What is the clinical evidence of Bulk Fill resins performance of in primary and permanent teeth? a systematic review and meta-analysis

With the increasing acceptance of the clinical use of bulk-fill resins, it is necessary to investigate the in vivo performance of these restorative materials. In this perspective, this systematic review to evaluate the clinical performance of Bulk-fill resins in restorations of vital, primary and permanent posterior teeth. PubMed, Cochrane, Scopus, LILACS, BBO and Capes publications search base were searched without restriction regarding the year of publication or language of the article. The inclusion criteria were clinical trials that evaluated the efficacy of resins composed of bulk-fill compared to the incremental technique. For the selection of articles and data extraction, two calibrated evaluators evaluated abstracts and complete articles. A total of 1443 abstracts were identified, of which 14 articles were included in the review. Of these, 01 was classified with a high level of evidence; 08 were moderate and 05 with a low level of evidence. The studies presented an average follow-up of the restorations of 35.1 months. A large part of the studies (75%) demonstrated that the occurrence of postoperative sensitivity. The high failure rate was more prevalent in class II restorations. The marginal adaptation/color change was material dependent and the occurrence of secondary caries in bulk-fill resin restorations was not significant concerning conventional resins in most studies. In the short term, the satisfactory clinical performance of bulk-fill resins used in primary and permanent restorations, with clinical outcomes and results equivalent to conventional composite resins were observed.


Introduction
The decrease in tension and polymerization shrinkage stresses of composite resin is a great desired challenge, contributing to a good clinical performance of direct restorations (Al Sunbul et al., 2016;Gonçalves et al., 2008;Stansbury et al., 2005). Thus, materials have been investigated, such as bulk-fill resins, which besides having a simplified technique, are promising for restorations in extensive cavities of posterior teeth (Alkurdi & Abboud, 2016;van Dijken & Pallesen, 2014. In vitro studies have demonstrated that bulk-fill resins present microhardness values (Fronza et al., 2015), polymerization shrinkage (Schneider et al., 2010), conversion degree (Czasch & Ilie, 2013;Fronza et al., 2015) and marginal sealing (Orlowski et al., 2015) equivalent to the conventional resins inserted by the incremental technique. Bulk-fill resins present as an advantage the reduction of clinical time, since they may be inserted and photopolymerized in large increments (4-5mm) (Olegário et al., 2017;Roggendorf et al., 2011).
The evaluation of the polymerization shrinkage of composite resin restorations is largely related to marginal adaptation and sealing within the cavity (Schneider et al., 2010). Clinical assessments have shown that an inappropriate marginal adaptation of the resin may lead to gaps formation and consequently trigger postoperative sensitivity (Reis et al., 2015), marginal discoloration (Heintze et al., 2009) and/or secondary caries (Dennison & Sarrett, 2012). Besides, high polymerization tension may lead to cusp deflection, increasing the likelihood of dental hypersensitivity or cracks/fractures formation in the cavity walls (Ferracane & Hilton, 2016).
It is known that the results of in vitro studies cannot be extrapolated to the definition of clinical behavior (Heintze et al., 2015). Once verified satisfactory laboratory results with the use of bulk-fill resins, the clinical performance and longevity of these treatments must be confirmed through randomized clinical trials (Alkurdi & Abboud, 2016;van Dijken & Pallesen, 2014. Through clinical evaluation of direct restorations, it is possible to evaluate parameters such as color stability, anatomical form, marginal adaptation/discoloration, postoperative sensitivity, and surface roughness, besides allowing the early diagnosis of secondary caries lesions (Alkurdi & Abboud, 2016;van Dijken & Pallesen, 2014. With the performance of randomized clinical trials (RCT) and systematic reviews of RCTs, more reliable evidence on the effects of interventions may be achieved (Higgins et al., 2011). A systematic analysis of the efficacy and longevity of bulkfill resins restorations in vital posterior teeth allows the acquisition of greater scientific evidence on the clinical performance of Research, Society andDevelopment, v. 10, n. 10, e552101018981, 2021 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v10i10.18981 3 these composite resins. Based on the investigations, it is possible to identify the operative steps and identify the clinical conditions capable of resulting in greater success in the restorative treatment.
Thus, the present study aimed to conduct a systematic review and meta-analysis to indicate more consistent evidence on the clinical efficacy of bulk-fill resins in restorations of primary and permanent posterior teeth. For this systematic review, the PICO question was applied: Population (posterior teeth with restorative need); Intervention (restorations class I and II with bulk-fill resins on posterior teeth); Comparison (restorations class I and II with composite conventional resins on posterior teeth); and Outcomes (postoperative sensibility, discoloration and marginal adaptation, secondary caries, anatomical form, texture and surface roughness).

