Introduction
Materials and methods
Eligibility criteria
Search strategy
Methodological evaluation of the publications
Statistical and analytical aspects
Results
Author- Year | Study design | Study population age(years) | Study group | Control group | Analysis | Results | Conclusions |
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Ahluwalia M, 2004. London [14] | Analytical prevalence | 6-16 | 81 | 41 | Microbiological culture Colony forming units (CFU/mL) Saliva samples | • Salivary levels of Streptococcus mutans, Lactobacillus spp and yeasts were significantly higher (p < 0.001) in children with cleft palate than in the control group. • Compared to children in the control group, children with cleft palate had significantly higher median DMFT 1 and median DFT 2 scores (p < 0.001). • Compared to children in the control group, children with cleft palate had a significantly higher gingival index (p < 0.001). | There was no clarity regarding the higher frequency of cavities in children with cleft palate. |
Lucas V, 2000. London [15] | Analytical prevalence | 3-15 | 60 | 60 | Microbiological culture Isolation frequency Dental plaque samples | • Streptococcus mutans, median 1.58 between the distal proximal site and the remote site of the maxillary cleft (p < 0.01) and median 2.13 between the contralateral anterior site and the remote site of the maxillary cleft (p < 0.04). • Lactobacillus spp., median of 0.46 between the distal proximal site, median of 0.23 in the anterior contralateral site and median of 0.18 in the remote site of the maxillary cleft (p > 0.05). | There were no significant differences between the children with CLP and the control group for the DMFT index, dental plaque and gingivitis in the deciduous and permanent dentition. |
Durhan M, 2018. Turkey [16] | Observational descriptive longitudinal prospective | 0-3 years (newborns) | 21 CLP | 13 | Microbiological culture CFU/mL Saliva samples | • Streptococcus mutans, present in the saliva samples of 10% of babies with CLP at birth. • Compared to the control group, 7 babies with CLP presented higher Lactobacillus spp infection at birth (p = 0.029), and 12 babies presented with a fissure after the eruption of the first deciduous tooth (p = 0.030). • There was no statistically significant relationship between initial caries and the presence of microorganisms. | Patients with CLP could be considered a group with a higher risk of caries. |
Sundell A, 2018. Sweden [6] | Cross section | 5 | 80 fissures | 144 | DNA–DNA hybridization Bacterial count Saliva samples | • Compared to the control group, children with fissures had a higher prevalence of caries (18% vs.36%; p < 0.05). • Streptococcus mitis (73% and 90%), Streptococcus gordonii (61% and 82%), Fusobacterium nucleatum (55% and 75%), and Rothia dentocariosa (50% and 58%) were frequently detected in the study and control groups, respectively. • Bifidobacterium dentium (6%), Fusobacterium nucleatum (55%), Streptococcus gordonii (61%), Streptococcus mitis (73%), Streptococcus salivarius (35%), and Veillonella parvula (6%) were less frequent in patients with CLP (p < 0.05). | Children with fissures had a higher prevalence of caries. |
Cocco JF, 2010. United States [17] | Analytical prevalence | 6-12 months | 35 primary cleft lip repair, 44 undergoing palatoplasty | --- | Microbiological culture Bacterial count Nasal, sublingual and oropharyngeal samples | • Klebsiella pneumoniae was present in the oropharynx of 56% of CLP patients with primary lip repair. • Increased Staphylococcus aureus colonization in 34% of patients with isolated cleft palate before the operation (p = 0.298). • Methicillin-resistant Staphylococcus aureus was present in 2.3% of patients at 6 months and increased to 4.5% at 12 months after palatoplasty. • Klebsiella pneumoniae and Enterobacter cloacae decreased significantly, by 14% and 4.5%, respectively, in the oropharynx 12 months after the closure of the palatal cleft (p < 0.05). • The major complication was palatal dehiscence and was directly related to group A beta-hemolytic Streptococcus (Streptococcus pyogenes) infection (no source data). | The colonization of Streptococcus pyogenes was associated with a high risk of wound dehiscence. |
