Primary molar pulpotomy: A systematic review and network meta-analysis

Primary molar pulpotomy: A systematic review and network meta-analysis

Journal of Dentistry, 2014-09-01, Volume 42, Issue 9, Pages 1060-1077, Copyright © 2014 Elsevier Ltd

Abstract

Objective

Pulpotomy is a common procedure to treat asymptomatic reversible pulpitis in primary molars. The aim of this study is to undertake a systematic review and a network meta-analysis to compare the clinical and radiographic outcomes of different pulpotomy procedures in primary molars.

Data

Three authors performed data extraction independently and in duplicate using data collection forms. Disagreements were resolved by discussion.

Sources

An electronic literature search was performed within MEDLINE (via PubMed), ScienceDirect, Web of Science, Cochrane, and ClinicalKey databases until December 2012. Medications for pulpotomy including formocresol, ferric sulfate, calcium hydroxide, and mineral trioxide aggregate (MTA), and laser pulpotomy are compared using Bayesian network meta-analyses. The outcome is the odds ratio for clinical and radiographic failure including premature tooth loss at 12 and 24 months after treatments amongst different treatment procedures. 37 studies were included in the systematic review, and 22 of them in the final network meta-analyses. After 18–24 months, in terms of treatment failure, the odds ratio for calcium hydroxide vs. formocresol was 1.94 [95% credible interval (CI): 1.11, 3.25]; 3.38 (95% CI: 1.37, 8.61) for lasers vs. formocresol; 2.16 (95% CI: 1.12, 4.31) for calcium hydroxide vs. ferric sulfate; 3.73 (95% CI: 1.27, 11.67) for lasers vs. ferric sulfate; 0.47 (95% CI: 0.26, 0.83) for MTA vs. calcium hydroxide; 3.76 (95% CI: 1.39, 10.08) for lasers vs. MTA.

Conclusions

After 18–24 months, formocresol, ferric sulfate, and MTA showed significantly better clinical and radiographic outcomes than calcium hydroxide and laser therapies in primary molar pulpotomies.

Clinical significance

The network meta-analyses showed that MTA is the first choice for primary molar pulpotomies. However, if treatment cost is an issue, especially when the treated primary molars are going to be replaced by permanent teeth, ferric sulfate may be the choice.

Introduction

Pulpotomy in primary teeth is a standard procedure to amputate the inflamed and infected dental coronal pulp tissue and is usually undertaken when coronal pulp tissues are exposed by caries, during caries removal or trauma . The objective of this treatment is to remove coronal inflammatory tissues, which usually contain microorganisms; therefore, healing is allowed to take place at the entrance of the root canal with essentially healthy pulp tissue.

After a coronal pulp is amputated, the pulp stump could be treated with several agents, leaving vital and uninfected radicular pulp tissue intact. Although dilute formocresol (1:5 Buckley’s solution) has long been regarded as the gold standard for wound dressing of pulpotomized primary teeth, other agents can also protect radicular pulp, promoting healing and providing good treatment outcomes. The use of formocresol has been questioned because of its adverse effects, such as potential carcinogenicity, mutagenicity, and cytotoxicity. Moreover, the major component of formocresol, formaldehyde, might be distributed systemically after pulpotomies . This led to investigations of alternative techniques and materials, such as ferric sulphate , gluatraldehyde preparations , mineral trioxide aggregate (MTA) , electrosurgery , calcium hydroxide , and even laser therapies .

Although some recent meta-analyses indicated that MTA and ferric sulfate may present similar or even better clinical or radiographic outcomes than formocresol, there is no comprehensive review for comparisons of different pulpotomy medications and techniques . Therefore, it is challenging for dentists to select the most appropriate medicaments, and the relative effectiveness of those treatments remains uncertain.

Traditional meta-analysis undertakes pair-wise comparisons between treatments, but when the number of available treatments is large, pair-wise comparisons may be inefficient or not feasible . Network meta-analysis is a methodology for direct and indirect statistical comparisons between different treatments and had been used in dental research . The aim of this study is to undertake a systematic review and network meta-analyses, comparing the clinical and radiographic outcomes in primary molar pulpotomy amongst different dressing materials. The null hypothesis is that there were no differences in clinical and radiographic outcomes among different materials when performing primary molar pulpotomies.

Materials and methods

Literature search

The literature search within MEDLINE (via PubMed), ScienceDirect, Web of Science, Cochrane, and ClinicalKey databases up to December 2012 was undertaken. To identify relevant studies, we used the following key words “(pulpotomy OR pulp therapy OR pulp treatment OR pulp exposure OR pulp devitalization OR pulp capping) AND (primary OR paediatric OR deciduous)”, limited in “clinical trials” and “humans”; no language restrictions were imposed. The reference lists of previously published reviews were also cross-checked for studies missed in our electronic literature search.

Inclusion criteria

  • Original prospective clinical trials comparing two or more pulpotomy agents.

  • Human vital primary molars with carious pulp exposure.

  • Follow-up periods of 6 months or more.

  • Reporting clinical or radiographic success and failure rates.

  • Clear definitions of success and failure. Clinical success was defined as asymptomatic, absence of sinus tract or fistula, no pathological tooth mobility, and absence of soft tissue swelling. Radiographic success was defined as absence of apical and furcal radiolucencies, absence of pathologic internal or external root resorption, absence of widening of periodontal ligament space, and absence of apical root resorption .

Study selection, quality assessment, and data extraction

Screening titles and abstracts of potentially relevant articles was performed before retrieving full articles. Full articles were reviewed to verify if they fit all the inclusion criteria above. The literature selection and data extractions ( Fig. 1 ) were done by three authors (PY Lin, HS Chen, YH Wang) repeatly. Quality assessment of included studies, such as randomization, allocation concealment, blinding, intention to treat and sample size calculation, were carried out independently by three authors (PY Lin, HS Chen, YH Wang). The following data were also extracted independently by three authors (PY Lin, HS Chen, YH Wang): mean age, age range, treatment agent, number of teeth receiving treatments at the beginning of the trial, drop-out rates, follow-up periods, study design, tooth numbers at follow-up visits, and clinical and radiographic success rates ( Table 1 ). The corresponding authors were contacted to obtain information of unclear or missing data. Any disagreements on study inclusions, quality assessment, or data extraction were resolved by discussions among the three authors.

