Efficacy of treatments used to relieve signs and symptoms associated with teething: a systematic review

Canto, Fernanda Michel Tavares; Costa Neto, Oswaldo de Castro; Loureiro, Jéssica Muniz; Marañón-Vásquez, Guido Artemio; Ferreira, Daniele Masterson Tavares Pereira; Maia, Lucianne Cople; Pithon, Matheus Melo

doi:10.1590/1807-3107bor-2022.vol36.0066

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Systematic Review, Pediatric Dentistry • Braz. oral. res. 36 • 2022 • https://doi.org/10.1590/1807-3107bor-2022.vol36.0066 copy

Efficacy of treatments used to relieve signs and symptoms associated with teething: a systematic review

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Abstract:

The purpose of this review was to systematically evaluate all the existing literature on the efficacy of treatments used to relieve the signs and symptoms associated with teething. A systematic search up to February 2021, without restrictions on language or date of publication, was carried out in MEDLINE/PubMed, SCOPUS, Web of Science, The Cochrane Library, EMBASE, LILACS, BBO, OpenGrey, Google Scholar, Portal de Periódicos da CAPES, clinicaltrials.gov, and the references of the included studies. Clinical studies that evaluated the effect of any intervention to alleviate the signs and symptoms associated with teething in babies and children were included. The risk of bias was assessed using the ROB-2 and ROBINS-I tools. The characteristics and results of the individual studies were extracted and synthesized narratively. The GRADE approach was followed to rate the certainty of the evidence. Three randomized and two non-randomized clinical trials were included. The outcomes of these five articles were classified as high or serious risk of bias. Three studies using homeopathy reported improvement in appetite disorders, gum discomfort, and excess salivation. One study showed a new gel with hyaluronic acid was more effective than an anesthetic gel in improving signs and symptoms such as pain, gingival redness, and poor sleep quality. Another study applied non-pharmacological treatments, which were more effective, especially against excess salivation. Although the present systematic review suggests some therapies could have a favorable effect on signs and symptoms related to teething, definitive conclusions on their efficacy cannot be drawn because of the very low certainty of the evidence. The existing literature on the subject is scarce and heterogeneous and has methodological flaws; therefore, further high-quality investigations are necessary.

Keywords:
Tooth Eruption; Therapeutics; Signs and Symptoms; Clinical Trial; Systematic Review