Rawashdeh MA, 2011. Jordan [8] | Analytical cross section | 5-17 | 60 with fissures | 60 | Fungi culture Identification of Candida species Tongue, nasal mucosa and palatal samples | • Colonization by Candida spp. was greater in patients with bilateral CLP (77.7%) than in patients with unilateral CLP and cleft palate (57.1%). • There was a statistically significant difference in the rate of colonization by Candida spp, between patients with cleft palate who underwent 3 surgical interventions (78.2%) and those who underwent 1 surgical intervention (40%) (p = 0.01). • Cleft patients and the control group showed a gingival and plaque index of 1. • Cleft patients had significantly higher DMFT (3.3) and ceod (2.93) scores than did the control group (p = 0.0001 and p = 0.015). • Type of cleft and number of surgical interventions did not influence the gingival index, plaque index, of DMFT and ceod scores. | The patients with cleft presented greater colonization by oral Candida than did the control group; this varied with age, type of cleft and number of surgical interventions. |
Tuna E, 2008. Turkey [18] | Correlation cross section | ----------- | Complete unilateral CLP and complete bilateral CLP | --------- | Microbiological culture CFU/mL Salivary and nasal samples | • Staphylococcus aureus was present in 53.1% of saliva samples and 40.6% of nasal samples in fissured patients. | Children with oronasal fistula had a higher count of Staphylococcus aureus in saliva than did children without fistula. |
Arief E, 2005. Malaysia [19] | Before-after intervention | 3-39 months | 15 CLP | 22 | Microbiological culture CFU/mL Salivary samples | • Streptococcus mitis, preoperative 6%, postoperative 0%; Streptococcus biovar preoperative 25%, postoperative 28.7%; Streptococcus salivarius preoperative 21%, postoperative 23.8% and Streptococcus oralis, preoperative 21%, postoperative 28.7%. • Staphylococcus aureus was more frequent in patients with CLP in the preoperative phase (47.4%), with 0% in the postoperative phase; the difference was statistically significant (p < 0.05). | Patients with CLP presented greater colonization of microorganisms in the oral cavity. Colonization decreased after lip and palate repair. |
Cheng Ll, 2007. Australia [20] | Nonrandomized clinical trial | 12-17 | Two study groups with and without CLP and with orthodontic treatment | Two control groups with and without palatal CLP without orthodontic treatment | CRT bacteria test CFU/mL Salivary samples | • Lactobacillus spp, statistically significant differences in the percentages of subjects with ≥ 10 5 CFU/mL between the group with treatment without cleft (76.7%), the group with cleft treatment (73.3%), the control group without cleft (46.7%) and the control group with cleft (40%) under treatment with fixed appliances. • Highest and lowest percentages of subjects with ≥ 10 5 CFU/mL of Streptococcus mutans were in the group without cleft with treatment (86.7%) and the group with cleft treatment (60%). | Children with CLP and fixed orthodontics had more favorable microbiological and salivary profiles for the development of caries. |