Flowchart for literature search and identifications of articles for review.
Fig. 1
Flowchart for literature search and identifications of articles for review.
Table 1
Summary of studies included for present primary molar pulpotomy systematic review.
Author, year, country Mean age (range) Treatment agent Restoration Teeth number at beginning Follow-up period (months) Teeth number at follow-up period Clinical success rate a Radiographic success rate a Study design Drop-out rate Clinical success rate b Radiographic success rate b
Alacam, 1989, Turkey (7–11) Formocresol Not mentioned 23 12 23 91.3% 82.6% Parallel 0.0% 91.3% 82.6%
(1:5 Buckley’s solution)
2% glutaraldehyde + ZOE 25 12 25 96.0% 92.0% 0.0% 96.0% 92.0%
2% glutaraldehyde + calcium hydroxide 21 12 21 90.4% 76.1% 0.0% 90.5% 81.0%
Prakash, 1989, India 6 (3.5–9.5) Formocresol Amalgam 30 6 22 66.6% 66.6% Parallel 26.7% 90.9% 90.9%
(1:5 Buckley’s solution)
2% glutaraldehyde 30 6 20 66.6% 66.6% 33.3% 100.0% 100.0%
Fei, 1991, USA c 6.6 (3.2–10.1) Formocresol Stainless steel crown N/A 6 N/A N/A N/A Parallel N/A 100.0% 83.3%
(1:5 Buckley’s solution) 12 N/A N/A N/A N/A 96.3% 81.5%
15.50% ferric sulfate N/A 6 N/A N/A N/A N/A 100.0% 96.3%
12 N/A N/A N/A N/A 100.0% 100.0%
Shumayrikh, 1999, Saudi Arabia (5–9) 2% glutaraldehyde + ZOE Stainless steel crown 30 12 29 93.3% 73.3% Parallel 3.3% 96.6% 75.9%
2% glutaraldehyde + calcium hydroxide 31 12 28 80.6% 64.5% 9.7% 89.3% 71.4%
Ibricevic, 2000/2003, Kuwait c 4.3 (3–6) Formocresol (not dilute) Stainless steel crown or amalgam 35 6 35 100.0% 100.0% Parallel 0.0% 100.0% 100.0%
9 35 100.0% N/A 0.0% 100.0% N/A
12 35 100.0% N/A 0.0% 100.0% N/A
15 35 100.0% N/A 0.0% 100.0% N/A
18 35 100.0% N/A 0.0% 100.0% N/A
20 35 100.0% 97.2% 0.0% 100.0% 97.1%
15.50% ferric sulfate 35 6 35 100.0% 100.0% 0.0% 100.0% 100.0%
9 35 100.0% N/A 0.0% 100.0% N/A
12 35 100.0% N/A 0.0% 100.0% N/A
15 35 100.0% N/A 0.0% 100.0% N/A
18 35 100.0% N/A 0.0% 100.0% N/A
20 35 100.0% 97.2% 0.0% 100.0% 97.1%
Waterhouse, 2000, UK c N/A Formocresol Stainless steel crown or amalgam or glass ionomer cement or compomer 46 6 44 71.7% N/A Parallel 4.3% 75.0% N/A
(1:5 Buckley’s solution) 12 44 65.2% 15.2% 4.3% 68.2% 15.9%
38 18 N/A N/A N/A 4.3% N/A N/A
Calcium hydroxide 24 N/A N/A N/A 4.3% N/A N/A
6 35 68.4% N/A 7.9% 74.3% N/A
12 35 73.7% 15.8% 7.9% 80.0% 17.1%
18 N/A N/A N/A 7.9% N/A N/A
24 N/A N/A N/A 7.9% N/A N/A
Dean, 2002, USA 5.49 (2.2–10.5) Formocresol (not dilute) Stainless steel crown 25 >6 25 100.0% 92.0% Parallel 0.0% 100.0% 92.0%
Electro-surgery (12 W) 25 >6 25 96.0% 84.0% 0.0% 96.0% 84.0%
Rivera, 2003, Venezuela (4–7) Formocresol Amalgam 40 6 40 100.0% 92.5% Split mouth 0.0% 100.0% 92.5%
(1:5 Buckley’s solution)
Electro-surgery 40 6 40 95.0% 97.5% 0.0% 95.0% 97.5%
Agamy, 2004, Egypt c 6.1 (4–8) Formocresol Stainless steel crown 24 6 20 83.3% 83.3% Split mouth 16.7% 100.0% 100.0%
12 20 75.0% 75.0% 16.7% 90.0% 90.0%
Grey MTA 24 6 20 79.2% 79.2% 16.7% 95.0% 95.0%
12 19 79.2% 79.2% 16.7% 100.0% 100.0%
White MTA 24 6 20 79.2% 79.2% 20.8% 95.0% 95.0%
12 19 66.7% 66.7% 20.8% 84.2% 84.2%
Kalaskar, 2004, Mumbai (4–7) Calcium hydroxide Stainless steel crown 28 6 28 96.4% 96.4% Parallel 0.0% 96.4% 96.4%
Lyophilized freeze dried platelet derived preparation 28 6 28 100.0% 100.0% 0.0% 100.0% 100.0%
Farsi, 2005, Saudi Arabia c 5.95 (3–8) Formocresol Stainless steel crown 60 6 36 60.0% 60.0% Parallel 40.0% 100.0% 100.0%
12 36 60.0% 60.0% 40.0% 100.0% 100.0%
18 36 60.0% 53.3% 40.0% 100.0% 88.9%
24 36 58.3% 51.7% 40.0% 97.2% 86.1%
MTA 60 6 38 63.3% 63.3% 36.7% 100.0% 100.0%
12 38 63.3% 63.3% 36.7% 100.0% 100.0%
18 38 63.3% 63.3% 36.7% 100.0% 100.0%
24 38 63.3% 63.3% 36.7% 100.0% 100.0%
Hu, 2005, China c (3–6) Formocresol Glass ionomer cement 40 6 40 87.5% 82.5% Parallel 0.0% 87.5% 82.5%
(1:5 Buckley’s solution) 12 40 72.5% 62.5% 0.0% 72.5% 62.5%
15.50% Ferric sulfate 40 6 40 82.5% 75.0% 0.0% 82.5% 75.0%
12 40 77.5% 70.0% 0.0% 77.5% 70.0%
Huth, 2005, Germany c 4.8 (2–8) Formocresol Stainless steel crown or composite resin 50 6 50 100.0% N/A Parallel 0.0% 100.0% N/A
(1:5 Buckley’s solution) 12 50 100.0% 96.0% 0.0% 100.0% 96.0%
18 47 92.0% N/A 6.0% 97.9% N/A
24 46 88.0% 84.0% 8.0% 96.7% 91.3%
15.50% Ferric sulfate 50 6 50 100.0% N/A 0.0% 100.0% N/A
12 50 100.0% 86.0% 0.0% 100.0% 86.0%
18 43 84.0% N/A 14.0% 97.7% N/A
24 42 84.0% 84.0% 16.0% 100.0% 100.0%
Calcium hydroxide 44 6 44 97.7% N/A 0.0% 97.7% N/A
12 43 97.7% 90.9% 2.3% 97.7% 90.7%
18 35 77.3% N/A 20.5% 97.1% N/A
24 34 65.9% 52.3% 22.7% 85.3% 67.7%
Er:YAG laser 47 6 47 100.0% N/A 0.0% 100.0% N/A
(2 Hz, 108 mJ) 12 47 95.7% 93.6% 0.0% 95.7% 93.6%
18 43 83.0% N/A 8.5% 90.7% N/A
24 39 74.5% 66.0% 17.0% 89.7% 79.5%
Markovic, 2005, Serbia and Montenegro c 6.4 (4–9) Formocresol Amalgam 33 6 N/A N/A N/A Parallel 0.0% N/A N/A
(1:5 dilution) 12 N/A N/A N/A 0.0% N/A N/A
18 33 90.9% 84.8% 0.0% 90.9% 84.9%
15.50% ferric sulfate 37 6 N/A N/A N/A 0.0% N/A N/A
12 N/A N/A N/A 0.0% N/A N/A
18 37 89.2% 81.1% 0.0% 89.2% 81.1%
Calcium hydroxide 34 6 N/A N/A N/A 0.0% N/A N/A
12 N/A N/A N/A 0.0% N/A N/A
18 34 82.3% 76.5% 0.0% 82.4% 76.5%
Naik, 2005, Mangalore N/A Formocresol Stainless steel crown 25 6 23 92.0% 92.0% Parallel 8.0% 100.0% 100.0%
(1:5 Buckley’s solution)
MTA 25 6 24 96.0% 96.0% 4.0% 100.0% 100.0%
Saltzman, 2005, Canada 5.1 (3.5–7.5) Formocresol Stainless steel crown 26 5.2 21 80.8% 80.8% Split mouth 19.2% 100.0% 100.0%
(Full strength) 9.5 20 76.9% 73.1% 23.1% 100.0% 95.0%
26 15.7 13 50.0% 42.3% 50.0% 100.0% 84.6%
MTA + diode laser 5.2 20 76.9% 73.1% 23.1% 100.0% 95.0%
(3 W, continuous mode) 9.5 18 69.2% 53.8% 30.8% 100.0% 77.8%
15.7 7 26.9% 19.2% 73.1% 100.0% 71.4%
Liu, 2006, Taiwan c 5.1 (4–7) Formocresol Stainless steel crown or composite resin 69 9–12 69 98.6% 95.7% Parallel 0.0% 98.6% 95.7%
(1:5 Buckley’s solution) 12–24 55 76.8% 73.9% 20.2% 96.4% 92.7%
24–36 30 37.7% 37.7% 56.5% 86.7% 86.7%
36–48 14 15.9% 14.5% 79.7% 78.6% 71.4%
48–60 6 8.7% 8.7% 91.3% 100.0% 100.0%
Nd:YAG laser 68 6–12 68 98.5% 98.5% 0.0% 98.5% 98.5%
(2 W, 20 Hz, 124 J/cm 2 ) 12–24 35 50.0% 50.0% 48.5% 97.1% 97.1%
24–36 21 30.9% 29.4% 69.1% 100.0% 95.2%
36–48 14 20.6% 19.1% 79.4% 100.0% 92.9%
48–60 11 16.2% 16.2% 83.8% 100.0% 100.0%
Vargas, 2006, USA 5 (4–9) Ferric sulfate Stainless steel crown 28 6 28 100.0% 67.9% Split mouth 0.0% 100.0% 67.9%
12 13 39.3% 28.6% 53.6% 84.6% 61.5%
5% NaOCl 32 6 32 100.0% 90.6% 0.0% 100.0% 90.6%
12 16 43.8% 34.4% 50.0% 87.5% 68.8%
Aeinehchi, 2007, Iran 6.51 (5–9) Formocresol Amalgam or glass ionomer cement 75 6 57 76.0% 68.0% Parallel 24.0% 100.0% 89.5%
MTA 51 6 43 84.3% 84.3% 15.7% 100.0% 100.0%
Odabas, 2007, Turkey c 7.9 (6–9) Formocresol Stainless steel crown or amalgam 21 6 21 90.5% 90.5% Split mouth 0.0% 90.5% 90.5%
(1:5 dilution) 9 21 90.5% 90.5% 0.0% 90.5% 90.5%
12 21 90.5% 90.5% 0.0% 90.5% 90.5%
Nd:YAG laser 21 6 21 90.5% 81.0% 0.0% 90.5% 81.0%
(2 W, 20 Hz) 9 21 85.7% 71.4% 0.0% 85.7% 71.4%
12 21 85.7% 71.4% 0.0% 85.7% 71.4%
Bahrololoomi, 2008, Iran 6.1 (5–1) Formocresol Amalgam 35 6 35 100.0% 97.1% Parallel 0.0% 100.0% 97.1%
(1:5 Buckley’s solution) 9 35 100.0% 97.1% 0.0% 100.0% 97.1%
Electro-surgery 35 6 33 91.4% N/A 5.7% 97.0% N/A
9 33 91.4% 80.0% 5.7% 97.0% 84.9%
Moretti, 2008, Brazil c 6.42 (5–9) Formocresol Glass ionomer cement 15 6 15 93.3% 93.3% Parallel 0.0% 93.3% 93.3%
(1:5 Buckley’s solution) 12 14 86.7% 86.7% 6.7% 92.9% 92.9%
18 13 80.0% 80.0% 13.3% 92.3% 92.3%
24 11 66.7% 66.7% 26.7% 90.9% 90.9%
Calcium hydroxide 15 6 14 80.0% 53.3% 6.7% 85.7% 57.1%
12 12 53.3% 53.3% 20.0% 66.7% 66.7%
18 8 46.7% 33.3% 46.7% 87.5% 62.5%
24 7 46.7% 33.3% 53.3% 100.0% 71.4%
Grey MTA 15 6 14 93.3% 93.3% 6.7% 100.0% 100.0%
12 14 86.7% 86.7% 6.7% 92.9% 92.9%
18 13 80.0% 80.0% 13.3% 92.3% 92.3%
24 12 60.0% 60.0% 20.0% 75.0% 75.0%
Noorollahain, 2008, Iran c 6.08 (5–7) Formocresol Stainless steel crown 30 6 27 90.0% 90.0% Parallel 10.0% 100.0% 100.0%
(1:5 Buckley’s solution) 12 24 80.0% 80.0% 20.0% 100.0% 100.0%
24 18 60.0% 60.0% 40.0% 100.0% 100.0%
White MTA 30 6 29 96.7% 96.7% 3.3% 100.0% 100.0%
12 29 96.7% 93.3% 3.3% 100.0% 96.6%
24 18 60.0% 56.7% 40.0% 100.0% 94.4%
Sabbarini, 2008, Egypt 5 (4–7) Formocresol Stainless steel crown 15 6 15 66.7% 66.7% Split mouth 0.0% 66.7% 13.3%
(1:5 Buckley’s solution)
Emdogain conditioned with polyacrylic acid 15 6 15 93.3% 93.3% 0.0% 93.3% 60.0%
Sonmez, 2008, Turkey c 6.6 (4–9) Formocresol Amalgam 16 6 13 81.3% 81.3% Split mouth 18.8% 100.0% 100.0%
(1:5 Buckley’s solution) 12 13 75.0% 68.8% 18.8% 92.3% 84.6%
18 11 62.5% 62.5% 31.3% 90.9% 90.9%
15.50% ferric sulfate 24 10 62.5% 62.5% 37.5% 100.0% 100.0%
16 6 15 93.8% 93.8% 6.3% 100.0% 100.0%
12 15 93.8% 87.5% 6.3% 100.0% 93.3%
18 14 87.5% 81.3% 12.5% 100.0% 92.9%
24 13 81.3% 68.8% 18.8% 100.0% 84.6%
Calcium hydroxide 16 6 13 81.3% 81.3% 18.8% 100.0% 100.0%
12 13 75.0% 56.3% 18.8% 92.3% 69.2%
18 9 56.3% 56.3% 43.8% 100.0% 100.0%
24 9 56.3% 37.5% 43.8% 100.0% 66.7%
MTA 16 6 15 93.8% 93.8% 6.3% 100.0% 100.0%
12 15 93.8% 81.3% 6.3% 100.0% 86.7%
18 13 75.0% 75.0% 18.8% 92.3% 92.3%
24 12 68.8% 62.5% 25.0% 91.7% 83.3%
Zurn, 2008, USA c 5.3 (2.3–8.5) Formocresol Stainless steel crown 38 6 34 86.8% 86.8% Split mouth 10.5% 97.1% 97.1%
(1:5 Buckley’s solution) 7–12 34 86.8% 86.8% 10.5% 97.1% 97.1%
13–24 31 78.9% 78.9% 18.4% 96.8% 96.8%
Calcium hydroxide 38 6 34 86.8% 86.8% 10.5% 97.1% 97.1%
7–12 34 84.2% 71.1% 10.5% 94.1% 79.4%
13–24 32 71.1% 60.5% 15.8% 84.4% 71.9%
Alacam, 2009, Turkey c 6.4 (4–8) Formocresol Stainless steel crown 35 6 33 91.4% 91.4% Parallel 5.7% 97.0% 97.0%
9 29 77.7% 77.7% 17.1% 93.1% 93.1%
12 29 74.3% 74.3% 17.1% 89.7% 89.7%
Calcium hydroxide 33 6 33 66.7% 48.5% 0.0% 66.7% 48.5%
9 33 66.7% 48.5% 0.0% 66.7% 48.5%
12 33 33.3% 33.3% 0.0% 33.3% 33.3%
Calcium hydroxide + iodoform 32 6 30 46.9% 25.0% 6.3% 50.0% 26.7%
9 29 40.6% 18.8% 9.4% 44.8% 20.7%
12 29 15.6% 12.5% 9.4% 17.2% 13.8%
Subramaniam, 2009, India c (6–8) Formocresol Stainless steel crown 20 6 20 100.0% 90.0% Split mouth 0.0% 100.0% 90.0%
(1:5 Buckley’s solution) 12 20 100.0% 85.0% 0.0% 100.0% 85.0%
24 20 100.0% 85.0% 0.0% 100.0% 85.0%
MTA 20 6 20 100.0% 95.0% 0.0% 100.0% 95.0%
12 20 100.0% 95.0% 0.0% 100.0% 95.0%
24 20 100.0% 95.0% 0.0% 100.0% 95.0%
Doyle, 2010, Canada c 3.9 15.50% ferric sulfate Stainless steel crown 58 >12 46 N/A 43.1% Parallel 20.7% N/A 54.4%
Eugenol-free 15.5% Ferric sulfate 78 >12 64 N/A 35.9% 17.9% N/A 43.8%
MTA
15.50% ferric sulfate + MTA 57 >12 47 N/A 73.7% 17.5% N/A 89.4%
77 >12 70 N/A 66.2% 9.1% N/A 72.9%
Golpayegani, 2010, Iran c 5.6 (4–7) Formocresol Stainless steel crown 23 6 18 78.2% 78.2% Split mouth 21.7% 100.0% 100.0%
(1:5 Buckley’s solution) 12 15 60.9% 52.2% 34.8% 93.3% 80.0%
Diode laser 23 6 18 78.2% 69.6% 21.7% 100.0% 88.9%
(Continuous mode, 4 J/cm 2 ) 12 15 65.2% 43.5% 34.8% 100.0% 66.7%
Erdem, 2011, Turkey c 6.2 (5–7) Formocresol Amalgam 32 6 25 78.1% 78.1% Split mouth 21.9% 100.0% 100.0%
(1:5 Buckley’s solution) 12 25 78.1% 78.1% 21.9% 100.0% 100.0%
24 25 59.4% 59.4% 21.9% 76.0% 76.0%
15.50% ferric sulfate 32 6 25 78.1% 78.1% 21.9% 100.0% 100.0%
12 25 78.1% 78.1% 21.9% 100.0% 100.0%
24 25 59.4% 59.4% 21.9% 76.0% 76.0%
MTA 32 6 25 78.1% 78.1% 21.9% 100.0% 100.0%
12 25 78.1% 78.1% 21.9% 100.0% 100.0%
24 25 75.0% 75.0% 21.9% 96.0% 96.0%
ZOE 32 6 25 78.1% 75.0% 21.9% 100.0% 96.0%
12 25 78.1% 71.9% 21.9% 100.0% 92.0%
24 25 62.5% 46.9% 21.9% 80.0% 60.0%
Malekafzali, 2011, Iran 6 (4–8) MTA Stainless steel crown or amalgam 40 6 36 90.0% 90.0% Split mouth 10.0% 100.0% 100.0%
12 33 82.5% 75.0% 17.5% 100.0% 90.9%
24 35 87.5% 80.0% 12.5% 100.0% 91.4%
Calcium enriched mixture 40 6 36 90.0% 90.0% 10.0% 100.0% 100.0%
12 33 82.5% 80.0% 17.5% 100.0% 97.0%
24 35 87.5% 85.0% 12.5% 100.0% 97.1%
Odabas, 2011, Turkey 6.1 (4–8) Calcium hydroxide Stainless steel crown 24 6 20 79.2% 79.2% Split mouth 16.7% 96.0% 95.0%
9 20 79.2% 75.0% 16.7% 96.0% 90.0%
12 20 75.0% 75.0% 16.7% 96.0% 90.0%
Calcium hydroxide + ankaferd blood stopper 24 6 20 83.3% 83.3% 16.7% 100.0% 100.0%
9 20 79.2% 83.3% 16.7% 96.0% 100.0%
12 20 79.2% 79.2% 16.7% 96.0% 95.0%
Srinivasan, 2011, India c (4–6) Formocresol Stainless steel crown 50 6 50 100.0% 90.0% Split mouth 0.0% 100.0% 90.0%
(1:5 Buckley’s solution) 9 48 88.0% 78.0% 4.0% 91.7% 81.3%
12 46 84.0% 72.0% 8.0% 91.3% 78.3%
Grey MTA 50 6 50 100.0% 100.0% 0.0% 100.0% 100.0%
9 47 100.0% 90.0% 6.0% 100.0% 95.7%
12 47 100.0% 90.0% 6.0% 100.0% 95.7%
Odabas, 2012, Turkey c 7.7 (5–10) 15.50% ferric sulfate Stainless steel crown 51 6 48 86.3% 74.5% Parallel 5.9% 91.7% 79.2%
9 48 86.3% 74.5% 5.9% 91.7% 79.2%
12 46 76.5% 74.5% 9.8% 84.8% 82.6%
MTA 42 6 41 95.2% 95.2% 2.4% 97.6% 97.6%
9 39 90.5% 85.7% 7.1% 97.4% 92.3%
12 38 85.7% 83.3% 9.5% 94.7% 92.1%
Sushynski, 2012, USA c 5.4 (2.5–10) Formocresol Stainless steel crown 133 6 114 84.2% 72.9% Parallel 14.3% 98.3% 85.1%
(1:5 Buckley’s solution) 12 90 67.7% 54.9% 32.3% 100.0% 81.1%
18 78 57.9% 45.9% 41.4% 98.7% 78.2%
24 66 48.9% 37.6% 50.4% 98.5% 75.8%
Grey MTA 119 6 108 90.8% 86.6% 9.2% 100.0% 95.4%
12 96 80.7% 74.8% 19.3% 100.0% 92.7%
18 77 64.7% 61.3% 35.3% 100.0% 94.8%
24 65 54.6% 52.1% 45.4% 100.0% 95.4%
Yaman, 2012, Turkey 7.3 (6–9) Formocresol Amalgam 30 6 30 96.7% 96.7% Split mouth 0.0% 100.0% 96.7%
(1:5 Buckley’s solution) 12 28 93.3% 83.3% 6.7% 100.0% 89.3%
Ankaferd blood stopper 30 6 30 96.7% 96.7% 0.0% 96.7% 96.7%
12 28 93.3% 80.0% 6.7% 100.0% 85.7%

a Success rate regarding drop-outs and premature tooth loss treated as failure.

b Success rate only considering patients who recalled (deleting drop-outs).

c Data included in final meta-analysis.

Data extraction and statistical analysis

Numbers of teeth at the beginning, number of teeth at each of follow-up period, and clinical and radiographic success rates were extracted or derived from the published results. Clinical and radiographic success rates are derived in this systematic review using two slightly different definitions: (1) drop-outs and premature tooth loss were treated as failure; (2) only considering patients who recalled ( Table 1 ). The meta-analyses were then undertaken on the success rates that considered drop-outs and premature tooth loss as failure to obtain a more conservative estimate for success rates.

To incorporate direct and indirect evidence, network meta-analyses were undertaken using the Bayesian hierarchical random-effects modelling . Because the included studies reported treatment outcomes with different lengths of follow-ups, the meta-analyses focus on the success rates of 9–12 months and 18–24 months follow-ups.

Although 7 articles , met all the inclusion criteria, they were not included due to either the tested treatments being rarely used or the use of a combination of treatment agents, such as electrosurgery , sodium hypochloride , calcium enriched mixture , ankaferd blood stopper , and enamel matrix derivative . Consequently, those treatment regimens did not connect with other commonly used treatments to form a network and therefore were excluded. The final network meta-analyses included five commonly used medicaments for primary molar pulpotomies: (1) formocresol, (2) ferric sulfate, (3) calcium hydroxide, (4) MTA, and (5) laser therapies. Standard pair-wise meta-analyses of direct comparisons between each group were also carried out and compared to the results from network meta-analyses. Odds ratio for clinical and radiographic failure including premature tooth loss between treatment agents is used as the effect size measure in both network and pair-wise meta-analyses. Note that a smaller odds for failure indicates a better treatment agent. Furthermore, meta-regressions with the adjustment for covariates such as study design and types of restoration were also undertaken within the network meta-analysis to investigate the impact of these covariates on the success of pulpotomies.

The Bayesian random-effects network meta-analysis and meta-regressions were performed using the statistical software WinBUGS (version 14.3, MRC Biostatistics Unit, Cambridge, UK) with 50,000 burn-in and further 50,000 simulations with three chains of different initial values. Non-informative priors were used throughout the analysis. The standard pair-wise random-effects meta-analysis, heterogeneity between studies and funnel plots were performed with statistical software STATA (version 11.2, StataCorp LP, College Station, TX, USA). The statistical significance level was set at 5%.

Results

Study selection

Fig. 1 summarizes the details of the study selection process and the reasons for exclusion. A total of 2083 potential relevant titles, abstracts and articles found electronically, plus reference lists of reviews and related articles, 171 of which were screened for further evaluation. Finally, we identified 37 trials that met all the inclusion criteria, and 22 of them entered further network and pair-wise meta-analyses. The characteristics of these included trials are listed in Table 1 .

Study description

The 37 trials included in the current systematic review were full reports published between 1989 and 2012, and 33 of them were published after 2000. Table 1 summarizes these studies. Of all 37 studies, 22 were parallel trials and the others were split-mouth trials. Follow-up periods were somewhat diverse in these studies, ranging from 5.2 months to 48–60 months . 22 studies were chosen for meta-analyses for 9–12 months, and 12 of them were chosen for meta-analyses for 18–24 months ( Table 1 ).

Quality of studies

Table 2 shows the quality of the included trials. 30 studies described as randomized, 11 of which clearly described their randomize methods. The allocation concealment methods were described in 12 trials , the remaining did not provide details about it. There were no trials that employed double blinding (patient and caregiver blinding), and only 2 trials performed patient blinding . Four of the included trials reported sample size and statistical power calculations .

