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European Archives of Paediatric Dentistry

https://doi.org/10.1007/s40368-021-00666-7

SYSTEMATIC REVIEW

Contemporary management of deep caries in primary teeth:


a systematic review and meta‑analysis
Eirini Stratigaki1 · Huei Jinn Tong2 · Kyriaki Seremidi3 · Dimitrios Kloukos4,5 · Monty Duggal6 · Sotiria Gizani3

Received: 6 July 2021 / Accepted: 12 September 2021


© European Academy of Paediatric Dentistry 2021

Abstract
Purpose  To systematically evaluate the available evidence regarding contemporary management of deep caries in vital pri-
mary teeth. This review was carried out to facilitate the development of European Academy of Paediatric Dentistry (EAPD)
guidelines on deep caries management of primary teeth in paediatric dentistry.
Methods  A systematic electronic literature search was conducted to locate studies reporting on interventions and medica-
ments used for the treatment of deep caries in vital primary teeth. To facilitate this, the Cochrane Library (1992 to up to
December 6th, 2020), MEDLINE (PubMed, 1946 to December Week 1, 2020), Ovid MEDLINE (In-Process & Other
Non-Indexed Citations, December 6th, 2020); EMBASE (Embase.com, 1974 to December 6th, 2020) and LILACS (1982
to December 6th, 2020) were accessed. Hand search of reference lists of included articles, as well as handbooks and grey
literature search was also performed. Study screening was done in duplicate and study inclusions were agreed upon by all
authors. Data extraction, and methodological quality and risk of bias assessment were carried out in duplicate for each of
the included studies. Overall success rate of each intervention and medicament within the intervention was reported. Meta-
analysis was also performed for high-quality studies reporting similar interventions and comparable outcomes in homoge-
neous population.
Results  A total of 1332 papers were identified. Following the primary and secondary assessment process, 36 papers were
included in the review. Of these, 8 papers were deemed to represent 4 individual studies, leaving a total of 32 unique stud-
ies eventually included in the final analysis. These studies were further categorized into three main vital pulp treatment
methods for analysis: indirect pulp capping (IPC), direct pulp capping (DPC), and pulpotomy (PP). Overall, IPC, DPC and
PP interventions have high success rates with the reported clinical success rates higher than radiographic success rates.
Medicaments used for IPC and DPC have similar success rates. Mineral trioxide aggregate (MTA), ferric sulfate (FS) and
formocresol (FC) PP showed similar success rates, and which were all higher than calcium hydroxide (CH). Majority of
included studies (n = 22; 63%) were rated low in terms of their potential risk of bias, 6 studies were rated high (17%), and
7 studies were of unclear risk (20%).
Conclusion  Within the limitations of the studies included, IPC, DPC, and PP can be recommended as effective treatment
modalities for primary teeth with deep caries under specific conditions.

Keywords  Deep caries · Vital pulp therapy · Primary teeth · Systematic review

4
* Sotiria Gizani Department of Orthodontics and Dentofacial Orthopedics,
sotiriagizani@gmail.com School of Dental Medicine, University of Bern, Bern,
Switzerland
1
Department of Pediatric Oral Health and Orthodontics, 5
Department of Orthodontics and Dentofacial Orthopedics,
University Center of Dental Medicine, Basel, Switzerland
251 Hellenic Air Force and VA General Hospital, Athens,
2
Discipline of Orthodontics and Paediatric Dentistry, Faculty Greece
of Dentistry, National University of Singapore, Singapore, 6
School of Dental Medicine, Qatar University, QU Health,
Singapore
Doha, Qatar
3
Department of Paediatric Dentistry, Athens School
of Dentistry, National & Kapodistrian University of Athens,
Athens, Greece

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European Archives of Paediatric Dentistry

Introduction (IPC) refers to the incomplete removal of dentine caries,


whereby affected dentine caries is intentionally allowed
Dental caries still remains one of the most pathological to remain adjacent to a vital pulp rather than risk pulp
conditions in children and even though there seems to be exposure, and a protective layer of cavity sealer or liner
an increased shift towards restoration of primary teeth material which promotes remineralisation of the softened
(Dye et al. 2015), dental caries is still associated with dentine is placed to stimulate tertiary dentine formation,
significant morbidity in children and remains the most followed by tooth restoration (Fuks et al. 2013). Direct
common reason for general anaesthesia in the early age pulp cap treatment (DPC) is indicated in cases of acci-
groups. There is a wide range in caries presentation which dental pulp exposure by removal of caries where the pulp
starts from early clinical signs of demineralisation and exposure is < 1 mm (pinpoint) (Fuks et al. 2013), in which
progresses towards considerable loss of tooth structure and the exposed vital pulp is covered with a protective dress-
eventually pulp involvement. Traditionally, when the mar- ing or base placed directly over the site of exposure in an
ginal ridge is involved in the carious process with proximal attempt to preserve pulpal vitality. Pulpotomy, is the most
cavitation seen clinically, the pulpal tissues were deemed commonly used treatment technique (Ni Chaollai et al.
to be inflamed (Curzon et al. 1996; Duggal et al. 2002). 2009) in primary teeth with extensive caries with pulp
In such cases, treatment was usually aimed at the removal exposure but no signs of radicular pathology (Rodd et al.
of pulpal tissues presumed to be inflamed, so as to pre- 2006). Based on the rationale that the radicular pulp is
serve pulp vitality and conserve as much remaining tooth healthy, the coronal pulp is entirely removed, haemostasis
structure and its supporting tissues as possible. For over is achieved, and the remaining radicular pulp is treated and
five decades, clinicians have managed deep caries using sealed with one of the available medicaments. Pulpectomy
a wide repertoire of pulp interventions and medicaments. involves the complete removal of the coronal and radicular
This ranged from more conservative treatment to more pulp tissue and obturation of the root canals with a resorb-
radical ones, where the pulp was completely extirpated or able filling material.
in some cases the tooth extracted. However, several stud-
ies in the last few years have focused on promoting a more
biological approach where the presumption of severe pul-
pal inflammation in proximal cavitated lesions has been Materials and methods
challenged, as have the inevitable pulpal interventions that
followed (BaniHani et al. 2018; Hu et al. 2018). These Study registration
approaches have generally been aimed at sparing the pulp,
and instead of removal of the presumed inflamed pulp The review protocol was registered in the PROSPERO inter-
tissue, have proposed interventions that facilitate pulpal national prospective register of systematic reviews hosted
healing. The Hall technique is an example of one such by the National Institute for Health Research (NIHR), Uni-
intervention that has gained popularity in recent years versity of York, UK, Center for Reviews and Dissemination
(Santamaría and Innes 2018). This has inevitably resulted (Ref: CRD42020183521).
in polarisation within the profession with some clinicians
not accepting this premise, with some supporting this to
the extent of condemning all traditional approaches that Reporting format
have been used in the past. With this in view, it was felt
that a thorough systematic review of the literature should The Preferred Reporting Items for Systematic Reviews and
be undertaken on both these approaches to search for a Meta-Analyses (PRISMA) were adopted throughout the pro-
consensus and to form a scientific basis for development cess of the present systematic review (Moher et al. 2009,
of guidelines for management of extensive carious lesions 2015).
in primary molar teeth. In this systematic review, the con-
temporary approaches are reviewed to establish whether
they are evidence based and if their effectiveness in man- Population (P), intervention (I), comparison (C),
aging extensive carious lesions in primary molars can be outcomes (O) (PICO scheme)
established.
The objective of this review is to identify the available The PICO methodology was utilized to formulate the
evidence for three conservative methods of deep caries research question: “What are the outcomes of the published
management that include direct and indirect pulp cap- studies on contemporary restorative management of caries
ping, as well as pulpotomy. Indirect pulp cap treatment in primary teeth with follow-up of at least 24 months post-
treatment?” (Table 1).

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Table 1  PICO
Criteria Definition

Population Children with primary teeth presenting with deep caries (i.e. radiographic lesions R3 and R4)
Intervention Treatment of deep carious lesions may be using any of the following conventional restorative management methods:
• Indirect pulp capping
• Direct pulp capping
• Pulpotomy
• Pulpectomy
Carious tissue removal restorative treatment must be carried out under aseptic conditions (i.e. rubber dam isolation under local
anaesthesia/general anaesthesia), and all cases must have a minimum follow-up period of 24 months
Comparators Comparators may be any of the following:
i. No treatment
ii. Comparison of conventional restorative methods against each other, i.e. direct pulp capping, indirect pulp capping, pulpotomy
and pulpectomy
iii. Biological intervention: ART, Hall technique, SDF
iv. Preventive management alone. The interventions may be any of the following, including but not limited to:
   – Diet: diet modification, diet advice
   – Plaque removal: prophylaxis; tooth brushing
   – Use of products: e.g. fluoride, tooth mousse, probiotics, xylitol containing products
Outcomes 1. Main outcomes
  (A) Clinical signs:
  `  • Sensibility (parameters for evaluation may be any of the following: EPT, cold test, mobility, tenderness to percussion,
tenderness to palpation)
    • Pain
    • Swelling, abscess, fistula
    • Discolouration
    • Presence, absence of tooth, longevity of tooth, tooth extraction
  (B) Radiographic presence/absence of:
    • Reparative dentinogenesis
    • Pulp pathology: periapical pathology, pulp canal obliteration
    • Pathological root resorption (i.e. not due to natural exfoliation)
2. Secondary outcomes
    • Treatment cost-effectiveness
    • Comparison of patient reported oral health-related quality of life

Inclusion and exclusion criteria 3. Post-treatment follow-up period of a minimum of


24 months duration.
The following inclusion criteria were used:
The exclusion criteria were defined as:
1. Children and adolescents with the following:
• Permanent teeth.
• Initial lesions with/without enamel breakdown (ICDAS
• Vital primary posterior teeth. 1–3 and/or R1–R2).
• Absence or presence of symptoms of reversible pulpitis • Management of teeth with irreversible pulpitis defined
(acute pain mainly upon thermal stimulus that stops as acute pain upon thermal stimulus that persists after
immediately after removal of stimulus). the removal of stimuli and/or spontaneous pain during
• Deep caries into dentine ICDAS 4–6 and/or radio- bedtime.
graphic lesions R3–R4 (Lunder and von der Fehr • Pre-clinical studies/abstracts/letters to editors/narrative
1996). reviews/case reports.
• Management of deep caries (i.e.)—either by restorative • Insufficient/unclear information not allowing data extrac-
or biological methods. tion.
• No author response to inquiry e-mail for data clarifica-
tion.
2. Treatment carried out under local or general anaesthesia,
and under aseptic conditions (i.e. rubber dam isolation).

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Search strategy Unpublished literature search

Detailed search strategies were developed and appropriately To further identify potential articles for inclusion, grey lit-
revised for each database, considering the differences in erature was searched in the register of clinical studies hosted
controlled vocabulary and syntax rules by the review team. by the US National Institutes of Health (www.​clini​caltr​ials.​
gov), the multidisciplinary European database (www.​openg​
Electronic search rey.​eu), the National Research Register, and Pro-Quest Dis-
sertation Abstracts and Thesis databases (https://a​ bout.p​ roqu​
The original search of computerized databases was con- est.​com).
ducted on 31 May 2020. A repeat search was conducted on
6th December 2020 to update the original search. The fol- Manual search
lowing electronic databases were utilised to locate reports
of relevant published studies: The reference lists of all identified eligible studies and other
published systematic reviews were hand-searched to identify
• The Cochrane Central Register of Controlled Trials further eligible studies. No time restrictions (year of publica-
(CENTRAL) (up to December 6th, 2020). tion) were applied.
• MEDLINE (PubMed) (1946 to December Week 1, 2020).
• Ovid MEDLINE (In-Process & Other Non-Indexed Cita- Study selection
tions, December 6th, 2020).
• Ovid EMBASE (1974 to December 6th, 2020). Study selection was performed independently and in dupli-
• LILACS (1982 to December 6th, 2020). cate. The authors were not blinded to the identity of the
authors of the studies, their institutions, or the results of their
The search strategy for Medline (PubMed) is shown in research. Calibration among the reviewers was performed in
Table 2. the first 20 studies retrieved.

Table 2  Pubmed search strategy


Search Search details Results
number

1 "caries"[Title/Abstract] OR "cavities"[Title/Abstract] OR "decay"[Title/Abstract] 146,994


2 (("caries"[Title/Abstract] OR "cavities"[Title/Abstract]) OR "decay"[Title/Abstract]) AND ((("primary"[Title/Abstract] OR 11,717
"milk"[Title/Abstract]) OR "deciduous"[Title/Abstract]) OR "temporary"[Title/Abstract])
3 ((("caries"[Title/Abstract] OR "cavities"[Title/Abstract]) OR "decay"[Title/Abstract]) AND ((("primary"[Title/Abstract] OR 651
"milk"[Title/Abstract]) OR "deciduous"[Title/Abstract]) OR "temporary"[Title/Abstract])) AND ("deep*"[Title/Abstract]
OR "dentine"[Title/Abstract])
4 ((("caries"[Title/Abstract] OR "cavities"[Title/Abstract]) OR "decay"[Title/Abstract]) AND ((("primary"[Title/Abstract] OR 94
"milk"[Title/Abstract]) OR "deciduous"[Title/Abstract]) OR "temporary"[Title/Abstract])) AND ("deep*"[Title/Abstract]
OR "dentine"[Title/Abstract])
5 ((("caries"[Title/Abstract] OR "cavities"[Title/Abstract]) OR "decay"[Title/Abstract]) AND ((("primary"[Title/Abstract] OR 93
"milk"[Title/Abstract]) OR "deciduous"[Title/Abstract]) OR "temporary"[Title/Abstract])) AND ("deep*"[Title/Abstract]
OR "dentine"[Title/Abstract])
6 "dental caries"[MeSH Terms] 45,787
7 "dental caries"[MeSH Major Topic] 32,773
8 "dental caries"[MeSH Terms] AND "therapeutics"[MeSH Terms] 6398
9 "dental caries"[MeSH Terms] AND ((("primary"[Title/Abstract] OR "milk"[Title/Abstract]) OR "deciduous"[Title/Abstract]) 5418
OR "temporary"[Title/Abstract])
10 ("dental caries"[MeSH Terms] AND ((("primary"[Title/Abstract] OR "milk"[Title/Abstract]) OR "deciduous"[Title/ 412
Abstract]) OR "temporary"[Title/Abstract])) AND ("deep*"[Title/Abstract] OR "dentine"[Title/Abstract])
11 ((caries[Title/Abstract] OR cavities[Title/Abstract] OR decay[Title/Abstract]) AND (primary[Title/Abstract] OR milk[Title/ 132
Abstract] OR deciduous[Title/Abstract])) AND (pulpotomy[Title/Abstract] OR pulpectomy[Title/Abstract])
12 ((caries[Title/Abstract] OR cavities[Title/Abstract] OR decay[Title/Abstract]) AND (primary[Title/Abstract] OR milk[Title/ 20
Abstract] OR deciduous[Title/Abstract])) AND (root canal treatment[Title/Abstract])
13 ((caries[Title/Abstract] OR cavities[Title/Abstract] OR decay[Title/Abstract]) AND (primary[Title/Abstract] OR milk[Title/ 90
Abstract] OR deciduous[Title/Abstract])) AND (vital pulp[Title/Abstract] OR pulp capping[Title/Abstract])

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Table 3  Reasons for exclusion of studies


Reasons for exclusion (*for studies with more than 1 reason, only Title, year and authors Number
1 reason will be given) of papers