Funahashi K, 2019. Japan [21] | Series of cases operated | 7-15 | 6 CLP | 4 | Bacterial identification 16S rRNA OTU (operational taxonomic units) Supragingival plaque samples | • The most predominant genera were Actinomyces spp (14.0% in the CLP group and 10.6% in the control group), Corynebacterium matruchotii and Leptotrichia hofstadii, (4.9 ± 0.80% in the cleft lip and palate group and 4.3 ± 4, 1% in the control group). • Fifteen taxa were identified in the group with CLP and 3 taxa in the control group: Lactobacillus rhamnosus, Lactobacillus fermentum, Streptococcus salivarius, Prevotella pallens, Aggregatibacter aphrophilus, Streptococcus gordonii, Streptococcus cristatus, Prevotella pleuritidis, Capnocytophaga gingivalis, Prevotella marshii, Prevotella micans, Streptococcus anginosus spp., Catonella morbi and Selenomonas artemidis in the CLP group and Prevotella loescheii, Stomatobaculum longum, and Streptococcus sanguinis in the control group. • Leptotrichia spp. and Neisseria spp. were the most predominant genera on average in the CLP group and in the control group (13.2% and 16.8%), respectively. • Gingival index score was higher than 0 for 2 subjects with CLP and 1 control subject. • DMFT score was greater than 0 for 3 subjects with CLP and 1 control subject. | Functional dysbiosis in the oral microbiota in patients with CLP changed unpredictably and could be associated with cariogenicity. |
Liu L, 2016. United States [9] | Before and after | 8-16 | 28 CLP | --- | Bacterial identification 16S rRNA OTU (operational taxonomic units) Saliva samples | • The most abundant phyla were Firmicutes spp (mean of 38.1% in the inflammation group and mean of 39.3% in the noninflammation group), Proteobacteria spp (31.2% in the inflammation group and 32.9% in the noninflammatory group), Bacteroidetes spp (17.8% in the inflammation group and 16.1% in the noninflammation group), Actinobacteria spp (7.4% in the groups with and without inflammation), and Fusobacteria spp (3.6% in the inflammation group and 2.5% in the noninflammation group). These five predominant phyla constituted 98.1% of the total microbiota in the inflammation group and 98.2% of the total microbiota in the noninflammation group. • Inflammation-related OTUs were Tannerella spp, Porphyromonas spp, Gemella spp, Moraxella spp, Prevotella nigrescens and Prevotella intermedia. • Related OTUs without the presence of inflammation were Lautropia spp, Neisseria spp, Capnocytophaga spp, Veillonella dispar, Veillonella parvula and Prevotella melaninogenica. • OTUs corresponding to Streptococcus spp. and Prevotella spp. were present in both groups. • Enriched OTUs in subjects without inflammation showed a positive correlation (Spearman's correlation coefficient t > 0.4, P < 0.05). • Inflammation-enriched OTUs included Tannerella spp., Porphyromonas spp., Gemella spp., Moraxella spp., and Prevotella nigrescens. | The salivary microbial composition varied significantly by surgical procedures between subjects with CLP with postoperative inflammation and without inflammation. |
Hassani H, 2020. United States [22] | Nonrandomized clinical trial | 2-11 months | 23 with nasoalveolar molding, 8 without nasoalveolar molding | 30 | CRT bacteria test Colony count Saliva samples | • Streptococcus mutans colony count, median 63; Lactobacillus spp. colony count, median 464.1; Streptococcus mutans caries risk test, median 3; and Lactobacillus risk test, median 2.6, were significantly different (p < 0.0001) in patients with CLP with a nasoalveolar molding. | There was a high bacterial count and high risk of caries in the group that used nasoalveolar molding. |
Zhang M, 2016. Amsterdam [2] | Nonrandomized clinical trial | 1 year | 10 | 10 | PCR-DGGE Bacterial composition Saliva and nasal samples | • Lautropia spp. (40%) and Bacillus spp. (10%) were significantly less present in the saliva samples of the group with complete cleft palate (P = 0.029). • Dolosigranulum spp. (100%) were more predominant in the nasal cavity of the control group and less frequent (50%) in the group with complete cleft palate (P = 0.016). • Bacillus spp. (10%) was present in the nasal samples of the group with complete cleft palate (P =.029). • Streptococcus spp. (80%) were more prevalent in nasal swabs from children with CLP than in those from children in the control group (p = 0.012). | The altered ecological ecosystem in the oral and nasal microbiome of children with cleft palate is presented as a consequence of abnormal communication between the two cavities. |