Table 2
Quality assessment of the included articles for present primary molar pulpotomy systematic review.
Study, Year Described as randomized Randomization methods Allocation concealment method Patient blinding Caregiver blinding Examiner blinding All patient accounted for at end of study Analysis account for patient losses a Sample size/statistical power calculation
Alacam, 1989 Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned N/A Not mentioned
Prakash, 1989 Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned No N/A Not mentioned
Fei, 1991 Yes Yes Yes Not mentioned Not mentioned Yes No No Not mentioned
Shumayrikh, 1999 Yes Not mentioned Not mentioned Yes Not mentioned Yes No No Not mentioned
Ibricevic, 2000/2003 Yes Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Yes N/A Not mentioned
Waterhouse, 2000, UK Yes Yes Yes Not mentioned Not mentioned Yes No No Not mentioned
Dean, 2002 Yes Yes Yes Not mentioned Not mentioned Yes N/A N/A Not mentioned
Rivera, 2003 Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned N/A N/A Not mentioned
Agamy, 2004 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes No No Not mentioned
Kalaskar, 2004 Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned N/A N/A Not mentioned
Farsi, 2005 Yes Yes Yes Not mentioned Not mentioned Not mentioned No No Not mentioned
Hu, 2005 Yes Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned N/A N/A Not mentioned
Huth, 2005 Yes Yes Yes Yes Not mentioned Yes No No Yes
Markovic, 2005 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes N/A N/A Not mentioned
Naik, 2005 Yes Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned No N/A Not mentioned
Saltzman, 2005 Yes Yes Yes Not mentioned Not mentioned Yes No No Not mentioned
Liu, 2006 Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned No Not mentioned
Vargas, 2006 Yes Yes Yes Not mentioned Not mentioned Yes No No Yes
Aeinehchi, 2007 Yes Yes Yes Not mentioned Not mentioned Yes No No Not mentioned
Odabas, 2007 Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Yes N/A N/A Not mentioned
Bahrololoomi, 2008 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes No No Not mentioned
Moretti, 2008 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes No No Not mentioned
Noorollahain, 2008 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes No No Not mentioned
Sabbarini, 2008 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes N/A N/A Not mentioned
Sonmez, 2008 Yes Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned No No Not mentioned
Zurn, 2008 Yes Yes Yes Not mentioned Not mentioned Yes No No Not mentioned
Alacam, 2009 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes No No Not mentioned
Subramaniam, 2009 Yes Yes Yes Not mentioned Not mentioned Not mentioned N/A N/A Not mentioned
Doyle, 2010 Yes Yes Yes Not mentioned Not mentioned Yes No No Not mentioned
Golpayegani, 2010 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes No No Not mentioned
Erdem, 2011 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes No No Not mentioned
Malekafzali, 2011 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes Yes No Yes
Odabas, 2011 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes No No Not mentioned
Srinivasan, 2011 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes No No Not mentioned
Odabas, 2012 Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Yes No No Not mentioned
Sushynski, 2012 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes No No Yes
Yaman, 2012 Yes Yes Yes Not mentioned Not mentioned Yes No No Not mentioned

a Yes – analysis with patient losses; No – patient lost but not included in analysis; N/A – no patient losses or not performed analysis.

Network meta-analysis

22 studies were grouped into 5 groups, according to their treatment agents, including formocresol, ferric sulfate, calcium hydroxide, MTA, and laser therapies, in the network meta-analysis, yielding 10 pairs of comparisons ( Fig. 2 ). Direct comparisons by head-to-head trials were available in 9 of 10 pairs ( Tables 3 and 4 ).

Network for the comparisons among different medicaments for primary molar pulpotomy. Dotted lines refer to those comparisons that have not been tested directly in clinical trials. The width of the solid lines is in proportion to the amount of evidence available in the literatures.
Fig. 2
Network for the comparisons among different medicaments for primary molar pulpotomy. Dotted lines refer to those comparisons that have not been tested directly in clinical trials. The width of the solid lines is in proportion to the amount of evidence available in the literatures.
Table 3
Failure odds ratio of network and standard meta-analysis for clinical and radiographic outcome for primary molar pulpotomy after 9–12 month follow-up.
Clinical outcome Radiographic outcome
Network meta-analysis Standard pair-wise meta-analysis Network meta-analysis Standard pair-wise meta-analysis
Estimates 95% CI Estimates 95% CI Estimates 95% CI Estimates 95% CI
FS vs. FC 0.70 (0.32, 1.43) 0.95 (0.84, 1.07) 1.04 (0.54, 1.83) 0.96 (0.87, 1.07)
Ca(OH) 2 vs. FC 2.08 (1.10, 4.26) * 1.13 (1.02, 1.26) * 2.57 (1.32, 4.86) * 1.29 (1.13, 1.48) *
MTA vs. FC 0.55 (0.32, 0.91) * 0.90 (0.83, 0.97) * 0.50 (0.31, 0.83) * 0.85 (0.78, 0.93) *
Lasers vs. FC 1.34 (0.46, 4.02) 1.01 (0.96, 1.08) 1.25 (0.50, 2.93) 1.04 (0.96, 1.12)
Ca(OH) 2 vs. FS 2.99 (1.20, 8.51) * 1.09 (1.00, 1.19) 2.47 (1.12, 5.75) * 1.07 (0.92, 1.26)
MTA vs. FS 0.80 (0.37, 1.75) 0.95 (0.83, 1.08) 0.49 (0.27, 0.96) * 0.77 (0.68, 0.88) *
Lasers vs. FS 1.94 (0.56, 7.27) 1.05 (0.97, 1.12) 1.21 (0.43, 3.34) 0.92 (0.80, 1.05)
MTA vs. Ca(OH) 2 0.27 (0.11, 0.57) * 0.71 (0.54, 0.95) * 0.20 (0.09, 0.43) * 0.65 (0.46, 0.93) *
Lasers vs. Ca(OH) 2 0.64 (0.19, 2.19) 1.00 (0.91, 1.09) 0.49 (0.17, 1.41) 0.95 (0.83, 1.08)
Lasers vs. MTA 2.41 (0.76, 8.29) 2.46 (0.88, 6.40)

* p < 0.05 Vs, versus; CI, credible interval; FC, formocresol; FS, ferric sulfate; MTA, mineral trioxide aggregate.

Table 4
Failure odds ratio of network and standard meta-analysis for clinical and radiographic outcome for primary molar pulpotomy after 18–24 month follow-up.
Clinical outcome Radiographic outcome
Network meta-analysis Standard pair-wise meta-analysis Network meta-analysis Standard pair-wise
Estimates 95% CI Estimates 95% CI Estimates 95% CI Estimates 95% CI
FS vs. FC 0.90 (0.48, 1.65) 1.00 (0.88, 1.12) 1.02 (0.60, 1.78) 1.00 (0.91, 1.11)
Ca(OH) 2 vs. FC 1.94 (1.11, 3.25) * 1.20 (1.05, 1.37) * 2.97 (1.78, 4.99) * 1.40 (1.19, 1.65) *
MTA vs. FC 0.90 (0.61, 1.32) 0.91 (0.79, 1.05) 0.66 (0.45, 0.98) * 0.83 (0.73, 0.96) *
Lasers vs. FC 3.38 (1.37, 8.61) * 1.35 (1.14, 1.60) * 2.54 (1.32, 4.76) * 1.38 (1.15, 1.66) *
Ca(OH) 2 vs. FS 2.16 (1.12, 4.31) * 1.22 (1.04, 1.42) * 2.90 (1.56, 5.54) * 1.37 (1.13, 1.67) *
MTA vs. FS 1.00 (0.54, 1.86) 0.91 (0.70, 1.19) 0.64 (0.35, 1.22) 0.88 (0.66, 1.18)
Lasers vs. FS 3.73 (1.27, 11.67) * 1.13 (0.92, 1.39) 2.47 (1.11, 5.23) * 1.27 (1.00, 1.62) *
MTA vs. Ca(OH) 2 0.47 (0.26, 0.83) * 0.80 (0.52, 1.23) 0.22 (0.12, 0.41) * 0.58 (0.33, 1.00)
Lasers vs. Ca(OH) 2 1.72 (0.62, 4.98) 0.89 (0.68, 1.16) 0.86 (0.40, 1.72) 0.79 (0.56, 1.12)
Lasers vs. MTA 3.76 (1.39, 10.08) * 3.88 (1.85, 8.05) *

* p < 0.05 Vs, versus; CI, credible interval; FC, formocresol; FS, ferric sulfate; MTA, mineral trioxide aggregate.

Table 3 shows the results of network meta-analysis of clinical and radiographic outcome for primary molar pulpotomy after 9–12 month follow-up. The odds ratio for calcium hydroxide vs. formocresol was 2.08 [95% credible interval (CI): 1.10, 4.26], indicating that formocresol had significantly better clinical outcome than calcium hydroxide after 9–12 months. The failure odds ratio between MTA vs. formocresol was 0.55 (95% CI: 0.32, 0.91); calcium hydroxide vs. ferric sulfate is 2.99 (95% CI: 1.20, 8.51); MTA vs. calcium hydroxide was 0.27 (95% CI: 0.11, 0.57). The results shows that MTA had significantly better clinical outcomes than formocresol and calcium hydroxide, and calcium hydroxide had more failures than formocresol and ferric sulfate. The radiographic outcomes showed almost the same pattern. The failure odds ratio between calcium hydroxide vs. formocresol was 2.57 (95% CI: 1.32, 4.86); MTA vs. formocresol was 0.50 (95% CI: 0.31, 0.83); calcium hydroxide vs. ferric sulfate was 2.47 (95% CI: 1.12, 5.75); MTA vs. ferric sulfate was 0.49 (95% CI: 0.27, 0.96); MTA vs. calcium hydroxide was 0.20 (95% CI: 0.09, 0.43). The results showed that MTA had significantly better radiographic outcomes than formocresol, ferric sulfate and calcium hydroxide, and calcium hydroxide had more failures than formocresol and ferric sulfate.

Table 4 shows the results of network meta-analysis for clinical and radiographic outcome for primary molar pulpotomy after 18–24 month follow-up, which were contributed by 12 trials (15, 17, 43–52). The failure odds ratio for calcium hydroxide vs. formocresol was 1.94 (95% CI: 1.11, 3.25); lasers vs. formocresol was 3.38 (95% CI: 1.37, 8.61); calcium hydroxide vs. ferric sulfate was 2.16 (95% CI: 1.12, 4.31); lasers vs. ferric sulfate was 3.73 (95% CI: 1.27, 11.67); MTA vs. calcium hydroxide was 0.47 (95% CI: 0.26, 0.83); lasers vs. MTA was 3.76 (95% CI: 1.39, 10.08). The results show that after 18–24 months, formocresol, ferric sulfate, and MTA had significantly better clinical outcomes than calcium hydroxide and laser therapies. Compared to the clinical failures for FC, ferric sulfate, and MTA, two and three times more of failures were observed for calcium hydroxide and laser treatments, respectively. The radiographic outcomes also showed that failure odds ratio for calcium hydroxide vs. formocresol was 2.97 (95% CI: 1.78, 4.99); MTA vs. formocresol was 0.66 (95% CI: 0.45, 0.98); lasers vs. formocresol was 2.54 (95% CI: 1.32, 4.76); calcium hydroxide vs. ferric sulfate was 2.90 (95% CI: 1.56, 5.54); lasers vs. ferric sulfate was 2.47 (95% CI: 1.11, 5.23); MTA vs. calcium hydroxide was 0.22 (95% CI: 0.12, 0.41); lasers vs. MTA was 3.88 (95% CI: 1.85, 8.05). The results show that after 18–24 months, MTA has better radiographic outcomes than formocresol, calcium hydroxide and laser therapies, but no significant differences when compared with ferric sulfate.

Pair-wise meta-analysis, heterogeneity, and network meta-regression

For pair-wise meta-analysis, trials with 100% success rates of both treatments were excluded . Results from standard pair-wise meta-analysis of overall studies show that after 9–12 months, MTA had better clinical outcomes than formocresol and calcium hydroxide and better radiographic outcomes than formocresol, ferric sulfate, and calcium hydroxide. After 18–24 months, formocresol and ferric sulfate had better clinical outcomes than calcium hydroxide, and had better radiographic outcomes than calcium hydroxide and laser therapies ( Tables 3 and 4 , Figs. 3–6 ). These results were similar to those from our network meta-analyses. The statistical heterogeneity of these comparisons was quite variable ( I -squared = 0.0–83.8%, Figs. 3–6 ). Appendix 1 shows the funnel plots of these pair-wise meta-analyses. Because the plots resemble symmetrical and inverted funnels, there was no likely of any publication bias. Network meta-regressions for covariates study design and types of restoration were tested separately and neither showed significant impacts on clinical or radiographic outcomes.

Forest plot of the standard pair-wise meta-analysis for clinical outcome for primary molar pulpotomy after 9–12 month follow-up.
Fig. 3
Forest plot of the standard pair-wise meta-analysis for clinical outcome for primary molar pulpotomy after 9–12 month follow-up.
Forest plot of the standard pair-wise meta-analysis for radiographic outcome for primary molar pulpotomy after 9–12 month follow-up.
Fig. 4
Forest plot of the standard pair-wise meta-analysis for radiographic outcome for primary molar pulpotomy after 9–12 month follow-up.
Forest plot of the standard pair-wise meta-analysis for clinical outcome for primary molar pulpotomy after 18–24 month follow-up.
Fig. 5
Forest plot of the standard pair-wise meta-analysis for clinical outcome for primary molar pulpotomy after 18–24 month follow-up.
Forest plot of the standard pair-wise meta-analysis for radiographic outcome for primary molar pulpotomy after 18–24 month follow-up.
Fig. 6
Forest plot of the standard pair-wise meta-analysis for radiographic outcome for primary molar pulpotomy after 18–24 month follow-up.

Discussion

The present study analyzed all published clinical trials to evaluate different treatment agents for primary molar pulpotomies. A total of 37 studies were included in the systematic review and 22 of them were used in the final meta-analyses ( Fig. 1 ). The results of network meta-analyses and standard pair-wise meta-analyses were in general consistent: after 9–12 months, MTA had significantly better clinical and radiographic outcomes than formocresol and calcium hydroxide. Calcium hydroxide had more failures than formocresol and ferric sulfate; after 18–24 months, formocresol, ferric sulfate, and MTA had significantly better clinical and radiographic outcomes than calcium hydroxide and laser therapies. The results were also similar to those reported by recent systematic reviews. In an evidence-based assessment of formocresol vs. ferric sulfate, 2 meta-analyses concluded that both materials produced similar clinical and radiographic success . Another 2 systematic reviews, focused on formocresol vs. MTA, concluded that MTA appeared to be superior to formocresol with a higher clinical and radiographic success rate . All of them showed that formocresol had similar outcomes as ferric sulfate, and MTA might be the most superior treatment agent in primary molar pulpotomies.

However, the current network meta-analysis showed that after 18–24 months, teeth treated with laser therapies were 2- to 3-times more likely to fail compared to formocresol, ferric sulfate, and MTA ( Table 4 ). Two studies provided direct comparisons between laser therapies and other treatment agents . Huth et al. compared Er:YAG laser irradiation in 47 primary molars to formocresol, ferric sulfate, and calcium hydroxide. After 24 months, because of 17.0% drop-outs, the success rates of laser group dropped to 74.5% clinically and 66.0% radiographically, compared to 84–88% in formocresol and ferric sulfate groups . On the other hand, Liu’s study compared the effects of pulsed Nd:YAG laser on 68 primary molars to formocresol. After 24 months follow-up, although the success rate of the recalled patients was 97.1% in laser group, the drop-out rates was relatively high as 48.5%. Thus, the clinical and radiographic success rates regarding drop-outs as failure dropped to 50.0% . Although using different lasers, the results of these 2 studies showed higher drop-out rates in laser pulpotomy group after 24 months.

Drop-outs may have been caused by a lot of reasons such as emigration or moving out, but for paediatric patients, the reason for dropouts from the trial is probably mainly caused by exfoliated teeth . Because drop-outs and premature tooth loss were regarded as failure in the final meta-analyses, the success rates were under-estimated. However, because the mean age of children in most trials was 5–7-year-old, considering tooth exfoliation within 24-months after pulpotomy as premature tooth loss was reasonable. In the current systematic review, only 14 trials provided data more than 18–24 months ( Table 1 ).

The pulpotomy medicaments can be classified into 3 mechanisms: (1) devitalization such as formocresol, electrosurgery, and laser therapy, (2) preservation such as ferric sulfate, and glutaraldehyde, and (3) regeneration such as MTA, calcium hydroxide. However, our network meta-analyses showed that the outcome of MTA was apparently better than calcium hydroxide. This indicates that the properties of the material itself and the biocompatibility to the remained pulp tissues determine the success rates, not the mechanism. MTA was introduced as a pulpotomy medicament with characteristics of liberation formation, odontogenic effect on the pulp, antimicrobial properties and preservation of pulp integrity after pulpotomy, and without cytotoxicities . Our network meta-analyses showed that MTA was better than calcium hydroxide and laser therapies after 18–24 months, and better than formocresol, calcium hydroxide, and laser therapies after 9–12 months. In conclusion, MTA may be recommended as an alternative to formocresol for primary molar pulpotomies.

However, because of the high cost of MTA, it may not the best choice for primary molar pulpotomies when considering cost effectiveness. In 2008, Fuks suggested to use ferric sulfate as a viable and inexpensive solution . In 2011, Malekafzali et al. conducted a randomized clinical trial to compare calcium enriched mixture and MTA for primary molar pulpotomy. After 24 months, the clinical and radiographic success rates of both groups were high (>80.0%) and showed no significant differences . Two other studies used a new hemostatic agent, ankaferd blood stopper, to perform primary molar pulpotomies. After 12 months of follow-up, the success rates were 79.2–93.3% compared with traditional materials . Both materials showed potential for the treatment. Also, these studies indicated that paediatric dentists were still looking for an appropriate and better medicament to replace formocresol. Our network meta-analyses showed that results from MTA were better than calcium hydroxide and laser therapies and comparable to ferric sulfate after 18–24 months, MTA seems to be the first choice for primary molar pulpotomies. If treatment cost is an issue, especially when the treated primary molars are going to be replaced by permanent teeth, ferric sulfate may be the choice.