Wrong population–either one or all groups not evaluating out- BaniHani et al. (2019), Dias et al. (2018) 2
come of vital pulp therapy
Treatment not done under aseptic conditions (rubber dam isola- de Amorim et al. (2014), Sonmez et al. (2008), Sushynski et al. 4
tion) (2012), Yildiz and Tosun (2014),
Follow-up period less than 24 months, or inconsistent follow-up Biedma et al. (2017), Doyle et al. (2010), Duque et al. (2009), 14
period with lower range < 24 months Holan et al. (2005), Kotsanos et al. (2014), Lima et al. (2005),
Liu et al. (2011), Mathur (2016), Nematollahi et al. (2011),
Olatosi et al. (2015), Orhan et al. (2010), Petrou et al. (2014),
Trairatvorakul and Sastararuji (2014), Zurn and Seale (2008)
Large dropout number Kirzioglu et al. (2011) 1
Wrong outcome—does not evaluate pulpal survival/radiographic Casagrande et al. (2009), Franzon et al. (2009), Franzon et al. 6
findings) (2015), Homer et al. (2020), Liberman et al. (2020), Schwen-
dicke et al. (2018),
Wrong study design (no control group) Godhi et al. (2016), Kornblit et al. (2008), Kotsanos and Arizos 6
(2011), Kotsanos et al. (2014), Luczaj-Cepowicz E et al. (2017),
Tang and Xu (2017)
Wrong study design (not prospective) Al-Zayer et al. (2003), Gruythuysen et al. 2010, Rubanenko et al. 3
(2019)
Wrong study design (in vitro/not clinical study) Rayner and Southam (1979) 1
Wrong publication type (i.e. review, systematic review, study Alsadat et al. (2018), Coll (2008), Coll et al. (2017), Cushley 22
protocol, conference proceeding, commentory) et al. (2020), da Rosa et al. (2019), da Silva et al. (2019), Dhar
et al. (2020), Fuks (2008), Garrocho-Rangel et al. (2020), Innes
et al. (2013), Jayaraman et al. (2020), Kopel (1992), Maguire A
et al. (2020), Nadin et al. (2013), Peng et al. (2007), Santama-
ria and Innes (2014), Schwendicke et al. (2018), Shafaee et al.
(2019), Simancas-Pallares et al. (2010), Smaïl-Faugeron et al.
(2018), Tedesco et al. (2020), Thillainathan and Duane (2014)
Not in English Maiwald (1971), Sfondrini et al. (1978), Wu (2018), Zivković 4
(1967)
Total: 63

Study selection procedure comprised of title-reading, in intervention and control groups, intervention applied, and
abstract-reading and full-text-reading stages. After exclu- outcome assessed with all relevant clinical and radiographic
sion of non-eligible studies, the full report of publications variables. If stated, the sources of funding, trial registration,
considered by either author as eligible for inclusion was and publishing of the trial's protocol were recorded. This
obtained and assessed independently. Studies published in information was used to aid assessment of heterogeneity
several manuscripts were identified and only the latest pub- and the external validity of the included studies. In case of
lication was considered, in the case of the same outcomes. missing data, attempts to contact the corresponding author
Disagreements were resolved by discussion and consultation were made. Studies without sufficient data for meta-analyses
with the third author of the review. A record of all decisions were kept in the systematic review but excluded from the
on study identification was kept. Reasons for exclusion of meta-analyses.
papers can be found in Table 3.
Recalculation of success rates
Data collection
Data collection for exfoliated teeth and those with restora-
Two authors performed data extraction independently and in tion failures varied among studies. Some studies considered
duplicate. Disagreements were resolved by discussion with normal asymptomatically exfoliated teeth to be dropouts and
a third author. Specifically, designed collection forms were removed them from the calculations for success (Fernández
used to record the desired information. The following data et al. 2013; Huth et al. 2012). Others removed teeth with
were collected: author/title/year of study, study affiliation restoration failure from the calculations (Marchi et al. 2006).
data, design of the study, number/age/gender of participants Some studies reported a failure at one time point but did

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not carry forward that calculation in the next time frame to be pooled. For dichotomous data, number of teeth with
(Fernández et al. 2013; Huth et al. 2012). There was also events and total number of teeth in experimental and control
variability in calculation of clinical and radiographic suc- groups were analysed. Regarding meta-analysis for dichoto-
cess among papers. mous data, risk ratios and their 95% confidence intervals
To standardize the determination of clinical and radio- (Cls) were calculated. Risk ratios (RR) were calculated for
graphic success among studies, the authors recalculated dichotomous data using random-effect models. If treatment
the clinical and radiographic success rate data presented effects were not reported in publications, corresponding
in each included paper based on criteria modified from authors were contacted to retrieve missing data.
the Vital Pulp Therapy Standardisation Rules by Coll and
co-workers (Coll et al. 2017). The standardization rules Heterogeneity
are as follows:
Clinical and methodological heterogeneity were assessed by
1. Following an intervention, if a tooth exfoliated in less examining the characteristics of the studies, the similarity
than six months, it was counted as both a clinical and between the types of participants, the interventions, and the
radiographic failure. outcomes as specified in the inclusion criteria for consid-
2. If a tooth exfoliated greater than six months after an ering studies for this review. Statistical heterogeneity was
intervention, it was always counted as both clinical and assessed using a ­Chi2 test and the I2 statistic, where I2 values
radiographic success in all future time frames. over 50% indicated substantial heterogeneity.
3. Once a tooth’s intervention failed at a particular time
frame, it was calculated as a failure in all subsequent Assessment of reporting bias
time frames.
4. Radiographic internal resorption and clinical excess In the presence of more than 10 studies in a meta-analysis,
mobility were counted as failures in any time frame. the possible presence of publication bias was investigated
5. Any restoration failure was not excluded from the total for the primary outcome.
number count, and counted as a clinical failure, but
radiographic success. Subgroup analyses
6. Pulp canal obliteration and dentine deposition/bridge
formation were not counted as failure but considered Where there was sufficient data, subgroup analyses to
physiological changes. explore the influence of study characteristics such as gender
7. A dropout in any time frame was removed from that and/or type of tooth was conducted.
time frame’s denominator and all future time frames in
calculating success. Sensitivity analysis
8. Data presenting with only overall success rates, were
counted as both clinical and radiographic success. Exploration on whether or not the analysis of studies strati-
fied by design or by risk of bias (i.e. overall low risk versus
unclear risk) yielded similar or different results was done.
Risk of bias assessment
Unit of analysis issues
For interventional, randomized controlled trials (RCTs)
the Risk of Bias 2.0. tool was used (Sterne et al. 2019) For It was anticipated that some of the included studies presented
interventional, non-randomized studies the ROBINS-I-tool data from repeated or paired observations on participants,
was used (Sterne et al. 2016). Risk of bias assessment was which could lead to unit-of-analysis errors. In such cases,
performed independently and in duplicate by two authors for advice provided in section 9.3.4 of the Cochrane Handbook
the primary outcomes. Any concern was resolved by discus- for Systematic Reviews of Interventions (Higgins and Green
sion with the third author. 2011) was followed.

Data analysis Results

Meta-analyses were conducted for included studies reporting Search results


similar interventions and comparable outcomes in homo-
geneous population, i.e. in the case of limited heterogene- A total of 1063 articles were initially identified, to which
ity. Only studies at low or unclear risk of bias were chosen 269 studies were added after a repeated electronic and hand

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Fig. 1  PRISMA flow
diagram.*Studies: appears to Records identified through database searching Additional records identified through
1st search till 31 May 2020 (n1 = 1063) other sources/handsearch
be same cohort (counted as 1
2nd search 31 May 2020 till 6 Dec 2020 (n2=242)

Identification
study). Casagrande et al. (2008, (n = 27)
2010), Casas et al. (2003, 2004),
Huth et al. (2005, 2012), Falster
et al. (2002), Casagrande et al.
(2009) Records after duplicates removed
Total = 915 (N1= 700; N2 = 188; Hand = 27)

Records screened Records excluded by title


Screening abstract screening
Total = 915
Total = 816

Full-text articles assessed for


eligibility Full-text articles excluded,
Eligibility

with reasons
TOTAL: 99 Total = 63

Studies included in qualitative synthesis

TOTAL = 36*(32)
Included

Studies included in quantitative synthesis


(meta-analysis)
(n = 2)

search on 6 Dec 2020. Following duplicates removal, a Ranjpour 2010; Erdem et al. 2011; Guven et al. 2017; Kho-
total of 915 articles underwent title and abstract screening, rakian et al. 2014; Malekafzali et al. 2011; Nematollahi et al.
of which 816 were excluded. A total of 99 articles were 2018; Tuna and Olmez 2008) had split-mouth designs, and
retrieved for full text appraisal. From these, 63 articles the rest (n = 28) were parallel group designs. The prospec-
were excluded due to wrong outcome, wrong study design tive study by Airen et al. (2012) had a parallel-arm design.
or shorter follow-up period (Table 3), leaving 36 published All included studies were conducted as single-sites
manuscripts meeting the inclusion criteria. Upon further studies, and majority were carried out in University set-
analysis, it was verified that four research groups published tings (at the paediatric dentistry departments). The sam-
two separate papers with the same cohort but with longer ple size ranged from 17 to 130 children, aged between 2
follow-up periods (Casagrande et  al. 2008, 2009, 2010; and 11 years. The corresponding number of included teeth
Casas et al. 2003, 2004; Falster et al. 2002; Huth et al. 2005, ranged between 27 and 291 primary molars. This yielded a
2012). The search and screening process are presented in total of 3260 teeth from 1791 patients.
detail in the PRISMA flowchart (Fig. 1). Regarding interventions, the majority of papers evalu-
ated medicaments used: pulpotomy (PP) (n = 17) (Airen
et al. 2012; Ansari and Ranjpour 2010; Celik et al. 2013;
Study characteristics Çelik et  al. 2019; Erdem et  al. 2011; Farsi et  al. 2005;
Fernández et al. 2013; Guven et al. 2017; Huth et al. 2005,
The characteristics of the included studies are summarized 2012; Jamali et al. 2018; Jayam et al. 2014; Khorakian et al.
in Table 4a–c. From the 36 individual papers included into 2014; Malekafzali et al. 2011; Moretti et al. 2008; Sakai
the analysis, all but one study (Airen et al. 2012) were ran- et al. 2008; Yildirim et al. 2016), indirect pulp capping
domized controlled trials, of which 7 papers (Ansari and (IPC) (n = 8) (Büyükgüral and Cehreli 2008; Casagrande

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Table 4  Characteristics of included studies


Study Country of origin RCT design Participants Intervention(s)/test group(s) Intervention/ Final restoration Follow-up Dropout (teeth) Outcome measures
randomized control (months) (%)
Clinical Radiographic

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(number of teeth)/
age range

a Direct pulp capping


Aminabadi et al. Iran Parallel arm • 84 children (120 DPC DPC SSC 6, 12, 18, 24 None Fistula, Pain, TTP I/E-Resorption,
(2010) teeth) • FC • CH P/F-Radiolucency
• 4–5 years
Demir er al. Turkey Parallel arm • 67 children (100 DPC DPC • All test groups: 7, 14, 30 days None Edema, Fistula, I/E-Resorption,
(2007) teeth) • Prime&Bond NT: • CH Polyacid-modi- 3, 6, 9, 12, 18, 24 Mobility, Pain P/F-Radiolucency
• 5–9 years • NRC + Prime&Bond NT: fied resin-based
• Total etch + Prime&Bond: composite
• Xeno III (Dyract AP)
• Control: Amal-
gam
Dimitraki et al. Greece Parallel arm 74 children (97 DPC PP • Class I cavities: 6, 12, 18, 24, • 65/97 (67%) Pain, Mobility, Disruption of
(2019) teeth) • MTA • MTA composite resin 30, 36 24 months Restoration lamina dura,
• 3–9 years • Class II or • 74/97 (76.3%) condition, peri- I/E-Resorption,
multi-surface 30 months odontal health, PCO
cavities: SSC • 82/97 (84.5%) contact point,
36 months occlusal surface
(intact/loss of
morphology)
Tuna and Olmez Turkey Split-mouth 25 children (50 DPC DPC Amalgam 1, 3, 6, 9, 12, 8/50 (16%) Fistula, Mobility, I/E-Resorption,
(2008) teeth) • MTA • CH 18, 24 Pain, Swelling, P/F-Radiolu-
• 5–8 years TTP cency, widened
PDL
b Indirect pulp capping
Chompu-Inwai Thailand Parallel arm 42 children (109 Incomplete caries removal Incomplete SSC 6, 12, 24 28/96 (29.2%) Abscess, Mobil- I/E-Resorption,
et al. (2015) teeth) technique caries removal ity, Pain, P/F-Radiolucency
• 3–11 years • MCR B/L RMGI technique Swelling widened PDL
• MCR L No base • IPT RMGI
(RMGI)
Büyükgüral et al. Turkey Parallel arm 97 children (240 IPC IPC • Test: Polyacid- 1, 3, 6, 9, 12, None Edema, Fistula, I/E-Resorption,
(2008) teeth) • 36% Phosphoric • CH modified 18, 24 Mobility, Pain, P/F-Radiolu-
• 5–10 years acid + Prime + Bond resin-based TTP cency widened
• Self-etch adhesive composite PDL, remaining
• Prime + Bond (Dyract AP) dentine thickness
• Control: Amal-
gam
Casagrande et al. Brazil Parallel arm 21 children (40 IPC IPC Composite resin Clinical: 1, 6, 9/40 (22.5%) Edema, Fistula, I/E-Resorption,
(2008, 2010) teeth) • CSE • CH 12, 24 24 months Mobility, Pain, P/F-Radiolucency
• 4–8 years Radiographic: 8/40 (20%) Swelling, signs
6, 12, 24, and  > 24 months of irreversible
yearly after pulpitis, TTP
24 months until
exfoliation
Falster et al. Brazil Parallel arm 21 children (48 IPC IPC Composite resin 15 days, • None Edema, Fistula, I/E-Resorption,
(2002) teeth) • Scotchbond • CH 1, 3, 6, 12, 18, 24 24 months Mobility, Pain, P/F-Radiolucency
Casagrande et al. • 3–5 years 36, 48, 60, 72 • 25/48 (52%) TTP
(2009) 4–5 years
European Archives of Paediatric Dentistry
Table 4  (continued)
Study Country of origin RCT design Participants Intervention(s)/test group(s) Intervention/ Final restoration Follow-up Dropout (teeth) Outcome measures
randomized control (months) (%)
(number of teeth)/ Clinical Radiographic
age range

Franzon et al. Brazil Parallel arm 20 Children (39 IPC IPC Composite resin 4–7, 24, 36 10/39 (25.6%) Edema, Fistula, I/E-Resorption,
(2007) teeth) • Guttapercha • CH Mobility, Pain, P/F-Radiolucency
• 4–7 years TTP
Franzon et al. Brazil Parallel arm 51 children (124 • IPC PCR: CH TCR​ Composite resin 3, 6, 12, 18, 24 4/124 (3.3%) Fistula, Mobility, I/E-Resorption,
(2014) teeth) • CH Pain, Swelling P/F-Radiolucency
• 3–8 years
Marchi et al. Brazil Parallel arm 17 children (27 IPC IPC • Test: GIC 1, 3, 6, 9, 12, 18, 1/27 (3.7%) Edema, Fistula, I/E-Resorption,
(2006) teeth) • GIC • CH • Control: Com- 24, 36, 48 Mobility, Pain, P/F-Radiolu-
European Archives of Paediatric Dentistry