Loveren C, 1998. The Netherlands [23] | Analytical prevalence | 12 to 18 months | 21 who use PNAM, 28 with cleft lip and palate | 35 | Microbiological cultures CFU/μL Saliva and dental plaque samples | • At 18 months of age, there was no difference in the prevalence of Streptococcus mutans (20%) (chi-square P = 0.4). • All children with an acrylic plate colonized with Streptococcus mutans, at the age of 9 and 13 months, were colonized with Lactobacillus spp. • In 6-month-old children, 80 strains of Lactobacillus spp. were identified Three of these strains were identified as Lactobacillus jensenii. • Presence of Lactobacillus spp., with the possibility of 8 (95% CI 1.5-43.2; p < 0.05) stemming from presurgical orthopedics. | The presence of Streptococcus mutans in the saliva of children with oral fissure was associated with the consumption of snacks and with the presence of Lactobacillus spp. |
Bokhout B, 1996. The Netherlands [24] | Analytical prevalence | 62 children between 18 months and their mothers | --- | ------ | Microbiological cultures CFU/mL Saliva and dental plaque samples | • Streptococcus mutans in saliva (45.2%) and in plaque (48.4%); Lactobacillus spp, 16.1% in saliva and 8.1% in plate. • Cleft lip: Streptococcus mutans in saliva (38.5%) and in teeth (23.1%); Lactobacillus spp in saliva and teeth (0%). • Alveolar cleft lip: Streptococcus mutans in saliva (50%), in teeth (40%); Lactobacillus spp in saliva (20%) and in teeth (0%). • Unilateral cleft lip and palate: Streptococcus mutans, in saliva (44.4%) and in teeth (61.1%); Lactobacillus spp., in saliva (33.3%) and in teeth (22.2%). • Bilateral cleft lip and palate: Streptococcus mutans, in saliva (57.1%) and in teeth (71.4%); Lactobacillus spp., in saliva (14.3%) and in teeth (14.3%). • Palatal cleft: Streptococcus mutans, in saliva (42.9%) and in teeth (50%); Lactobacillus spp, in saliva (7.1%) and in teeth (0%). • Lactobacillus spp, in saliva OR 4.7 (95% CI, 1.00-22.45). • Lactobacillus spp in the saliva of the children depended on the presurgical orthopedics, OR 4.8 (95% CI, 1.10-20.92). | Children with fissures had an increased risk of being infected with Streptococcus mutans and Lactobacillus spp. at a very early age, and colonization indicated a high risk of caries in the primary dentition. |
Perdikogianni H, 2009. Greece [11] | Analytical cross section | 4-18 | 41 | 41 | Microbiological culture CFU/mL Subgingival plaque samples | • Gram-positive facultative anaerobic cocci, Gemella haemolysans, Streptococcus spp., 7.9 x 106 in fissured children's molars and 8.7 X 107 in control molars; gram-positive facultative anaerobic bacilli, Actinomyces spp., Lactobacillus spp., and Rothia dentocariosa, 5.2 X 106 in fissured child molars and 4.3 X 106 in control molars; facultative gram-negative anaerobic bacilli Capnocytophaga spp., Eikenella corrodens, and Haemophilus spp., 3.8 X 106 in fissured children's molars and 3.0 X 107 in control molars; gram-negative anaerobic bacilli, Bacteroides spp., Bilophila wadsworthia, Campylobacter spp., Wolinella spp., Fusobacterium spp, Porphyromonas gingivalis, Prevotella intermedia / nigrescens, Prevotella loeschii, Prevotella melaninogenica, Prevotella melaninogenica, and Prevotella spp., 5.5X 106 in fissured child molars and 4.0 X 105 in control molars (p < 0.005). • There was a significant difference in the probing depth of the upper anterior teeth between the study group and the control group (p < 0.05). • The teeth close to the cleft in the study group were significantly different (p < 0.05), with a higher percentage of surfaces that bled (42%) on probing compared to the upper incisors (IU) of the control group (29%). Children with CLP had a 20% of teeth mobility score of 3. | Compared to controls, young people with CLP showed poor oral hygiene and poor periodontal status. |