To minimize the differences between the trials, we explored the heterogeneity by undertaking network meta-regressions with study design and types of restoration as covariates, but the results showed no significant impact of these two covariates. Stainless steel crowns provide an effective means for restoration of a decayed primary teeth so they have been recommended as the restoration of choice for the long-term success of pulp therapy and retention of the treated tooth among the functional dentition. Several clinical trials and a systematic review by Attari and Roberts in 2006 also indicated that the success rate of stainless steel crowns for the restoration of badly broken down primary molars was superior to other restorative materials . Although our network meta-regression did not find a significant impact of restoration types, it should be noted that the statistical power of meta-regression for multiple treatment comparisons may be sufficiently high to detect the potential differences.

The current systematic review presented several limitations. Firstly, most trials did not present their randomization methods and allocation concealing procedures, and blinding was unclear, although it is sometimes difficult to blind caregivers because of the diversity of material and device of treatment options. Secondly, success and failure rates in the network meta-analyses might be under-estimated because we regarded drop-outs and premature tooth loss as failure. Finally, trials with new and alternative medicaments and those with shorter (less than 9 months) follow-up periods were not included in the network meta-analyses.

Conclusion

In conclusion, the results from network meta-analyses showed that after 9–12 months, MTA had significantly better clinical and radiographic outcomes than formocresol and calcium hydroxide, and calcium hydroxide had more failures than formocresol and ferric sulfate; after 18–24 months, formocresol, ferric sulfate, and MTA had significantly better clinical and radiographic outcomes than calcium hydroxide and laser therapies in primary molar pulpotomies.

Conflicts of interest

None declared.

Acknowledgements

This project was partly supported by a grant from the National Science Council in Taiwan (grant number: NSC 101-2314-B-002-197-MY2 ). The authors thanked Renee Tseng (Medical library of Taiwan Adventist Hospital) for her contribution to the literature search.

See Fig. A1 .

Funnel plots of clinical and radiographic outcomes for primary molar pulpotomy after 9–12 and 18–24 month follow-up. (1: FS vs. FC; 2: Ca(OH) 2 vs. FC; 3: MTA vs. FC; 4: Lasers vs. FC; 5: Ca(OH) 2 vs. FS; 6: MTA vs. FS; 7: Lasers vs. FS; 8: MTA vs. Ca(OH) 2 ; 9: Lasers vs. Ca(OH) 2 ).
Fig. A1
Funnel plots of clinical and radiographic outcomes for primary molar pulpotomy after 9–12 and 18–24 month follow-up. (1: FS vs. FC; 2: Ca(OH) 2 vs. FC; 3: MTA vs. FC; 4: Lasers vs. FC; 5: Ca(OH) 2 vs. FS; 6: MTA vs. FS; 7: Lasers vs. FS; 8: MTA vs. Ca(OH) 2 ; 9: Lasers vs. Ca(OH) 2 ).

References

  • 1. Fuks A.B.: Current concepts in vital primary pulp therapy. European Journal of Paediatric Dentistry 2002; 3: pp. 115-120.
  • 2. Block R.M., Lewis R.D., Sheats J.B., Burke S.G.: Antibody formation to dog pulp tissue altered by formocresol uithin the root canal. Oral Surgery, Oral Medicine, Oral Pathology 1978; 45: pp. 282-292.
  • 3. Fei A.L., Udin R.D., Johnson R.: A clinical study of ferric sulfate as a pulpotomy agent in primary teeth. Pediatric Dentistry 1991; 13: pp. 327-332.
  • 4. Ibricevic H., Al-Jame Q.: Ferric sulphate and formocresol in pulpotomy of primary molars: long term follow-up study. European Journal of Paediatric Dentistry 2003; 4: pp. 28-32.
  • 5. Alacam A.: Pulpal tissue changes following pulpotomies with formocresol, glutaraldehyde-calcium hydroxide, glutaraldehyde-zinc oxide eugenol pastes in primary teeth. Journal of Pedodontics 1989; 13: pp. 123-132.
  • 6. Prakash C., Chandra S., Jaiswal J.N.: Formocresol and glutaraldehyde pulpotomies in primary teeth. Journal of Pedodontics 1989; 13: pp. 314-322.
  • 7. Shumayrikh N.M., Adenubi J.O.: Clinical evaluation of glutaraldehyde with calcium hydroxide and glutaraldehyde with zinc oxide eugenol in pulpotomy of primary molars. Endodontics and Dental Traumatology 1999; 15: pp. 259-264.
  • 8. Eidelman E., Holan G., Fuks A.B.: Mineral trioxide aggregate vs. formocresol in pulpotomized primary molars: a preliminary report. Pediatric Dentistry 2001; 23: pp. 15-18.
  • 9. Aeinehchi M., Dadvand S., Fayazi S., Bayat-Movahed S.: Randomized controlled trial of mineral trioxide aggregate and formocresol for pulpotomy in primary molar teeth. International Endodontic Journal 2007; 40: pp. 261-267.
  • 10. Ansari G., Ranjpour M.: Mineral trioxide aggregate and formocresol pulpotomy of primary teeth: a 2-year follow-up. International Endodontic Journal 2010; 43: pp. 413-418.
  • 11. Doyle T.L., Casas M.J., Kenny D.J., Judd P.L.: Mineral trioxide aggregate produces superior outcomes in vital primary molar pulpotomy. Pediatric Dentistry 2010; 32: pp. 41-47.
  • 12. Dean J.A., Mack R.B., Fulkerson B.T., Sanders B.J.: Comparison of electrosurgical and formocresol pulpotomy procedures in children. International Journal of Paediatric Dentistry 2002; 12: pp. 177-182.
  • 13. Rivera N., Reyes E., Mazzaoui S., Moron A.: Pulpal therapy for primary teeth: formocresol vs electrosurgery: a clinical study. Journal of Dentistry for Children (Chicogo) 2003; 70: pp. 71-73.
  • 14. Bahrololoomi Z., Moeintaghavi A., Emtiazi M., Hosseini G.: Clinical and radiographic comparison of primary molars after formocresol and electrosurgical pulpotomy: a randomized clinical trial. Indian Journal of Dental Research 2008; 19: pp. 219-223.
  • 15. Zurn D., Seale N.S.: Light-cured calcium hydroxide vs formocresol in human primary molar pulpotomies: a randomized controlled trial. Pediatric Dentistry 2008; 30: pp. 34-41.
  • 16. Alacam A., Odabas M.E., Tuzuner T., Sillelioglu H., Baygin O.: Clinical and radiographic outcomes of calcium hydroxide and formocresol pulpotomies performed by dental students. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics 2009; 108: pp. e127-e133.
  • 17. Liu J.F.: Effects of Nd:YAG laser pulpotomy on human primary molars. Journal of Endodontics 2006; 32: pp. 404-407.
  • 18. Odabas M.E., Bodur H., Baris E., Demir C.: Clinical, radiographic, and histopathologic evaluation of Nd:YAG laser pulpotomy on human primary teeth. Journal of Endodontics 2007; 33: pp. 415-421.
  • 19. Golpayegani M.V., Ansari G., Tadayon N., Shams S., Mir M.: Low-level laser therapy for pulpotomy treatment of primary molars. Journal of Dentistry, Tehran University of Medical Sciences 2009; 6: pp. 168-174.
  • 20. Peng L., Ye L., Tan H., Zhou X.: Evaluation of the formocresol versus mineral trioxide aggregate primary molar pulpotomy: a meta-analysis. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics 2006; 102: pp. e40-e44.
  • 21. Peng L., Ye L., Guo X., Tan H., Zhou X., Wang C., et. al.: Evaluation of formocresol versus ferric sulphate primary molar pulpotomy: a systematic review and meta-analysis. International Endodontic Journal 2007; 40: pp. 751-757.
  • 22. Simancas-Pallares M.A., Diaz-Caballero A.J., Luna-Ricardo L.M.: Mineral trioxide aggregate in primary teeth pulpotomy. A systematic literature review. Medicina Oral Patologia Oral y Cirugia Bucal 2010; 15: pp. e942-e946.
  • 23. Nadin G., Goel B.R., Yeung C.A., Glenny A.M.: Pulp treatment for extensive decay in primary teeth. Cochrane Database of Systematic Reviews 2003; pp. CD003220.
  • 24. Fuks A.B.: Vital pulp therapy with new materials for primary teeth: new directions and treatment perspectives. Pediatric Dentistry 2008; 30: pp. 211-219.
  • 25. Tu Y.K., Woolston A., Faggion C.M.: Do bone grafts or barrier membranes provide additional treatment effects for infrabony lesions treated with enamel matrix derivatives? A network meta-analysis of randomized-controlled trials. Journal of Clinical Periodontology 2010; 37: pp. 59-79.
  • 26. Tu Y.K., Needleman I., Chambrone L., Lu H.K., Faggion C.M.: A Bayesian network meta-analysis on comparisons of enamel matrix derivatives, guided tissue regeneration and their combination therapies. Journal of Clinical Periodontology 2012; 39: pp. 303-314.
  • 27. Hoaglin D.C., Hawkins N., Jansen J.P., Scott D.A., Itzler R., Cappelleri J.C., et. al.: Conducting indirect-treatment-comparison and network-meta-analysis studies: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 2. Value in Health 2011; 14: pp. 429-437.
  • 28. Jansen J.P., Fleurence R., Devine B., Itzler R., Barrett A., Hawkins N., et. al.: Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 1. Value in Health 2011; 14: pp. 417-428.
  • 29. Lin P.Y., Cheng Y.W., Chu C.Y., Chien K.L., Lin C.P., Tu Y.K.: In-office treatment for dentin hypersensitivity: a systematic review and network meta-analysis. Journal of Clinical Periodontology 2013; 40: pp. 53-64.
  • 30. Llewelyn D.R.: Faculty of dental surgery RCoS UK National Clinical Guidelines in Paediatric Dentistry. The pulp treatment of the primary dentition. International Journal of Paediatric Dentistry 2000; 10: pp. 248-252.
  • 31. Ranly D.M., Garcia-Godoy F.: Current and potential pulp therapies for primary and young permanent teeth. Journal of Dentistry 2000; 28: pp. 153-161.
  • 32. Loh A., O’Hoy P., Tran X., Charles R., Hughes A., Kubo K., et. al.: Evidence-based assessment: evaluation of the formocresol versus ferric sulfate primary molar pulpotomy. Pediatric Dentistry 2004; 26: pp. 401-409.
  • 33. Srinivasan V., Patchett C.L., Waterhouse P.J.: Is there life after Buckley’s Formocresol? Part I – a narrative review of alternative interventions and materials. International Journal of Paediatric Dentistry 2006; 16: pp. 117-127.
  • 34. De Coster P., Rajasekharan S., Martens L.: Laser-assisted pulpotomy in primary teeth: a systematic review. International Journal of Paediatric Dentistry 2013; 23: pp. 389-399.
  • 35. Lu G., Ades A.E.: Combination of direct and indirect evidence in mixed treatment comparisons. Statistics in Medicine 2004; 23: pp. 3105-3124.
  • 36. Saltzman B., Sigal M., Clokie C., Rukavina J., Titley K., Kulkarni G.V.: Assessment of a novel alternative to conventional formocresol-zinc oxide eugenol pulpotomy for the treatment of pulpally involved human primary teeth: diode laser-mineral trioxide aggregate pulpotomy. International Journal of Paediatric Dentistry 2005; 15: pp. 437-447.
  • 37. Vargas K.G., Packham B., Lowman D.: Preliminary evaluation of sodium hypochlorite for pulpotomies in primary molars. Pediatric Dentistry 2006; 28: pp. 511-517.
  • 38. Malekafzali B., Shekarchi F., Asgary S.: Treatment outcomes of pulpotomy in primary molars using two endodontic biomaterials. A 2-year randomised clinical trial. European Journal of Paediatric Dentistry 2011; 12: pp. 189-193.
  • 39. Odabas M.E., Cinar C., Tulunoglu O., Isik B.: A new haemostatic agent’s effect on the success of calcium hydroxide pulpotomy in primary molars. Pediatric Dentistry 2011; 33: pp. 529-534.
  • 40. Yaman E., Gorken F., Pinar Erdem A., Sepet E., Aytepe Z.: Effects of folk medicinal plant extract Ankaferd Blood Stopper(®) in vital primary molar pulpotomy. European Journal of Paediatric Dentistry 2012; 13: pp. 197-202.
  • 41. Sabbarini J., Mohamed A., Wahba N., El-Meligy O., Dean J.: Comparison of enamel matrix derivative versus formocresol as pulpotomy agents in the primary dentition. Journal of Endodontics 2008; 34: pp. 284-287.
  • 42. Waterhouse P.J., Nunn J.H., Whitworth J.M.: An investigation of the relative efficacy of Buckley’s Formocresol and calcium hydroxide in primary molar vital pulp therapy. British Dental Journal 2000; 188: pp. 32-36.
  • 43. Farsi N., Alamoudi N., Balto K., Mushayt A.: Success of mineral trioxide aggregate in pulpotomized primary molars. Journal of Clinical Pediatric Dentistry 2005; 29: pp. 307-311.
  • 44. Huth K.C., Paschos E., Hajek-Al-Khatar N., Hollweck R., Crispin A., Hickel R., et. al.: Effectiveness of 4 pulpotomy techniques – randomized controlled trial. Journal of Dental Research 2005; 84: pp. 1144-1148.
  • 45. Subramaniam P., Konde S., Mathew S., Sugnani S.: Mineral trioxide aggregate as pulp capping agent for primary teeth pulpotomy: 2 year follow up study. Journal of Clinical Pediatric Dentistry 2009; 33: pp. 311-314.
  • 46. Sushynski J.M., Zealand C.M., Botero T.M., Boynton J.R., Majewski R.F., Shelburne C.E., et. al.: Comparison of gray mineral trioxide aggregate and diluted formocresol in pulpotomized primary molars: a 6- to 24-month observation. Pediatric Dentistry 2012; 34: pp. 120-128.
  • 47. Ibricevic H., al-Jame Q.: Ferric sulfate as pulpotomy agent in primary teeth: twenty month clinical follow-up. Journal of Clinical Pediatric Dentistry 2000; 24: pp. 269-272.
  • 48. Markovic D., Zivojinovic V., Vucetic M.: Evaluation of three pulpotomy medicaments in primary teeth. European Journal of Paediatric Dentistry 2005; 6: pp. 133-138.
  • 49. Moretti A.B., Sakai V.T., Oliveira T.M., Fornetti A.P., Santos C.F., Machado M.A., et. al.: The effectiveness of mineral trioxide aggregate, calcium hydroxide and formocresol for pulpotomies in primary teeth. International Endodontic Journal 2008; 41: pp. 547-555.
  • 50. Noorollahian H.: Comparison of mineral trioxide aggregate and formocresol as pulp medicaments for pulpotomies in primary molars. British Dental Journal 2008; 204: pp. E20.
  • 51. Sonmez D., Sari S., Cetinbas T.: A comparison of four pulpotomy techniques in primary molars: a long-term follow-up. Journal of Endodontics 2008; 34: pp. 950-955.
  • 52. Erdem A.P., Guven Y., Balli B., Ilhan B., Sepet E., Ulukapi I., et. al.: Success rates of mineral trioxide aggregate, ferric sulfate, and formocresol pulpotomies: a 24-month study. Pediatric Dentistry 2011; 33: pp. 165-170.
  • 53. Tziafas D., Pantelidou O., Alvanou A., Belibasakis G., Papadimitriou S.: The dentinogenic effect of mineral trioxide aggregate (MTA) in short-term capping experiments. International Endodontic Journal 2002; 35: pp. 245-254.
  • 54. Al-Zayer M.A., Straffon L.H., Feigal R.J., Welch K.B.: Indirect pulp treatment of primary posterior teeth: a retrospective study. Pediatric Dentistry 2003; 25: pp. 29-36.
  • 55. Sonmez D., Duruturk L.: Success rate of calcium hydroxide pulpotomy in primary molars restored with amalgam and stainless steel crowns. British Dental Journal 2010; 208: pp. E18. [discussion 408–9]
  • 56. Attari N., Roberts J.F.: Restoration of primary teeth with crowns: a systematic review of the literature. European Archives of Paediatric Dentistry 2006; 7: pp. 58-62. [discussion 63]
  • 57. Agamy H.A., Bakry N.S., Mounir M.M., Avery D.R.: Comparison of mineral trioxide aggregate and formocresol as pulp-capping agents in pulpotomized primary teeth. Pediatric Dentistry 2004; 26: pp. 302-309.
  • 58. Kalaskar R.R., Damle S.G.: Comparative evaluation of lyophilized freeze dried platelet derived preparation with calcium hydroxide as pulpotomy agents in primary molars. Journal of the Indian Society of Pedodontics and Preventive Dentistry 2004; 22: pp. 24-29.
  • 59. Hu L.Y., Qian H.: Clinical efficiency of ferric sulphate as a pulpotomy agent in primary molars. Journal of Oral Biology and Craniofacial Research 2005; 21: pp. 445-446.
  • 60. Huth K.C., Hajek-Al-Khatar N., Wolf P., Ilie N., Hickel R., Paschos E.: Long-term effectiveness of four pulpotomy techniques: 3-year randomised controlled trial. Clinical Oral Investigations 2012; 16: pp. 1243-1250.
  • 61. Naik S., Hegde A.H.: Mineral trioxide aggregate as a pulpotomy agent in primary molars: an in vivo study. Journal of the Indian Society of Pedodontics and Preventive Dentistry 2005; 23: pp. 13-16.
  • 62. Srinivasan D., Jayanthi M.: Comparative evaluation of formocresol and mineral trioxide aggregate as pulpotomy agents in deciduous teeth. Indian Journal of Dental Research 2011; 22: pp. 385-390.
  • 63. Odabas M.E., Alacam A., Sillelioglu H., Deveci C.: Clinical and radiographic success rates of mineral trioxide aggregate and ferric sulphate pulpotomies performed by dental students. European Journal of Paediatric Dentistry 2012; 13: pp. 118-122.

