Photobiomodulation in Pediatric Dentistry: A Current State-of-the-Art

Abstract

Objective:

Given the tremendous progress in biophotonics applications in biology and engineering, we sought to examine the evidence for the use of low-dose biophotonics treatments, termed photobiomodulation (PBM) therapy, in pediatric dentistry.

Background:

PBM therapy has been noted to alleviate pain and inflammation while promoting tissue healing and regeneration. These basic processes contribute to the fundamental etiopathogenesis of various oral diseases, and hence, there is now a growing list of potential clinical applications with PBM therapy in children.

Materials and methods:

An exhaustive literature search was conducted for PBM studies in pediatric dentistry that includes patients up to 21 years of age. An analysis of the quality of the included studies was also performed to evaluate the rigor of the evidence. Specific emphasis was placed on the treatment efficacy on the relevant specified outcomes for individual applications.

Results:

From a total of over 420 initial hits, 19 studies were deemed suitable for inclusion in this review. Among them, PBM therapy has been used in pediatric dentistry for prevention and treatment of oral mucositis associated with oncotherapy (chemotherapy, radiation, and transplants), for postsurgical oral pain and for pulpotomies. Overall, all studies reported therapeutic benefits, and no adverse effects were reported.

Conclusions:

This review noted that PBM therapy is a safe and effective treatment modality for various clinical applications in pediatric dentistry. Despite potential positive publication bias, there appears to be clear evidence of clinical benefit with this treatment, and we recommend well-designed randomized, placebo-controlled human clinical trial be pursued.

Introduction

Photobiomodulation (PBM) is the term, today universally accepted, to define a wide range of low-parameter laser applications, in the visible and infrared range of the electromagnetic spectrum that is capable of alleviating pain and inflammation while promoting wound healing and tissue regeneration. The term “PBM” was formally adopted by the field that was considered most suitable to replace a plethora of older terms such as “Low-Level Light/Laser Therapy” (LLLT), “Biostimulation,” “Photostimulation,” “soft laser,” and “cold laser” among many others that have been used since the 1970s.^1
–3 Endre Mester, a Hungarian physician, performed the very first animal studies of PBM therapy in 1960s. He was examining the possible carcinogenic effects of the coherent light (ruby laser, wavelength of 694.3 nm) in animal models. Contrary to their expectations, they were surprised to find that laser treatments at very low-energy densities (1 J/cm²) were capable of promoting phagocytosis of bacteria by leukocytes, improve hemoglobin synthesis, and stimulating wound healing and tissue repair, especially in healing of ulcerative lesions unresponsive to conventional therapies.^4,5

The broad clinical impact of PBM therapy extends to its ability to stimulate healing in both soft tissues such as mucosa and skin as well as mineralized tissues such as bone and teeth. A better understanding of the biological responses to PBM therapy has outlined three discrete cellular mechanisms involving the cytochrome c oxidase in the mitochondria, light-sensitive receptors on the cell membrane, and an extracellular latent growth factor complex, TGF-β1.⁶ These discrete mechanisms have been down to modulate the specific PBM therapeutic benefits on pain, inflammation, and wound healing. These effects, together with the noninvasive nature of the treatment, absence of any known side effects or adverse events, and relatively fast learning curve for the operator are some of the reasons PBM is gaining tremendous popularity.

The term “Pediatric dentistry,” once called “Pedodontics,” is the branch of dentistry dealing with children from birth through adolescence. The Forsyth Dental Infirmary for Children opened in Boston in 1914 to provide dental treatment for children and is considered the first institution of its kind in the world that is uniquely dedicated to clinical dental care for children.⁷ A major limitation with these groups of patients treated is related to the anxiety and fear of dentistry, especially with special needs.⁸ Hence, novel noninvasive technologies can alleviate pain and anxiety and facilitate improved relationship between dentist and the patient along with reinforcing an overall positive attitude toward oral health.^9,10 The aim of this work was to critically analyze the peer-reviewed literature describing the use of PBM treatments in pediatric dentistry and outline the evidence and clinical treatment parameters.

Materials and Methods

Search strategy

The review strategy followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). To access relevant articles, an electronic search in Medline (PubMed), Google Scholar, Science Direct, and Cochrane Controlled Register of Trials (Central) were performed. English language published articles were looked for using the following keywords: “Laser PBM” [MeSH]) OR Low Level Laser Therapy [MeSH] OR “Laser Biomodulation” [MeSH] OR “Photobiomodulation” [MeSH] AND “Pediatric Dentistry” [MeSH]). The search performed using the “age” filter to limit the publications involving subjects up to 21 years as per the determination of pediatric age published by the American Academy of Pediatrics.¹¹

A second search was performed, with the same kind of filter, for every topic found in the first search: “pulpotomy,” “oral mucositis,” “postoperative oral pain,” “oral herpetic lesion,” and “oral aphthous lesion.” Two reviewers (E.M. and C.F.) have contributed to the search and evaluated the article database and checked the reference list of relevant articles and previous reviews on the subject: initial article selection was done examining titles and abstracts of all selected articles. The full texts of potentially suitable articles were obtained for final assessment according to the exclusion and inclusion criteria. The following data were extracted from the studies: study design, sample size, mean age or ages range, laser characteristics (wavelength, frequency, energy density, power, power density, time of application, and number of sessions), evaluation criteria, and success rate. Mean values, standard deviations, and sample size were also extracted from the articles where they were reported. Where fluences and power densities were not reported, the authors (E.M. and C.F.) calculated them on the basis of other reported parameters. In addition, a manual search of the table of contents from 2000 to current issues of all major dental laser journals, including Lasers in Medical Science; Photodiagnosis and Photodynamic Therapy; Photobiomodulation, Photomedicine, and Laser Surgery; Laser in Surgery and Medicine, and Photochemistry and Photobiology B. The references in all final articles identified for the review were also cross-examined for relevance.

