Tooth Anomalies in Patients With Nonsyndromic Orofacial Cleft: A Systematic Review and Meta‐Analysis
Authors: Azevedo Sara Garcia , de Oliveira Lilianny Querino Rocha , Martelli‐Júnior Hercílio , Coletta Ricardo D. , Machado Renato Assis 
Published: January 2025

ABSTRACTObjectiveTo evaluate the frequency of tooth anomalies (TA) in the deciduous and permanent dentition of patients with nonsyndromic orofacial clefts (NSOC), both inside and outside the cleft area.MethodsThe following databases were searched for the relevant literature: Cochrane, OVID, SciELO, Embase, Livivo, PubMed, Scopus, and Web of Science. The risk of bias was analyzed using the Joanna Briggs Institute. Fixed and random‐effects meta‐analysis was performed comparing the presence and absence of NSOC subtypes. The certainty of evidence was evaluated using the GRADE approach.ResultsOut of 1939 articles identified, after applying the inclusion and exclusion criteria, a total of 75 articles were included (46 cohort and 29 case–control), including 27,703 patients (16,450 with NSOC and 11,253 healthy controls) from 34 countries. The meta‐analyses revealed higher odds for tooth agenesis (ORNSOC: 3.72; p = 0.001) and macrodontia (ORNSOC: 8.04; p = 0.04) across the different cleft subtypes outside the cleft area compared with the control group in the permanent dentition, whereas the frequency of root dilaceration was significantly lower in nonsyndromic cleft lip only (NSCLO) (ORNSCLO: 0.38; p < 0.0001) and in nonsyndromic cleft lip and palate (NSCLP) (ORNSCLP: 0.44; 95% p < 0.0001). The results also demonstrated a higher risk of tooth agenesis (ORNSOC: 16.49; p < 0.0001), microdontia (ORNSOC: 17.14; p < 0.0001), macrodontia (ORNSOC: 10.41; p = 0.02), supernumerary tooth (ORNSOC: 10.03; p < 0.0001), and enamel hypoplasia (ORNSOC: 5.62; p < 0.0001) in the permanent dentition inside the cleft area of patients with NSOC. However, for the deciduous dentition, outside the cleft area, microdontia was the only TA significantly more frequent in patients with NSOC (ORNSOC: 6.24; p = 0.006) and nonsyndromic cleft palate only (NSCPO) (ORNSCPO: 8.45; p = 0.02) compared with the control group. TA associations varied across populations. In Europe, no significant associations were found for NSOC, while in Asia, strong associations were observed for NSCLP and NSCL ± P (ORNSCLP and NSCL±P: 139.19; p < 0.0001). In South America, significant associations were identified for NSCLP (ORNSCLP: 2.16; p < 0.0001), NSCL ± P (ORNSCL±P: 2.48; p < 0.0001), and NSOC (ORNSOC: 2.72; p < 0.0001). In North America, tooth agenesis was more frequent in NSCL ± P (ORNSCL±P: 4.75; p < 0.0001), though no significant associations were found for NSCLP or NSOC. In the cleft area, significant associations were observed in European populations for NSOC, including increased frequencies of tooth agenesis (ORNSOC: 19.57; p = 0.003) and supernumerary teeth (ORNSOC: 9.77; p < 0.0001). Asian populations showed similar patterns (ORNSOC: 19.23; p = 0.002), while no significant associations were noted in South America due to limited data. Root dilaceration remained less frequent in NSCLO (ORNSCLO: 0.38; p < 0.0001) and NSCLP (ORNSCLP: 0.44; p < 0.0001), with no associations identified for microdontia, taurodontism, supernumerary tooth, impacted tooth, or transposition.ConclusionThe results confirm a higher frequency of TA in the permanent dentition of patients with NSOC compared to controls, regardless of cleft subtype. However, significant differences were observed depending on whether the TA occurred inside or outside the cleft area. Although only a limited number of studies were included, microdontia was the only TA significantly more prevalent in the cleft area of patients with NSOC in the deciduous dentition. Variations in the frequency of TA across populations highlight the complex interplay of genetic, environmental, and methodological factors influencing these associations. Despite these findings, the quality of the existing evidence is moderate, with limitations stemming from small sample sizes, methodological variations, and study heterogeneity. These results emphasize the importance of tailored dental management and early intervention strategies for individuals with different cleft subtypes to effectively address and mitigate the impact of these tooth anomalies on oral health and development.