Was this article helpful?

Primary molar pulpotomy: A systematic review and network meta-analysis Po-Yen Lin , Hsueh-Szu Chen , Yu-Hsiang Wang and Yu-Kang Tu Journal of Dentistry, 2014-09-01, Volume 42, Issue 9, Pages 1060-1077, Copyright © 2014 Elsevier Ltd Abstract Objective Pulpotomy is a common procedure to treat asymptomatic reversible pulpitis in primary molars. The aim of this study is to undertake a systematic review and a network meta-analysis to compare the clinical and radiographic outcomes of different pulpotomy procedures in primary molars. Data Three authors performed data extraction independently and in duplicate using data collection forms. Disagreements were resolved by discussion. Sources An electronic literature search was performed within MEDLINE (via PubMed), ScienceDirect, Web of Science, Cochrane, and ClinicalKey databases until December 2012. Medications for pulpotomy including formocresol, ferric sulfate, calcium hydroxide, and mineral trioxide aggregate (MTA), and laser pulpotomy are compared using Bayesian network meta-analyses. The outcome is the odds ratio for clinical and radiographic failure including premature tooth loss at 12 and 24 months after treatments amongst different treatment procedures. 37 studies were included in the systematic review, and 22 of them in the final network meta-analyses. After 18–24 months, in terms of treatment failure, the odds ratio for calcium hydroxide vs. formocresol was 1.94 [95% credible interval (CI): 1.11, 3.25]; 3.38 (95% CI: 1.37, 8.61) for lasers vs. formocresol; 2.16 (95% CI: 1.12, 4.31) for calcium hydroxide vs. ferric sulfate; 3.73 (95% CI: 1.27, 11.67) for lasers vs. ferric sulfate; 0.47 (95% CI: 0.26, 0.83) for MTA vs. calcium hydroxide; 3.76 (95% CI: 1.39, 10.08) for lasers vs. MTA. Conclusions After 18–24 months, formocresol, ferric sulfate, and MTA showed significantly better clinical and radiographic outcomes than calcium hydroxide and laser therapies in primary molar pulpotomies. Clinical significance The network meta-analyses showed that MTA is the first choice for primary molar pulpotomies. However, if treatment cost is an issue, especially when the treated primary molars are going to be replaced by permanent teeth, ferric sulfate may be the choice. 1 Introduction Pulpotomy in primary teeth is a standard procedure to amputate the inflamed and infected dental coronal pulp tissue and is usually undertaken when coronal pulp tissues are exposed by caries, during caries removal or trauma . The objective of this treatment is to remove coronal inflammatory tissues, which usually contain microorganisms; therefore, healing is allowed to take place at the entrance of the root canal with essentially healthy pulp tissue. After a coronal pulp is amputated, the pulp stump could be treated with several agents, leaving vital and uninfected radicular pulp tissue intact. Although dilute formocresol (1:5 Buckley's solution) has long been regarded as the gold standard for wound dressing of pulpotomized primary teeth, other agents can also protect radicular pulp, promoting healing and providing good treatment outcomes. The use of formocresol has been questioned because of its adverse effects, such as potential carcinogenicity, mutagenicity, and cytotoxicity. Moreover, the major component of formocresol, formaldehyde, might be distributed systemically after pulpotomies . This led to investigations of alternative techniques and materials, such as ferric sulphate , gluatraldehyde preparations , mineral trioxide aggregate (MTA) , electrosurgery , calcium hydroxide , and even laser therapies . Although some recent meta-analyses indicated that MTA and ferric sulfate may present similar or even better clinical or radiographic outcomes than formocresol, there is no comprehensive review for comparisons of different pulpotomy medications and techniques . Therefore, it is challenging for dentists to select the most appropriate medicaments, and the relative effectiveness of those treatments remains uncertain. Traditional meta-analysis undertakes pair-wise comparisons between treatments, but when the number of available treatments is large, pair-wise comparisons may be inefficient or not feasible . Network meta-analysis is a methodology for direct and indirect statistical comparisons between different treatments and had been used in dental research . The aim of this study is to undertake a systematic review and network meta-analyses, comparing the clinical and radiographic outcomes in primary molar pulpotomy amongst different dressing materials. The null hypothesis is that there were no differences in clinical and radiographic outcomes among different materials when performing primary molar pulpotomies. 2 Materials and methods 2.1 Literature search The literature search within MEDLINE (via PubMed), ScienceDirect, Web of Science, Cochrane, and ClinicalKey databases up to December 2012 was undertaken. To identify relevant studies, we used the following key words “(pulpotomy OR pulp therapy OR pulp treatment OR pulp exposure OR pulp devitalization OR pulp capping) AND (primary OR paediatric OR deciduous)”, limited in “clinical trials” and “humans”; no language restrictions were imposed. The reference lists of previously published reviews were also cross-checked for studies missed in our electronic literature search. Inclusion criteria Original prospective clinical trials comparing two or more pulpotomy agents. Human vital primary molars with carious pulp exposure. Follow-up periods of 6 months or more. Reporting clinical or radiographic success and failure rates. Clear definitions of success and failure. Clinical success was defined as asymptomatic, absence of sinus tract or fistula, no pathological tooth mobility, and absence of soft tissue swelling. Radiographic success was defined as absence of apical and furcal radiolucencies, absence of pathologic internal or external root resorption, absence of widening of periodontal ligament space, and absence of apical root resorption . 2.2 Study selection, quality assessment, and data extraction Screening titles and abstracts of potentially relevant articles was performed before retrieving full articles. Full articles were reviewed to verify if they fit all the inclusion criteria above. The literature selection and data extractions ( Fig. 1 ) were done by three authors (PY Lin, HS Chen, YH Wang) repeatly. Quality assessment of included studies, such as randomization, allocation concealment, blinding, intention to treat and sample size calculation, were carried out independently by three authors (PY Lin, HS Chen, YH Wang). The following data were also extracted independently by three authors (PY Lin, HS Chen, YH Wang): mean age, age range, treatment agent, number of teeth receiving treatments at the beginning of the trial, drop-out rates, follow-up periods, study design, tooth numbers at follow-up visits, and clinical and radiographic success rates ( Table 1 ). The corresponding authors were contacted to obtain information of unclear or missing data. Any disagreements on study inclusions, quality assessment, or data extraction were resolved by discussions among the three authors. Fig. 1 Flowchart for literature search and identifications of articles for review. Table 1 Summary of studies included for present primary molar pulpotomy systematic review. Author, year, country Mean age (range) Treatment agent Restoration Teeth number at beginning Follow-up period (months) Teeth number at follow-up period Clinical success rate a Radiographic success rate a Study design Drop-out rate Clinical success rate b Radiographic success rate b Alacam, 1989, Turkey (7–11) Formocresol Not mentioned 23 12 23 91.3% 82.6% Parallel 0.0% 91.3% 82.6% (1:5 Buckley's solution) 2% glutaraldehyde + ZOE 25 12 25 96.0% 92.0% 0.0% 96.0% 92.0% 2% glutaraldehyde + calcium hydroxide 21 12 21 90.4% 76.1% 0.0% 90.5% 81.0% Prakash, 1989, India 6 (3.5–9.5) Formocresol Amalgam 30 6 22 66.6% 66.6% Parallel 26.7% 90.9% 90.9% (1:5 Buckley's solution) 2% glutaraldehyde 30 6 20 66.6% 66.6% 33.3% 100.0% 100.0% Fei, 1991, USA c 6.6 (3.2–10.1) Formocresol Stainless steel crown N/A 6 N/A N/A N/A Parallel N/A 100.0% 83.3% (1:5 Buckley's solution) 12 N/A N/A N/A N/A 96.3% 81.5% 15.50% ferric sulfate N/A 6 N/A N/A N/A N/A 100.0% 96.3% 12 N/A N/A N/A N/A 100.0% 100.0% Shumayrikh, 1999, Saudi Arabia (5–9) 2% glutaraldehyde + ZOE Stainless steel crown 30 12 29 93.3% 73.3% Parallel 3.3% 96.6% 75.9% 2% glutaraldehyde + calcium hydroxide 31 12 28 80.6% 64.5% 9.7% 89.3% 71.4% Ibricevic, 2000/2003, Kuwait c 4.3 (3–6) Formocresol (not dilute) Stainless steel crown or amalgam 35 6 35 100.0% 100.0% Parallel 0.0% 100.0% 100.0% 9 35 100.0% N/A 0.0% 100.0% N/A 12 35 100.0% N/A 0.0% 100.0% N/A 15 35 100.0% N/A 0.0% 100.0% N/A 18 35 100.0% N/A 0.0% 100.0% N/A 20 35 100.0% 97.2% 0.0% 100.0% 97.1% 15.50% ferric sulfate 35 6 35 100.0% 100.0% 0.0% 100.0% 100.0% 9 35 100.0% N/A 0.0% 100.0% N/A 12 35 100.0% N/A 0.0% 100.0% N/A 15 35 100.0% N/A 0.0% 100.0% N/A 18 35 100.0% N/A 0.0% 100.0% N/A 20 35 100.0% 97.2% 0.0% 100.0% 97.1% Waterhouse, 2000, UK c N/A Formocresol Stainless steel crown or amalgam or glass ionomer cement or compomer 46 6 44 71.7% N/A Parallel 4.3% 75.0% N/A (1:5 Buckley's solution) 12 44 65.2% 15.2% 4.3% 68.2% 15.9% 38 18 N/A N/A N/A 4.3% N/A N/A Calcium hydroxide 24 N/A N/A N/A 4.3% N/A N/A 6 35 68.4% N/A 7.9% 74.3% N/A 12 35 73.7% 15.8% 7.9% 80.0% 17.1% 18 N/A N/A N/A 7.9% N/A N/A 24 N/A N/A N/A 7.9% N/A N/A Dean, 2002, USA 5.49 (2.2–10.5) Formocresol (not dilute) Stainless steel crown 25 >6 25 100.0% 92.0% Parallel 0.0% 100.0% 92.0% Electro-surgery (12 W) 25 >6 25 96.0% 84.0% 0.0% 96.0% 84.0% Rivera, 2003, Venezuela (4–7) Formocresol Amalgam 40 6 40 100.0% 92.5% Split mouth 0.0% 100.0% 92.5% (1:5 Buckley's solution) Electro-surgery 40 6 40 95.0% 97.5% 0.0% 95.0% 97.5% Agamy, 2004, Egypt c 6.1 (4–8) Formocresol Stainless steel crown 24 6 20 83.3% 83.3% Split mouth 16.7% 100.0% 100.0% 12 20 75.0% 75.0% 16.7% 90.0% 90.0% Grey MTA 24 6 20 79.2% 79.2% 16.7% 95.0% 95.0% 12 19 79.2% 79.2% 16.7% 100.0% 100.0% White MTA 24 6 20 79.2% 79.2% 20.8% 95.0% 95.0% 12 19 66.7% 66.7% 20.8% 84.2% 84.2% Kalaskar, 2004, Mumbai (4–7) Calcium hydroxide Stainless steel crown 28 6 28 96.4% 96.4% Parallel 0.0% 96.4% 96.4% Lyophilized freeze dried platelet derived preparation 28 6 28 100.0% 100.0% 0.0% 100.0% 100.0% Farsi, 2005, Saudi Arabia c 5.95 (3–8) Formocresol Stainless steel crown 60 6 36 60.0% 60.0% Parallel 40.0% 100.0% 100.0% 12 36 60.0% 60.0% 40.0% 100.0% 100.0% 18 36 60.0% 53.3% 40.0% 100.0% 88.9% 24 36 58.3% 51.7% 40.0% 97.2% 86.1% MTA 60 6 38 63.3% 63.3% 36.7% 100.0% 100.0% 12 38 63.3% 63.3% 36.7% 100.0% 100.0% 18 38 63.3% 63.3% 36.7% 100.0% 100.0% 24 38 63.3% 63.3% 36.7% 100.0% 100.0% Hu, 2005, China c (3–6) Formocresol Glass ionomer cement 40 6 40 87.5% 82.5% Parallel 0.0% 87.5% 82.5% (1:5 Buckley's solution) 12 40 72.5% 62.5% 0.0% 72.5% 62.5% 15.50% Ferric sulfate 40 6 40 82.5% 75.0% 0.0% 82.5% 75.0% 12 40 77.5% 70.0% 0.0% 77.5% 70.0% Huth, 2005, Germany c 4.8 (2–8) Formocresol Stainless steel crown or composite resin 50 6 50 100.0% N/A Parallel 0.0% 100.0% N/A (1:5 Buckley's solution) 12 50 100.0% 96.0% 0.0% 100.0% 96.0% 18 47 92.0% N/A 6.0% 97.9% N/A 24 46 88.0% 84.0% 8.0% 96.7% 91.3% 15.50% Ferric sulfate 50 6 50 100.0% N/A 0.0% 100.0% N/A 12 50 100.0% 86.0% 0.0% 100.0% 86.0% 18 43 84.0% N/A 14.0% 97.7% N/A 24 42 84.0% 84.0% 16.0% 100.0% 100.0% Calcium hydroxide 44 6 44 97.7% N/A 0.0% 97.7% N/A 12 43 97.7% 90.9% 2.3% 97.7% 90.7% 18 35 77.3% N/A 20.5% 97.1% N/A 24 34 65.9% 52.3% 22.7% 85.3% 67.7% Er:YAG laser 47 6 47 100.0% N/A 0.0% 100.0% N/A (2 Hz, 108 mJ) 12 47 95.7% 93.6% 0.0% 95.7% 93.6% 18 43 83.0% N/A 8.5% 90.7% N/A 24 39 74.5% 66.0% 17.0% 89.7% 79.5% Markovic, 2005, Serbia and Montenegro c 6.4 (4–9) Formocresol Amalgam 33 6 N/A N/A N/A Parallel 0.0% N/A N/A (1:5 dilution) 12 N/A N/A N/A 0.0% N/A N/A 18 33 90.9% 84.8% 0.0% 90.9% 84.9% 15.50% ferric sulfate 37 6 N/A N/A N/A 0.0% N/A N/A 12 N/A N/A N/A 0.0% N/A N/A 18 37 89.2% 81.1% 0.0% 89.2% 81.1% Calcium hydroxide 34 6 N/A N/A N/A 0.0% N/A N/A 12 N/A N/A N/A 0.0% N/A N/A 18 34 82.3% 76.5% 0.0% 82.4% 76.5% Naik, 2005, Mangalore N/A Formocresol Stainless steel crown 25 6 23 92.0% 92.0% Parallel 8.0% 100.0% 100.0% (1:5 Buckley's solution) MTA 25 6 24 96.0% 96.0% 4.0% 100.0% 100.0% Saltzman, 2005, Canada 5.1 (3.5–7.5) Formocresol Stainless steel crown 26 5.2 21 80.8% 80.8% Split mouth 19.2% 100.0% 100.0% (Full strength) 9.5 20 76.9% 73.1% 23.1% 100.0% 95.0% 26 15.7 13 50.0% 42.3% 50.0% 100.0% 84.6% MTA + diode laser 5.2 20 76.9% 73.1% 23.1% 100.0% 95.0% (3 W, continuous mode) 9.5 18 69.2% 53.8% 30.8% 100.0% 77.8% 15.7 7 26.9% 19.2% 73.1% 100.0% 71.4% Liu, 2006, Taiwan c 5.1 (4–7) Formocresol Stainless steel crown or composite resin 69 9–12 69 98.6% 95.7% Parallel 0.0% 98.6% 95.7% (1:5 Buckley's solution) 12–24 55 76.8% 73.9% 20.2% 96.4% 92.7% 24–36 30 37.7% 37.7% 56.5% 86.7% 86.7% 36–48 14 15.9% 14.5% 79.7% 78.6% 71.4% 48–60 6 8.7% 8.7% 91.3% 100.0% 100.0% Nd:YAG laser 68 6–12 68 98.5% 98.5% 0.0% 98.5% 98.5% (2 W, 20 Hz, 124 J/cm 2 ) 12–24 35 50.0% 50.0% 48.5% 97.1% 97.1% 24–36 21 30.9% 29.4% 69.1% 100.0% 95.2% 36–48 14 20.6% 19.1% 79.4% 100.0% 92.9% 48–60 11 16.2% 16.2% 83.8% 100.0% 100.0% Vargas, 2006, USA 5 (4–9) Ferric sulfate Stainless steel crown 28 6 28 100.0% 67.9% Split mouth 0.0% 100.0% 67.9% 12 13 39.3% 28.6% 53.6% 84.6% 61.5% 5% NaOCl 32 6 32 100.0% 90.6% 0.0% 100.0% 90.6% 12 16 43.8% 34.4% 50.0% 87.5% 68.8% Aeinehchi, 2007, Iran 6.51 (5–9) Formocresol Amalgam or glass ionomer cement 75 6 57 76.0% 68.0% Parallel 24.0% 100.0% 89.5% MTA 51 6 43 84.3% 84.3% 15.7% 100.0% 100.0% Odabas, 2007, Turkey c 7.9 (6–9) Formocresol Stainless steel crown or amalgam 21 6 21 90.5% 90.5% Split mouth 0.0% 90.5% 90.5% (1:5 dilution) 9 21 90.5% 90.5% 0.0% 90.5% 90.5% 12 21 90.5% 90.5% 0.0% 90.5% 90.5% Nd:YAG laser 21 6 21 90.5% 81.0% 0.0% 90.5% 81.0% (2 W, 20 Hz) 9 21 85.7% 71.4% 0.0% 85.7% 71.4% 12 21 85.7% 71.4% 0.0% 85.7% 71.4% Bahrololoomi, 2008, Iran 6.1 (5–1) Formocresol Amalgam 35 6 35 100.0% 97.1% Parallel 0.0% 100.0% 97.1% (1:5 Buckley's solution) 9 35 100.0% 97.1% 0.0% 100.0% 97.1% Electro-surgery 35 6 33 91.4% N/A 5.7% 97.0% N/A 9 33 91.4% 80.0% 5.7% 97.0% 84.9% Moretti, 2008, Brazil c 6.42 (5–9) Formocresol Glass ionomer cement 15 6 15 93.3% 93.3% Parallel 0.0% 93.3% 93.3% (1:5 Buckley's solution) 12 14 86.7% 86.7% 