Inclusion criteria

All the original in vivo studies applying PBM or low-level laser on patients younger than 21 years of age were included in this study. All animal studies and in vitro studies were excluded, as well as case reports, guideline articles, and reviews. The inclusion criteria were as follows: (1) human clinical studies utilizing PBM treatments with/without a control or placebo treatment group; (2) participants with age ≤21 years; (3) studies where outcomes were clearly described, for example, intensity and duration of pain using the visual analog scale (VAS), Numeric Rating Scale, or other types of questionnaires; and (4) studies published in English. Following further discussions among reviewers on the initial search results, all relevant clinical studies even without controls or placebo were included in this review due to the very limited number of publications available.

Exclusion criteria

The exclusion criteria were as follows: (1) studies in vitro or in animals; (2) studies that used high-power lasers; and (3) literature reviews, case reports, letter to editors, unpublished theses, or abstracts of meeting presentations.

Data summary, quality, and meta-analyses

Any discrepancies were resolved by discussion or consultation with a third reviewer (J.P.R. and P.A.). Methodological quality of included studies was realized on the basis of Cochrane's collaboration tool analyzing selection bias (adequate random sequence generation and allocation concealment), performance bias (adequate participant and personnel blinding), attrition bias (acceptable and described dropout rate), reporting bias (no selective outcome reporting), and detection bias (adequate outcome assessor blinding).¹²

Meta-analysis was performed with Review Manager Software (5.0.16 Version). Results, as for example pain intensity, reported as continuous data with standard mean difference were calculated and pooled using the weighted mean difference and 95% confidence interval (CI), for dichotomous data, as for example incidence of oral mucositis (OM), data were synthesized using odds ratio as the effect measure with its 95% CI.

Results

Study selection

The PubMed Search Provided 294 hits, Google Scholar search 402 hits, Cochrane Search 41 hits, and Science Direct 84 hits. Following the initial screening of titles and abstracts and final screening of full texts, 19 articles completely fulfilled the inclusion criteria of this study (Fig. 1). All original data are summarized to enable optimal illustration of key data (Tables 1 –4). Furthermore, all laser parameters, particularly Fluence and Irradiance (Fig. 2), were summarized (Tables 5 –7) and methodological quality of all included studies described (Fig. 3 or Tables 8).¹¹

FIG. 1.

Screening of titles and abstracts and final screening of full texts to obtain the 19 articles completely fulfilling the inclusion criteria.

FIG. 2.

Laser parameters, particularly fluence, and irradiance.

FIG. 3.

Methodological analysis of all included studies described.

Table 1.

Baseline Characteristics of Included Studies on Prevention of Oral Mucositis

References	Study design	Patients number (M/F) N°ctrl/N°laser	Mean age ± SD/age range (years)	Population	Outcome/s	Effectiveness	Authors comments and conclusions	Results control	Results laser
Cruz et al.¹⁷	RCT	60 (39M–21F) 31/29	8.7 ± 4.3	Children receiving conditioning for HSCT, ICE or Irinotecan or other kind of CTher	Grade of OM	No	This study showed no evidence of benefit from the prophylactic use of LEL in children and adolescents with cancer treated with CT when optimal dental and oral care was provided	1st day 100% patients without OM 8th day 75% without OM 17.9% Grade I OM 3.55% Grade II OM 3.55% Grade III OM 0% Grade IV OM 15th day 64.5% without OM 22.6% Grade I OM 3.2% Grade II OM 9.7% Grade III OM 0% Grade IV OM	1st day 100% patients without OM 8th day 53.6% without OM 21.7% Grade I OM 17.9% Grade II OM 7.15% Grade III OM 0% Grade IV OM 15th day 53.6% without OM 25% Grade I OM 14.25% Grade II OM 7.15% Grade III OM 0% Grade IV OM
De Oliveira et al.¹⁵	CT	222 CT cycles—121/101	Up to 17	Pediatric patients with acute leukemia	Development and grade of OM	Yes/no	The use of LLL at the beginning of each chemotherapy cycle did not reduce the risk of occurrence of OM but did reduce the severity of the condition.	41.3% of patients with OM, 78% grade I–II OM^* 22% grade III–IV OM^*	42.6% of patients with OM, 93% grade I–II OM^* 7% grade III–IV OM^*
De Castro et al.¹⁶	CT	40 (27M/13F) 20/20	6.83/1–18	Pediatric patients with acute lymphoblastic leukemia treated with high doses of methotrexate	Development and grade of OM	Yes	LLLT effective in the prevention of OM No difference between 660 and 830 nm.	75% of patients with OM, 20% of these patients with grade IV OM	40% of patients with OM, 62.5% on 830 nm laser group, 37.5% on 660 nm laser group. No grade IV OM.
Abramoff et al.¹⁴	Prospective RCT (vs. placebo)	14Total: 22 CT cycles 7/7	14.6/7–23	Young patients undergoing CT for osteosarcoma treatment or high-risk acute lymphoid leukemia	Grade of OM	Yes	At the 3rd evaluation 73% of patients without OM in laser group vs. 27% of patients without OM in placebo group… This demonstrates that LLLT has a preventive role.	1st evaluation 73% of patients without OM 27% Grade I OM 3rd evaluation ^* 27% of patients without OM 45% Grade I OM 18% Grade II OM 9% Grade III OM	1st evaluation 100% of patients without OM 3rd evaluation ^* 73% of patients without OM 18% Grade I OM 9% Grade II OM
Soto et al.¹³	CT (retrospective CTRL group)	24 (17M/7F) 12/12	8.28/2.1–16.3	Children undergoing HSCT	Grade of OM—FMS	Yes	In conclusion, this study indicates that a combined protocol of intra and extraoral application of LLLT can reduce the severity of OM in pediatric patients undergoing HSCT.	OM Grade^* 0% without OM 8.33% Grade I OM 50% Grade II OM 33.33% Grade III OM 8.33% Grade IV OM FMS Grade 0% Grade 0 FMS 33.33% Grade I FMS 16.67% Grade II FMS 50% Grade III FMS 0% Grade IV FMS	OM Grade^* 25% without OM 33.33% Grade I OM 33.33% Grade II OM 8.33% Grade III OM 0% Grade IV OM FMS Grade 0% Grade 0 FMS 58.33% Grade I FMS 25% Grade II FMS 16.67% Grade III FMS 0% Grade IV FMS

p Lower than 0.05 for comparison laser versus control.

