Azevedo Sara Garcia, de Oliveira Lilianny Querino Rocha, Martelli-Júnior Hercílio, Coletta Ricardo D, Machado Renato Assis
Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, São Paulo, Brazil.
Graduate Program in Oral Biology, School of Dentistry, University of Campinas, Piracicaba, São Paulo, Brazil.
Oral Dis. 2025 Jan 6. doi: 10.1111/odi.15226.
To 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.
The 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.
Out 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 (OR: 3.72; p = 0.001) and macrodontia (OR: 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) (OR: 0.38; p < 0.0001) and in nonsyndromic cleft lip and palate (NSCLP) (OR: 0.44; 95% p < 0.0001). The results also demonstrated a higher risk of tooth agenesis (OR: 16.49; p < 0.0001), microdontia (OR: 17.14; p < 0.0001), macrodontia (OR: 10.41; p = 0.02), supernumerary tooth (OR: 10.03; p < 0.0001), and enamel hypoplasia (OR: 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 (OR: 6.24; p = 0.006) and nonsyndromic cleft palate only (NSCPO) (OR: 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 (OR: 139.19; p < 0.0001). In South America, significant associations were identified for NSCLP (OR: 2.16; p < 0.0001), NSCL ± P (OR: 2.48; p < 0.0001), and NSOC (OR: 2.72; p < 0.0001). In North America, tooth agenesis was more frequent in NSCL ± P (OR: 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 (OR: 19.57; p = 0.003) and supernumerary teeth (OR: 9.77; p < 0.0001). Asian populations showed similar patterns (OR: 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 (OR: 0.38; p < 0.0001) and NSCLP (OR: 0.44; p < 0.0001), with no associations identified for microdontia, taurodontism, supernumerary tooth, impacted tooth, or transposition.
The 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.
评估非综合征性口腔颌面部裂隙（NSOC）患者乳牙列和恒牙列中牙齿异常（TA）的发生频率，包括裂隙区域内外。
检索以下数据库中的相关文献：Cochrane、OVID、SciELO、Embase、Livivo、PubMed、Scopus和Web of Science。使用乔安娜·布里格斯研究所分析偏倚风险。进行固定效应和随机效应荟萃分析，比较NSOC亚型的有无。使用GRADE方法评估证据的确定性。
在识别出的1939篇文章中，应用纳入和排除标准后，共纳入75篇文章（46篇队列研究和29篇病例对照研究），包括来自34个国家的27,703名患者（16,450名NSOC患者和11,253名健康对照）。荟萃分析显示，与恒牙列对照组相比，裂隙区域外不同裂隙亚型的牙齿缺失（OR：3.72；p = 0.001）和巨牙症（OR：8.04；p = 0.04）的比值比更高，而仅非综合征性唇裂（NSCLO）（OR：0.38；p < 0.0001）和非综合征性唇腭裂（NSCLP）（OR：0.44；95% p < 0.0001）中牙根弯曲的频率显著更低。结果还表明，NSOC患者裂隙区域内恒牙列中牙齿缺失（OR：16.49；p < 0.0001）、小牙症（OR：17.14；p < 0.0001）、巨牙症（OR：10.41；p = 0.02）、多生牙（OR：10.03；p < 0.0001）和釉质发育不全（OR：5.62；p < 0.0001）的风险更高。然而，对于乳牙列，在裂隙区域外，与对照组相比，小牙症是NSOC患者（OR：6.24；p = 0.006）和仅非综合征性腭裂（NSCPO）患者（OR：8.45；p = 0.02）中唯一显著更常见的TA。TA关联在不同人群中有所不同。在欧洲，未发现NSOC有显著关联，而在亚洲，观察到NSCLP和NSCL±P有强关联（OR：139.19；p < 0.0001）。在南美洲，发现NSCLP（OR：2.16；p < 0.0001）、NSCL±P（OR：2.48；p < 0.0001）和NSOC（OR：2.72；p < 0.0001）有显著关联。在北美洲，NSCL±P中牙齿缺失更常见（OR：4.75；p < 0.0001），尽管未发现NSCLP或NSOC有显著关联。在裂隙区域，欧洲人群中NSOC有显著关联，包括牙齿缺失频率增加（OR：19.57；p = 0.003）和多生牙频率增加（OR：9.77；p < 0.0001）。亚洲人群表现出类似模式（OR：19.23；p = 0.002），而南美洲由于数据有限未发现显著关联。NSCLO（OR：0.38；p < 0.0001）和NSCLP（OR：0.44；p < 0.0001）中牙根弯曲仍然较少见，未发现小牙症、牛牙症、多生牙、阻生牙或牙齿移位的关联。
结果证实，与对照组相比，NSOC患者恒牙列中TA的发生频率更高，无论裂隙亚型如何。然而，根据TA发生在裂隙区域内还是外，观察到显著差异。尽管仅纳入了有限数量的研究，但小牙症是NSOC患者乳牙列裂隙区域中唯一显著更普遍的TA。TA频率在不同人群中的差异突出了影响这些关联的遗传、环境和方法学因素的复杂相互作用。尽管有这些发现，但现有证据的质量中等，存在样本量小、方法学差异和研究异质性等局限性。这些结果强调了针对不同裂隙亚型个体进行个性化牙科管理和早期干预策略的重要性，以有效解决和减轻这些牙齿异常对口腔健康和发育的影响。