6.7% 92.9% 92.9% 18 13 80.0% 80.0% 13.3% 92.3% 92.3% 24 11 66.7% 66.7% 26.7% 90.9% 90.9% Calcium hydroxide 15 6 14 80.0% 53.3% 6.7% 85.7% 57.1% 12 12 53.3% 53.3% 20.0% 66.7% 66.7% 18 8 46.7% 33.3% 46.7% 87.5% 62.5% 24 7 46.7% 33.3% 53.3% 100.0% 71.4% Grey MTA 15 6 14 93.3% 93.3% 6.7% 100.0% 100.0% 12 14 86.7% 86.7% 6.7% 92.9% 92.9% 18 13 80.0% 80.0% 13.3% 92.3% 92.3% 24 12 60.0% 60.0% 20.0% 75.0% 75.0% Noorollahain, 2008, Iran c 6.08 (5–7) Formocresol Stainless steel crown 30 6 27 90.0% 90.0% Parallel 10.0% 100.0% 100.0% (1:5 Buckley's solution) 12 24 80.0% 80.0% 20.0% 100.0% 100.0% 24 18 60.0% 60.0% 40.0% 100.0% 100.0% White MTA 30 6 29 96.7% 96.7% 3.3% 100.0% 100.0% 12 29 96.7% 93.3% 3.3% 100.0% 96.6% 24 18 60.0% 56.7% 40.0% 100.0% 94.4% Sabbarini, 2008, Egypt 5 (4–7) Formocresol Stainless steel crown 15 6 15 66.7% 66.7% Split mouth 0.0% 66.7% 13.3% (1:5 Buckley's solution) Emdogain conditioned with polyacrylic acid 15 6 15 93.3% 93.3% 0.0% 93.3% 60.0% Sonmez, 2008, Turkey c 6.6 (4–9) Formocresol Amalgam 16 6 13 81.3% 81.3% Split mouth 18.8% 100.0% 100.0% (1:5 Buckley's solution) 12 13 75.0% 68.8% 18.8% 92.3% 84.6% 18 11 62.5% 62.5% 31.3% 90.9% 90.9% 15.50% ferric sulfate 24 10 62.5% 62.5% 37.5% 100.0% 100.0% 16 6 15 93.8% 93.8% 6.3% 100.0% 100.0% 12 15 93.8% 87.5% 6.3% 100.0% 93.3% 18 14 87.5% 81.3% 12.5% 100.0% 92.9% 24 13 81.3% 68.8% 18.8% 100.0% 84.6% Calcium hydroxide 16 6 13 81.3% 81.3% 18.8% 100.0% 100.0% 12 13 75.0% 56.3% 18.8% 92.3% 69.2% 18 9 56.3% 56.3% 43.8% 100.0% 100.0% 24 9 56.3% 37.5% 43.8% 100.0% 66.7% MTA 16 6 15 93.8% 93.8% 6.3% 100.0% 100.0% 12 15 93.8% 81.3% 6.3% 100.0% 86.7% 18 13 75.0% 75.0% 18.8% 92.3% 92.3% 24 12 68.8% 62.5% 25.0% 91.7% 83.3% Zurn, 2008, USA c 5.3 (2.3–8.5) Formocresol Stainless steel crown 38 6 34 86.8% 86.8% Split mouth 10.5% 97.1% 97.1% (1:5 Buckley's solution) 7–12 34 86.8% 86.8% 10.5% 97.1% 97.1% 13–24 31 78.9% 78.9% 18.4% 96.8% 96.8% Calcium hydroxide 38 6 34 86.8% 86.8% 10.5% 97.1% 97.1% 7–12 34 84.2% 71.1% 10.5% 94.1% 79.4% 13–24 32 71.1% 60.5% 15.8% 84.4% 71.9% Alacam, 2009, Turkey c 6.4 (4–8) Formocresol Stainless steel crown 35 6 33 91.4% 91.4% Parallel 5.7% 97.0% 97.0% 9 29 77.7% 77.7% 17.1% 93.1% 93.1% 12 29 74.3% 74.3% 17.1% 89.7% 89.7% Calcium hydroxide 33 6 33 66.7% 48.5% 0.0% 66.7% 48.5% 9 33 66.7% 48.5% 0.0% 66.7% 48.5% 12 33 33.3% 33.3% 0.0% 33.3% 33.3% Calcium hydroxide + iodoform 32 6 30 46.9% 25.0% 6.3% 50.0% 26.7% 9 29 40.6% 18.8% 9.4% 44.8% 20.7% 12 29 15.6% 12.5% 9.4% 17.2% 13.8% Subramaniam, 2009, India c (6–8) Formocresol Stainless steel crown 20 6 20 100.0% 90.0% Split mouth 0.0% 100.0% 90.0% (1:5 Buckley's solution) 12 20 100.0% 85.0% 0.0% 100.0% 85.0% 24 20 100.0% 85.0% 0.0% 100.0% 85.0% MTA 20 6 20 100.0% 95.0% 0.0% 100.0% 95.0% 12 20 100.0% 95.0% 0.0% 100.0% 95.0% 24 20 100.0% 95.0% 0.0% 100.0% 95.0% Doyle, 2010, Canada c 3.9 15.50% ferric sulfate Stainless steel crown 58 >12 46 N/A 43.1% Parallel 20.7% N/A 54.4% Eugenol-free 15.5% Ferric sulfate 78 >12 64 N/A 35.9% 17.9% N/A 43.8% MTA 15.50% ferric sulfate + MTA 57 >12 47 N/A 73.7% 17.5% N/A 89.4% 77 >12 70 N/A 66.2% 9.1% N/A 72.9% Golpayegani, 2010, Iran c 5.6 (4–7) Formocresol Stainless steel crown 23 6 18 78.2% 78.2% Split mouth 21.7% 100.0% 100.0% (1:5 Buckley's solution) 12 15 60.9% 52.2% 34.8% 93.3% 80.0% Diode laser 23 6 18 78.2% 69.6% 21.7% 100.0% 88.9% (Continuous mode, 4 J/cm 2 ) 12 15 65.2% 43.5% 34.8% 100.0% 66.7% Erdem, 2011, Turkey c 6.2 (5–7) Formocresol Amalgam 32 6 25 78.1% 78.1% Split mouth 21.9% 100.0% 100.0% (1:5 Buckley's solution) 12 25 78.1% 78.1% 21.9% 100.0% 100.0% 24 25 59.4% 59.4% 21.9% 76.0% 76.0% 15.50% ferric sulfate 32 6 25 78.1% 78.1% 21.9% 100.0% 100.0% 12 25 78.1% 78.1% 21.9% 100.0% 100.0% 24 25 59.4% 59.4% 21.9% 76.0% 76.0% MTA 32 6 25 78.1% 78.1% 21.9% 100.0% 100.0% 12 25 78.1% 78.1% 21.9% 100.0% 100.0% 24 25 75.0% 75.0% 21.9% 96.0% 96.0% ZOE 32 6 25 78.1% 75.0% 21.9% 100.0% 96.0% 12 25 78.1% 71.9% 21.9% 100.0% 92.0% 24 25 62.5% 46.9% 21.9% 80.0% 60.0% Malekafzali, 2011, Iran 6 (4–8) MTA Stainless steel crown or amalgam 40 6 36 90.0% 90.0% Split mouth 10.0% 100.0% 100.0% 12 33 82.5% 75.0% 17.5% 100.0% 90.9% 24 35 87.5% 80.0% 12.5% 100.0% 91.4% Calcium enriched mixture 40 6 36 90.0% 90.0% 10.0% 100.0% 100.0% 12 33 82.5% 80.0% 17.5% 100.0% 97.0% 24 35 87.5% 85.0% 12.5% 100.0% 97.1% Odabas, 2011, Turkey 6.1 (4–8) Calcium hydroxide Stainless steel crown 24 6 20 79.2% 79.2% Split mouth 16.7% 96.0% 95.0% 9 20 79.2% 75.0% 16.7% 96.0% 90.0% 12 20 75.0% 75.0% 16.7% 96.0% 90.0% Calcium hydroxide + ankaferd blood stopper 24 6 20 83.3% 83.3% 16.7% 100.0% 100.0% 9 20 79.2% 83.3% 16.7% 96.0% 100.0% 12 20 79.2% 79.2% 16.7% 96.0% 95.0% Srinivasan, 2011, India c (4–6) Formocresol Stainless steel crown 50 6 50 100.0% 90.0% Split mouth 0.0% 100.0% 90.0% (1:5 Buckley's solution) 9 48 88.0% 78.0% 4.0% 91.7% 81.3% 12 46 84.0% 72.0% 8.0% 91.3% 78.3% Grey MTA 50 6 50 100.0% 100.0% 0.0% 100.0% 100.0% 9 47 100.0% 90.0% 6.0% 100.0% 95.7% 12 47 100.0% 90.0% 6.0% 100.0% 95.7% Odabas, 2012, Turkey c 7.7 (5–10) 15.50% ferric sulfate Stainless steel crown 51 6 48 86.3% 74.5% Parallel 5.9% 91.7% 79.2% 9 48 86.3% 74.5% 5.9% 91.7% 79.2% 12 46 76.5% 74.5% 9.8% 84.8% 82.6% MTA 42 6 41 95.2% 95.2% 2.4% 97.6% 97.6% 9 39 90.5% 85.7% 7.1% 97.4% 92.3% 12 38 85.7% 83.3% 9.5% 94.7% 92.1% Sushynski, 2012, USA c 5.4 (2.5–10) Formocresol Stainless steel crown 133 6 114 84.2% 72.9% Parallel 14.3% 98.3% 85.1% (1:5 Buckley's solution) 12 90 67.7% 54.9% 32.3% 100.0% 81.1% 18 78 57.9% 45.9% 41.4% 98.7% 78.2% 24 66 48.9% 37.6% 50.4% 98.5% 75.8% Grey MTA 119 6 108 90.8% 86.6% 9.2% 100.0% 95.4% 12 96 80.7% 74.8% 19.3% 100.0% 92.7% 18 77 64.7% 61.3% 35.3% 100.0% 94.8% 24 65 54.6% 52.1% 45.4% 100.0% 95.4% Yaman, 2012, Turkey 7.3 (6–9) Formocresol Amalgam 30 6 30 96.7% 96.7% Split mouth 0.0% 100.0% 96.7% (1:5 Buckley's solution) 12 28 93.3% 83.3% 6.7% 100.0% 89.3% Ankaferd blood stopper 30 6 30 96.7% 96.7% 0.0% 96.7% 96.7% 12 28 93.3% 80.0% 6.7% 100.0% 85.7% a Success rate regarding drop-outs and premature tooth loss treated as failure. b Success rate only considering patients who recalled (deleting drop-outs). c Data included in final meta-analysis. 2.3 Data extraction and statistical analysis Numbers of teeth at the beginning, number of teeth at each of follow-up period, and clinical and radiographic success rates were extracted or derived from the published results. Clinical and radiographic success rates are derived in this systematic review using two slightly different definitions: (1) drop-outs and premature tooth loss were treated as failure; (2) only considering patients who recalled ( Table 1 ). The meta-analyses were then undertaken on the success rates that considered drop-outs and premature tooth loss as failure to obtain a more conservative estimate for success rates. To incorporate direct and indirect evidence, network meta-analyses were undertaken using the Bayesian hierarchical random-effects modelling . Because the included studies reported treatment outcomes with different lengths of follow-ups, the meta-analyses focus on the success rates of 9–12 months and 18–24 months follow-ups. Although 7 articles , met all the inclusion criteria, they were not included due to either the tested treatments being rarely used or the use of a combination of treatment agents, such as electrosurgery , sodium hypochloride , calcium enriched mixture , ankaferd blood stopper , and enamel matrix derivative . Consequently, those treatment regimens did not connect with other commonly used treatments to form a network and therefore were excluded. The final network meta-analyses included five commonly used medicaments for primary molar pulpotomies: (1) formocresol, (2) ferric sulfate, (3) calcium hydroxide, (4) MTA, and (5) laser therapies. Standard pair-wise meta-analyses of direct comparisons between each group were also carried out and compared to the results from network meta-analyses. Odds ratio for clinical and radiographic failure including premature tooth loss between treatment agents is used as the effect size measure in both network and pair-wise meta-analyses. Note that a smaller odds for failure indicates a better treatment agent. Furthermore, meta-regressions with the adjustment for covariates such as study design and types of restoration were also undertaken within the network meta-analysis to investigate the impact of these covariates on the success of pulpotomies. The Bayesian random-effects network meta-analysis and meta-regressions were performed using the statistical software WinBUGS (version 14.3, MRC Biostatistics Unit, Cambridge, UK) with 50,000 burn-in and further 50,000 simulations with three chains of different initial values. Non-informative priors were used throughout the analysis. The standard pair-wise random-effects meta-analysis, heterogeneity between studies and funnel plots were performed with statistical software STATA (version 11.2, StataCorp LP, College Station, TX, USA). The statistical significance level was set at 5%. 3 Results 3.1 Study selection Fig. 1 summarizes the details of the study selection process and the reasons for exclusion. A total of 2083 potential relevant titles, abstracts and articles found electronically, plus reference lists of reviews and related articles, 171 of which were screened for further evaluation. Finally, we identified 37 trials that met all the inclusion criteria, and 22 of them entered further network and pair-wise meta-analyses. The characteristics of these included trials are listed in Table 1 . 3.2 Study description The 37 trials included in the current systematic review were full reports published between 1989 and 2012, and 33 of them were published after 2000. Table 1 summarizes these studies. Of all 37 studies, 22 were parallel trials and the others were split-mouth trials. Follow-up periods were somewhat diverse in these studies, ranging from 5.2 months to 48–60 months . 22 studies were chosen for meta-analyses for 9–12 months, and 12 of them were chosen for meta-analyses for 18–24 months ( Table 1 ). 3.3 Quality of studies Table 2 shows the quality of the included trials. 30 studies described as randomized, 11 of which clearly described their randomize methods. The allocation concealment methods were described in 12 trials , the remaining did not provide details about it. There were no trials that employed double blinding (patient and caregiver blinding), and only 2 trials performed patient blinding . Four of the included trials reported sample size and statistical power calculations . Table 2 Quality assessment of the included articles for present primary molar pulpotomy systematic review. Study, Year Described as randomized Randomization methods Allocation concealment method Patient blinding Caregiver blinding Examiner blinding All patient accounted for at end of study Analysis account for patient losses a Sample size/statistical power calculation Alacam, 1989 Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned N/A Not mentioned Prakash, 1989 Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned No N/A Not mentioned Fei, 1991 Yes Yes Yes Not mentioned Not mentioned Yes No No Not mentioned Shumayrikh, 1999 Yes Not mentioned Not mentioned Yes Not mentioned Yes No No Not mentioned Ibricevic, 2000/2003 Yes Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Yes N/A Not mentioned Waterhouse, 2000, UK Yes Yes Yes Not mentioned Not mentioned Yes No No Not mentioned Dean, 2002 Yes Yes Yes Not mentioned Not mentioned Yes N/A N/A Not mentioned Rivera, 2003 Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned N/A N/A Not mentioned Agamy, 2004 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes No No Not mentioned Kalaskar, 2004 Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned N/A N/A Not mentioned Farsi, 2005 Yes Yes Yes Not mentioned Not mentioned Not mentioned No No Not mentioned Hu, 2005 Yes Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned N/A N/A Not mentioned Huth, 2005 Yes Yes Yes Yes Not mentioned Yes No No Yes Markovic, 2005 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes N/A N/A Not mentioned Naik, 2005 Yes Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned No N/A Not mentioned Saltzman, 2005 Yes Yes Yes Not mentioned Not mentioned Yes No No Not mentioned Liu, 2006 Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned No Not mentioned Vargas, 2006 Yes Yes Yes Not mentioned Not mentioned Yes No No Yes Aeinehchi, 2007 Yes Yes Yes Not mentioned Not mentioned Yes No No Not mentioned Odabas, 2007 Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Yes N/A N/A Not mentioned Bahrololoomi, 2008 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes No No Not mentioned Moretti, 2008 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes No No Not mentioned Noorollahain, 2008 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes No No Not mentioned Sabbarini, 2008 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes N/A N/A Not mentioned Sonmez, 2008 Yes Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned No No Not mentioned Zurn, 2008 Yes Yes Yes Not mentioned Not mentioned Yes No No Not mentioned Alacam, 2009 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes No No Not mentioned Subramaniam, 2009 Yes Yes Yes Not mentioned Not mentioned Not mentioned N/A N/A Not mentioned Doyle, 2010 Yes Yes Yes Not mentioned Not mentioned Yes No No Not mentioned Golpayegani, 2010 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes No No Not mentioned Erdem, 2011 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes No No Not mentioned Malekafzali, 2011 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes Yes No Yes Odabas, 2011 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes No No Not mentioned Srinivasan, 2011 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes No No Not mentioned Odabas, 2012 Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Yes No No Not mentioned Sushynski, 2012 Yes Not mentioned Not mentioned Not mentioned Not mentioned Yes No No Yes Yaman, 2012 Yes Yes Yes Not mentioned Not mentioned Yes No No Not mentioned a Yes – analysis with patient losses; No – patient lost but not included in analysis; N/A – no patient losses or not performed analysis. 