CT, controlled trial; CTher, chemotherapy; d, days; FMS, functional Mucositis Score; HCT, hematopoietic cells transplantation; HSCT, hematopoietic stem cells transplant; LEL, low-energy laser; LLLT, low-level laser therapy; M, male; OM, oral mucositis; RCT, randomized controlled trial; SD, standard deviation; W, woman.

Table 2.

Baseline Characteristics of Included Studies on Treatment of Oral Mucositis

Refs.	Study design	Patients number (M/F) N°ctrl/N°laser	Mean age ± SD/age range (years)	Population	Outcome	Effectiveness	Authors comments and conclusions	Results control	Results laser
Gobbo et al.¹⁸	Multicentric RCT	101 (54M/47F) 50/51	11.8/7–15	Children receiving CTher in the last 3 weeks, at least grade 3 OM	Grade OM, pain, analgesic use, side effects	Yes	At present, our study confirms that PBM is safe, feasible and effective and should be introduced as the standard therapy for pediatric patients affected by OM.	% of OM Grade 3–4 4th day: 62% ^* 7th day: 28% ^* 11th day: 20%^* Median pain score 4th day: 5^* 7th day: 2.5^* 11th day: 1^*	% of OM Grade 3–4 4th day: 45%^* 7th day: 6%^* 11th day: 2%^* Median pain score 4th day: 4^* 7th day: 1^* 11th day: 0^*
Vitale et al.¹⁹	RCT single blind	16	3–18	Oncohematological pediatric patients receiving CTher or HSCT, affected by at least grade 3 OM	Grade OM and pain	Yes	According to our results it could be concluded that HPLT seems safe and noninvasive treatment to limit the need of hospitalization and parenteral nutrition in patients undergoing HSCT and CT improving children's quality of life.	Median OM grade 3rd day: 3.38 7th day: 2.38 11th day: 1.88 Median pain on VAS 3rd day: 5 7th day: 1.5 11th day: 2.25	Median OM grade 3rd day: 2.75 7th day: 1.5 11th day: 0.38 Median pain on VAS 3rd day: 4.75 7th day: 2.75 11th day: 1.25
Amadori et al.²⁰	RCT vs. placebo	123, —, 61/62	3–18	Children and adolescents receiving CTher for hematological malignancies, solid tumors or HSCT who developed grade 2 OM or greater.	Grade of OM and pain	Yes	This study demonstrated the efficacy of LLLT in reducing pain due to chemotherapy-induced OM	Median OM Grade T0 (1st day): 3 T1 (4th day): 2 T2 (7th day): 1 Median pain on VAS T0 (1st day): 4 T1 (4th day): 2^* T2 (7th day): 1^*	Median OM Grade T0 (1st day): 3 T1 (4th day): 2 T2 (7th day): 0 Median pain on VAS T0 (1st day): 4 T1 (4th day): 1^* T2 (7th day): 0^*
Chermetz et al.²¹	Prospective, one arm, single blind	18 (12M/6F)	13/10–17	Children receiving CTher or HSCT, at least grade 2 OM	Grade of OM and pain	Yes	Given Class IV laser therapy appears to be safe, noninvasive and potentially effective, prospective, randomized, controlled trials are necessary to further assess efficacy and to determine optimal treatments parameters	—	Pain on VAS Baseline VAS (5 for 61% of patients VAS (mean) 1st day: 5 4th day: 2 11th day: 0 Difficulty in swallowing 4th day: 60% 11th day: 20%
de Castro et al.¹⁶	Not RCT	15—	1–18	Pediatric patients with acute lymphoblastic leukemia	Grade of OM	Yes	LLLT effective in the treatment of OM.	—	—
Cauwels and Martens²²	One arm study	16 (8M/8F) 16	9.4	Children with OM induced by CTher for leukemia, lymphoma, neuroblastoma, osteosarcoma, Ewing's sarcoma or germ cell tumor	Grade of OM. Pain on VAS	Yes	The three main effects applicable to LLLT are: (1) an immediate analgesic effect, (2) an anti-inflammatory impact and (3) a faster wound healing. Based on these properties (…) it can be concluded that in the present study these objectives were obtained with the GaAlAs 830 nm diode laser. Depending on the severity of OM, a mean of 2.5 visits per episode could be realized.	—	At the next visit the new initial pain score corresponded to the final (lowest) score from the visit of 2 days before. At each subsequent visit, a clear progress in healing was observed. Some children needed only one laser therapy session, while others needed 6.
Kuhn et al.²³	RCT vs. placebo	21 (17M–4F) 12/9	8.2 ± 3.1	Children and adolescents receiving CTher or HSCT for leukemia, lymphoma or solid tumors who developed grade 2 OM or greater.	Grade and duration of OM	Yes	Our results confirmed the promising results observed in adult cancer patients and should encourage pediatric oncologists to use laser therapy as first line option for children with CTher-induced OM	Duration of OM 8.9 ± 2.4 d^* Day 7 OM (2: 9/12 (75%)^*	Duration of OM 5.8 ± 2 d^* Day 7 OM( 2: 1/9 (11%)^*
Abramoff et al.¹⁴	Not RCT	6 (10 cycles CTher) (5M/8F)	14.6/7–23	Young patients under CTher	Grade of OM—pain	Yes	The ease use of LLLT, high patient acceptance, and the positive results achieved, make this therapy feasible for the (prevention and) treatment of OM in young patients.	—	% 1st visit vs. 3rd visit Grade 0 OM 0% vs. 40% Grade I OM 30% vs. 20% Grade II OM 60% vs. 40% Grade III OM 10% vs. 0% Grade IV OM 0% vs. 0%

p Lower than 0.05 for comparison laser versus control.

CTher, chemotherapy; HSCT, hematopoietic stem cells transplant; RCT, randomized controlled trial; VAS, visual analog scale.

Table 3.

