparing lifetime treatment burden, functional outcomes, and orthodontic treatment trajectories in patients managed through extraction versus conservative restoration would provide critical health services research evidence. Such investigations should incorporate quality of life measures, treatment satisfaction assessments, and economic analyses comparing total lifetime treatment costs across different management strategies.

Interdisciplinary treatment protocol development

FPM extraction decision-making is often demanding, and the structure and timing of an interdisciplinary collaboration remain largely undefined. Future research should develop, test, and validate standardized interdisciplinary protocols incorporating clear diagnostic criteria for mandatory orthodontic consultation, shared decision-making frameworks integrating paediatric dental and orthodontic perspectives, and defined communication pathways ensuring consistent information exchange. Implementation science approaches examining barriers and facilitators to adopting evidence-based collaborative protocols would help establish whether structured interdisciplinary protocols improve outcomes compared to traditional siloed specialist care. Research investigating optimal timing of orthodontic consultation—whether pre-extraction planning yields superior outcomes compared to post-extraction follow-up—would inform clinical practice guidelines. A prospective controlled design would probably fit this scope better, since randomisation would trigger ethical issues. Additionally, investigations examining whether specific orthodontic conditions (severe crowding, skeletal discrepancies, dental agenesis) meaningfully predict post-extraction treatment needs would enable targeted referral strategies.

Patient-centred outcome research

Current evidence base mainly emphasizes clinical outcomes including space closure percentages and tooth angulation parameters (Hajdarevic et al. 2025b; Jälevik & Möller 2007; Brusevold et al. 2022). Nevertheless, it substantially underrepresents patient-reported functional, aesthetic, and psychosocial outcomes. Future research should prioritize patient-centred investigations incorporating validated quality of life instruments, dental anxiety and fear assessments, functional outcome measures, and treatment satisfaction scales. Qualitative research examining patient and family perspectives on extraction versus restoration decision-making could illuminate previously unexplored aspects of shared decision-making. Notably, several patients in existing studies declined orthodontic treatment despite clinically evident treatment indications, suggesting that subjective treatment needs may diverge substantially from objective clinical findings. Future research should investigate factors determining this divergence and examine whether factors identified (patient age, socioeconomic status, dental anxiety, cultural perspectives) could guide clinicians in patient counselling regarding realistic expectations.