3.4 Network meta-analysis 22 studies were grouped into 5 groups, according to their treatment agents, including formocresol, ferric sulfate, calcium hydroxide, MTA, and laser therapies, in the network meta-analysis, yielding 10 pairs of comparisons ( Fig. 2 ). Direct comparisons by head-to-head trials were available in 9 of 10 pairs ( Tables 3 and 4 ). Fig. 2 Network for the comparisons among different medicaments for primary molar pulpotomy. Dotted lines refer to those comparisons that have not been tested directly in clinical trials. The width of the solid lines is in proportion to the amount of evidence available in the literatures. Table 3 Failure odds ratio of network and standard meta-analysis for clinical and radiographic outcome for primary molar pulpotomy after 9–12 month follow-up. Clinical outcome Radiographic outcome Network meta-analysis Standard pair-wise meta-analysis Network meta-analysis Standard pair-wise meta-analysis Estimates 95% CI Estimates 95% CI Estimates 95% CI Estimates 95% CI FS vs. FC 0.70 (0.32, 1.43) 0.95 (0.84, 1.07) 1.04 (0.54, 1.83) 0.96 (0.87, 1.07) Ca(OH) 2 vs. FC 2.08 (1.10, 4.26) * 1.13 (1.02, 1.26) * 2.57 (1.32, 4.86) * 1.29 (1.13, 1.48) * MTA vs. FC 0.55 (0.32, 0.91) * 0.90 (0.83, 0.97) * 0.50 (0.31, 0.83) * 0.85 (0.78, 0.93) * Lasers vs. FC 1.34 (0.46, 4.02) 1.01 (0.96, 1.08) 1.25 (0.50, 2.93) 1.04 (0.96, 1.12) Ca(OH) 2 vs. FS 2.99 (1.20, 8.51) * 1.09 (1.00, 1.19) 2.47 (1.12, 5.75) * 1.07 (0.92, 1.26) MTA vs. FS 0.80 (0.37, 1.75) 0.95 (0.83, 1.08) 0.49 (0.27, 0.96) * 0.77 (0.68, 0.88) * Lasers vs. FS 1.94 (0.56, 7.27) 1.05 (0.97, 1.12) 1.21 (0.43, 3.34) 0.92 (0.80, 1.05) MTA vs. Ca(OH) 2 0.27 (0.11, 0.57) * 0.71 (0.54, 0.95) * 0.20 (0.09, 0.43) * 0.65 (0.46, 0.93) * Lasers vs. Ca(OH) 2 0.64 (0.19, 2.19) 1.00 (0.91, 1.09) 0.49 (0.17, 1.41) 0.95 (0.83, 1.08) Lasers vs. MTA 2.41 (0.76, 8.29) 2.46 (0.88, 6.40) * p < 0.05 Vs, versus; CI, credible interval; FC, formocresol; FS, ferric sulfate; MTA, mineral trioxide aggregate. Table 4 Failure odds ratio of network and standard meta-analysis for clinical and radiographic outcome for primary molar pulpotomy after 18–24 month follow-up. Clinical outcome Radiographic outcome Network meta-analysis Standard pair-wise meta-analysis Network meta-analysis Standard pair-wise Estimates 95% CI Estimates 95% CI Estimates 95% CI Estimates 95% CI FS vs. FC 0.90 (0.48, 1.65) 1.00 (0.88, 1.12) 1.02 (0.60, 1.78) 1.00 (0.91, 1.11) Ca(OH) 2 vs. FC 1.94 (1.11, 3.25) * 1.20 (1.05, 1.37) * 2.97 (1.78, 4.99) * 1.40 (1.19, 1.65) * MTA vs. FC 0.90 (0.61, 1.32) 0.91 (0.79, 1.05) 0.66 (0.45, 0.98) * 0.83 (0.73, 0.96) * Lasers vs. FC 3.38 (1.37, 8.61) * 1.35 (1.14, 1.60) * 2.54 (1.32, 4.76) * 1.38 (1.15, 1.66) * Ca(OH) 2 vs. FS 2.16 (1.12, 4.31) * 1.22 (1.04, 1.42) * 2.90 (1.56, 5.54) * 1.37 (1.13, 1.67) * MTA vs. FS 1.00 (0.54, 1.86) 0.91 (0.70, 1.19) 0.64 (0.35, 1.22) 0.88 (0.66, 1.18) Lasers vs. FS 3.73 (1.27, 11.67) * 1.13 (0.92, 1.39) 2.47 (1.11, 5.23) * 1.27 (1.00, 1.62) * MTA vs. Ca(OH) 2 0.47 (0.26, 0.83) * 0.80 (0.52, 1.23) 0.22 (0.12, 0.41) * 0.58 (0.33, 1.00) Lasers vs. Ca(OH) 2 1.72 (0.62, 4.98) 0.89 (0.68, 1.16) 0.86 (0.40, 1.72) 0.79 (0.56, 1.12) Lasers vs. MTA 3.76 (1.39, 10.08) * 3.88 (1.85, 8.05) * * p < 0.05 Vs, versus; CI, credible interval; FC, formocresol; FS, ferric sulfate; MTA, mineral trioxide aggregate. Table 3 shows the results of network meta-analysis of clinical and radiographic outcome for primary molar pulpotomy after 9–12 month follow-up. The odds ratio for calcium hydroxide vs. formocresol was 2.08 [95% credible interval (CI): 1.10, 4.26], indicating that formocresol had significantly better clinical outcome than calcium hydroxide after 9–12 months. The failure odds ratio between MTA vs. formocresol was 0.55 (95% CI: 0.32, 0.91); calcium hydroxide vs. ferric sulfate is 2.99 (95% CI: 1.20, 8.51); MTA vs. calcium hydroxide was 0.27 (95% CI: 0.11, 0.57). The results shows that MTA had significantly better clinical outcomes than formocresol and calcium hydroxide, and calcium hydroxide had more failures than formocresol and ferric sulfate. The radiographic outcomes showed almost the same pattern. The failure odds ratio between calcium hydroxide vs. formocresol was 2.57 (95% CI: 1.32, 4.86); MTA vs. formocresol was 0.50 (95% CI: 0.31, 0.83); calcium hydroxide vs. ferric sulfate was 2.47 (95% CI: 1.12, 5.75); MTA vs. ferric sulfate was 0.49 (95% CI: 0.27, 0.96); MTA vs. calcium hydroxide was 0.20 (95% CI: 0.09, 0.43). The results showed that MTA had significantly better radiographic outcomes than formocresol, ferric sulfate and calcium hydroxide, and calcium hydroxide had more failures than formocresol and ferric sulfate. Table 4 shows the results of network meta-analysis for clinical and radiographic outcome for primary molar pulpotomy after 18–24 month follow-up, which were contributed by 12 trials (15, 17, 43–52). The failure odds ratio for calcium hydroxide vs. formocresol was 1.94 (95% CI: 1.11, 3.25); lasers vs. formocresol was 3.38 (95% CI: 1.37, 8.61); calcium hydroxide vs. ferric sulfate was 2.16 (95% CI: 1.12, 4.31); lasers vs. ferric sulfate was 3.73 (95% CI: 1.27, 11.67); MTA vs. calcium hydroxide was 0.47 (95% CI: 0.26, 0.83); lasers vs. MTA was 3.76 (95% CI: 1.39, 10.08). The results show that after 18–24 months, formocresol, ferric sulfate, and MTA had significantly better clinical outcomes than calcium hydroxide and laser therapies. Compared to the clinical failures for FC, ferric sulfate, and MTA, two and three times more of failures were observed for calcium hydroxide and laser treatments, respectively. The radiographic outcomes also showed that failure odds ratio for calcium hydroxide vs. formocresol was 2.97 (95% CI: 1.78, 4.99); MTA vs. formocresol was 0.66 (95% CI: 0.45, 0.98); lasers vs. formocresol was 2.54 (95% CI: 1.32, 4.76); calcium hydroxide vs. ferric sulfate was 2.90 (95% CI: 1.56, 5.54); lasers vs. ferric sulfate was 2.47 (95% CI: 1.11, 5.23); MTA vs. calcium hydroxide was 0.22 (95% CI: 0.12, 0.41); lasers vs. MTA was 3.88 (95% CI: 1.85, 8.05). The results show that after 18–24 months, MTA has better radiographic outcomes than formocresol, calcium hydroxide and laser therapies, but no significant differences when compared with ferric sulfate. 3.5 Pair-wise meta-analysis, heterogeneity, and network meta-regression For pair-wise meta-analysis, trials with 100% success rates of both treatments were excluded . Results from standard pair-wise meta-analysis of overall studies show that after 9–12 months, MTA had better clinical outcomes than formocresol and calcium hydroxide and better radiographic outcomes than formocresol, ferric sulfate, and calcium hydroxide. After 18–24 months, formocresol and ferric sulfate had better clinical outcomes than calcium hydroxide, and had better radiographic outcomes than calcium hydroxide and laser therapies ( Tables 3 and 4 , Figs. 3–6 ). These results were similar to those from our network meta-analyses. The statistical heterogeneity of these comparisons was quite variable ( I -squared = 0.0–83.8%, Figs. 3–6 ). Appendix 1 shows the funnel plots of these pair-wise meta-analyses. Because the plots resemble symmetrical and inverted funnels, there was no likely of any publication bias. Network meta-regressions for covariates study design and types of restoration were tested separately and neither showed significant impacts on clinical or radiographic outcomes. Fig. 3 Forest plot of the standard pair-wise meta-analysis for clinical outcome for primary molar pulpotomy after 9–12 month follow-up. Fig. 4 Forest plot of the standard pair-wise meta-analysis for radiographic outcome for primary molar pulpotomy after 9–12 month follow-up. Fig. 5 Forest plot of the standard pair-wise meta-analysis for clinical outcome for primary molar pulpotomy after 18–24 month follow-up. Fig. 6 Forest plot of the standard pair-wise meta-analysis for radiographic outcome for primary molar pulpotomy after 18–24 month follow-up. 4 Discussion The present study analyzed all published clinical trials to evaluate different treatment agents for primary molar pulpotomies. A total of 37 studies were included in the systematic review and 22 of them were used in the final meta-analyses ( Fig. 1 ). The results of network meta-analyses and standard pair-wise meta-analyses were in general consistent: after 9–12 months, MTA had significantly better clinical and radiographic outcomes than formocresol and calcium hydroxide. Calcium hydroxide had more failures than formocresol and ferric sulfate; after 18–24 months, formocresol, ferric sulfate, and MTA had significantly better clinical and radiographic outcomes than calcium hydroxide and laser therapies. The results were also similar to those reported by recent systematic reviews. In an evidence-based assessment of formocresol vs. ferric sulfate, 2 meta-analyses concluded that both materials produced similar clinical and radiographic success . Another 2 systematic reviews, focused on formocresol vs. MTA, concluded that MTA appeared to be superior to formocresol with a higher clinical and radiographic success rate . All of them showed that formocresol had similar outcomes as ferric sulfate, and MTA might be the most superior treatment agent in primary molar pulpotomies. However, the current network meta-analysis showed that after 18–24 months, teeth treated with laser therapies were 2- to 3-times more likely to fail compared to formocresol, ferric sulfate, and MTA ( Table 4 ). Two studies provided direct comparisons between laser therapies and other treatment agents . Huth et al. compared Er:YAG laser irradiation in 47 primary molars to formocresol, ferric sulfate, and calcium hydroxide. After 24 months, because of 17.0% drop-outs, the success rates of laser group dropped to 74.5% clinically and 66.0% radiographically, compared to 84–88% in formocresol and ferric sulfate groups . On the other hand, Liu's study compared the effects of pulsed Nd:YAG laser on 68 primary molars to formocresol. After 24 months follow-up, although the success rate of the recalled patients was 97.1% in laser group, the drop-out rates was relatively high as 48.5%. Thus, the clinical and radiographic success rates regarding drop-outs as failure dropped to 50.0% . Although using different lasers, the results of these 2 studies showed higher drop-out rates in laser pulpotomy group after 24 months. Drop-outs may have been caused by a lot of reasons such as emigration or moving out, but for paediatric patients, the reason for dropouts from the trial is probably mainly caused by exfoliated teeth . Because drop-outs and premature tooth loss were regarded as failure in the final meta-analyses, the success rates were under-estimated. However, because the mean age of children in most trials was 5–7-year-old, considering tooth exfoliation within 24-months after pulpotomy as premature tooth loss was reasonable. In the current systematic review, only 14 trials provided data more than 18–24 months ( Table 1 ). The pulpotomy medicaments can be classified into 3 mechanisms: (1) devitalization such as formocresol, electrosurgery, and laser therapy, (2) preservation such as ferric sulfate, and glutaraldehyde, and (3) regeneration such as MTA, calcium hydroxide. However, our network meta-analyses showed that the outcome of MTA was apparently better than calcium hydroxide. This indicates that the properties of the material itself and the biocompatibility to the remained pulp tissues determine the success rates, not the mechanism. MTA was introduced as a pulpotomy medicament with characteristics of liberation formation, odontogenic effect on the pulp, antimicrobial properties and preservation of pulp integrity after pulpotomy, and without cytotoxicities . Our network meta-analyses showed that MTA was better than calcium hydroxide and laser therapies after 18–24 months, and better than formocresol, calcium hydroxide, and laser therapies after 9–12 months. In conclusion, MTA may be recommended as an alternative to formocresol for primary molar pulpotomies. However, because of the high cost of MTA, it may not the best choice for primary molar pulpotomies when considering cost effectiveness. In 2008, Fuks suggested to use ferric sulfate as a viable and inexpensive solution . In 2011, Malekafzali et al. conducted a randomized clinical trial to compare calcium enriched mixture and MTA for primary molar pulpotomy. After 24 months, the clinical and radiographic success rates of both groups were high (>80.0%) and showed no significant differences . Two other studies used a new hemostatic agent, ankaferd blood stopper, to perform primary molar pulpotomies. After 12 months of follow-up, the success rates were 79.2–93.3% compared with traditional materials . Both materials showed potential for the treatment. Also, these studies indicated that paediatric dentists were still looking for an appropriate and better medicament to replace formocresol. Our network meta-analyses showed that results from MTA were better than calcium hydroxide and laser therapies and comparable to ferric sulfate after 18–24 months, MTA seems to be the first choice for primary molar pulpotomies. If treatment cost is an issue, especially when the treated primary molars are going to be replaced by permanent teeth, ferric sulfate may be the choice. To minimize the differences between the trials, we explored the heterogeneity by undertaking network meta-regressions with study design and types of restoration as covariates, but the results showed no significant impact of these two covariates. Stainless steel crowns provide an effective means for restoration of a decayed primary teeth so they have been recommended as the restoration of choice for the long-term success of pulp therapy and retention of the treated tooth among the functional dentition. Several clinical trials and a systematic review by Attari and Roberts in 2006 also indicated that the success rate of stainless steel crowns for the restoration of badly broken down primary molars was superior to other restorative materials . Although our network meta-regression did not find a significant impact of restoration types, it should be noted that the statistical power of meta-regression for multiple treatment comparisons may be sufficiently high to detect the potential differences. The current systematic review presented several limitations. Firstly, most trials did not present their randomization methods and allocation concealing procedures, and blinding was unclear, although it is sometimes difficult to blind caregivers because of the diversity of material and device of treatment options. Secondly, success and failure rates in the network meta-analyses might be under-estimated because we regarded drop-outs and premature tooth loss as failure. Finally, trials with new and alternative medicaments and those with shorter (less than 9 months) follow-up periods were not included in the network meta-analyses. 