Baseline Characteristics of Included Studies on Postoperative Pain

Reference	Study design	Patients number (M/F) N°ctrl/N°laser	Mean age SD/age range (years)	Population	Type of control	Results control (mean ± SD)	Results laser (mean ± SD)	Authors comments and conclusions
Elbay et al.²⁵	Double blind RCT	37 (M24/F13) 98 extractions (49/49)	8.08 ± 2.046	Children undergoing primary molar extraction.	Internal	1st day VAS 2.05 ± 2.027, PRS 2.00 ± 2.00 2nd day VAS 0.59 ± 1.404, PRS 0.38 ± 1.139 3rd day VAS 0.16 ± 0.727, PRS 0.11 ± 0.458	1st day VAS 1.68 ± 1.973, PRS 1.62 ± 1.991 2nd day VAS 0.49 ± 0.0989, PRS 0.49 ± 1.096 3rd day VAS 0.22 ± 0.787, PRS 0.22 ± 0.787	In the present study, although LLLT was, in general, found to be ineffective in reducing postoperative pain following primary tooth extraction, LLLT may still prove beneficial for some individuals.
Paschoal and Santos-Pinto et al.²⁴	Double blind RCT	14 (M6/F8) 40 extractions (20/20)	15 ± 1.51	Adolescents undergoing premolar extraction	Internal	No statistically difference in analgesic effect between the groups for any evaluated periods. Wound healing scores (%Score 1 vs. %Score 2) 1st day 93% vs. 7% 2nd day 10% vs. 90% 7th day 45% vs. 55% 15th day 35% vs. 65%	No statistically difference in analgesic effect between the groups for any evaluated periods. Wound healing scores (%Score 1 vs. %Score 2) 1st day 89% vs. 11% 2nd day 5.5% vs. 95.5% 7th day 45% vs. 55% 15th day 45% vs. 55%	These findings show that the application of intraoral LLLT with an 830 nm diode laser with the specific parameters used in this study does not reduce pain or accelerate the wound healing process after surgical removal of premolars in adolescents.
Ezzat et al.²⁶	Double blind RCT	20 (M12/F8) 10/10	5.8 ± 1.8	Children undergoing secondary palatal operations.	External	1st day VAS 6.2 ± 0.447^, edema 4 ± 0^, analgesic dose 6 ± 0 2nd day VAS 5.2 ± 0.447^, edema 4 ± 0^, Analgesic dose 5.6 ± 0.894^* 3rd day VAS 3.8 ± 0.447^, edema 4 ± 0^, analgesic dose 3.8 ± 0.447^* 4th day VAS 3 ± 0^, edema 3 ± 0^, analgesic dose 2.8 ± 0.447 5th day VAS 3.0 ± 0^, edema 2.4 ± 0.548^ - analgesic dose 1.6 ± 0.548 6th day VAS 1.8 ± 0.447^, edema 1.4 ± 0.548^, analgesic dose 0.8 ± 0.447 7th day VAS 0.25 ± 0.500, edema 0.8 ± 0.447^*, analgesic dose 0.4 ± 0.548	1st day VAS 4.6 ± 0.548^, edema 3.4 ± 0.548^, analgesic dose 6 ± 0 2nd day VAS 3.8 ± 0.447^, edema 2.2 ± 0.447^, analgesic dose 4 ± 0^* 3rd day VAS 3.0 ± 0.000^, edema 2.2 ± 0.447^, analgesic dose 3 ± 0^* 4th day VAS 1.8 ± 0.447^, edema 1.2 ± 0.447^, analgesic dose 2.2 ± 0.447 5th day VAS 2.4 ± 0.548^, edema 0.2 ± 0.447^, analgesic dose 1.4 ± 0.548 6th day VAS 1.00 ± 0.0^, edema 0.00 ± 0.0^, analgesic dose 0.4 ± 0.548 7th day VAS 0.2 ± 0.447, edema 0 ± 0.0^*, analgesic dose 0 ± 0	Preliminary results showed that LLLT is effective in the reduction of postoperative pain and edema with minimizing the need of analgesic medication after secondary palatal operations.
Çakir-Özkan et al.²⁷	RCT	9 (M6/F3) 4/5	14.8 (13–16)	Patients subjected to mandibular midline distraction	External	12 weeks Bone density (HU) 320 ± 250^*	12 weeks Bone density (HU) 479 ± 179^*	It can be concluded that the retention period can be shortened and stability maybe increased by using LLLT in the mandibular midline.

p Lower than 0.05 for comparison laser versus control.

Table 4.