• 4–9 years posite resin TTP cency, widened


PDL
c: Pulpotomy
Airen et al. India Parallel arm/ 70 children (70 PP PP SSC 6, 12, 24 10/70 (14%) Pain, Swelling, I/E-Resorption,
(2012) NOT RCT​ teeth) • MTA • FC Sinus/Fistula P/F-Radiolucency
• 6–8 years
Ansari et al. Iran Split-mouth 17 children (40 PP PP SSC or amalgam 1, 6, 12, 24 10/40, (25%) Pain, Swelling, I/E-Resorption,
(2010) teeth) • MTA • FC (no criteria for Sinus/Fistula P/F-Radiolu-
• 4–9 years choice) cency, PCO,
widen PDL
Casas et al. Canada Parallel arm 130 children (291 PP Pulpectomy SSC 12, 24, 36 • 175/291 Edema, Fistula, I/E-Resorption,
(2003, 2004) teeth) • FS • ZOE (60.1%) Mobility, Pain, P/F-Radiolu-
• 3–6 years 24 months TTP, Missing cency, widened
• 262/291 (90%) restoration, PDL, PCO
36 months Recurrent car-
ies, Parulis
Celik et al. (2013) Turkey Parallel arm 75 children (139 PP PP Amalgam 1, 3, 6, 12, 18, 24 5/139 (3%) Fistula, Pain, I/E-Resorption,
teeth) • White MTA • CH Swelling, P/F-Radiolu-
• 3–9 years • Angelus MTA Sinus, TTP cency, PCO
Celik et al. (2019) Turkey Parallel arm 39 children (44 PP PP SSC 3, 6, 12, 18, 24 2/44 (4.5%) Fistula, Gingiva I/E-Resorption,
teeth) • BioD • White MTA inflamma- P/F-Radiolucency
• 5–9 years tion, Mobility,
Swelling, TTP
Chen et al. (2020) China Parallel arm 67 children (175 PP: IPC: Composite resin 6, 12, 18, 24 7/168 Abscess, Fistula, I/E-Resorption,
teeth rand- • iRoot BP Plus Bioceramic • RMGI (4.4%) Mobility, Pain P/F-Radiolucency
omized, 168 *Based on
evaluated) numbers that
• 3–7 years received inter-
vention
Erdem et al. Turkey Split mouth 32 children PP PP Amalgam 6, 12, 24 28/128 (21.9%) Mobility, Pain, I/E-Resorption,
(2011) (128 teeth) – • MTA • FC Swelling, TTP P/F-Radiolucency
enrolled; • FS
25 children (100 • ZOE
teeth) – evalu-
ated
▪5–7 years

13

Table 4  (continued)
Study Country of origin RCT design Participants Intervention(s)/test group(s) Intervention/ Final restoration Follow-up Dropout (teeth) Outcome measures
randomized control (months) (%)
(number of teeth)/ Clinical Radiographic

13
age range

Farsi et al. (2005) Saudi Arabia Parallel arm 100 children (120 PP PP SSC 6, 12, 18, 24 46/120 (38.3%) Pain, Swelling, I/E-Resorption,
teeth) • MTA • FC Sinus P/F-Radiolucency
• 3–8
Fernandez et al. Spain Parallel arm 81 children (100 PP PP SSC 6, 12, 18, 24 24/100 (24%) Fistula, Mobility, I/E-Resorption,
(2013) teeth) • MTA • FC Pain, Swelling P/F-Radiolucency
• 5–9 • FS
• NaOCl
Guven et al. Turkey Split mouth 38 children (116 PP PP Amalgam 6, 12, 18, 24 36/116 Fistula, Mobility, I/E-Resorption,
(2017) teeth) • BioD • FS (31%) Pain, Swelling P/F-Radiolu-
• 5–7 • MTA-P cency, PCO
• PR-MTA
Huth et al. (2005, Germany Parallel arm 107 children (200 PP PP • SSC Clinical: 6, 12, • 4/191 (2.1%) Fistula, Gingival I/E-Resorption,
2012) teeth) • Er:YAG​ • FC • Composite resin 18, 24 mos ± 2 24 months inflammation, P/F-Radiolu-
• 2–8 • CH wks; • 8/191 (4.2%) Mobility, Pain, cency, widened
• FS Radiographic:12, 36 months Swelling, TTP; PDL
24, 36 Restoration
performance
Jamali et al. Iran Parallel arm 114 children (150 PP PP Amalgam 6, 12, 24 28/150 (18.6%) Mobility, Pain, DBF, DLD, PCO,
(2018) teeth) • 3Mixtatin • FC Swelling, I/E-Resorption,
• 3–6 • MTA Sinus, TTP P/F-Radiolu-
cency, widened
PDL
Jayam et al. India Parallel arm 66 children (100 PP PP • SSC 1, 3, 6, 12, 24 18/100 (18%) Mobility, Pain, DBF, DLD, PCO,
(2014) teeth) • MTA • FC • Amalgam Swelling, I/E-Resorption,
• 3–7 • GIC Sinus, TTP P/F-Radiolu-
cency, widened
PDL
Khorakian et al. Iran Split mouth 51 children (102 PP PP SSC 6, 12, 24 20/102 Mobility, Pain, I/E-Resorption,
(2014) teeth) • CEM • ES/ZOE (19.6%) Swelling, P/F-Radiolu-
• 4–6 Sinus, TTP cency, widened
PDL, PCO
Malekhafzali Iran Split mouth 40 children (80 PP PP • SSC 6, 12, 24 10/80 (12.5%) Abscess, Mobil- I/E-Resorption,
et al. (2011) teeth) • CEM • MTA • Amalgam ity, Swelling, P/F-Radiolu-
• 4–8 Sinus cency, PCO,
widened PDL,
(arrested)internal
resorption with
calcific meta-
morphosis of the
pulp
Moretti et al. Iran Parallel arm 23 children (45 PP PP GIC 3, 6, 12, 18, 24 2/45 (4.4%) Fistula, Mobility, DBF, I/E-Resorp-
(2008) teeth) • CH • FC Pain, Swelling, tion, P/F-
• 5–9 • MTA Smell Radiolucency,
intracanal
calcifications
European Archives of Paediatric Dentistry
Table 4  (continued)
Study Country of origin RCT design Participants Intervention(s)/test group(s) Intervention/ Final restoration Follow-up Dropout (teeth) Outcome measures
randomized control (months) (%)
(number of teeth)/ Clinical Radiographic
age range

Nematollahi et al. Iran Split mouth 25 children (50 Partial PP PP SSC 6, 12, 24 8/50 (16%) Fistula, Mobility, I/E-Resorption,
(2018) teeth) • MTA • FC Pain, Swelling, P/F-Radiolu-
• 5–8 Sinus, TTP cency, widened
PDL, PCO
Noorollahian Brazil Parallel arm 46 children (60 Partial PP PP SSC 6, 12, 24 23/60 (38.3%) Fistula, Mobility, I/E-Resorption,
et al. (2008) teeth) • MTA • FC Pain, Swelling, P/F-Radiolu-
• 5–7 Sinus, TTP cency, widened
PDL, PCO
European Archives of Paediatric Dentistry

Sakai et al. (2008) Thailand Parallel arm 30 children (30 PP PP RMGIC 6, 12, 18, 24 1/30 (3.33%) Fistula, Mobility, DBF, I/E-Resorp-
teeth) • PC • MTA Pain, Swelling, tion, P/F-
• 5–9 Smell Radiolucency,
intracanal
calcifications
Trairatvorakul Turkey Parallel arm 56 children (86 Partial PP PP SSC 6, 12, 18, 24, • 14/86 (16.3%) Abscess, Mobil- I/E-Resorption,
et al. (2012) teeth) • CH • FC 30, 36 24 months ity, Pain, Sinus, P/F-Radiolucency
• 3–7 • 20/86 (23.3%) TTP
30 months
• 23/86 (26.7%)
36 months
Yildirim et al. Iran Parallel arm 65 children (140 PP PP SSC 3, 6, 12, 18, 24 13/140 Fistula, Pain, I/E-Resorption,
(2016) teeth) • MTA • FC (9.3%) Swelling P/F-Radiolu-
Age not reported • PC cency, PCO
• EMD

BioD biodentine; CEM calcium-enriched mixture cement; CH calcium hydroxide; CSE clearfill SE bond; DBF dentine bridge formation; DLD disruption of lamina dura; DPT direct pulp treat-
ment; EMD enamel matrix derivative; Er:CrYSGG erbium, chronium-doped yttrium, scandium, gallium and garnet laser; ES/ZOE electrosurgery-zinc oxide eugenol; FC formocresol; FS ferric
sulfate; GI gingival inflammation; I/E-Resorption internal/external root resorption; IP irreversible pulpitis; IPT indirect pulp treatment; MCRB/L minimal caries removal with resin-modified glass
ionomer (RMGI) base material and luting cement; MCRL minimal caries removal with only RMGI luting cement; MTA mineral trioxide aggregate; MTA-P MTA plus; NRC non-rinse condi-
tioner; PBD periapical bone destruction; PC Portland Cement; PCO pulp canal obliteration; PCR partial caries removal; PDL periodontal dental ligament; P/F-radiolucency periapical/furcation
radiolucency; PP pulpotomy; PR-MTA MTA-ProRoot; PPT pulpectomy; RCT​ randomized controlled trial; RDT remaining dentine thickness; RMGIC resin-modified glasionomer cement; SCB
Scotchbond; TCR​total caries removal; TTP tenderness to percussion; ZOE zinc oxide eugenol

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European Archives of Paediatric Dentistry

et al. 2008, 2009, 2010; Falster et al. 2002; Franzon et al. 2010; Chen et al. 2021; Dimitraki et al. 2019; Falster et al.
2007, 2014; Marchi et al. 2006), direct pulp capping (DPC) 2002; Franzon et al. 2007, 2014; Huth et al. 2005, 2012;
(n = 3) (Aminabadi et al. 2010; Demir and Cehreli 2007; Marchi et al. 2006), amalgam restorations (n = 9) (Ansari and
Tuna and Olmez 2008) and incomplete caries removal Ranjpour 2010; Büyükgüral and Cehreli 2008; Celik et al.
(n = 1) (Chompu-inwai et al. 2015). In the remaining seven 2013; Demir and Cehreli 2007; Erdem et al. 2011; Guven
papers, the success rates of the various clinical techniques et al. 2017; Jamali et al. 2018; Jayam et al. 2014; Malekaf-
were compared against each other, with the main focus being zali et al. 2011; Tuna and Olmez 2008), compomer (n = 2)
on comparisons of partial pulpotomy versus full coronal (Büyükgüral and Cehreli 2008; Demir and Cehreli 2007),
pulpotomy (Nematollahi et al. 2018; Noorollahian 2008; or glass ionomer cements (n = 4) (Jayam et al. 2014; Marchi
Trairatvorakul and Koothiratrakarn 2012), pulpotomy ver- et al. 2006; Moretti et al. 2008; Sakai et al. 2008). Some
sus pulpectomy (Casas et al. 2003, 2004), pulpotomy versus studies used multiple different materials as final restorations
indirect pulp capping (Chen et al. 2021), and direct pulp (across the teeth treated) (Huth et al. 2005, 2012; Jayam et al.
capping versus pulpotomy (Dimitraki et al. 2019). 2014; Malekafzali et al. 2011), of which some had different
Regardless of clinical technique used, the dental material materials for the test versus control group (Büyükgüral and
appraised the most among studies was MTA. In 18 studies Cehreli 2008; Demir and Cehreli 2007; Marchi et al. 2006).
(Airen et al. 2012; Ansari and Ranjpour 2010; Celik et al. One study had a combination of restorations (amalgam/SSC)
2013; Çelik et al. 2019; Dimitraki et al. 2019; Erdem et al. but did not specify the rational behind the choice on each
2011; Farsi et al. 2005; Fernández et al. 2013; Guven et al. case (Ansari and Ranjpour 2010). One study had composite
2017; Jamali et al. 2018; Jayam et al. 2014; Malekafzali resin restorations for class I cavities, and SSC for Class II or
et al. 2011; Moretti et al. 2008; Nematollahi et al. 2018; multi-surface restorations (Dimitraki et al. 2019).
Noorollahian 2008; Sakai et al. 2008; Tuna and Olmez 2008; All included studies evaluated treatment outcomes based
Yildirim et al. 2016), it was used as a pulpotomy or direct on clinical and radiographic findings. The main clinical out-
pulp capping medicament and was evaluated against or in comes reported among majority of papers were pain, swell-
conjunction with other dental materials. This was followed ing, mobility, tenderness and presence/absence of sinus or
by formocresol (n = 14), calcium hydroxide (n = 13) and fistula. Radiographic parameters included assessments of
ferric sulphate (n = 5). Other medicaments less frequently presence/absence of periapical or furcation radiolucency,
evaluated included Biodentine (n = 2) (Çelik et al. 2019; root resorption (internal and external), widening of peri-
Guven et al. 2017), novel endodontic bioceramics (n = 1) odontal ligament space or loss of lamina dura. Widening
(Chen et al. 2021), electrosurgery (n = 2) (Huth et al. 2005, of periodontal ligament space was not always considered
2012), ZOE (n = 4) (Casas et al. 2003, 2004; Erdem et al. as radiographic failure. In some papers, presence of pulp
2011; Khorakian et  al. 2014), dentine bonding agents canal obliteration (n = 12) (Airen et al. 2012; Ansari and
(n = 6) (Büyükgüral and Cehreli 2008; Casagrande et al. Ranjpour 2010; Casas et al. 2003, 2004; Celik et al. 2013;
2008, 2009, 2010; Demir and Cehreli 2007; Falster et al. Çelik et al. 2019; Erdem et al. 2011; Farsi et al. 2005; Guven
2002), sodium hypochlorite (n = 1) (Fernández et al. 2013), et al. 2017; Khorakian et al. 2014; Nematollahi et al. 2018;
calcium-enriched mixture cement (n = 2) (Khorakian et al. Noorollahian 2008; Sakai et al. 2008) and dentine bridge
2014; Malekafzali et  al. 2011), Portland cement (n = 2) formation/remaining dentine thickness (n = 2) (Moretti et al.
(Sakai et al. 2008; Yildirim et al. 2016), RMGIC/GIC (n = 3) 2008; Sakai et al. 2008) were also evaluated, but were gener-
(Chen et al. 2021; Chompu-inwai et al. 2015; Marchi et al. ally not categorised as pathology.
2006), triple antibiotics (n = 1) (Jamali et al. 2018), gutta All included studies had a minimum of 24 months follow-
percha (n = 1) (Franzon et al. 2007) and Er:CrYSGG laser up, with eight papers presenting results for longer periods,
(n = 2) (Huth et al. 2005, 2012) and enamel matrix derivative ranging between 30 and 72 months (Casagrande et al. 2009,
(n = 1) (Yildirim et al. 2016). 2010; Casas et al. 2004; Dimitraki et al. 2019; Franzon et al.
Materials used for final restoration of the teeth after 2007; Huth et al. 2012; Marchi et al. 2006; Trairatvorakul
vital pulp therapy varied across studies, with stainless steel and Koothiratrakarn 2012).
crowns (SSC) being the one most used (n = 17) (Airen et al.
2012; Aminabadi et al. 2010; Ansari and Ranjpour 2010; Quality assessment
Casas et al. 2003, 2004; Çelik et al. 2019; Chompu-inwai
et al. 2015; Dimitraki et al. 2019; Farsi et al. 2005; Fernán- Risk of bias for RCTs
dez et al. 2013; Huth et al. 2005, 2012; Jayam et al. 2014;
Khorakian et al. 2014; Malekafzali et al. 2011; Nematollahi Overall quality assessment of included RCTs, as presented
et al. 2018; Noorollahian 2008; Trairatvorakul and Koothi- via assessment of their potential risk of bias (Table 5 and
ratrakarn 2012; Yildirim et al. 2016). Other materials used Fig. 2), was rated high in majority of papers (n = 22; 63%),
were composite resin (n = 8) (Casagrande et al. 2008, 2009, low in six studies (17%) (Çelik et al. 2019; Chen et al. 2021;

13
European Archives of Paediatric Dentistry

Table 5  Risk of bias
(randomised controlled trials)

Franzon et al. 2014; Huth et al. 2005, 2012; Moretti et al. In general, regarding sample size calculation only 13
2008) and unclear in seven studies (20%) (Aminabadi et al. studies reported on the exact mechanism and supported
2010; Büyükgüral and Cehreli 2008; Celik et  al. 2013; the evidence for the sample size selected. Most used power
Demir and Cehreli 2007; Falster et al. 2002; Marchi et al. analysis (Çelik et al. 2019; Chompu-inwai et al. 2015; Demir
2006; Yildirim et al. 2016). and Cehreli 2007; Farsi et al. 2005; Franzon et al. 2014;

13
European Archives of Paediatric Dentistry

Quality Assessment for potenal risk of bias of Çelik et al. 2019; Chen et al. 2021; Demir and Cehreli 2007;
included RCTs Falster et al. 2002; Franzon et al. 2014; Huth et al. 2005,
2012; Marchi et al. 2006; Moretti et al. 2008; Yildirim et al.
Overall bias
2016) were rated as being at low risk of attrition bias as
their reported dropout rates ranged between 0% (Falster et al.
Bias in measurement of the outcome
2002; Marchi et al. 2006) and 12% (Çelik et al. 2019). There
Bias due to deviaons from the...
was one study (Aminabadi et al. 2010) rated as being at
Bias in selecon of the reported result
unclear risk, due to insufficient information pertaining to
Bias due to missing outcome data
attrition reported in the paper.
Bias arising from the randomisaon...