Author, Year, Country	Study design	Total sample size	Sample age	Treatment strategies		Outcomes-related information			Results	Conclusion	Funding source	Conflict of interest report
Author, Year, Country	Study design	Total sample size	Sample age	Group(s) / Interventions assessed	Therapy details	Outcomes assessed	Assessment methods	Evaluation periods	Results	Conclusion	Funding source	Conflict of interest report
Taneja et al., 2018, India	Non randomized clinical trial	n = 11426	6 to 12 months	Calcarea phosphoricum 6x	Tablet twice a day regularly for 12 months (6 to 12 months)	Fever, colic, running nose, irritability, crankiness, crankiness, restlessness, no sleep, refusal to eat food, green stools, diarrhea, yellow stool.	visited the household frequently by ASHAs (Accredited Social Health Activists) or were in contact with the parents by telephone or through a messenger to confirm health of the telephone or through a messenger to confirm health of the child.	month to month	ASHAs (n = 566) who had provided care to children gave their feedback: CP. 6X-330 ASHAs responded that CP helped in easy teething	Children responded favorably to the medicines given by ASHAs at the time of diarrhea/URTI episodes, and ASHAs expressed satisfaction with the program.	Central Council for Research in Homoeopathy, an autonomous body of the Ministry of AYUSH, Government of India.	None declared
									41 ASHAs : it reduced complaints associated with teething 195 responded CP eased teething as well as reduced associated complaints.
									515/581 ASHAs responded:the six medicines IMPROVE: (Symptoms of teething such as increased salivation, irritability, and gum swelling
				Ferrum phosphoricum 3X,	2 tablets 4x/day for maximum 3 days (Child with fever)				307/581 ASHAs responded: six medicines IMPROVE : (Diarrhea)
				Magnesium phosphoricum (mp) 6x	2 tablets dissolved in hot water for 1 to maximum 2 days (child with colic)
									11/581 ASHAs responded:the six medicines NO EFFECT
Taneja et al., 2018, India				Belladonna 30C	3 pills 4x/day for maximum 3 days (Child with running nose, fever)			month to month		Children responded favorably to the medicines given by ASHAs at the time of diarrhea/URTI episodes, and ASHAs expressed satisfaction with the program.
Taneja et al., 2018, India	Non randomized clinical trial	n = 11426	6 to 12 months	Chamomilla 30C	3 pills 4x/day for maximum 3 days (Child with irritability, crankiness, restlessness, no sleep, refusal to eat food, green stools)			month to month
				Podophyllum 30c	3 pills 4x/day for maximum 3 days. (Child with diarrhea, yellow, offensive stool)
Jong et al., 2015, The Netherlands	Randomized Open Comparative Clinical Trial	n = 200	Infants < 12 months	ChamBell 5: 02 tablets (Dentokind®; intervention group)	ChamBell 5: 02 tablets containing: Belladonna D6,	Unmotivated anxiety, gingival tenderness and appetite disorder, otalgy, stool softening, sleep-onset insomnia and frequent awakenings kin pallor, gingiva condition: hyperemia, swelling, hematoma and hyperemia around the mouth, drooling and hyperthermia.	interview	0	Individual signs improved after seven days of treatment: intervention(n=100) /control group(n=100):unmotivated anxiety (88%/79%), gingival tenderness (73%/55%) (p=0.0130), appetite disorder (83%/66%) (p=0.0107), otalgy (56%/18%), stool softening (75%/36%), sleep-onset insomnia (57%/54%) and frequent awakenings (74%/59%), skin pallor (33%/30%), gingival hyperemia (91%/ 75%) (p = 0,0057); gingival swelling (59%/41%) (p = 0,0157); drooling (86%/83%), hyperemia around the mouth (51%/37%), hyperthermia(82%/86%).	ChamBell 5: 02 tablets showed to be effective, safe and well tolerated.	Deutsche Homöopathie-Union, DHU-Arzneimittel GmbH & Co. KG, Karlsruhe, Germany	M. Jong was an employee of VSM Geneesmiddelen (sister company of Deutsche Homöopathie Union) from 2001 to 2008 P. Klement and J. Burkart are employees of Deutsche Homöopathie Union, DHU Arzneimittel GmbH & Co. KG, Karlsruhe, Germany.)
Jong et al., 2015, The Netherlands	Randomized Open Comparative Clinical Trial	n = 200	Infants < 12 months	ChamBell 5: 02 tablets (Dentokind®; intervention group)	Chamomilla D6, Ferrum		interview	7 days			.
Jong et al., 2015, The Netherlands	Randomized Open Comparative Clinical Trial	n = 200	Infants < 12 months	ChamBell 5: 02 tablets (Dentokind®; intervention group)	phosphoricum D6, Hepar sulfuris D12 and Pulsatilla D6 (for seven days).		interview			ChamBell 5: 02 tablets showed to be effective, safe and well tolerated.
Jong et al., 2015, The Netherlands	Randomized Open Comparative Clinical Trial	n = 200	Infants < 12 months	ChamBell 5: 02 tablets (Dentokind®; intervention group)	six tablets per day (acute symptoms). After symptoms reduced one tablet three times a day was administered		interview
				homeopathic suppositories	Chamomilla recutita D1, Atropa bella donna D2, Solanum dulcamara				(ChamBell-5-02 tablets showed to be effective)
				(Viburcol®; control group).	D4, Plantago major D3, Pulsatilla pratensis D2, Calcium carbonicum