5 Conclusion In conclusion, the results from network meta-analyses showed that after 9–12 months, MTA had significantly better clinical and radiographic outcomes than formocresol and calcium hydroxide, and calcium hydroxide had more failures than formocresol and ferric sulfate; after 18–24 months, formocresol, ferric sulfate, and MTA had significantly better clinical and radiographic outcomes than calcium hydroxide and laser therapies in primary molar pulpotomies. Conflicts of interest None declared. Acknowledgements This project was partly supported by a grant from the National Science Council in Taiwan (grant number: NSC 101-2314-B-002-197-MY2 ). The authors thanked Renee Tseng (Medical library of Taiwan Adventist Hospital) for her contribution to the literature search. Appendix A See Fig. A1 . Fig. A1 Funnel plots of clinical and radiographic outcomes for primary molar pulpotomy after 9–12 and 18–24 month follow-up. (1: FS vs. FC; 2: Ca(OH) 2 vs. FC; 3: MTA vs. FC; 4: Lasers vs. FC; 5: Ca(OH) 2 vs. FS; 6: MTA vs. FS; 7: Lasers vs. FS; 8: MTA vs. Ca(OH) 2 ; 9: Lasers vs. Ca(OH) 2 ). References 1. Fuks A.B.: Current concepts in vital primary pulp therapy. European Journal of Paediatric Dentistry 2002; 3: pp. 115-120. 2. Block R.M., Lewis R.D., Sheats J.B., Burke S.G.: Antibody formation to dog pulp tissue altered by formocresol uithin the root canal. Oral Surgery, Oral Medicine, Oral Pathology 1978; 45: pp. 282-292. 3. Fei A.L., Udin R.D., Johnson R.: A clinical study of ferric sulfate as a pulpotomy agent in primary teeth. Pediatric Dentistry 1991; 13: pp. 327-332. 4. Ibricevic H., Al-Jame Q.: Ferric sulphate and formocresol in pulpotomy of primary molars: long term follow-up study. European Journal of Paediatric Dentistry 2003; 4: pp. 28-32. 5. Alacam A.: Pulpal tissue changes following pulpotomies with formocresol, glutaraldehyde-calcium hydroxide, glutaraldehyde-zinc oxide eugenol pastes in primary teeth. Journal of Pedodontics 1989; 13: pp. 123-132. 6. Prakash C., Chandra S., Jaiswal J.N.: Formocresol and glutaraldehyde pulpotomies in primary teeth. Journal of Pedodontics 1989; 13: pp. 314-322. 7. Shumayrikh N.M., Adenubi J.O.: Clinical evaluation of glutaraldehyde with calcium hydroxide and glutaraldehyde with zinc oxide eugenol in pulpotomy of primary molars. Endodontics and Dental Traumatology 1999; 15: pp. 259-264. 8. Eidelman E., Holan G., Fuks A.B.: Mineral trioxide aggregate vs. formocresol in pulpotomized primary molars: a preliminary report. Pediatric Dentistry 2001; 23: pp. 15-18. 9. Aeinehchi M., Dadvand S., Fayazi S., Bayat-Movahed S.: Randomized controlled trial of mineral trioxide aggregate and formocresol for pulpotomy in primary molar teeth. International Endodontic Journal 2007; 40: pp. 261-267. 10. Ansari G., Ranjpour M.: Mineral trioxide aggregate and formocresol pulpotomy of primary teeth: a 2-year follow-up. International Endodontic Journal 2010; 43: pp. 413-418. 11. Doyle T.L., Casas M.J., Kenny D.J., Judd P.L.: Mineral trioxide aggregate produces superior outcomes in vital primary molar pulpotomy. Pediatric Dentistry 2010; 32: pp. 41-47. 12. Dean J.A., Mack R.B., Fulkerson B.T., Sanders B.J.: Comparison of electrosurgical and formocresol pulpotomy procedures in children. International Journal of Paediatric Dentistry 2002; 12: pp. 177-182. 13. Rivera N., Reyes E., Mazzaoui S., Moron A.: Pulpal therapy for primary teeth: formocresol vs electrosurgery: a clinical study. Journal of Dentistry for Children (Chicogo) 2003; 70: pp. 71-73. 14. Bahrololoomi Z., Moeintaghavi A., Emtiazi M., Hosseini G.: Clinical and radiographic comparison of primary molars after formocresol and electrosurgical pulpotomy: a randomized clinical trial. Indian Journal of Dental Research 2008; 19: pp. 219-223. 15. Zurn D., Seale N.S.: Light-cured calcium hydroxide vs formocresol in human primary molar pulpotomies: a randomized controlled trial. Pediatric Dentistry 2008; 30: pp. 34-41. 16. Alacam A., Odabas M.E., Tuzuner T., Sillelioglu H., Baygin O.: Clinical and radiographic outcomes of calcium hydroxide and formocresol pulpotomies performed by dental students. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics 2009; 108: pp. e127-e133. 17. Liu J.F.: Effects of Nd:YAG laser pulpotomy on human primary molars. Journal of Endodontics 2006; 32: pp. 404-407. 18. Odabas M.E., Bodur H., Baris E., Demir C.: Clinical, radiographic, and histopathologic evaluation of Nd:YAG laser pulpotomy on human primary teeth. Journal of Endodontics 2007; 33: pp. 415-421. 19. Golpayegani M.V., Ansari G., Tadayon N., Shams S., Mir M.: Low-level laser therapy for pulpotomy treatment of primary molars. Journal of Dentistry, Tehran University of Medical Sciences 2009; 6: pp. 168-174. 20. Peng L., Ye L., Tan H., Zhou X.: Evaluation of the formocresol versus mineral trioxide aggregate primary molar pulpotomy: a meta-analysis. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics 2006; 102: pp. e40-e44. 21. Peng L., Ye L., Guo X., Tan H., Zhou X., Wang C., et. al.: Evaluation of formocresol versus ferric sulphate primary molar pulpotomy: a systematic review and meta-analysis. International Endodontic Journal 2007; 40: pp. 751-757. 22. Simancas-Pallares M.A., Diaz-Caballero A.J., Luna-Ricardo L.M.: Mineral trioxide aggregate in primary teeth pulpotomy. A systematic literature review. Medicina Oral Patologia Oral y Cirugia Bucal 2010; 15: pp. e942-e946. 23. Nadin G., Goel B.R., Yeung C.A., Glenny A.M.: Pulp treatment for extensive decay in primary teeth. Cochrane Database of Systematic Reviews 2003; pp. CD003220. 24. Fuks A.B.: Vital pulp therapy with new materials for primary teeth: new directions and treatment perspectives. Pediatric Dentistry 2008; 30: pp. 211-219. 25. Tu Y.K., Woolston A., Faggion C.M.: Do bone grafts or barrier membranes provide additional treatment effects for infrabony lesions treated with enamel matrix derivatives? A network meta-analysis of randomized-controlled trials. Journal of Clinical Periodontology 2010; 37: pp. 59-79. 26. Tu Y.K., Needleman I., Chambrone L., Lu H.K., Faggion C.M.: A Bayesian network meta-analysis on comparisons of enamel matrix derivatives, guided tissue regeneration and their combination therapies. Journal of Clinical Periodontology 2012; 39: pp. 303-314. 27. Hoaglin D.C., Hawkins N., Jansen J.P., Scott D.A., Itzler R., Cappelleri J.C., et. al.: Conducting indirect-treatment-comparison and network-meta-analysis studies: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 2. Value in Health 2011; 14: pp. 429-437. 28. Jansen J.P., Fleurence R., Devine B., Itzler R., Barrett A., Hawkins N., et. al.: Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 1. Value in Health 2011; 14: pp. 417-428. 29. Lin P.Y., Cheng Y.W., Chu C.Y., Chien K.L., Lin C.P., Tu Y.K.: In-office treatment for dentin hypersensitivity: a systematic review and network meta-analysis. Journal of Clinical Periodontology 2013; 40: pp. 53-64. 30. Llewelyn D.R.: Faculty of dental surgery RCoS UK National Clinical Guidelines in Paediatric Dentistry. The pulp treatment of the primary dentition. International Journal of Paediatric Dentistry 2000; 10: pp. 248-252. 31. Ranly D.M., Garcia-Godoy F.: Current and potential pulp therapies for primary and young permanent teeth. Journal of Dentistry 2000; 28: pp. 153-161. 32. Loh A., O’Hoy P., Tran X., Charles R., Hughes A., Kubo K., et. al.: Evidence-based assessment: evaluation of the formocresol versus ferric sulfate primary molar pulpotomy. Pediatric Dentistry 2004; 26: pp. 401-409. 33. Srinivasan V., Patchett C.L., Waterhouse P.J.: Is there life after Buckley's Formocresol? Part I – a narrative review of alternative interventions and materials. International Journal of Paediatric Dentistry 2006; 16: pp. 117-127. 34. De Coster P., Rajasekharan S., Martens L.: Laser-assisted pulpotomy in primary teeth: a systematic review. International Journal of Paediatric Dentistry 2013; 23: pp. 389-399. 35. Lu G., Ades A.E.: Combination of direct and indirect evidence in mixed treatment comparisons. Statistics in Medicine 2004; 23: pp. 3105-3124. 36. Saltzman B., Sigal M., Clokie C., Rukavina J., Titley K., Kulkarni G.V.: Assessment of a novel alternative to conventional formocresol-zinc oxide eugenol pulpotomy for the treatment of pulpally involved human primary teeth: diode laser-mineral trioxide aggregate pulpotomy. International Journal of Paediatric Dentistry 2005; 15: pp. 437-447. 37. Vargas K.G., Packham B., Lowman D.: Preliminary evaluation of sodium hypochlorite for pulpotomies in primary molars. Pediatric Dentistry 2006; 28: pp. 511-517. 38. Malekafzali B., Shekarchi F., Asgary S.: Treatment outcomes of pulpotomy in primary molars using two endodontic biomaterials. A 2-year randomised clinical trial. European Journal of Paediatric Dentistry 2011; 12: pp. 189-193. 39. Odabas M.E., Cinar C., Tulunoglu O., Isik B.: A new haemostatic agent's effect on the success of calcium hydroxide pulpotomy in primary molars. Pediatric Dentistry 2011; 33: pp. 529-534. 40. Yaman E., Gorken F., Pinar Erdem A., Sepet E., Aytepe Z.: Effects of folk medicinal plant extract Ankaferd Blood Stopper(®) in vital primary molar pulpotomy. European Journal of Paediatric Dentistry 2012; 13: pp. 197-202. 41. Sabbarini J., Mohamed A., Wahba N., El-Meligy O., Dean J.: Comparison of enamel matrix derivative versus formocresol as pulpotomy agents in the primary dentition. Journal of Endodontics 2008; 34: pp. 284-287. 42. Waterhouse P.J., Nunn J.H., Whitworth J.M.: An investigation of the relative efficacy of Buckley's Formocresol and calcium hydroxide in primary molar vital pulp therapy. British Dental Journal 2000; 188: pp. 32-36. 43. Farsi N., Alamoudi N., Balto K., Mushayt A.: Success of mineral trioxide aggregate in pulpotomized primary molars. Journal of Clinical Pediatric Dentistry 2005; 29: pp. 307-311. 44. Huth K.C., Paschos E., Hajek-Al-Khatar N., Hollweck R., Crispin A., Hickel R., et. al.: Effectiveness of 4 pulpotomy techniques – randomized controlled trial. Journal of Dental Research 2005; 84: pp. 1144-1148. 45. Subramaniam P., Konde S., Mathew S., Sugnani S.: Mineral trioxide aggregate as pulp capping agent for primary teeth pulpotomy: 2 year follow up study. Journal of Clinical Pediatric Dentistry 2009; 33: pp. 311-314. 46. Sushynski J.M., Zealand C.M., Botero T.M., Boynton J.R., Majewski R.F., Shelburne C.E., et. al.: Comparison of gray mineral trioxide aggregate and diluted formocresol in pulpotomized primary molars: a 6- to 24-month observation. Pediatric Dentistry 2012; 34: pp. 120-128. 47. Ibricevic H., al-Jame Q.: Ferric sulfate as pulpotomy agent in primary teeth: twenty month clinical follow-up. Journal of Clinical Pediatric Dentistry 2000; 24: pp. 269-272. 48. Markovic D., Zivojinovic V., Vucetic M.: Evaluation of three pulpotomy medicaments in primary teeth. European Journal of Paediatric Dentistry 2005; 6: pp. 133-138. 49. Moretti A.B., Sakai V.T., Oliveira T.M., Fornetti A.P., Santos C.F., Machado M.A., et. al.: The effectiveness of mineral trioxide aggregate, calcium hydroxide and formocresol for pulpotomies in primary teeth. International Endodontic Journal 2008; 41: pp. 547-555. 50. Noorollahian H.: Comparison of mineral trioxide aggregate and formocresol as pulp medicaments for pulpotomies in primary molars. British Dental Journal 2008; 204: pp. E20. 51. Sonmez D., Sari S., Cetinbas T.: A comparison of four pulpotomy techniques in primary molars: a long-term follow-up. Journal of Endodontics 2008; 34: pp. 950-955. 52. Erdem A.P., Guven Y., Balli B., Ilhan B., Sepet E., Ulukapi I., et. al.: Success rates of mineral trioxide aggregate, ferric sulfate, and formocresol pulpotomies: a 24-month study. Pediatric Dentistry 2011; 33: pp. 165-170. 53. Tziafas D., Pantelidou O., Alvanou A., Belibasakis G., Papadimitriou S.: The dentinogenic effect of mineral trioxide aggregate (MTA) in short-term capping experiments. International Endodontic Journal 2002; 35: pp. 245-254. 54. Al-Zayer M.A., Straffon L.H., Feigal R.J., Welch K.B.: Indirect pulp treatment of primary posterior teeth: a retrospective study. Pediatric Dentistry 2003; 25: pp. 29-36. 55. Sonmez D., Duruturk L.: Success rate of calcium hydroxide pulpotomy in primary molars restored with amalgam and stainless steel crowns. British Dental Journal 2010; 208: pp. E18. [discussion 408–9] 56. Attari N., Roberts J.F.: Restoration of primary teeth with crowns: a systematic review of the literature. European Archives of Paediatric Dentistry 2006; 7: pp. 58-62. [discussion 63] 57. Agamy H.A., Bakry N.S., Mounir M.M., Avery D.R.: Comparison of mineral trioxide aggregate and formocresol as pulp-capping agents in pulpotomized primary teeth. Pediatric Dentistry 2004; 26: pp. 302-309. 58. Kalaskar R.R., Damle S.G.: Comparative evaluation of lyophilized freeze dried platelet derived preparation with calcium hydroxide as pulpotomy agents in primary molars. Journal of the Indian Society of Pedodontics and Preventive Dentistry 2004; 22: pp. 24-29. 59. Hu L.Y., Qian H.: Clinical efficiency of ferric sulphate as a pulpotomy agent in primary molars. Journal of Oral Biology and Craniofacial Research 2005; 21: pp. 445-446. 60. Huth K.C., Hajek-Al-Khatar N., Wolf P., Ilie N., Hickel R., Paschos E.: Long-term effectiveness of four pulpotomy techniques: 3-year randomised controlled trial. Clinical Oral Investigations 2012; 16: pp. 1243-1250. 61. Naik S., Hegde A.H.: Mineral trioxide aggregate as a pulpotomy agent in primary molars: an in vivo study. Journal of the Indian Society of Pedodontics and Preventive Dentistry 2005; 23: pp. 13-16. 62. Srinivasan D., Jayanthi M.: Comparative evaluation of formocresol and mineral trioxide aggregate as pulpotomy agents in deciduous teeth. Indian Journal of Dental Research 2011; 22: pp. 385-390. 63. Odabas M.E., Alacam A., Sillelioglu H., Deveci C.: Clinical and radiographic success rates of mineral trioxide aggregate and ferric sulphate pulpotomies performed by dental students. European Journal of Paediatric Dentistry 2012; 13: pp. 118-122.

Related Articles

Leave A Comment?

You must be logged in to post a comment.