Reporting bias
Fig. 2  Bar graph: risk of bias
Almost all papers (n = 29; 82.9%) were rated as being at low
risk of reporting bias, as there was complete description of
Guven et al. 2017; Jamali et al. 2018; Khorakian et al. 2014; the standardized outcome measures. Only six papers (Casa-
Nematollahi et al. 2018; Trairatvorakul and Koothiratrakarn grande et al.2008, 2010; Casas et al. 2003, 2004; Jayam et al.
2012), one used independent sample rates and performed 2014; Sakai et al. 2008) were rated as being at unclear risk as
using PASS software (Chen et al. 2021), one was based the criteria used to determine success and failure of the pro-
upon failure rates of MTA when used as a pulptotomy agent cedures and materials were not mentioned or not described
(Dimitraki et al. 2019) and two upon an internal pilot study in detail.
comparing success rates of CH and FC and on a study com-
paring FS and FC (Huth et al. 2005, 2012). Performance bias

Selection bias Blinding of both participants and personnel was achieved


in ten papers (Çelik et al. 2019; Chen et al. 2021; Chompu-
Selection bias involved both random sequence generation inwai et al. 2015; Farsi et al. 2005; Franzon et al. 2014; Huth
and allocation concealment. Regarding allocation conceal- et al. 2005, 2012; Khorakian et al. 2014; Moretti et al. 2008;
ment, most papers (n = 24; 68.6%) were rated as being at Nematollahi et al. 2018). In the remaining papers (n = 25;
low risk of bias as sequence was generated by one of the 71.4%) there was insufficient information to make a clear
following techniques: random number systems, randomiza- judgement regarding performance bias. The difficulty refers
tion blocks, sealed envelopes, and coin tossing. to the blinding of the personnel performing the procedures
There were three papers (Erdem et al. 2011; Franzon et al. that reflect the nature of the materials used in such type of
2007; Yildirim et al. 2016) that did not report any informa- studies.
tion regarding randomisation of treatment allocation and
were therefore rated as being at unclear risk of bias. Nine Detection bias
studies despite reporting adequate allocation concealment,
had missing data on random sequence generation mainly More than 2/3 (n = 26; 74.3%) were rated as being at low
related to the origin and sample selection, and were, there- risk, as clinical and radiographic outcome assessment was
fore, rated as being at unclear risk of bias (Büyükgüral and performed by examiners blinded to the intervention and
Cehreli 2008; Casagrande et al. 2008, 2010; Demir and material used. Only two studies were rated as being at high
Cehreli 2007; Falster et al. 2002; Fernández et al. 2013; risk of bias. In the first study by Fernández et al. (2013), out-
Marchi et al. 2006; Sakai et al. 2008; Tuna and Olmez 2008). comes were evaluated initially by the operator who had per-
formed the procedure and then re-evaluated independently
Attrition bias by two blinded observers who were experienced in paedo-
dontics. In the second study by Dimitraki et al. (2019), clini-
Risk of bias for incomplete outcome data, was high in major- cal evaluation was performed by two clinical instructors and
ity of papers (n = 22; 90.4%) since the reported dropout rates the author, and radiographic evaluation was not blinded. In
were above the statistically accepted rate set at 13%. Drop- the remaining seven papers (Büyükgüral and Cehreli 2008;
out rates in these papers ranged from as low as 16% at the Falster et al. 2002; Farsi et al. 2005; Franzon et al. 2007;
24-month follow-up (Nematollahi et al. 2018) to as high as Jayam et al. 2014; Marchi et al. 2006; Yildirim et al. 2016)
90% at the 36-month follow-up (Casas et al. 2004). Twelve there was insufficient information to make a clear judgement
studies (Büyükgüral and Cehreli 2008; Celik et al. 2013; on possible bias in measurement of the outcome.

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European Archives of Paediatric Dentistry

Risk of bias for included prospective study highest value for both clinical and radiographic success was
recorded with MTA (100% for both), followed by bonding
Quality assessment of the study by Airen et al. (2012), the agents (93–96%). CH presented the lowest values, presenting
only non-randomized trial included in the review, is pre- higher number of cases reporting pain and presenting with
sented in Table 6. Overall, the study was rated as being sinus/fistula formation, periapical pathology and root resorp-
at serious risk of bias, mainly due to lack of information tion. The above findings are based on studies with unclear
regarding measurement of outcomes. Blinding of the asses- or high risk of bias.
sors of the treatment outcome was not mentioned, neither In the paper by Dimitraki et al. (2019), DPC showed good
were the clear criteria for the assessment of success/failure clinical and radiographic success rates (75%). Compared to
of the procedures and there was no assessment of methodo- pulpotomy it presented a lower clinical (75% against 87.5%
logical error. Furthermore, it was rated at being at moderate for pulpotomy) but higher radiographic success rate (75%
risk regarding missing data, as the dropout rate was mar- against 68.8% for pulpotomy). However, this is based on low
ginally acceptable for the 24-month follow-up. Selection of quality of the evidence.
participants was based on participants characteristics and
there was no risk of bias due to confounding as allocation Indirect pulp capping (IPC)
and follow-up time was equally distributed. Classification of
intervention was clearly defined and so were any deviations Efficacy of IPC was evaluated in five papers (Büyükgüral
from intended interventions. and Cehreli 2008; Casagrande et al. 2008; Chompu-inwai
et al. 2015; Falster et al. 2002; Franzon et al. 2014). In
Analysis of outcomes (Tables 7a–c and 8) three studies (Büyükgüral and Cehreli 2008; Casagrande
et al. 2008; Falster et al. 2002), CH was compared to other
Overall success rates exceeded 70% in majority of studies, medicaments such as dentine bonding agents, CSE, or SCB.
irrespective of procedure and medicament used. Clinical In all papers, clinical success was excellent for all medica-
success in all studies was higher than radiographic success, ments (> 90% in all cases), with CH demonstrating 100%
with the most common cause of failure being pathological success in all studies. Radiographically though, CH seemed
root resorption. Table 7a–c presents overall success rates to perform worse than CSE (86.7% vs 87.5, respectively) and
and secondary outcomes reported in studies with a follow-up SCB (82.6% vs 96%). These findings are based on low and
period of up to 24 months. unclear quality of evidence.
CH IPC was also compared to FS PP and CH total caries
Direct pulp capping (DPC) removal (TCR) in 1 paper (Franzon et al. 2014). The clinical
success rates for PCR and TCR were 92% and 98%, respec-
Direct pulp capping was evaluated in four papers (Amin- tively. Corresponding values for radiographic success were
abadi et al. 2010; Demir and Cehreli 2007; Dimitraki et al. 94% and 98%. The differences calculated were not statisti-
2019; Tuna and Olmez 2008), of which three evaluated suc- cally significant and the results were based on evidence of
cess rates of different medicaments as capping agents and high quality.
one (Dimitraki et al. 2019) compared the intervention with In the study by Chompu-Inwai et al. (2008), IPC was
pulpotomy. Overall, regardless of the medicament used, compared to both resin-modified glass ionomer (RMGI)
clinical success rates ranged between 62 and 100% and base material and luting cement with minimal caries removal
radiographic success rate ranged between 53 and 100%. The with both RMGI base material and luting cement ­(MCRB/L)

Table 6  Risk bias assessment—non-randomized controlled trial

Quality Assessment of potenal risk of bias in non-RCTs.


Confounding Selection of Classification Intended Missing Measurement Selection Overall
participants of Intervention data of outcomes of
intervention reported
result

Airen
et al.
2012

Legend: Low Moderate Serious Critical

13
European Archives of Paediatric Dentistry

and only RMGI luting cement alone (­ MCRL). Results indi- 86%) vs 99% for white MTA. There was also a marginally
cated success rates exceeded 85% in all cases, with ­MCRL better clinical performance of MTA-P and PR-MTA (100%)
having the highest clinical success rate (100%) and M
­ CRB/L compared to Angelus (96%) and white MTA (98%), although
the highest radiographic success (92%). the significance of the differences cannot be determined as
they refer to different studies.
Pulpotomy (PP)
Results from studies with a follow‑up of >24 months
Pulpotomy was evaluated in 21 papers, from which five eval-
uated PP against other vital pulp techniques and 16 evalu- Table 8 presents the outcomes of the eight papers with a
ated various PP medicaments. Pulpotomy was compared to follow-up period of more than 24 months. One study (Dim-
partial pulpotomy in three papers (Nematollahi et al. 2018; itraki et al. 2019) refers to DPC calculating an overall suc-
Noorollahian 2008; Trairatvorakul and Koothiratrakarn cess rate for the procedure equal to 75.8% after 36 months
2012), to IPC in one study (Chen et al. 2021) and to pulpec- with the corresponding value for pulpotomy being 77.1,
tomy in one paper (Casas et al. 2003). Clinical success rate with clinical success being higher than radiographic in
of FC or FS PP ranged between 87.1% and 100% among both cases. Four papers (Casagrande et al. 2009, 2010;
the studies (mean value 96.9%). These values are margin- Franzon et al. 2007; Marchi et al. 2006) reported on IPC,
ally higher than the corresponding values for pulpectomy showing an overall success rate equal to 82.7%, regardless
(85.5%) and IPC (93.8%) and lower than the value of MTA of the lining used. CH showed a success rate (both clini-
partial pulpotomy (98.4%). Mean value for radiographic cal and radiographic) equal to 74.8% in all papers, with
success was of pulpotomy was 91.1% (range: 80.6–100%), corresponding values for Clearfill SE Bond (CSE) being
which was higher than the corresponding values for partial 82.4% after 60 months, 93.3% for SCB after 48 months
pulpotomy (87.8%) but lower than values for IPC (96.3%) and 85.7% for gutta percha (GP) after 36 months. CH’s
and pulpectomy (95.5%). The most frequent failure was peri- failure was mainly attributed to increased numbers of peri-
apical pathology and root resorption, while pulp canal oblit- apical pathology (6/25 cases, 24%), while GP showed a
eration was commonly seen in pulpotomized teeth. Although small percentage of root resorption (1/15 cases, 7%). All
outcomes between different interventions presented differ- the differences between capping materials, reported above,
ences, survival rates were not statistically different and were were not considered statistically significant. Although evi-
based mainly on low-quality evidence. dence was of unclear or high risk of bias.
Regarding pulpotomy medicaments, the one with the Three papers reported on pulpotomy, two of which
highest success rate was MTA, with a mean value of 98.2% (Casas et al. 2004; Trairatvorakul and Koothiratrakarn
(range: 88.1–100%) for clinical and 93.8% (range: 75–100%) 2012) compared the procedure with partial pulpotomy or
for radiographic success, respectively. This was followed pulpectomy and one (Huth et al. 2012) compared differ-
by FS, with the mean value for clinical and radiographic ent pulpotomy medicaments. It was evident that partial
success being 94.4% (range: 85.7–100%) and 84.9% (range: pulpotomy performed equally well compared to complete
75.9–92%), respectively. FC had the corresponding values of pulpotomy after 3 years post-treatment. Clinical success
93.5% (range: 80–100%) clinical success and 81.7% (range: was excellent, reaching 100% in both cases, while radio-
33.3–96%) radiographic success. CH had the lowest mean graphic success was lower with minor differences between
calculated success rates equal to 74.1% (range: 57.1–88.6%) the two techniques (75% and 74% respectively). Both pul-
for clinical success and 52.7% (range: 42.9–70.5%) for radio- potomy procedures showed increased periapical pathology
graphic success. Quality of evidence for the above findings (6.5% for pulpotomy and 9% for partial pulpotomy), root
varies, with most studies (11/16) being at high risk of bias. resorption (19.4% and 18.8%, respectively) and pulp canal
Other medicaments less commonly used among the obliteration (average 70%). When FS pulpotomy was com-
included studies also reported high success rates, with an pared to pulpectomy, radiographic survival rate of the lat-
average value of 94.6% clinical success and 88.3% radio- ter was significantly greater after 3 year (71.4% vs 33.3%),
graphic success. The highest reported values for clinical with pulpotomised molars presenting periapical pathology,
and radiographic success were for CEM (100% and 97%, root resorption and pulp canal obliteration. Cumulative
respectively). The lowest clinical success rate was for BioD percentages of widening of PDL and loss of lamina dura
(89.5%), and the lowest radiographic success was for ZOE seen in both groups was similar (range: 27–29%).
(72%). Further comparisons could not be performed as the When pulpotomy medicaments are considered, it was
above medicaments were only used in one or two papers. evident that all materials performed equally well, with
Also, regarding the different MTAs used, the calculated success rates exceeding 65% in all cases after 36 months.
success rates were similar with small differences for radi- The highest clinical success rate was calculated for FS
ographic success of Angelus MTA and MTA-P (91% and and the highest radiographic for FC. The lowest values for