Quirynen M, 2003. Belgium [25] | Analytical cross section | 8-18 | 75 Bilateral CLP with orthodontic treatment | ---- | Microbiological culture CFU/mL Saliva, dental plaque and teeth samples | • Prevotella intermedia (58.7% vs. 38.7%), Peptostreptococcus micros (24% vs. 16%), and Campylobacter rectus (56% vs. 46.6%) were slightly higher but not significantly different for neighboring cleavage sites than for contralateral opponents. • There was a significant difference in the median plaque index (1.03) between the sites neighboring the cleft, the contralateral tooth and the teeth neighboring the cleft (p = 0.01). • Teeth near or neighboring the cleft had a significantly (p < 0.01) greater probing depth and greater losses > 2 mm than their contralaterals. | The teeth adjacent to the unilateral cleft of the lip and palate were not necessarily predisposed to attachment loss. |
Da Silva J, 2018. Brazil [26] | Prospective longitudinal descriptive | 0-12 | 46 orofacial clefts indicated for surgical rehabilitation | ------- | Fungi cultivation Identification of Candida species Presurgical samples of the orofacial and postsurgical fissure of the oral cavity | • Before asepsis in the operating room, they observed oral colonization of candida species in 18 patients (39.1%): Candida albicans (15.2%; ≥ or <350 cfu/mL), Candida tropicalis (17, 4%; ≥ or <350 cfu/mL) and Candida krusei (8.7%; ≥ or <350 cfu/mL) • Candida spp. frequency of 39.1%, with no correlation with the different types of orofacial clefts or surgical history. • A patient with CLP was suspected to have Candida tropicalis ≥ 350 cfu/mL. | The anatomical and physiological characteristics of patients with orofacial clefts could influence the frequencies and dynamics of oral colonization of Candida spp. |
Costa B, 2003. Brazil [10] | Cross section | 5-6 | 30 CLP | 27 | Microbiological cultures CFU/mL Subgingival plaque samples | • Prevotella nigrescens (16.67%) was detected in the experimental group and in the control group (11.11%); Porphyromonas gingivalis and Treponema denticola were not detected. • Mean gingival index in the experimental group (1.82 ± 0.38) was significantly higher (p < 0.05) than that in the control group (0.79 ± 0.33). • Children in the experimental and control groups presented moderate plaque index scores (73.33% and 81.48%, respectively) and high prevalences of mild gingivitis (53.33% and 70.37%). | Children with cleft showed greater gingival inflammation and prevalence of pathogenic microorganisms. |
Thomas G, 2012. United Kingdom [27] | Prospective longitudinal descriptive (Incidence) | 12 months | 144 patients: | --- | Microbiological cultivation Nasal and oropharyngeal samples | • 47 patients were positive for Staphylococcus aureus (21%), < Streptococcus B-hemolytic (3%) and Streptococcus pneumonia, Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus millerae, Enterococci spp., Coliforms spp., Moraxella spp., and Isolate diphteroides spp. • Beta-hemolytic Streptococcus was more common in patients with bilateral CLP before surgery (no source data). • No significant difference was detected in the number of patients with a positive microbiological culture preoperatively compared to perioperatively (48% and 50%). | Preoperative microbiota could not be considered as a predictor of the nasal and oropharyngeal flora at the time of surgery. |
Hupkens P, 2007. The Netherlands [28] | Before-after intervention | 1-12 | 124 palatal surgery patients | --- | Microbiological cultures Nasal samples and oropharyngeal mucosa | • Positive cultures for Streptococcus spp. presented in combination with cultures with Staphylococcus aureus. • 8 patients with wound infection presented 46 Haemophilus influenzae, 10 Staphylococcus aureus, 30 Streptococcus pneumoniae, 8 Streptococcus Hemolytic group A, 8 Streptococcus Hemolytic group B, 3 Streptococcus Hemolytic group C, 0 Streptococcus Hemolytic group G, 1 Klebsiella ozaena, 4 Klebsiella pneumoniae, 2 Serratia liquefaciens, 31 Moraxella catarrhalis, 4 Pseudomonas spp., 9 Escherichia coli, 5 Acinetobacter spp., 1 Citrobacter spp., 3 Enterobacter cloacae, 1 Xanthomonas maltoph, 1 Candida albicans, and 1 other yeast. • Of the 124 patients, 8 had positive preoperative cultures for group A Streptococcus. | The surgical wound represented the entry of microorganisms which invaded the surgical field. |