Methodology
The systematic review was conducted according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) (Moher et al., 2009) and submitted to PROSPERO (CRD 42017064063).

Eligibility Criteria
In this systematic review were included randomized and non-randomized clinical trials, without considering a minimum follow-up time, which was in agreement with the PICO question. The exclusion criteria were: cohort studies; casecontrol studies; case reports or case series; letters to the editor; abstracts and randomized and non-randomized clinical trials evaluating anterior tooth restorations, early-stage clinical studies, in vitro studies; dissertations and theses that did not generate a published article. Source: Authors. .

Results
A total of 1436 articles were identified in the detailed searches. And through additional searches, 7 articles were found. With the removal of duplicate articles, a total of 937 articles remained (Figure 1). After the reading of the titles and abstracts, 18 articles were pre-selected. After the complete reading of the articles, 14 articles were included in the systematic review. The excluded studies were due to the following reasons: 01 article (Olegário et al., 2017) it was a clinical study in the early phase/l and the treatment application had not yet begun; 01 study (Karaman et al., 2016) was performed only with endodontically treated teeth, being excluded because it did not allow the evaluation of the postoperative sensitivity criterion; 01 study did not approach bulk-fill resins (Casagrande et al., 2013); finally 01 study (Kurdi & Abboud, 2016) was excluded because it is the same study published in two different journals. In this case, the paper with the greatest impact was selected (Alkurdi & Abboud, 2016). The final selection consisted of 14 articles that were included in the systematic review. For the quantitative evaluation, only 12 studies were included, 02 studies were excluded (Costa et al., 2017;Hickey et al., 2016) due to their short follow-up.

Characteristics of the included articles
Among the studies included in this review, 04 studies (Arhun et al., 2010;Atabek et al., 2017;Bayraktar et al., 2017;Çolak et al., 2017) did not describe the sample calculation. The number of restorations performed in these studies ranged from 60 to 236. The method of assessing the clinical outcomes for the majority (85.7%) of the studies followed the modified USPHS criteria, with only one study (Hickey et al., 2016) having applied a LIKERT scale, and other (Costa et al., 2017) using the World Dental Federation criteria and SQUACE criterion.  (Oter et al., 2018) in these studies the evaluators were not masked for outcome assessment either, as in the study by Bayraktar et al.(Bayraktar et al., 2017) the evaluators also were not masked.
Among all the restorations included in the evaluated studies, most failed due to the occurrence of caries, composite resin fracture, marginal discoloration, among other causes over time (Table 2).
According to the results obtained; only one clinical trial involving the evaluation of bulk-fill resin in primary teeth was found; (Oter et al., 2018). Regarding the severe postoperative sensitivity, only the study by Alkurdi and Abboud (Alkurdi & Abboud, 2016) demonstrated the need to exchange the restoration in the bulk-fill group.
The highest failure rate occurred in class II restorations, with no significant difference between conventional and bulk-fill resins (Costa et al., 2017;van Dijken & Pallesen, 2015. These failures in Class II restorations occurred on average with 2.5 years after their confection and had several reasons, such as: tooth fracture, caries occurrence or fracture of the composite resin (Arhun et al., 2010;van Dijken & Pallesen, 2015

Evaluation of the study quality
The quality of the studies is presented in Table 3. The value of the methodological quality scores of the studies ranged from 20-90%, with an average score of 48.57%. Only the study by Costa et al.(Costa et al., 2017) was classified with a high level of evidence. Eight studies were classified with a moderate level of evidence and five as a low level of evidence (Table 3).
With the studies quality data, it may be observed that two studies ( (Yazici et al., 2017). The losses in the follow-up were lower than 20% of the total sample (Table 3).