13
European Archives of Paediatric Dentistry

both clinical and radiographic success was calculated for The results of this systematic review and meta-analysis
CH, that showed the highest percentages of fistula forma- revealed variable success rates for the different treatment
tion (6/41 cases, 14.6%), periapical pathology (6/41 cases, modalities and medicaments. Overall success rates for all
14.6%) and root resorption (7/41 cases, 17.1%). Based on procedures exceeded 70% in majority of studies, with clini-
high-quality evidence, it was shown that CH performed cal success being higher than radiographic success. The
significantly worse than FC or FS and, therefore, is less most common radiographic failure was pathological root
suitable as a pulpotomy medicament. resorption. All medicaments used for IPC and DPC showed
similar success rates. For PP, mineral trioxide aggregate
(MTA), ferric sulfate (FS) and formocresol (FC) showed
Secondary outcomes similar success rates, which were all higher than calcium
hydroxide (CH). These findings were in line with that of
None of the secondary outcomes intended for evaluation in other reviews (Coll et al. 2017; Smaïl-Faugeron et al. 2018).
this review (i.e. on cost-effectiveness or oral health-related It should be noted that there remains some inconsistency
quality of life or patient centred outcomes) were reported in in the understanding and use of terms amongst research
the included papers. groups such as deep caries, selective caries removal or irre-
versible and reversible pulpitis (Bjørndal et al. 2019), and
Quantitative synthesis thus it is important to treat the outcomes of each study with
caution. Apart from the technique and medicament used for
Two papers of low risk of bias could be mathematically the protection of the pulp, there are various other factors
combined and CH was compared to FC as pulpotomy agents that may influence treatment success rates, such as accu-
(Huth et al. 2005; Moretti et al. 2008). Random-effect meta- racy of pre-treatment pulpal diagnosis, practice of aseptic
analysis indicated a statistically significant difference in the techniques, and adequate removal of infected dentine lead-
risk of clinical failure between the treatment groups (RR: ing to reduction of bacterial load. The success of vital pulp
4.13; 95% CI: 1.22, 13.99; p = 0.02) (Fig. 3). For radio- therapy is largely dependent on the pre-treatment pulpal
graphic failure, a statistically significant difference in the condition and the removal of adequate microorganisms
risk between the treatment groups was calculated (RR: 3.51; from the tooth (Al-Hiyasat et al. 2006). The understanding
95% CI: 1.50, 8.21; p = 0.004) (Fig. 4). In both comparisons, of the complex pulpal innervation determines not only the
results were in favor of FC indicating that it performs signifi- diagnosis but also the potential reaction mechanisms to the
cantly better as a pulpotomy agent when compared to CH. treatment and medicament applied. Furthermore, it should
The degree of heterogeneity between studies was found to be acknowledged that even though primary teeth undergo
be low (I2 = 0%). Statistical analysis of publication bias was physiological root resorption, it has been shown that there
not indicated, as fewer than ten studies were included in the is presence of “physiologic” pulp tissue that is susceptible to
quantitative synthesis. pain perception, healing and repair, up to the time of exfolia-
tion (Monteiro et al. 2009). The current methods for accu-
rately ascertaining the state of pulpal inflammation remain
Discussion largely inadequate (Mejàre et al. 2012). This step, however,
is essential, as erroneous pulpal diagnosis will likely lead to
The aim of this systematic review was to investigate the failure outcomes.
quality of the evidence in the published literature regard- The European Society of Endodontology (ESE) recom-
ing contemporary restorative management of deep caries in mends that a detailed pain history and meticulous clinical
vital primary teeth. Despite the stringent inclusion/exclusion examination supplemented with a high-quality periapical
criteria set for this systematic review, a total of 32 controlled radiograph and pulp sensibility testing using low tempera-
trials with a minimum follow-up period of 24 months, span- ture cold testing in combination with electrical pulp test-
ning across various types of restorative interventions and ing (EPT) are necessary to assess the status of the pulp in
medicaments, were included in the study. This indicates that permanent teeth. EPT exhibits a higher accuracy than that
the management of deep caries in primary teeth remains of cold test, but these results seem to be very dependent on
a challenge to clinicians. Although the majority of the the level of root resorption in primary teeth (Asfour et al.
included studies evaluated the pulpotomy technique where 1996; Hori et al. 2011). Also, the application of the EPT is
total caries removal is practised, a substantial number of considered relatively crude and subjective, and even more
papers evaluated indirect and direct pulp capping methods, questionable in very young children especially since the reli-
thus signalling a shift in the management of deep caries in ability of the patient’s answer cannot always be secured or
primary teeth towards approaches where only infected and substantiated.
not affected carious tissue is removed.

13

Table 7  Outcomes
Study; Inter- Treatment agent Dropout Overall success (based on VPT rules) Breakdown of clinical and radiographic parameters (based on VPT rules)
Country ven- distribution (tooth
tion level) Clinical Radiographic

13
Clinical Radiographic Pathological Non-pathological
N (%) N (%)
Pain Swell- Mobil- TTP Sinus tract/ Periapical/furca- Root Wid- PCO Dentine bridge
ing/ ity fistula tion radiolucency resorption ened RDT
abscess/ (pulp pathosis) (internal PDL/
inflam- and loss of
mation external) lamina
dura

a Direct pulp capping


Aminabadi DPC • FC: 60 None • CH: 37/60 • CH: 32/60 • CH: 17 Not Not • CH 8 • CH: 9 • CH: 10 • CH: 14 Not Eval Not Eval Not Eval
et al. • CH: 60 (61.7%) (53.3%) • FC: 8 Eval Eval • FC: 2 • FC: 5 • FC: 2 • FC: 7
(2010) • FC: 54/60 (90%) • FC: 51/60 (85%)
Iran
Demir and DPC • CH: 20 None • CH: 20/20 (100%) • CH: 20/20 (100%) • CH: 0 NR NR Not Eval NR • CH: 0 None Not Eval Not Eval Not Eval
Cehreli • Prime& • Prime& • Prime& • Prime&Bond NT: 0 • Prime& Bond in all
(2007) Bond NT: 20 Bond NT: 20/20 Bond NT: 20/20 (100%) • NRC + Prime&Bond NT: 0 groups
Turkey • NRC + Prime& (100%) • NRC + Prime& NT: 0 • NRC + Prime&
Bond NT: 20 • NRC + Prime& Bond NT: 18/20 (90%) • Total Bond NT: 2
• Total etch + Prime& Bond NT: 20/20 • Total etch + Prime& etch + Prime&Bond:2 • Total
Bond: 20 (100%) Bond: 15/20 (75%) • Xeno III: 1 etch + Prime&
• Xeno III: 20 • Total etch + Prime& • Xeno III: 19/20 (95%) Bond: 5
Bond:18/20 (90%) • Xeno III: 1
• Xeno III: 19/20
(95%)
Dimitraki DPC vs • DPC: 40 65/97 • DPC: 12/16 (75%) • DPC: 12/16 (75%) NR NR NR NR NR NR NR NR NR NR
et al. PP • PP: 57 (67%) • PP: 14/16 (87.5%) • PP: 11/16 (68.8%)
(2019) 24mths
Greece • DPC: 24
• PP: 41
Tuna et al. DPC • CH: 25 8/50 • CH: 20/20 (100%) • CH: 20/20 (100%) None None None None None None None None None None
(2008) • MTA: 25 (16%) • MTA:22/ 22 (100%) • MTA: 22/
• CH: 5 22 (100%)
• MTA: 3

Study; Interven- Treatment agent distribu- Dropout (tooth Overall success (based on numbers analysed) Breakdown of clinical and radiographic parameters (based on numbers analysed)
country tion tion level)
Clinical Radiographic

Clinical Radiographic Pathological Non-pathological


N (%) N (%)
Pain Swell- Mobility TTP Sinus Periapical/ Root Widened PCO Dentine bridge
ing/ tract/ furcation resorption PDL/loss RDT
abscess/ fistula radiolu- (internal of lamina
inflam- cency (pulp and exter- dura
mation pathosis) nal)

b Indirect Pulp capping


Chompu- IPC vs • IPC: 32 28/96 = 29.2% • IPC: 19/20 (95%) • IPC: 18/20 (90%) • IPC: 1 None • IPC: 1 • IPC: 1 None • IPC: 2 • IPC: 1 None None None
Inwai Mini- • MCR B/L: 32 • IPC: 12 • MCR B/L: 24/25 (96%) • MCR B/L: 23/25 (92%) • MCR • MCR • MCR • MCR • MCR
et al. mum • MCR L:32 • ­MCRB/L: 7 • MCR L: 0/23 (100%) • MCR L: 20/23 (87%) B/L: 1 B/L: 1 B/L: 1 B/L: 2 B/L: 2
(2015) caries • MCR L:9 • ­MCRL: • ­MCRL: 0 • MCR • MCR L: 3 • MCR
Thailand removal 0 L: 0 L: 2
European Archives of Paediatric Dentistry
Table 7  (continued)
Study; Interven- Treatment agent distribu- Dropout (tooth Overall success (based on numbers analysed) Breakdown of clinical and radiographic parameters (based on numbers analysed)
country tion tion level)
Clinical Radiographic

Clinical Radiographic Pathological Non-pathological


N (%) N (%)
Pain Swell- Mobility TTP Sinus Periapical/ Root Widened PCO Dentine bridge
ing/ tract/ furcation resorption PDL/loss RDT
abscess/ fistula radiolu- (internal of lamina
inflam- cency (pulp and exter- dura
mation pathosis) nal)

Büyük- IPC • 36% Phosphoric None • 36% Phosphoric • 36% Phosphoric None None None None None None None None None None
güral acid + Prime + Bond: acid + Prime + Bond: acid + Prime + Bond:
et al. 60 60/60 (100%) 60/60 (100%)
European Archives of Paediatric Dentistry

(2008) • Self-etch adhesive: 60 • Self-etch adhesive: 60/60 • Self-etch adhesive: 60/60


Turkey • Prime + Bond: 60 (100%) (100%)
• CH: 60 • Prime + Bond: 60/60 • Prime + Bond: 60/60
(100%) (100%)
• CH: 60/60 (100%) • CH: 60/60 (100%)
Casagrande IPC • CSE: 19 9/40 (22.5%) • CSE: 16/16 • CSE: 14/16 (87.5%) NR NR NR NR NR NR NR NR NR NR
et al. • CH: 21 • CSE: 3 (100%) • CH: 13/15 (86.7%)
(2008) • CH: 6 • CH: 15/15 (100%)
Brazil
Falster et al IPC • SCB: 25 None at 24 • SCB: 25/25 (100%) • SCB: 24/25 (96%) None None None None None • SCB: 1 • SCB: 0 NR NR NR
(2002) • CH: 23 mths • CH: 23/23 (100%) • CH: 20/23 (87%) • CH: 3 • CH: 1
Brazil
Franzon IPC • PCR: 67 4/124 • PCR: 61/66 (92.4%) • PCR: 62/66 (94%) None None None None • PCR: • PCR: 4 None None • None None
et al. • TCR: 57 (3.3%) • TCR: 53/54 (98.2%) • TCR: 53/54 (98.2%) 5 • TCR: 1
(2014) • PCR: 1 • TCR:
Brazil • TCR: 3 1

Study; Interven- Treatment Dropout (tooth level) Overall success (based on numbers Breakdown of clinical and radiographic parameters (based on numbers analysed)
country tion agent dis- analysed)
tribution Clinical Radiographic

Clinical Radio- Pathological Non-pathological


N (%) graphic
N (%) Pain Swelling/ Mobility TTP Sinus Periapical/ Root Widened PCO Dentine
abscess/ tract/fis- furcation resorption PDL/loss bridge
inflamma- tula radio- (internal of lamina RDT
tion lucency and exter- dura
(pulp nal)
pathosis)

c Pulpotomy
Airen PP • FC: 35 10/70 • FC: 24/30 (80%) • FC: • FC: 6 None Not Eval Not Eval None • FC: 5 • FC: 15 None • FC: 0 None
et al. • MTA: (14%) • MTA: 29/30 (96.7%) 10/30 • MTA: 1 • MTA: 1 • MTA: 2 • MTA: 1
(2012) 35 • FC: 5 (33.3%)
India • MTA:5 • MTA:
(NOT 27/30
RCT) (90%)
Ansari PP • FC: 20 10/40, (25%) • FC: 14/15 (93.3%) • FC: 9/15 None None Not Eval Not Eval • FC: 1 • FC: 6 • FC: 5 • FC:8 • FC: 4 Not Eval
et al. • MTA: • FC: 5 • MTA: 15/15 (60%) • MTA: 0 • MTA: 2 • MTA: 2 • MTA: 2 • MTA: 6
(2010) 20 • MTA: 5 (100%) • MTA:
Iran 13/15
(86.7%)

13

Table 7  (continued)
Study; Interven- Treatment Dropout (tooth level) Overall success (based on numbers Breakdown of clinical and radiographic parameters (based on numbers analysed)
country tion agent dis- analysed)
tribution Clinical Radiographic

13
Clinical Radio- Pathological Non-pathological
N (%) graphic
N (%) Pain Swelling/ Mobility TTP Sinus Periapical/ Root Widened PCO Dentine
abscess/ tract/fis- furcation resorption PDL/loss bridge
inflamma- tula radio- (internal of lamina RDT
tion lucency and exter- dura
(pulp nal)
pathosis)

Casas PP vs • FS PP: 175/291 (60.1%) • FS PP: 27/31 • FS PP: • FS PP: 1 • FS PP: 3 None None None • FS PP: • FS PP: • FS PP: • FS PP: 22 Not Eval
et al. Pulpec- 182 24 mths (87.1%) 25/31 • PPT: 1 • PPT: 0 in all in all in all 12 22 19 • PPT: N/A
(2003)* tomy • PPT: • FS: 109; • PPT: 21/22 (85.5%) (80.6%) groups groups groups • PPT: 12 • PPT: 2 • PPT: 7
Canada (PPT) 109 • PPT: 66 • PPT:
21/22
(95.5%)
Celik et al. PP • White 5/139 • White MTA: 42/43 • White • White • White None • White • White • White • White • White • White Not Eval
(2013) MTA: (3%) (97.7%) MTA: MTA: 0 MTA: 0 in all MTA: 0 MTA: 1 MTA: 0 MTA: 0 MTA: 0 MTA: 1
Turkey 46 • White MTA: 3 • Angelus MTA: 42/43 • Angelus • Angelus groups • Angelus • Angelus • Angelus • Angelus • Angelus • Angelus
• Angelus • Angelus MTA: 1 42/44 (95.5%) (97.7%) MTA: 1 MTA: 0 MTA: 2 MTA: 2 MTA: 1 MTA: 3 MTA: 0 MTA: 1
MTA: • CH: 1 • CH: 36/47 (76.6%) • Angelus • CH: 1 • CH: 1 • CH: 3 • CH: 7 • CH:27 • CH: 23 • CH: 14 • CH: 0
45 MTA:
• CH: 48 40/44
(90.9%)
• CH:
21/47
(44.7%)
Celik et al. PP • White 2/44 (4.5%) • White MTA: 23/23 • White NR NR NR NR NR NR NR NR • White Not Eval
(2019) MTA: ▪White MTA: 1 (100%) MTA: MTA: 0
Turkey 24 ▪BioD: 1 • BioD: 17/19 (89.5%) 23/23 • BioD: 2
• BioD: (100%)
20 • BioD:
17/19
(89.5%)
Chen et al. PP vs IPC • IPT: 81 7/168 • IPC: 76/81 • IPC: NR NR NR NR NR NR NR NR NR Not Eval
(2020) • PP: 87 (4.4%) (93.8%) 78/81
China • IPT:6 • PP: 85/87 (97.7%) (96.3%)
• PP: 1 • PP: 86/87
Based on numbers that (98.9%)
received intervention
Erdem • MTA: 28/128 (21.9%) • MTA: 24/25 • MTA: NR NR NR • MTA: 1 NR • MTA: 1 • MTA: 0 NR • MTA: 5 Not Eval
et al. 32 • MTA: 7 (96%) 24/25 • FS: 2 • FS: 0 • FS: 1 • FS: 1
(2011) • FS: 32 • FS:7 • FS: 23/25 (92%) (96%) • FC: 2 • FC: 0 • FC: 1 • FC: 2
Turkey • FC:32 • FC: 7 • FC: 23/25 (92%) • FS: 23/25 ZOE:2 • ZOE: 0 • ZOE: 6 • ZOE: 0
• ZOE: 32 • ZOE: 7 • ZOE:23/25 (92%) (92%)
• FC:
23/25
(92%)
• ZOE:
18/25
(72%)
European Archives of Paediatric Dentistry
Table 7  (continued)
Study; Interven- Treatment Dropout (tooth level) Overall success (based on numbers Breakdown of clinical and radiographic parameters (based on numbers analysed)
country tion agent dis- analysed)
tribution Clinical Radiographic