Baseline Characteristics of Included Studies on Pulpotomy

Refs.	Study design	Patients number (M/F) N°ctrl/N°laser	Mean age ± SD/age range (years)	Population	Effectiveness	Results control	Results laser	Authors' comments and conclusions
Kuo et al.³¹	Retrospective	74 patients (46M/28W), 145 teeth	4.46 (2.15–6.48)	145 teeth (100 first and 45 se molars or 63 maxillary and 82 mandibular molars) from 74 children	Yes/no	% Clinical success 6 months No medication 100% Sodium hypochlorite 98.8% 12 months No medication 100% Sodium hypochlorite 96.2% 18 months No medication 100% Sodium hypochlorite 94.4%^* 24 months No medication 100% Sodium hypochlorite 88.9%^* %Rx success 6 months No medication 100% Sodium hypochlorite 98.8% 12 months No medication 92.6% Sodium hypochlorite 85.7%^* 18 months No medication 92.6% Sodium hypochlorite 82.2%^* 24 months No medication 87.5% Sodium hypochlorite 65.7%^*	% Clinical success Diode laser 6 months 100% 12 months 100% 18 months 100% 24 months 100%^* %Rx success 6 months 100% 12 months 97.6%^* 18 months 97.4%^* 24 months 90.9%^*	No significant differences in clinical and radiographic success rates were found among primary molars treated by pulpotomy using diode laser, sodium hypochlorite or no medication….
Ansari et al.³⁰	RCT	40 patients, 160 teeth	3–9 years	160 first and second molars including 41 (25.6%) upper first molars, 55 (34.4%) lower first molars, 25 (15.6%) upper second molars and 39 (24.4%) lower second molars.	Yes/No	% clinical success 6 months Phormocresol 100% Ferric sulfate 97.5% CEM 100% 12 months Phormocresol 100% Ferric sulfate 95% CEM 97.5% %Rx success 6 months Phormocresol 100% Ferric sulfate 97.5% CEM 100% 12 months Phormocresol 100% ferric sulfate 92.5% CEM 95%	CEM + LLLT % clinical success 6 months 100% 12 months 100% % Rx success 6 months 100% 12 months 100%	Comparing the 4 pulpotomy techniques in treatment of primary teeth it did not show any significant difference
Uloopi et al.²⁸	RCT	29 subjects, 40 mandibular teeth	Mean age 5.6 years—4–7 years	40 primary molars with vital carious pulp exposures that bleed upon entering the pulp chambers, or without clinical signs and symptoms of pulp degeneration such as swelling, pathologic mobility, excessive bleeding from amputated radicular stumps and tenderness on percussion.	Yes/No	MTA % success 3 months 94.7% 6 months 94.7% 12 months 94.7%	LLLT % success 3 months 95% 6 months 85% 12 months 80%	Findings of the present study confirmed that LLLT can be used successfully as a complementary step to pulpotomy procedure
Fernandes et al.²⁹	Single blind RCT	60 teeth (15 × 4)	Mean age 6.5 5–9	Mandibular primary molar first or second teeth compromised by deep caries cavities with vital pulp; absence of history of spontaneous pain; no clinical or radiographic evidence of fistula or abscess, absence of internal and external root resorption, interradicular and/or furcal bone destruction; and the possibility of proper restoration of the teeth.	Yes	6 months % Rx success FC 100% − CH 60% 12 months % Rx success FC 100% − CH 50% 18 months % Rx success FC 100% − CH 66.7%	6 months % Rx success LLLT 80% LLLT + CH 85.7% 12 months % Rx success LLLT 80% LLLT + CH 78.6% 18 months % Rx success LLLT 73.3% LLLT + CH 75%	These findings suggest that LLLT may be considered as an adjuvant alternative for vital pulp therapy on human primary teeth. LLLT preceding the use of calcium hydroxide showed satisfactory results.

CH, calcium hydroxide; FC, diluted formocresol; CH preceded by LLLT (LLLT + CH), calcium-enriched mixture cement CEM; MTA, mineral trioxide aggregate.

p Lower than 0.05 for comparison laser versus control.

Table 5.

Laser Parameters of Included Studies on Prevention and Treatment of Oral Mucositis

Refs.	Laser type/wavelength	Power density (W/cm²)	Fluence (J/cm²)	Time of application (sec)	Other information/parameters	Intraoral application/extraoral application
Soto et al.¹³	InGaAIP/685 nm GaAlAs/830 nm	12.38 W/cm² per intraoral point 28.30 W/cm² per extraoral point	2353 J/cm² intraoral 5085 J/cm² extraoral (total dose)	10 per intraoral point 30 per extraoral point	19 intraoral points and 6 extraoral points—CW 685 nm for intraoral application 830 nm for extraoral application	Intraoral/extraoral
de Oliveira et al.¹⁵	GaAlAs/660 nm	—	4 J/cm²	10 per intraoral point	Laser application every 24 h from day 1 to day 3 of CT Not specified laser mode (CW or PW)	Intraoral
de Castro et al.¹⁶ (prevention)	660 + 830 nm	3.75 W/cm²	35 J/cm²	10	Laser application every 24 h from day 1 to day 5 of CT 19 intraoral points of applications Not specified laser mode (CW or PW)	Intraoral
Abramoff et al.¹⁴	AsGaAl/685 nm	12.38 W/cm²	72 J/cm²	54	Within the 24 h from the beginning of CT 3 times—CW 19 intraoral points of applications	Intraoral (extraoral for labial commissures)
Cruz et al.¹⁷	780 nm	—	4 J/cm²		60 mW, 5 sites—CW5 Consecutive days from the beginning of CT	Intraoral
Gobbo et al.¹⁸	GaAlAs/970 nm +660 nm	0.32 W/cm²	36.8 J/cm²	2 sessions of 3 min 45 sec, once/day for 4 consecutive days	All the sites with or without mucositis—PW	Intraoral
Vitale et al.¹⁹	GaAlAs/970 nm	4.076 W/cm²	—	230 sec, once/day, 4 consecutive days	All over the intraoral cavity—PW	Intraoral
Amadori et al.²⁰	830 nm	0.15 W/cm²	4.5 J/cm²	30	On mucositis lesions, 3 consecutive days starting from the observation of OM (4 sessions)—CW	Intraoral
Chermetz et al.²¹	GaAlAs/970 nm	5 W/cm²	—	230	All the sites with or without mucositis, twice/day—PW	Intraoral
de Castro et al.¹⁶ (treatment)	660 + 830 nm	—	70 J/cm²	20	Laser treatment every 24 h from the diagnosis to remission—not specified laser mode (CW or PW)	Intraoral
Cauwels and ²²	GaAlAs/830 nm	—	Grade 1 OM:2J/cm² Grade 2 OM: 4J/cm² Grade 3 OM: 8 J/cm² Grade 4 om: 16 J/cm²	—	Laser treatment every 48 h until healing —CW	Intraoral
Khun et al.²³	GaAlAs/830 nm	—	4 J/cm²	—	100 mW power—On mucositis lesions—5 consecutive days starting from the observation of OM—CW	Intraoral
Abramoff et al.¹⁴ (treatment)	AsGaAl/685 nm	12.38 W/cm²	72 J/cm²	54	10 sites—within the 24 h from the beginning of CT, 3 times. For therapeutic group since the beginning of OM, 3 sessions or until healing—CW	Intraoral (extraoral for labial commissures)

CT, chemotherapy; CW, continuous wave; PW, pulsed-wave.

Table 6.