Sundell A, 2015. Norway [29] | Cases and controls | 5-10 | 133 CLP | 297 | Dentocult® SM-Strip mutans, Dentocult® LB Microbiological evaluation Saliva samples | • Compared with children in the control group, children with CLP presented significantly higher counts of Lactobacillus spp.; low risk, 81%; moderate risk, 17%; and high risk, 2% (p < 0.05). • There was no increase in Streptococcus mutans counts in children with CLP. • Probability of being categorized with high caries risk in the CLP group was significantly high (OR = 1.89; 95% CI = 1.25-2.86). | Children with CLP were more likely to be classified at high risk of cavities and high counts of Lactobacillus spp. |
Machorowska A, 2017. Poland [1] | Cases and controls | Neonates | 30 patients, after 37 weeks, with complete unilateral or bilateral cleft lip and palate 25 patients with isolated soft palate cleft. | ---- | Microbiological cultures Palatal mucosa samples at the margin of the fissure, dorsum of the tongue and palatal mucosa. | • Patients with CLP presented with significantly higher levels of Streptococcus mitis, 63.3% (p = 0,002); Streptococcus salivarius, 26.6% (p = 0,022); Staphylococcus aureus MSSA, 40% (p < 0.001); Staphylococcus epidermidis, 33.3% (p < 0.001); Enterobacter cloacae, 10% (p = 0.007); Klebsiella pneumoniae, 20% (p < 0.001); and Klebsiella oxytoca, 16.6% (p < 0.001). • After surgery, there was a statistically significant increase in the percentage of Gemella morbillorum (24%) (p = 0.041). • Streptococcus salivarius in the CLP group after surgery was 22 times higher than before surgery, OR = 22 [95% CI, 2.96-16.21]. • Odds ratio for Staphylococcus aureus MSSA, OR = 16 [95% CI, 2.12-12.65] and Klebsiella oxytoca, OR = 18 [95% CI, 2.40-13.83], was between 16 and 18 times higher after surgery. | The development of the microbiota in children with CLP was accompanied by a significant increase in commensal and potentially pathogenic organisms. Patients with CLP are at increased risk of developing oral infectious |
Risk of bias analysis of the studies included in the meta-analysis
Cariogenic microbiota and its relationship with dental status
Periodontopathogenic microbiota and its relationship with the periodontal state.
Oral microbiota and its relationship with type of fissure
Oral microbiota and its relationship with surgical intervention
Quantitative analysis
Results of the meta-analysis
Streptococcus mutans
Lactobacillus
Caries risk
Discussion
Conclusions
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The present investigation identified that patients with CLP had higher counts of Streptococcus mutans and Lactobacillus spp.
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The results of the meta-analysis suggest that individuals with CLP may have greater risk of developing dental caries; therefore, this risk should be taken into account when making clinical decisions and adopting preventive measures to reduce oral comorbidities in these patients.
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Periodontopathogenic bacteria were observed in fissure areas, highlighting the presence of Porphyromonas gingivalis.
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The sites adjacent to a fissure have higher plaque index and gingival index values, a deeper probing depth and greater loss of attachment.
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The larger the oronasal fistula is, the greater the percentage of Staphylococcus spp.