Clinical Radio- Pathological Non-pathological


N (%) graphic
N (%) Pain Swelling/ Mobility TTP Sinus Periapical/ Root Widened PCO Dentine
abscess/ tract/fis- furcation resorption PDL/loss bridge
inflamma- tula radio- (internal of lamina RDT
tion lucency and exter- dura
(pulp nal)
pathosis)

Farsi et al. PP • FC: 60 46/120 (38.3%) • FC: 35/36 (97.2%) • FC: • FC: 1 None Not eval Not eval None • FC: 2 • FC: 5 NR • FC: 1 Not eval
European Archives of Paediatric Dentistry

(2005) • MTA: • FC: 24 • MTA: 38/38 (100%) 31/36 • MTA:0 in all in all • MTA: 0 • MTA: 0 • MTA: 3
Saudi 60 • MTA: 22 (86.1%) groups groups
Arabia • MTA:
38/38
(100%)
Fernandez PP • FC: 25 24/100 • FC: 25/25 (100%) • FC: • FC: 0/25 • FC: 0 None None None • FC: 0 • FC: 1 Not eval Not eval Not eval
et al. • MTA: (24%) • FS:12/14 (85.7%) 24/25 (0%) • FS: 2 in all in all in all • FS:1 • FS:2
(2013) 25 • FC: 0 • MTA: 20/20 (100%) (96%) • FS:2/14 • MTA: 0 groups groups groups • MTA: 0 • MTA: 1
Spain • FS: 25 • FS: 11 • NaOCl: 16/17 (96%) • FS:11/14 (14.3%) • NaOCl:1 • NaOCl: • NaOCl:
• NaOCl: • MTA: 5 (85.7%) • MTA: 0 3
25 • NaOCl: 8 • MTA: 0/18
19/20 (0%)
(94.4%) ▪NaOCl:
• NaOCl: 1/17
5/17 (4%)
(82.4%)
Guven PP ▪BioD: 29 36/116 (31%) ▪BioD: 29/29 (100%) ▪BioD: None ▪BioD: 0 ▪BioD: 0 ▪BioD: 0 None NR NR NR ▪BioD: 3 Not eval
et al ▪MTA-P: Breakdown of dropouts ▪MTA-P: 29/29 24/29 in all ▪MTA- ▪MTA- ▪MTA- in all ▪MTA-P: 4
2017 29 not reported (100%) (82.8%) groups P: 0 P: 0 P: 0 groups ▪PR-MTA: 1
Turkey ▪PR- ▪PR-MTA: 28/29 ▪MTA-P: ▪PR- ▪PR- ▪PR- ▪FS: 0
MTA: (96.6%) 25/29 MTA: 1 MTA: 1 MTA: 1
29 ▪FS: 29/29 (100%) (86.2%) ▪FS: 0 ▪FS: 0 ▪FS: 0
▪FS: 29 ▪PR-MTA:
27/29
(93.1%)
▪FS: 22/29
(75.9%)
Huth et al. PP • FC:50 4/191 (2.1%) ▪FC:48/50(96%) ▪FC:45/50 None ▪FC:1 None ▪FC:1 None ▪FC:3 ▪FC:2 None Not eval Not eval
(2005) • Er:YAG: 24 months ▪Er:YAG: 44/ 47 (90%) in all ▪Er:YAG: in all ▪Er:YAG: in all ▪Er:YAG: ▪Er:YAG: in all
Germany 47 • FC: 1 (93.6%) ▪Er:YAG: groups 0 groups 3 groups 3 3 groups
• CH: 44 • Laser: 0 ▪CH: 39/44 (88.6%) 41/ 47 ▪CH: 0 ▪CH: 5 ▪CH: 6 ▪CH: 7
• FS: 50 • CH: 3 ▪FS: 50/50 (100%) (87.2%) ▪FS: 0 ▪FS: 0 ▪FS: 5 ▪FS: 2
• FS: 0 ▪CH: 31/44
(70.5%)
▪FS: 43/50
(86%)

13

Table 7  (continued)
Study; Interven- Treatment Dropout (tooth level) Overall success (based on numbers Breakdown of clinical and radiographic parameters (based on numbers analysed)
country tion agent dis- analysed)
tribution Clinical Radiographic

13
Clinical Radio- Pathological Non-pathological
N (%) graphic
N (%) Pain Swelling/ Mobility TTP Sinus Periapical/ Root Widened PCO Dentine
abscess/ tract/fis- furcation resorption PDL/loss bridge
inflamma- tula radio- (internal of lamina RDT
tion lucency and exter- dura
(pulp nal)
pathosis)

Jamali PP ▪FC: 50 28/150 • FC: 33/38 • FC: • FC: 2 Not eval None • FC: 3 • FC: 0 None • FC: 3 None Not eval Not eval
et al ▪3Mixta- (18.6%) (86.8%) 35/38 • 3Mixta- in all • 3Mixta- • 3Mixta- in all • 3Mixta- in all
2018 tin: 50 • FC: 12 • 3Mixtatin: 38/42 (92.1%) tin: 4 groups tin: 0 tin: 0 groups tin: 0 groups
Iran ▪MTA: 50 • 3Mixtatin: 8 (90.5%) • 3Mixta- • MTA: 4 • MTA: 0 • MTA: 1 • MTA: 0
• MTA: 8 • MTA: 37/42 (88.1%) tin: 42/42
(100%)
• MTA:
42/42
(100%)
Jayam PP • MTA: 18/100 • MTA: 40/40 (100%) • MTA: NR NR NR NR NR NR NR NR NR NR
et al. 50 (18%) • FC: 42/42 (100%) 40/40
(2014) • FC: 50 • MTA: 10 (100%)
India • FC: 8 • FC:
38/42
(90.5%)
Khorakian PP • ES/ 16/102 • ES/ZOE: • ES/ZOE: None None None None None NR NR NR • ES/ZOE: Not Eval
et al. ZOE: (15.7%) 43/43(100%) 40/43 in all in all in all in all in all 33
(2014) 51 • CEM: 8 • CEM: 43/43 (100%) (93%) groups groups groups groups groups • CEM:
Iran • CEM: • ES/ZOE:8 • CEM: 27** at
51 36/43 12 months
(83.7%)
Male- PP • CEM: 10/80 • CEM: 35/35 (100%) • CEM: None None None None None None • CEM: 1 None NR Not eval
khafzali 40 (12.5%) • MTA: 35/35 (100%) 34/35 in all in all in all in all in all in all • MTA: 3 in all
et al. • MTA: • CEM: 5 (97.1%) groups groups groups groups groups groups groups
(2011) 40 • MTA: 5 • MTA:
Iran 32/35
(91.4%)
Moretti PP • FC: 15 2/45 • FC: 14/15 • FC: None None • FC: 0 None • FC: 0 None • FC: 0 • FC: 0 Not Eval • Dentine
et al. • CH: 15 (4.4%) (93%) 14/15 in all in all • CH: 4 in all • CH: 4 in all • CH: 6 • CH: 4 bridge
(2008) • MTA: • FC: 0 • CH: 8/14 (57.1%) (93%) groups groups • MTA:0 groups • MTA: 0 groups • MTA: 0 • MTA: 0 • FC: 0
Iran 15 • CH: 1 • MTA: 14/14 (100%) • CH: 6/14 • CH: 7
• MTA: 1 (42.9%) • MTA: 4
• MTA:
14/14
(100%)
European Archives of Paediatric Dentistry
Table 7  (continued)
Study; Interven- Treatment Dropout (tooth level) Overall success (based on numbers Breakdown of clinical and radiographic parameters (based on numbers analysed)
country tion agent dis- analysed)
tribution Clinical Radiographic

Clinical Radio- Pathological Non-pathological


N (%) graphic
N (%) Pain Swelling/ Mobility TTP Sinus Periapical/ Root Widened PCO Dentine
abscess/ tract/fis- furcation resorption PDL/loss bridge
inflamma- tula radio- (internal of lamina RDT
tion lucency and exter- dura
(pulp nal)
pathosis)

Nematol- PP vs • MTA 8/50 • MTA partial PP: • MTA None • MTA • MTA • MTA None • MTA • MTA • MTA • MTA par- Not Eval
European Archives of Paediatric Dentistry

lahi partial partial (16%) 20/21 (95.2%) partial in all partial partial partial in all partial partial partial tial PP: 6
et al. PP PP: 25 • MTA partial PP: 4 • FC PP: 21/21 PP: groups PP: 1 PP: 1 PP: 1 groups PP: 3 PP: 2 PP: 1 • FC PP: 16
(2018) • FC PP: • FC PP: 4 (100%) 19/21 • FC • FC • FC • FC • FC • FC
Iran 25 (90.5%) PP: 0 PP: 0 PP: 0 PP: 0 PP: 1 PP: 0
• FC PP:
20/21
(95.2%)
Noorol- PP vs • MTA 23/60 • MTA partial PP: • MTA NR NR NR NR NR • MTA NR NR • MTA par- Not Eval
lahian partial partial (38.3%) 19/19 partial partial tial PP: 1
et al. PP PP: 30 • MTA: 11 (100%) PP: PP: 2 • FC PP: 4
(2008) • FC PP: • FC: 12 • FC PP: 18/18 17/19 • FC
Brazil 30 (100%) (89.5%) PP: 0
• FC PP:
18/18
(100%)
Sakai PP • MTA: 1/30 • MTA: 14/14 (100%) • MTA: None None None None None None None None • MTA: 11 • MTA: 4
et al. 15 (3.33%) • PC: 15/15 (100%) 14/14 in all in all in all in all in all in all in all in all • PC: 15 • PC: 2
(2008) • PC: 15 • MTA: 1 (75%) groups groups groups groups groups groups groups groups
Thailand • PC: 0 • PC:
15/15
(100%)
Trairat- PP vs • CH 14/86 (16.3%) • CH partial PP: 36/36 • CH par- None None None None None Cannot be Cannot be Cannot be Cannot be Cannot be
vorakul partial partial 24 mths (100%) tial PP: in all in all in all in all in all ascer- ascer- ascer- ascer- ascer-
et al. PP PP: 43 • CH partial PP: 7 • FC PP: 36/36 30/36 groups groups groups groups groups tained tained tained tained tained
(2012) • FC PP: • FC PP: 7 (100%) (83.3%)
Turkey 43 • FC PP:
29/36
(80.6%)
Yildirim PP • FC: 35 13/140 • FC: 31/32 (96.9%) • FC: • FC: 1 • None • FC: 0 • FC: 1 • FC: 2 • FC: 1 • FC: 2 • FC: 1 NR Not Eval
et al. • MTA: (9.3%) • MTA: 33/33 (100%) 27/32 • MTA: 0 in all • MTA: 0 • MTA: 0 • MTA: 1 • MTA: 1 • MTA: 0 • MTA: 1
(2016) 35 • FC:3 • PC: 28/30 (93.3%) (84.4%) • PC: 1 groups • PC: 1 • PC: 0 • PC: 2 • PC: 2 • PC: 2 • PC: 1
Iran • PC: 35 • MTA: 2 • EMD: 29/32 (90.6%) • MTA: • EMD: 1 • EMD: 2 • EMD: 1 • EMD: 3 • EMD: 3 • EMD: 2 • EMD: 2
• EMD: • PC: 5 31/33
35 • EMD: 3 (93.9%)
• PC:
26/30
(86.7%)
• EMD:
25/32
(78.1%)

13
European Archives of Paediatric Dentistry

Additionally, caution should be taken during radiographic


ment; EMD enamel matrix derivative; Er CrYSGG erbium, chronium-doped yttrium, scandium, gallium and garnet laser; ES/ZOE electrosurgery-zinc oxide eugenol; FC formocresol; FS ferric
BioD Biodentine; CEM calcium-enriched mixture cement; CH calcium hydroxide; CSE Clearfill SE Bond; DBF dentine bridge formation; DLD disruption of lamina dura; DPT direct pulp treat-

sulfate; GI gingival Inflammation; I/E-Resorption internal/external root resorption;; IP irreversible pulpitis; IPT indirect pulp treatment; MCR B/L minimal caries removal with resin-modified

tion radiolucency; PP Pulpotomy; PR-MTA MTA-ProRoot; PPT Pulpectomy; RCT​randomized controlled trial; RDT remaining dentine thickness; RMGIC resin-modified glasionomer cement;
glass ionomer (RMGI) base material and luting cement; MCR L minimal caries removal with only RMGI luting cement; MTA mineral trioxide aggregate; MTA-P MTA plus; NRC non-rinse con-

SCB Scotchbond;TCR​ total caries removal; TTP tenderness to percussion; ZOE zinc oxide eugenol; NR—supposedly evaluated but not reported in manuscript; None—evaluated but not seen in
ditioner; PBD periapical bone destruction; PC Portland cement; PCO pulp canal obliteration; PCR partial caries removal; PDL periodontal dental ligament;; P/F-Radiolucency periapical/furca-
analysis as radiolucent areas at the apices of teeth may be the
result of non-vital pulp with periapical pathology or other
pathological processes related to the permanent successor
which is developing very close to the apices of the primary
teeth. It is, therefore, imperative that radiographic evalua-
tions be combined with good clinical examination to arrive
at an accurate pulpal diagnosis prior to commencement of
treatment. The ESE recommends the use of a paralleling
technique, and a film holder device to help capture diag-
nostically acceptable periapical radiographs. Additionally,
when assessing the image, the whole tooth should be visible
as well as clear evidence of apical tissues (> 3 mm) beyond
the root tip with no interproximal overlap, distortion or pro-
cessing errors (European Society of Endodontology 2006).
However, taking radiographs may be challenging in young
patients due to difficulties with structural differences, e.g.
shallower palates or floor of mouths, resulting in deviations
in horizontal angulations that may render resultant radio-
graphs inaccurate for radiographic analysis. Previous studies
have described the use of an individualized bite blocks that
help to enable radiographs to be taken under the same repro-
ducible geometrical conditions, therefore allowing accurate
comparison of radiographic images taken (Hamanaka et al.
2013). A similar method using a customized jig constructed
for each tooth using impression material attached to a Rinn
XCP film holder was described by Chailertvanitkul et al.
(2014) to further control the angulations of the radiographs
taken during review appointments. While this approach may
not be generalized to daily clinical practice, it might be con-
sidered for future studies requiring radiography in paediatric
patients, especially those which require reproducible and
any case; Not Eval—not evaluated (i.e. was not one of the parameters looked at)

standardized radiographs for comparison of the pulp and


root status.
In this systematic review, one of the inclusion criteria
set was the use of rubber dam isolation to secure an aseptic
working environment. The use of rubber dam (RDI) is con-
sidered an integral part of restorative dentistry. In the litera-
ture, there is a wide variation of RDI use with its opponents
advocating reduction in clinical time, better isolation with-
out it and treatment or material used not requiring dry field.
Nevertheless, a recent Cochrane review (Smaïl-Faugeron
et al. 2018) showed evidence of the benefits of RDI in the
longevity of restorations (Wang et al. 2016). Additionally,
benefits such as better view of operating field, reduction of
Bisphenol A exposure, moisture control as well as reduction
of environmental contamination through salivary aerosol are
well documented (Christensen 2001; Cochran et al. 1989;
Table 7  (continued)

Lynch and McConnell 2007; Soldani and Foley 2007).