Laser Parameters of Included Studies on Postoperative Pain

Refs.	Laser type/wavelength	Power density and parameters	Fluence (J/cm²)	Time of application (sec)	Other information	Intraoral application extraoral application
Elbay et al.²⁵	GaAlAs/810 nm	Spot size 400 micrometer—non contact mode, 0.3 W—power density (theoretical) 238 W/cm²	4 J/cm²	60	3 points of application after bilateral extraction of primary molarsCW	Intraoral 1 cm from area
Benini Paschoal and Santos-Pinto²⁴	GaAlAs/830 nm	spot size 1 mm, >—power density 12.74 W/cm² Fluence 649 J/cm² and not 60 J/cm² as reported	1.71 J/cm² per point —5.1 J/cm² total	17	17 sec for 3 points of application after at least bilateral extraction of premolarsCW	Intraoral1 cm from area
Ezzat et al.²⁶	GaAlAs/970 nm	Spot size 320 μm, CW, non contact mode 2 W—power density (theoretical) 2488 W/cm²	35 J/cm²	60	60 sec × 3 times—1 session immediately after surgeryCW	Intraoral
Çakir-Özkan et al.²⁷	GaAlAs/830 nm	40 mW, 2 points	8.4 J/cm²	—	24 h after surgery and then every 48 h—Total 8 treatmentsNot specified laser mode (CW or PW)	Intraoral

Table 7.

Laser Parameters of Included Studies on Pulpotomy

Refs.	Laser type	Wavelength (nm)	Power density and parameters	Fluence (J/cm²)	Time of application (sec)	Other informations	Intraoral application extraoral application
Kuo et al.³¹	—	970 nm	Output power 3 W, duty cycle 50%—5 Hz optical fiber tip under water cooling	—	—	Laser vs. 6% NaOCl vs. Compression without medication	Intraoral
Ansari et al.³⁰	—	632 nm	CW	4	135	CEM vs. CEM + LLLT vs. ferric sulfate vs. formocresol	Intraoral
Uloopi et al.²⁸	—	810 nm	CW	2	10	MTA vs. LLLT	Intraoral
Fernandes et al.²⁹	InGaAIP	660 nm	Fiber 320 μm, contact way 10 mW, area 0.04 cm² power density 0.25 W/cm² PW	2.5	10	1 treatment: formocresol vs. calcium hydroxide vs. LLLT vs. calcium hydroxide + LLLT	Intraoral

Table 8.

Methodological Quality of Included Studies on Prevention and Treatment of Oral Mucositis on the Basis of Cochrane's Collaboration Tool Analyzing Selection Bias of Included Studies

Refs.	Random sequence generation	Allocation concealment	Blinding of participants and personnel	Blinding of outcome assessment	Incomplete outcome data	Selective outcome reporting
Soto et al.¹³	Retrospective control group	No	No	No	Yes	Yes
de Oliveira et al.¹⁵	Patients were randomly allocated…Unclear	Unclear	No	Unclear	Yes	Yes
de Castro et al.¹⁶ (prevention)	On the order in which they were hospitalizedNo	No	No	Unclear	Yes	Yes
Abramoff et al.¹⁴	Unclear	Unclear	Unclear	Unclear	Yes	Yes
Cruz et al.¹⁷	Patients were randomized according to group allocation—unclear	Unclear	No	Unclear	Yes	Yes
Gobbo et al.¹⁸	Yes	Yes	No	Yes	Yes	Yes
Vitale et al.¹⁹	Yes	Yes	No (only patients blind)	Yes	Unclear	Yes
Amadori et al.²⁰	Yes	Yes	No (only patients blind)	Yes	Yes	Yes
Chermetz et al.²¹	Not RCT	No	No	No	No	No
de Castro et al.¹⁶ (treatment)	No	No	No	Unclear	Yes	Yes
Cauwels and Martens et al.²²	Not RCT	No	No	No	No	No
Khun et al.²³	Yes	Yes	No (only patients blind)	Yes	Yes	Yes
Abramoff et al.¹⁴ (treatment)	No	No	Unclear	Unclear	Yes	Yes

Quality of the included studies

The most frequently unsatisfactory methodological criteria were the blinding of participants and personnel: the 85.7% of the included studies were at high risk and the remaining 14.3% were unclear, while the blinding of the evaluation was at high risk for the 19% and unclear for the 43% (Fig. 3). Among the selection bias, random sequence allocation was at high risk in the 38% and unclear in the 28.5%, while allocation concealment was at high risk in 47.6% and unclear in 28.5%. Blinding outcome assessment was unclear in the most part of the studies (42.85%). Among attrition bias, incomplete data outcome was at low risk for the most part of included studies (85.7%), and among reporting bias, selective outcome reporting was at low risk for the 90.5% of included studies.

Laser source, parameters, and frequency of treatments

All the devices used in the included studies were diode lasers, in particular near infrared laser devices with wavelengths of 830 and 970 nm, and were the most used for analyzed trials, followed by visible red light at 660 nm. Power density or fluence was not fully described in all the studies, even if for some study, the reported parameters allowed reviewers to calculate them based on these equations (Fig. 2). Another consideration to make is that the frequently reported fluence is theoretical because it is calculated on the basis of the fiber or handpiece diameter but not on the spot area (in defocalized mode) or on the treated area (in scanning mode).

For all the included treatments, the application was only at intraoral level, except on the prevention of mucositis, for the study of Soto et al.,¹³ the application was at 19 intraoral and 6 extraoral points, and for the study of Abramoff et al.,¹⁴ the application was also involving labial commissures. For the prevention of OM, treatment was performed starting at day 1 of chemotherapy or conditioning every day until day 5,^13

–17 while for OM, treatment was performed at the appearance of OM every day.^{14,16

–21} For OM prevention, PBM duration was variable between 10 and 54 sec per point,^13,14 while for OM treatment, PBM duration was variable between 20¹⁶ and 230 sec.²¹ In study performed to check the effect of PBM on postsurgical or postextractive pain, the application of laser, varying between 17²⁴ and 60 sec^25
–27 per application point, was realized every 24–48 h, starting from immediate postsurgical time until eight treatments.^24

–27 For pulpotomy, a single laser-assisted procedure was performed in all studies and the duration of laser application was variable between 10^28,29 and 135 sec.^30,31

PBM for prevention and therapy for oral mucositis

Prevention of OM

Out of the five studies on prevention of OM included in this review, four^13

–16 reported a positive effect with a reduction of incidence and grading of OM for laser groups compared with control groups and in three out the four studies in a statistically significative way (Fig. 4).^13
–15 Only the study of Cruz et al.¹⁷ did not describe an evidence of benefit from the prophylactic use of PBM in children and adolescents with cancer treated with chemotherapy when optimal dental and oral care were provided.¹⁷

FIG. 4.