Discussion
With the increasing acceptance of the clinical use of bulk-fill resins, it is necessary to investigate the in vivo performance of these restorative materials. In this perspective, this systematic review indicates that the composite resins; conventional (incremental technique) and bulk-fill (increment up to 5mm), presented in short and medium-term, a satisfactory clinical performance in primary and permanent posterior teeth. Most of the clinical outcomes evaluated in the different studies were similar for the two types of resin used.
The systematic review and meta-analysis performed by Veloso et al., 2018(Veloso et al., 2018  showing no difference between conventional resin and bulk-fill resin when evaluated for a period of up to 10 years of followup. The selection of quality clinical studies, that is, with a low occurrence of bias (Hickel et al., 2007;Schulz et al., 2011) gives validity to the findings. However, for this systematic review, no clinical study was free of potential biases. In the clinical trials analyzed, were observed failures in the randomization (Alkurdi & Abboud, 2016; Atabek et al., 2017), masking (Hickey et al., 2016) and calibration (Bayraktar et al., 2017;van Dijken & Pallesen, 2014 that as reposted in the literature (Ástvaldsdóttir et al., 2015) may compromise the interpretation of findings that should be carefully analyzed.
The clinical longevity of composite resin restorations was analyzed in the study through outcomes such as: postoperative sensitivity, marginal discoloration/adaptation, secondary caries, anatomical form, texture and surface roughness.
Most of the studies (87,5%) (Alkurdi & Abboud, 2016;Bayraktar et al., 2017;Oter et al., 2018;van Dijken & Pallesen, 2014Yazici et al., 2017) clinically evaluated the restorations by the modified USPHS method, which is a widely used instrument (Hickel et al., 2010) and congregate all the outcomes previously mentioned. However, in the study by Hickey et al. (Hickey et al., 2016), the LIKERT scale was used, which is a validated scale used to verify the outcome of the dental sensitivity and masticatory discomfort (Hickey et al., 2016) .
The postoperative sensitivity outcome may be influenced by factors, such as: the previous condition of the teeth regarding the extension and depth of the cavities (Hickey et al., 2016), the formation of gaps (Reis et al., 2015), the polymerization stress and shrinkage (Braga et al., 2005;Kwon et al., 2012), observed in the teeth restored with bulk-fill resin and conventional resin, although two days after the procedure, the teeth restored with bulk-fill presented a significant increase in the degree of postoperative sensitivity when compared to the conventional resin. However, after the 7th day, this difference was not significant (Hickey et al., 2016). It is suggested that the postoperative sensitivity has been influenced by the previous existence of carious lesions and depth/extension of the cavity preparation since there was no standardization or depth measurement of the same.
A severe postoperative sensitivity was verified by Alkurdi and Abboud (Alkurdi & Abboud, 2016) in two cases of class II restorations with bulk-fill resin (Tetric N-Ceram Bulk-fill) in premolars, requiring the replacement of the restorations and performing the endodontic treatment. It is worth mentioning that the premolar teeth present more evident pulp horns, with less dentin on the pulp chamber when compared to the permanent molars (Alkurdi & Abboud, 2016), and carious lesions in deep dentin cover an area with a greater number of tubules and with a greater diameter (Fosse et al., 1992). In deep cavities, lower monomer conversion rates and monomer extravasation into the pulp tissue may also cause dental sensitivity and progress to irreversible pulp irritation (Alkurdi & Abboud, 2016). The Bis-GMA monomer is considered very viscous and less flexible due to the strong intramolecular hydrogen bonding through its hydroxyl-OH groups and the presence of rigid aromatic nuclei in its structure (Khatri et al., 2003). This implies a low reactivity and final conversion degree of this material (Alshali et al., 2013;Sideridou et al., 2002). Once the Tetric N-Ceram Bulk-fill resin presents a high concentration of Bis-GMA in its composition, such fact may explain the occurrence of greater postoperative sensitivity reported in the study by Alkurdi and Abboud (Alkurdi & Abboud, 2016). However, in this systematic review, according to the results found, 75% of studies (Bayraktar et al., 2017;van Dijken & Pallesen, 2014Yazici et al., 2017) reported that there's no significant difference between the type of resin used and the occurrence of postoperative sensitivity, while 25% of the studies found a significant difference (Alkurdi & Abboud, 2016;Hickey et al., 2016). Restorations in primary teeth were verified only in the study of Oter et al. (Oter et al., 2018), in which they observed a higher occurrence of postoperative sensitivity in the teeth restored with bulk-fill. But there was no statistically significant difference between these two materials (P > 0.05), during 6-12 months for postoperative sensitivity (Oter et al., 2018).