The 24-month overall success rates for the DPC, IPC, PP
and pulpectomy ranged from 44 to 100%. All four treatment
modalities and the medicaments used, can be considered
viable options for the conservative management of deep

13
Table 8  Outcomes: IPC, DPC, PP at > 24 months
Study; Interven- Treat- Dropout Overall success (based Breakdown of clinical and radiographic parameters (based on numbers analysed)
country; tion ment (tooth on numbers analysed)
follow-up agent level) Clinical Radiographic
(mths) distribu- Clinical Radio- Pathological Non-pathological
tion N (%) graphic
N (%) Pain Swelling Mobility TTP Sinus tract/ Periapical/ Root Widened PCO Dentine
fistula furcation resorption PDL/ bridge
radio- (internal loss of RDT
lucency and exter- lamina
(pulp nal) dura
pathosis)
European Archives of Paediatric Dentistry

Dimitraki DPC vs • DPC: 82/97 • DPC: 5/6 • DPC: 4/6 NR NR NR NR NR NR NR NR NR NR


et al. PP 40 (84.5%) (77.9%) (73.6%)
(2019) • PP: 57 • DPC: • PP: 8/9 • PP: 6/9
Greece 34 (85.6%) (68.6%)
36 • PP: 48
Casa- IPC • SCB: 25/48 48 months 48 months NR NR NR NR NR • SCB: 1 NR NR NR NR
grande 25 (52%) • SCB: • SCB: • CH: 2
et al. • CH: 4–5 yrs 14/15 14/15
(2009) 23 • SCB: (93.3%) (93.3%)
Brazil 10 • CH: 8/10 • CH: 8/10
60 • CH:13 (80%) (80%)
Casa- IPC • CSE: 8/40 • CSE: • CSE: NR NR NR NR NR NR NR NR NR NR
grande 19 (20%) 14/17 14/17
et al. • CH: • CSE: 2 (82.4%) (82.4%)
(2010) 21 • CH: 6 • CH: • CH:
Brazil 11/15 11/15
25–60 (73.3%) (73.3%)
Franzon IPC • CH: 10/39 • CH: • CH: None None None None None • CH: 4 • CH: 0 NR NR NR
et al. 20 (25.6%) 11/15 11/15 • GP: 1 • GP: 1
(2007) • GP: 19 • CH: 5 (73.3%) (73.3%)
Brazil • GP: 5 • GP: • GP:
36 12/14 12/14
(85.7%) (85.7%)
Marchi IPC • GIC: 1/27 • GIC: • GIC: NR NR NR NR • GIC: 1 • GIC: 1 None in all NR NR NR
et al. 15 (3.7%) 14/15 14/15 • CH & • CH & groups
(2014) • CH & • GIC: 0 (93.3%) (93.3%) CR: 1 CR: 1
Brazil CR: • CH & • CH & • CH &
48 12 CR: 1 CR: 8/11 CR:
(72.7%) 11/11
(72.7%)

13

Table 8  (continued)
Study; Interven- Treat- Dropout Overall success (based Breakdown of clinical and radiographic parameters (based on numbers analysed)
country; tion ment (tooth on numbers analysed)

13
follow-up agent level) Clinical Radiographic
(mths) distribu- Clinical Radio- Pathological Non-pathological
tion N (%) graphic
N (%) Pain Swelling Mobility TTP Sinus tract/ Periapical/ Root Widened PCO Dentine
fistula furcation resorption PDL/ bridge
radio- (internal loss of RDT
lucency and exter- lamina
(pulp nal) dura
pathosis)

Casas et al. PP vs • PPT: 262/291 • NR • PPT: NR NR NR NR NR • PPT: 4 • PPT: 1 • PPT: 4 • PPT: Not Eval
(2004) Pulpec- 109 (90%) 10/14 • FS PP: 7 • FS PP: • FS NA
Canada tomy • FS PP: • PPT: 95 (71.4%) 10 PP: 4 • FS
36 (PPT) 182 • FS PP: • FS PP: PP: 9
167 5/15
(33.3%)
Huth et al. PP • FC: 50 8/191 • FC:44/46 • FC:40/46 None • FC: 1 None None • FC: 1 • FC: 4 • FC: 2 None Not Eval Not Eval
(2012) • Er: (4.2%) (95.7%) (86.9%) in all • Er:YAG: in all in all • Er:YAG: • Er:YAG: • Er:YAG: in all
Germany YAG: • FC: 4 • Er:YAG: • Er:YAG: groups 0 groups groups 3 3 3 groups
36 months 47 • Er: 44/47 41/47 • CH: 0 • CH: 6 • CH: 6 • CH: 7
• CH: YAG: 0 (93.6%) (87.2%) • FS: 0 • FS: 1 • FS: 6 • FS: 3
44 • CH: 3 • CH: • CH:
• FS:50 • FS:1 35/41 28/41
(85.4%) (68.3%)
• FS: 48/49 • FS: 40/49
(97.6%) (81.6%)
Trairat- PP vs • FC PP: 23/86 • FC PP: • FC PP: None None in all None None None in all • FC PP: 2 • FC PP: 6 Not Eval • FC PP: Not Eval
vorakul partial 43 (26.7%) 31/31 23/31 in all groups in all in all groups • Partial • Partial 21
et al. PP • Partial • FC PP: (100%) (74.2%) groups groups groups PP: 3 PP: 6 • Partial
(2012) PP: 43 12 • Partial • Partial PP: 23
Turkey • Partial PP: 32/32 PP: 24/32
36 PP: 11 (100%) (75%)

CH Calcium hydroxide; CR composite resin; CSE Clearfill SE Bond; DPC direct pulp cap treatment;; ErCrYSGG erbium, chronium-doped yttrium, scandium, gallium and garnet laser; ES/ZOE
electrosurgery–zinc oxide eugenol; FC formocresol; FS ferric sulfate; GP Gutta Percha; IPC indirect pulp cap treatment; MCR B/L minimal caries removal with resin-modified glass ionomer
(RMGI) base material and luting cement; MCRL minimal caries removal with only RMGI luting cement; MTA mineral trioxide aggregate; MTA-P MTA plus; NRC non-rinse conditioner; PC
Portlant cement; PCO pulp canal obliteration; PCR partial caries removal; PDL periodontal dental ligament; PP pulpotomy; PPT pulpectomy; PR-MTA MTA-ProRoot; RCT​randomized con-
trolled trial; RDT remaining dentine thickness; RMGIC Resin-modified glasionomer cement; SCB Scotchbond; TCR​total caries removal; TTP tenderness to percussion; ZOE zinc oxide eugenol;
NR—supposedly evaluated but not reported in manuscript; None—evaluated but not seen in any case; Not Eval—not evaluated (i.e. was not one of the parameters looked at)
European Archives of Paediatric Dentistry
European Archives of Paediatric Dentistry

Fig. 3  Forest plot clinical failure

Fig. 4  Forest plot radiographic failure

caries in primary teeth. They range from more conserva- to be recruited. Additionally, time factors such as age, oral
tive and less invasive, such as IPC and DPC, to more inva- hygiene level, medical health can also be eliminated as pos-
sive interventions such as PP and pulpectomy. In the DPC sible confounding factors for bias. However, this design
studies (Aminabadi et al. 2010; Dimitraki et al. 2019; Tuna carries the risk of “carry over effect” or “contamination”,
and Olmez 2008), high clinical success rates were shown that has to be evaluated and analysed by the investigator,
with all the medicaments used. However, the trials included since it cannot be statistically assessed (Pozos-Guillén et al.
were rated low in terms of quality assessment and showed 2017). Recruitment of patients is hampered because of the
a very high dropout rate, thus diminishing the validity of need for symmetrical disease patterns. Such a restriction to
their outcomes. Similarly, although IPC showed better clini- patients’ recruitment may seriously compromise the validity
cal and radiographic performance, but in view of the high of the results. For instance, when evaluating two restora-
dropout rate in those studies, the risk of bias is deemed to tive materials in a split-mouth study, only patients with at
be increased. Majority of clinical studies included in this least two cavities in different quadrants can be allowed. This
review investigated different medicaments used in pulpot- restriction might bias the selection of patients towards those
omies. The overall clinical success rates were high in all with a higher number of cavities, and hence greater risk for
trials, however MTA and FC pulpotomy exhibited a better cavities and possibly poorer brushing and dietary behaviour.
clinical and radiographic performance as opposed to CH Lastly, the statistical analysis of a split-mouth design is more
pulpotomy. complex than the one of the parallel designs.
The quality of evidence for the treatment modalities at
24 months was variable. Several factors, such as initial sam-
Quality of evidence ple size calculation, randomization, blinding technique as
well as higher or lower dropout rate, are considered impor-
This review included studies with both split-mouth (7/32) tant factors for determination of the quality of evidence
and parallel-arm (25/32) designs. To evaluate the out- provided. Although many authors reported that randomiza-
comes of each clinical trial, it is important to understand tion and allocation concealment were carried out in their
the benefits but also the drawbacks of each study design. study, few presented details of the method used. Based on
Proponents of the split-mouth designs argue that this design the nature of the procedures, it is to be expected that dou-
minimises the risk of inter-subject variability and/or random ble-blinding is difficult to be achieved. Nevertheless, major-
error, as each subject has a dual role (study–control) in the ity of studies attempted to minimise performance bias by
trial and at the same time reduces the number of subjects

13
European Archives of Paediatric Dentistry

means of excluding the operator from assessing the effect This in part is also depended on the age of the child when the
of interventions. tooth was recruited into the study. The age ranges of patients
An illustration of the characteristics of the trials included recruited across the studies were variable (range 2–11 years),
may be seen in Table 4a–c. A considerable amount of clini- and it is possible that older children who were recruited were
cal and radiographic outcomes was supposedly assessed in more likely to have the teeth exfoliate earlier.
the studies, however not all outcomes (even if assessed) were Given the small numbers of papers with > 24 months
reported, with many trials reporting only overall clinical and follow-up duration which met the inclusion criteria, there is
radiographic success rates without breakdown numbers. inadequate evidence to inform about the long-term survival
Very few studies had longer follow-up times which made rates of teeth treated with the various pulp treatment inter-
comparisons and reporting on the long-term clinical/radio- ventions beyond the 24 months period. Consequently, it is
graphic success of the interventions or medicament inves- not possible to draw conclusions on whether these methods
tigated challenging. Furthermore, the high dropout rate are able to sustain the tooth for longer durations, which is
alongside the high number of exfoliations across studies did particularly essential in very young child patients where
not allow for clear conclusions on the success of the inter- it is desirable for the tooth to last its natural lifespan until
ventions at longer follow-up periods. This is in part influ- physiological eruption of the permanent successor tooth.
enced by the wide age range of children recruited across the There was a limited response as well from the authors
studies, in which it is unknown how many were recruited at when contacted to obtain further information on the study
ages closer to the timing of physiological tooth exfoliation. methodology but also in the breakdown of the overall num-
Therefore, it remains uncertain as to how successful these bers provided. Even though the low response rate of the
vital pulp interventions are in relation to treatment of pri- authors when being contacted during the review was to be
mary teeth in very young children, who would undeniably expected, it is still to be accounted for the weaknesses of the
require retention of the molars in the oral cavity for periods current review along with the fact that only studies published
greater than 2–3 years duration. in English were included. In addition, the fact that most of
the studies had split-mouth design, influence the reported
Strengths and limitations outcome and quality of the studies.

The current review through its stringent criteria (i.e. con-


trolled studies carried out under aseptic conditions, with Conclusion
minimum of 24 months follow-up duration) attempted to
bridge the gap of previous reviews, thus allowing for a • Within the limitations of the studies included, IPC, DPC
more thorough interpretation of the outcomes of the initial and PP interventions have high success rates and can be
studies included under the challenging conditions of daily recommended as effective treatment modalities for pri-
practice. Recalculation of the success rates reported in each mary teeth with deep caries under specific conditions.
trial ensured the standardization of the outcomes to proceed • Clinical success rates of IPC, DPC and PP interventions
in the meta-analysis, which is the biggest strength of this were higher than their respective radiographic success
review since it allows for direct comparisons. However, there rates. Medicaments used for direct and indirect pulp cap-
were a large number of medicaments which were evaluated ping have similar success rates.
across the studies, and the variability of their usage in the • MTA, FS and FC pulpotomy showed similarly high suc-
various interventions as well as their different levels of risk cess rates, which were all higher than the success rates
of bias did not allow for many studies to be included into of CH.
the meta-analysis. • Meta-analysis showed superiority of FC as a pulpotomy
The 24-months follow-up was considered imperative agent compared to CH.
in this review, to draw conclusions about each treatment
method that are related to the clinical longevity and sus- Further research
tainability of each method. While the results for 24 months
follow-up period show reasonably high success rates, this In this current review, it was noted that there is a great need
was not necessarily the case for those with longer follow- for more well conducted RCTs of parallel-arm designs
up timings. Studies with longer follow-ups are inherently focusing mainly on comparisons between different treatment
subjected to attrition bias due to higher risks of dropouts modalities. Well-designed protocols with standardized crite-
and teeth exfoliations, thus making it difficult to assess the ria for reporting core outcomes with increased homogeneity
actual clinical/radiographic success of those treated teeth.