Meta-analysis for PBM in prevention protocols for OM: results for incidence of OM (upper) and for incidence of Grade 3 and 4 of OM (lower). OM, oral mucositis; PBM, photobiomodulation.

Treatment of OM

All nine studies on treatment of OM included in this review reported positive effect for PBM on grading,^{14,16,18
–20} pain,^18

–21 and duration²³ of OM, and in three of them a statistically significative difference;^18,20,23 Chermetz et al. reported also an improved swallowing. Results for analysis in depth are reported in Fig. 5.²¹

FIG. 5.

Meta-analysis for PBM in treatment protocols for OM: effects on pain evaluated by VAS at 7 days. VAS, visual analog scale.

PBM therapy to alleviate postoperative pain

Two of the four included studies^24,25 did not describe a significative difference in postoperative pain of treated and not treated adolescent following primary molar or premolar extraction (Fig. 6). Conversely Ezzat et al.²⁶ described a statistical difference in pain evaluated with a VAS at different times of evaluation, precisely in the first 3 days after the secondary palatal operations. Only Çakir-Özkan et al.²⁷ analyzed the bone density after mandibular midline distraction with a difference at 12 weeks relevant also from a statistical point of view. Analysis in depth was realized for postoperative pain 1 day after surgery for the studies of Ezzat et al.²⁶ and Elbay et al.²⁵ (Fig. 6).

FIG. 6.

Meta-analysis for PBM in treatment protocols for postoperative pain: effects on pain evaluated by VAS at the first day after surgery.

PBM treatments for pulp healing

Only the study of Fernandes et al.²⁹ described the effectiveness of the pulp treatment adding PBM to calcium hydroxide even if without statistically significant differences. Uloopi et al.²⁸ described PBM as a complementary step to pulpotomy procedure in the comparison between PBM and mineral trioxide aggregate, while Ansari et al.³⁰ and Kuo et al.³¹ did not describe any difference by adding or not adding PBM (Fig. 7).

FIG. 7.

Meta-analysis for PBM in pulp treatment protocols: effects on clinical (upper) and radiological (lower) success at 12 months after treatment.

Discussion

The present systematic review included randomized clinical trials to evaluate the performance of PBM when used in pediatric dentistry. The studies presented in these systematic reviews and meta-analysis showed that PBM is a technique, which may represent a great help also when used in the field of the pediatric dentistry. In fact, the literature reports a large number of publications, where the success of this technique is statistically significant and the absence of side effects and contraindications is confirmed, this being a strong indication to use PBM for this kind of patients.

The clinical applications of PBM in pediatric dentistry analyzed in this study included its utilization in the fields of the treatment and prevention of OM, control of postsurgical oral pain, and its use for pulpotomy procedures. The most interesting and clinically useful aspect concerning PBM is represented by the choice of the parameters to use: in fact, in the field of PBM is necessary not to exceed a certain energy to avoid the possibility of provoking opposite effects, according to the Arndt-Schultz law;³² unfortunately, several of the analyzed studies did not report power density, a fluence used, and in many other articles these parameters were calculated only on the basis of the fiber diameter, and this, particularly when laser is not used in contact mode, does not correspond to the real evaluation.

The devices of all the studies were diode lasers, which are solid-state semiconductor lasers typically using a combination of Gallium (Ga), Arsenide (Ar), and other elements such as Aluminum (Al), and Indium (In), to change electrical energy into light energy, emitting both in visible and near infrared portions of the electromagnetic spectrum. In almost all the articles, laser device was used intraorally, while the modes were both in continuous wave and pulsed; in the majority of the cases, the handpiece was positioned not in contact with the tissues and maintained perpendicular to it for reducing the quantity of the reflected energy of the beam. In none of the studies were reported the side effects or incidents related to the use of laser device, and this aspect is very important for confirming the safety of PBM, when using with the respect of the ANSI safety rules, which are mandatory to be observed by operators, nurses, and patients. The highest number among the publications of this study is with regard to the utilization of PBM for the treatment and the prevention of chemo- and radio-induced OM, while less articles are referred to utilization of PBM for the pulpotomy in the primary teeth. Other different applications of PBM in pedodontics, such as its utilization for controlling the gag reflex in children during intraoral radiography or for treating Recurrent Labial Herpes Simplex, were not taken in consideration due to the low number of publications (one for each of the topics).

Conclusions

In summary, the present systematic review demonstrated the positive effects of PBM utilization in pediatric dentistry with the different protocols and light parameters described in the analyzed articles. Therefore, more future clinical researches will be necessary to further explore the efficacy of PBM in pediatric dentistry, also by enlarging the indications and the fields of utilization.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

Funding Information

There was no funding provided for this article.

References

Enwemeka

. Low level laser therapy is not low. Photomed Laser Surg, 2005; 23:529–530.

Karu

. Photobiology of low-power laser effects. Health Phys, 1989; 56:691–704.

Anders

, Lanzafame

, Arany

. Low-level light/laser therapy versus photobiomodulation therapy. Photomed Laser Surg, 2015; 33:183–184.

Mester

, Spiry

, Szende

, Tota

. Effect of laser rays on wound healing. Am J Surg, 1971; 122:532–535.

Mester

, Mester

. The biomedical effects of laser application. Lasers Surg Med, 1985; 5:31–39.

Tang

, Khan

, Andreana

, Arany

. Laser-activated transforming growth factor-β1 induces human β-defensin 2: implications for laser therapies for periodontitis and peri-implantitis. J Periodontal Res, 2017; 52:360–367.