The marginal discoloration/adaptation and secondary caries are clinical outcomes that occur more in the interproximal areas, by being the most challenging regions(van Dijken & Pallesen, 2015). While there are studies (Alkurdi & Abboud, 2016;Bayraktar et al., 2017) that found no influence of materials on discoloration and marginal adaptation of restorations. Yazici et al. (Yazici et al., 2017), verified better clinical results for the bulk-fill restoration (Tetric EvoCeram Bulk-fill). It has been observed that the volume of shrinkage polymerization is similar in bulk-fill and conventional resins and that this shrinkage has a positive correlation with the formation of gaps (Almeida Junior et al., 2017). The occurrence of small defects or the formation of gaps allows the passage of cariogenic bacteria and/or retention of pigments that may generate color change in the margin of the restoration (14). However, the presence of gaps at the margins of the restorations does not always appear to be related to the development of caries (Kidd & Beighton, 1996). This relationship only seems to have a significant effect when the marginal gap has a width compatible with the thickness of the active tip of the periodontal probe (400 μm) (Heintze et al., 2009). However, the longevity of the restorations may be compromised, when the replacement of the restoration is premature, generating an overtreatment due to the misdiagnosis of secondary caries (Sarrett DC, 2007).
Secondary caries was verified in 37.5% of the restorations (Bayraktar et al., 2017;van Dijken & Pallesen, 2016, after 1 to 5 years of follow-up, regardless of the type of the material used. Recurrences of lesions and caries evolve mainly in the proximal surfaces (Mjor IA, 1998;Oter et al., 2018;van Dijken & Pallesen, 2016), and this systematic review had demonstrated that the restorations failure rate were more prevalent in proximal (class II) than in the occlusal (class I) of the teeth (van Dijken & Pallesen, 2014. In proximal restorations factors such as: the absence of enamel on the gingival wall and subgingival endings may compromise the adhesion of resinous materials (Poggio et al., 2013). Besides, inadequate sealing of the margins may allow the penetration of fluids, bacteria, and debris into the cavity (Marí et al., 2019).
Also, the difficulty of sanitizing areas near the gingival wall makes small marginal interface defects to be associated with the development of secondary caries (Mjor IA, 1998).
The anatomical form, texture and surface roughness of the restorations are factors that are directly related among them. However, the lack of standardization of the performed restorations makes it difficult to compare the studies. For the restoration of posterior teeth, the bulk-fill resin is being used alone in a single increment (Alkurdi & Abboud, 2016;Bayraktar et al., 2017;Yazici et al., 2017) or associated with the last layer in a conventional composite resin (Bayraktar et al., 2017;van Dijken & Pallesen, 2014. A significant change over time in the color of the conventional resins restoration was observed, which could be explained by a change in surface texture, despite this aspect presented satisfactory over time (van Dijken & Pallesen, 2014. In the studies that were used the single-increment bulk-fill resins, similar color stability was observed to restorations with conventional resins (Alkurdi & Abboud, 2016;Bayraktar et al., 2017;Yazici et al., 2017).
The limitations of this review is that few clinical studies with longer follow-up time was conducted to evaluate the behavior of bulk-fill resins because so far, most studies have less than 5 years of evaluation. In the short term, clinical studies point out a satisfactory behavior of bulk-fill resins.

Conclusion
From this systematic review , it may be concluded that the lack of standardization of the studies makes it difficult to compare the materials, however in the short term, the restorations in primary and permanent teeth with bulk-fill resins present satisfactory clinical performance when evaluating outcomes such as postoperative sensitivity, secondary caries, marginal adaptation, anatomical form, color matching, texture and surface roughness.
Besides that the failures occurrence that compromises the longevity of the restorations in primary and permanent teeth may be more associated with the inherent characteristics of the cavity preparation and location of the lesions, than to the type of resin and the technique used.