13
European Archives of Paediatric Dentistry

will increase the quality of evidence and allow for better showed similar success rates for the pulpotomy and indirect
comparisons between studies. Increased power analysis pulp capping. With the majority of the studies investigat-
(> 90%) is also required for adequate sample sizes to be cal- ing different pulpotomy agents, it can be stated that MTA
culated and in order compensate for the high dropout rates and MTA-like medicaments exhibit a better performance
of studies with long follow-up periods. as capping agents. The most unfavourable performance was
Furthermore, periods of at least 2 years are required to shown by CH.
follow-up treatment outcomes at specific intervals to report
evolution of clinical and radiographic changes. Failures at
a specific follow-up appointment should always be carried Author contributions  This systematic review is commissioned by the
European Academy for Paediatric Dentistry, to facilitate the develop-
over as numbers in the next follow-up appointment other- ment of European Academy of Paediatric Dentistry (EAPD) guidelines
wise clearly stated. on deep caries management of primary teeth in paediatric dentistry. ES,
One of the biggest problems faced in all similar studies HJT, KS, MD and SG were involved in formulating the search terms
is the ambiguity raised when reporting dropouts, as there and strategy. Literature search was conducted by DK. Data analysis and
synthesis were carried out by all authors. Meta-analysis was carried out
is no clearly defined line between dropouts and teeth that by DK. All authors wrote and critically revised the work for content.
exfoliated in the follow-ups. This also underlines the need
for studies with narrower age ranges that will elucidate the Declarations 
longevity of treatment modality or medicament used. Fur-
thermore, consistency in the reporting of the exfoliation time Conflict of interest  The authors have no conflicts of interest to declare
of the teeth is required to differentiate between an acceler- that are relevant to the content of this article.
ated exfoliation process due to pathology versus physiologi-
cal exfoliation.
It should be noted that there is substantial heterogene-
ity in pulpotomy medicaments among the included studies, References
in which medicaments with different mechanism of action
were often compared against each other, e.g. Formocresol Airen P, Shigli A, Airen B. Comparative evaluation of formocresol
and mineral trioxide aggregate in pulpotomized primary molars–2
(bactericidal and devitalizing agent) versus ferric sulphate year follow up. J Clin Pediatr Dent. 2012;37(2):143–7.
(haemostatic agent) versus MTA (initiation of reparative Al-Hiyasat AS, Barrieshi-Nusair KM, Al-Omari MA. The radio-
dentinogenesis and pulp capping agent). There is a possi- graphic outcomes of direct pulp-capping procedures performed
bility that comparisons of these nature may be equivocal. by dental students: a retrospective study. J Am Dent Assoc.
2006;137(12):1699–705.
For future studies, it may therefore be prudent to compare Aminabadi NA, Farahani RM, Oskouei SG. Formocresol versus cal-
medicaments with similar mechanism of action so that out- cium hydroxide direct pulp capping of human primary molars: two
comes are comparable. Specifically for DPC, more studies year follow-up. J Clin Pediatr Dent. 2010;34(4):317–21.
are necessary to produce evidence for the efficacy of this Ansari G, Ranjpour M. Mineral trioxide aggregate and formocresol
pulpotomy of primary teeth: a 2-year follow-up. Int Endod J.
treatment modality and its medicaments. 2010;43(5):413–8.
Finally, there is a clear call for more studies that inves- Asfour MA, Millar BJ, Smith PB. An assessment of the reliability of
tigate the quality of life of those patients with a focus on pulp testing deciduous teeth. Int J Paediatr Dent. 1996;6(3):163–6.
the time spent before, during and after treatment related to BaniHani A, Duggal M, Toumba J, Deery C. Outcomes of the con-
ventional and biological treatment approaches for the manage-
the school absence for the patient and work absence for the ment of caries in the primary dentition. Int J Paediatr Dent.
carers, the cost-effectiveness of the treatment, as well as the 2018;28(1):12–22.
impact of those treatment methods on the future compliance Bjørndal L, Simon S, Tomson PL, Duncan HF. Management of deep
of the patient. The effect of caries risk, dental age and patient caries and the exposed pulp. Int Endod J. 2019;52(7):949–73.
Büyükgüral B, Cehreli ZC. Effect of different adhesive protocols vs
co-operation on the outcome should be also evaluated. calcium hydroxide on primary tooth pulp with different remain-
ing dentin thicknesses:24-month results. Clin Oral Investig.
Implications for clinical practice 2008;12(1):91–6.
Casagrande L, Bento LW, Rerin SO, Lucas Ede R, Dalpian DM,
de Araujo FB. In  vivo outcomes of indirect pulp treatment
It is imperative for the clinical practitioner to fully under- using a self-etching primer versus calcium hydroxide over the
stand the terminology and the biological background of demineralized dentin in primary molars. J Clin Pediatr Dent.
each restorative modality as well as the biological effect 2008;33(2):131–5.
of the medicament used. Pulp reaction to the treatment Casagrande L, Falster CA, Di Hipolito V, De Góes MF, Straffon LH,
Nör JE, et al. Effect of adhesive restorations over incomplete den-
and medicament applied relies very much in the status of tin caries removal: 5-year follow-up study in primary teeth. J Dent
the pulp before the intervention but also in the conditions Child (chic). 2009;76(2):117–22.
under which the pulp is being treating (patient’s compli-
ance, effect of LA, RDI). The results of this current review

13
European Archives of Paediatric Dentistry

Casagrande L, Bento LW, Dalpian DM, García-Godoy F, de Araujo four dressing materials in pulpotomized primary molars: a ran-
FB. Indirect pulp treatment in primary teeth: 4-year results. Am domized clinical trial with 2-year follow-up. Int J Paediatr Dent.
J Dent. 2010;23(1):34–8. 2013;23(6):400–7.
Casas MJ, Layug MA, Kenny DJ, Johnston DH, Judd PL. Two-year Franzon R, Casagrande L, Pinto AS, García-Godoy F, Maltz M, de
outcomes of primary molar ferric sulfate pulpotomy and root Araujo FB. Clinical and radiographic evaluation of indirect pulp
canal therapy. Pediatr Dent. 2003;25(2):97–102. treatment in primary molars: 36 months follow-up. Am J Dent.
Casas MJ, Kenny DJ, Johnston DH, Judd PL. Long-term outcomes of 2007;20(3):189–92.
primary molar ferric sulfate pulpotomy and root canal therapy. Franzon R, Guimarães LF, Magalhães CE, Haas AN, Araujo FB. Out-
Pediatr Dent. 2004;26(1):44–8. comes of one-step incomplete and complete excavation in pri-
Celik B, Ataç AS, Cehreli ZC, Uysal S. A randomized trial of mineral mary teeth: a 24-month randomized controlled trial. Caries Res.
trioxide aggregate cements in primary tooth pulpotomies. J Dent 2014;48(5):376–83.
Child (chic). 2013;80(3):126–32. Fuks A, Kupietzki A, Guelmann M. Pulp therapy for the primary denti-
Çelik BN, Mutluay MS, Arıkan V, Sarı Ş. The evaluation of MTA tion. In: Casamassimo P, Fields H, McTigue D, Nowak A, editors.
and biodentine as a pulpotomy materials for carious exposures in Pediatric dentistry: infancy through adolescence. 5th ed. St Louis,
primary teeth. Clin Oral Investig. 2019;23(2):661–6. MO: Elsevier/Saunders; 2013. p. 338–40.
Chailertvanitkul P, Paphangkorakit J, Sooksantisakoonchai N, Pumas Guven Y, Aksakal SD, Avcu N, Unsal G, Tuna EB, Aktoren O. Success
N, Pairojamornyoot W, Leela-Apiradee N, Abbott PV. Rand- rates of pulpotomies in primary molars using calcium silicate-
omized control trial comparing calcium hydroxide and mineral based materials: a randomized control trial. Biomed Res Int.
trioxide aggregate for partial pulpotomies in cariously exposed 2017;2017:4059703.
pulps of permanent molars. Int Endod J. 2014;47(9):835–42. Hamanaka EF, Poi WR, Salzedas LM, Alves LC, Panzarini SR, Sonoda
Chen X, Zhang H, Zhong J, Yan W, Lin B, Ding M, et al. Comparison CK, et al. A method for the geometric standardization of intraoral
of indirect pulp treatment and iRoot BP Plus pulpotomy in pri- radiographs for long-term follow up of replanted teeth: a case
mary teeth with extremely deep caries: a prospective randomized report. Dent Traumatol. 2013;29(2):121–6.
trial. Clin Oral Investig. 2021;25(5):3067–76. Higgins J, Green S. Cochrane handbook for systematic reviews of inter-
Chompu-inwai P, Boonsongsawat K, Sastraruji T, Sophasri T, Mankaen ventions. 2011. www.​handb​ook.​cochr​ane.​org.
S, Nondon S, et al. Three incomplete caries removal techniques Hori A, Poureslami HR, Parirokh M, Mirzazadeh A, Abbott P. The
compared over two years in primary molars with asymptomatic ability of pulp sensibility tests to evaluate the pulp status in pri-
deep caries or reversible pulpitis. Pediatr Dent. 2015;37(5):41–8. mary teeth. Int J Paediatr Dent. 2011;21(6):441–5.
Christensen GJ. Restorative dentistry for pediatric teeth. State of the Hu S, Meyer B, Duggal M. A silver renaissance in dentistry. Eur Arch
art 2001. J Am Dent Assoc. 2001;132(3):379–81. Paediatr Dent. 2018;19(4):221–7.
Cochran MA, Miller CH, Sheldrake MA. The efficacy of the rubber Huth KC, Paschos E, Hajek-Al-Khatar N, Hollweck R, Crispin A,
dam as a barrier to the spread of microorganisms during dental Hickel R, et al. Effectiveness of 4 pulpotomy techniques–rand-
treatment. J Am Dent Assoc. 1989;119(1):141–4. omized controlled trial. J Dent Res. 2005;84(12):1144–8.
Coll JA, Seale NS, Vargas K, Marghalani AA, Al Shamali S, Graham Huth KC, Hajek-Al-Khatar N, Wolf P, Ilie N, Hickel R, Paschos E.
L. Primary tooth vital pulp therapy: a systematic review and meta- Long-term effectiveness of four pulpotomy techniques: 3-year ran-
analysis. Pediatr Dent. 2017;39(1):16–123. domised controlled trial. Clin Oral Investig. 2012;16(4):1243–50.
Curzon ME, Pollard MA, Duggal MS. Restoration of primary molars. Jamali Z, Alavi V, Najafpour E, Aminabadi NA, Shirazi S. Randomized
Br Dent J. 1996;180(7):246. controlled trial of pulpotomy in primary molars using MTA and
Demir T, Cehreli ZC. Clinical and radiographic evaluation of adhe- formocresol compared to 3Mixtatin: a novel biomaterial. J Clin
sive pulp capping in primary molars following hemostasis Pediatr Dent. 2018;42(5):361–6.
with 1.25% sodium hypochlorite: 2-year results. Am J Dent. Jayam C, Mitra M, Mishra J, Bhattacharya B, Jana B. Evaluation and
2007;20(3):182–8. comparison of white mineral trioxide aggregate and formocresol
Dimitraki D, Papageorgiou SN, Kotsanos N. Direct pulp capping versus medicaments in primary tooth pulpotomy: clinical and radio-
pulpotomy with MTA for carious primary molars: a randomised graphic study. J Indian Soc Pedod Prev Dent. 2014;32(1):13–8.
clinical trial. Eur Arch Paediatr Dent. 2019;20(5):431–40. Khorakian F, Mazhari F, Asgary S, Sahebnasagh M, Alizadeh Kaseb
Duggal MS, Nooh A, High A. Response of the primary pulp to inflam- A, Movahhed T, et al. Two-year outcomes of electrosurgery and
mation: a review of the Leeds studies and challenges for the calcium-enriched mixture pulpotomy in primary teeth: a ran-
future. Eur J Paediatr Dent. 2002;3(3):111–4. domised clinical trial. Eur Arch Paediatr Dent. 2014;15(4):223–8.
Dye BA, Hsu KL, Afful J. Prevalence and measurement of dental caries Lunder N, von der Fehr FR. Approximal cavitation related to bite-
in young children. Pediatr Dent. 2015;37(3):200–16. wing image and caries activity in adolescents. Caries Res.
Erdem AP, Guven Y, Balli B, Ilhan B, Sepet E, Ulukapi I, et al. Success 1996;30(2):143–7.
rates of mineral trioxide aggregate, ferric sulfate, and formocresol Lynch CD, McConnell RJ. Attitudes and use of rubber dam by Irish
pulpotomies: a 24-month study. Pediatr Dent. 2011;33(2):165–70. general dental practitioners. Int Endod J. 2007;40(6):427–32.
European Society of Endodontology. Quality guidelines for endodontic Malekafzali B, Shekarchi F, Asgary S. Treatment outcomes of pul-
treatment: consensus report of the European Society of Endodon- potomy in primary molars using two endodontic biomateri-
tology. Int Endod J. 2006;39(12):921–30. als. A 2-year randomised clinical trial. Eur J Paediatr Dent.
Falster CA, Araujo FB, Straffon LH, Nör JE. Indirect pulp treatment: 2011;12(3):189–93.
in vivo outcomes of an adhesive resin system vs calcium hydrox- Marchi JJ, de Araujo FB, Fröner AM, Straffon LH, Nör JE. Indirect
ide for protection of the dentin-pulp complex. Pediatr Dent. pulp capping in the primary dentition: a 4 year follow-up study. J
2002;24(3):241–8. Clin Pediatr Dent. 2006;31(2):68–71.
Farsi N, Alamoudi N, Balto K, Mushayt A. Success of mineral trioxide Mejàre IA, Axelsson S, Davidson T, Frisk F, Hakeberg M, Kvist T,
aggregate in pulpotomized primary molars. J Clin Pediatr Dent. et al. Diagnosis of the condition of the dental pulp: a systematic
2005;29(4):307–11. review. Int Endod J. 2012;45(7):597–613.
Fernández CC, Martínez SS, Jimeno FG, Lorente Rodríguez AI,
Mercadé M. Clinical and radiographic outcomes of the use of

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European Archives of Paediatric Dentistry

Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew Portland cement: a randomised controlled trial. Br Dent J.
M, et al. Preferred reporting items for systematic review and 2009;207(3):E5; discussion 128–129.
meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. Santamaría R, Innes N. Sealing carious tissue in primary teeth using
2015;4(1):1. crowns: the Hall technique. Monogr Oral Sci. 2018;27:113–23.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items Smaïl-Faugeron V, Glenny AM, Courson F, Durieux P, Muller-Bolla
for systematic reviews and meta-analyses: the PRISMA statement. M, Fron CH. Pulp treatment for extensive decay in primary teeth.
PLoS Med. 2009;6(7): e1000097. Cochrane Database Syst Rev. 2018;5(5):C003220.
Monteiro J, Day P, Duggal M, Morgan C, Rodd H. Pulpal status of Soldani F, Foley J. An assessment of rubber dam usage amongst spe-
human primary teeth with physiological root resorption. Int J Pae- cialists in paediatric dentistry practising within the UK. Int J Pae-
diatr Dent. 2009;19(1):16–25. diatr Dent. 2007;17(1):50–6.
Moretti AB, Sakai VT, Oliveira TM, Fornetti AP, Santos CF, Machado Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswa-
MA, et al. The effectiveness of mineral trioxide aggregate, cal- nathan M, et al. ROBINS-I: a tool for assessing risk of bias in
cium hydroxide and formocresol for pulpotomies in primary teeth. non-randomised studies of interventions. BMJ. 2016;355:i4919.
Int Endod J. 2008;41(7):547–55. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I,
Nematollahi H, Noorollahian H, Bagherian A, Yarbakht M, Nematol- et al. RoB 2: a revised tool for assessing risk of bias in randomised
lahi S. Mineral trioxide aggregate partial pulpotomy versus formo- trials. BMJ. 2019;366:l4898.
cresol pulpotomy: a randomized, split-mouth, controlled clinical Trairatvorakul C, Koothiratrakarn A. Calcium hydroxide partial pul-
trial with 24 months follow-up. Pediatr Dent. 2018;40(3):184–9. potomy is an alternative to formocresol pulpotomy based on a
Ni Chaollai A, Monteiro J, Duggal MS. The teaching of manage- 3-year randomized trial. Int J Paediatr Dent. 2012;22(5):382–9.
ment of the pulp in primary molars in Europe: a preliminary Tuna D, Olmez A. Clinical long-term evaluation of MTA as a
investigation in Ireland and the UK. Eur Arch Paediatr Dent. direct pulp capping material in primary teeth. Int Endod J.
2009;10(2):98–103. 2008;41(4):273–8.
Noorollahian H. Comparison of mineral trioxide aggregate and formo- Wang Y, Li C, Yuan H, Wong MC, Zou J, Shi Z, et al. Rubber dam
cresol as pulp medicaments for pulpotomies in primary molars. isolation for restorative treatment in dental patients. Cochrane
Br Dent J. 2008;204(11):E20. Database Syst Rev. 2016;9(9):CD009858.
Pozos-Guillén A, Chavarría-Bolaños D, Garrocho-Rangel A. Split- Yildirim C, Basak F, Akgun OM, Polat GG, Altun C. Clinical and radi-
mouth design in paediatric dentistry clinical trials. Eur J Paediatr ographic evaluation of the effectiveness of formocresol, mineral
Dent. 2017;18(1):61–5. trioxide aggregate, portland cement, and enamel matrix derivative
Rodd HD, Waterhouse PJ, Fuks AB, Fayle SA, Moffat MA. Pulp in primary teeth pulpotomies: a two year follow-up. J Clin Pediatr
therapy for primary molars. Int J Paediatr Dent. 2006;16(Suppl Dent. 2016;40(1):14–20.
1):15–23.
Sakai VT, Moretti AB, Oliveira TM, Fornetti AP, Santos CF, Machado Publisher's Note Springer Nature remains neutral with regard to
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