Gelbier

. History of the International Association of Paediatric Dentistry. Part 2: early events in the USA—the American Society of Dentistry for Children. Int J Paediatr Dent, 1995; 5:55–57.

Soares

, Souto

, Lofrano

, Colares

. Anxiety related to dental care in children and adolescents in a low-income Brazilian community. Eur Arch Paediatr Dent, 2015; 16:149–152.

Fornaini

, Riceputi

, Lupi-Pegurier

, Rocca

. Patient responses to Er:YAG laser when used for conservative dentistry. Lasers Med Sci, 2012; 27:1143–1149.

10.

Merigo

, Fornaini

, Clini

, Fontana

, Cella

, Oppici

. Er:YAG laser dentistry in special needs patients. Laser Ther. 2015; 24:189–193.

11.

Hardin

, Hackell

; Committee on Practice and Ambulatory Medicine. Age limit of pediatrics. Pediatrics, 2017; 140:3.

12.

Higgins

, Altman

, Gøtzsche

, et al. Cochrane Bias Methods Group; Cochrane Statistical Methods Group. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ, 2011; 343:d5928.

13.

Soto

, Lalla

, Gouveia

, Zecchin

, Seber

, Lopes

. Pilot study on the efficacy of combined intraoral and extraoral low-level laser therapy for prevention of oral mucositis in pediatric patients undergoing hematopoietic stem cell transplantation. Photomed Laser Surg, 2015; 33:540–546.

14.

Abramoff

, Lopes

, et al. Low-level laser therapy in the prevention and treatment of chemotherapy-induced oral mucositis in young patients. Photomed Laser Surg, 2008; 26:393–400.

15.

Sousa de Oliveira

, Moreira Lanza

, Ferreira Fernandes

, Travassos

, Serufo

. Low-level laser for prevention of chemotherapy-induced oral mucositis in pediatric patients with acute leukemia, HC/UFMG 2012–2013. Global J Med Res, 2014; 14:6–10.

16.

de Castro

, Abreu

, Correia

, da Mota Vasconcelos Brasil

, da Cruz Perez

, de Paula Ramos Pedrosa

. Low-level laser in prevention and treatment of oral mucositis in pediatric patients with acute lymphoblastic leukemia. Photomed Laser Surg, 2013; 31:613–618.

17.

Cruz

, Ribeiro

, Rech

, Rosa

, Castro

Jr , Brunetto

. Influence of low-energy laser in the prevention of oral mucositis in children with cancer receiving chemotherapy. Pediatr Blood Cancer, 2007; 48:435–440.

18.

Gobbo

, Verzegnassi

, Ronfani

, et al. Multicenter randomized, double-blind controlled trial to evaluate the efficacy of laser therapy for the treatment of severe oral mucositis induced by chemotherapy in children: laMPO RCT. Pediatr Blood Cancer, 2018; 65:e27098.

19.

Vitale

, Modaffari

, Decembrino

, Zhou

, Zecca

, Defabianis

. Preliminary study in a new protocol for the treatment of oral mucositis in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT) and chemotherapy (CT). Lasers Med Sci, 2017; 32:1423–1428.

20.

Amadori

, Bardellini

, Conti

, Pedrini

, Schumacher

, Majorana

. Low-level laser therapy for treatment of chemotherapy-induced oral mucositis in childhood: a randomized double-blind controlled study. Lasers Med Sci, 2016; 31:1231–1236.

21.

Chermetz

, Gobbo

, Ronfani

, et al. Class IV laser therapy as treatment for chemotherapy-induced oral mucositis in onco-haematological paediatric patients: a prospective study. Int J Paediatr Dent, 2014; 24:441–449.

22.

Cauwels

, Martens

. Low level laser therapy in oral mucositis: a pilot study. Eur Arch Paediatr Dent, 2011; 12:118–123.

23.

Kuhn

, Porto

, Miraglia

, Brunetto

. Low-level infrared laser therapy in chemotherapy-induced oral mucositis: a randomized placebo-controlled trial in children. J Pediatr Hematol Oncol, 2009; 31:33–37.

24.

Paschoal

, Santos-Pinto

. Therapeutic effects of low-level laser therapy after premolar extraction in adolescents: a randomized double-blind clinical trial. Photomed Laser Surg, 2012; 30:559–564.

25.

Elbay

, Tak Ö, Şermet

Elbay Ü

, Kaya

, Eryılmaz

. The use of low-level laser therapy for controlling the gag reflex in children during intraoral radiography. Lasers Med Sci, 2016; 31:355–361.

26.

Ezzat

, El-Shenawy

, El-Begermy

, Eid

, Akel

, Abbas

. The effectiveness of low-level laser on postoperative pain and edema in secondary palatal operation. Int J Pediatr Otorhinolaryngol, 2016; 89:183–186.

27.

Çakir-Özkan

, Bereket

, Arici

, Elmali

, Şener

, Bekar

. The Radiological and stereological analysis of the effect of low-level laser therapy on the mandibular midline distraction osteogenesis. J Craniofac Surg, 2015; 26:e595–e599.

28.

Uloopi

, Vinay

, Ratnaditya

, Gopal

, Mrudula

, Rao

. Clinical evaluation of low level diode laser application for primary teeth pulpotomy. J Clin Diagn Res, 2016; 10:ZC67–ZC70.

29.

Fernandes

, Lourenço Neto

, Teixeira Marques

, et al. Clinical and radiographic outcomes of the use of low-level laser therapy in vital pulp of primary teeth. Int J Paediatr Dent, 2015; 25:144–150.

30.

Ansari

, Morovati

, Asgary

. Evaluation of four pulpotomy techniques in primary molars: a Randomized Controlled Trial. Iran Endod J, 2018; 13:7–12.

31.

Kuo

, Lin

, Huang

, Chiang

. Clinical outcomes for primary molars treated by different types of pulpotomy: a retrospective cohort study. J Formos Med Assoc, 2018; 117:24–33.

32.

Baxter

. Therapeutic Lasers: Theory and Practice. Edinburgh: Churchill Livingstone, 1994.