					Hahnemanni D8.(seven days). For children aged up to six months: two suppositories a day. Children older than six months: four suppositories.)
Rosu et al., 2017, Romania	Randomized, open-label, parallel-group (multicentre study)	n = 54	3 to 36 months	Group A: high molecular weight hyaluronic acid (HMWHA) gel :0.54% Hyaluronic Acid; (test group)	Group A: massaging the surface around the teeth and applying locally a small amount of gel, up to a maximum of 6 times per day.	Pain, swelling and redness, mouth spasm, sleep quality.	Questionnaire and clinical examination Verbal Rating Scale: (VRS)Absent = 0; Moderate = 1; Intense = 2.	baseline (T0), three days (T1)	Pain	The novel gel containing HMWHA proved to be an effective and safe alternativeto the anesthetic gel in the relief of teething symptoms in infants.	Ricerfarma S.r.l. (www.ricerfarma.com)	Have no financial interest
								seven days (T2)	T0 : test: 1.59 (0.50)/control:1.44 (0.51) p=0.2849
								14 days	T1:test: 1.18 (0.62)/control:1.7 (0.47) p=0.0018
								(T3)	T2:test:0.10 (0.33)/control:0.86 (0.73) p<0.0001
									Swelling: T0: test:1.70 (0.47)/control: 1.56 (0.51) p=0.2686 T1:test: 1.44 (0.51)/control:1.63 (0.49) p=0.1796 T2:test: 0.39 (0.57)/control:0.91 (0.71) p=0.0087
									Redness: T0: test:1.63 (0.56)/control: 1.63 (0.49) p=0.8678 T1:test:1.19 (0.56) /control:1.70 (0.47) p=0.0009 T2:test: 0.13 (0.40)/control:1.01 (0.63) p<0.0001
									mouth spasm: T0 – T1 (p=0.1648); T0 – T2 (p=0.1184);T2-T3 (p=0.3363).
									Sleep quality was better in the test group than in the control group at T1 (p=0.0171) and T2 (p=0.0016
				Group B: standard anesthetic gel: cetylpyridinium chloride and lidocaine hydrochloride (control group)	Group B: massaging the surface around the teeth and applying locally a small amount of gel, up to a maximum 4 times per day.
Kazyukova et al., 2018, Russia	Randomized clinical trial	n = 63	6 months to 2,5 years	Principal Group: Dantinorm Baby (Homeopathy -liquid)	Principal Group: Dantinorm Baby :2/3 to 5 times(maximum) / 3 days (maximum, no more than 5 days). dripping content into the child's mouth (1 dose = 1 ml). The main components: chamomile (chamomilla vulgaris) reduces tantrum and body temperature; (phytolacca decandra) reduces nausea and inflamed gums; (rheum officinale) relieves digestion symptoms	Pain and swelling of the gums	Visits and parent's report	Visit 1: initial inspection	teething symptoms and their severity in the groups compared with initial examination before study therapy (visit 1)	«Dantinorm Baby» drug, which is designed on the basis of plant substances, in a liquid dosage form. It has no contraindications, does not cause side effects, does not increase the pharmacological load on the growing organism, and can be recommended for wide use in pediatric practice.	None declared	Have no financial interest
Kazyukova et al., 2018, Russia	Randomized clinical trial	n = 63	6 months to 2,5 years	Principal Group: Dantinorm Baby (Homeopathy -liquid)		Increased salivation	Visits and parent's report	Visit 2: 3rd to 5th day	Dantinorm Baby : (%) (n=31) Pain and swelling of the gums (100%) /Increased salivation(100%)/ Wish to bite / bite(100%)/Irritability (96,8%)/Decreased appetite (77,4%)/Sound disorders (74,2%); Increased body temperature> 37 0 (61,3%)/Running nose (48,4%); Cough (48,4%)/Irritation of the skin around the mouth (35,5%);Increased stool (25,8%).		None declared	Have no financial interest
Kazyukova et al., 2018, Russia	Randomized clinical trial	n = 63	6 months to 2,5 years	Principal Group: Dantinorm Baby (Homeopathy -liquid)		Wish to bite / bite	Visits and parent's report		Calgel : (%) (n=32) Pain and swelling of the gums(100%)/Increased salivation(100%)/Wish to bite / bite(100%)/Irritability (100%)/ Decreased appetite (81,3%)/Sound disorders (65,6%)/Increased body temperature> 37 0 (62,5%)/ Running nose (40,6%)/Cough (40,6%)/Irritation of the skin around the mouth (37,5%)/ Increased stool (28,1%) teething symptoms and their severity in the groups compared with initial examination before study therapy (visit 2): Pain and swelling of the gums(90,3%) /Increased salivation(90,3%)/ Wish to bite / bite(87,1%)/Irritability (58,1%)/Decreased appetite (35,5%)/Sound disorders (32,3%) -Increased body temperature> 37 0 (35,5%)/Running nose (35,5%)	«Dantinorm Baby» drug, which is designed on the basis of plant substances, in a liquid dosage form. It has no contraindications, does not cause side effects, does not increase the pharmacological load on the growing organism, and can be recommended for wide use in pediatric practice.	None declared	Have no financial interest
						Irritability
						Decreased appetite
						Sound disorders
						Increased body temperature
						Running nose
						Cough
						Irritation of the skin around the mouth
						Increase sed stool
									Adverse events: G control: 6/32
				Control Group: Calgel	Control Group: Calgel applying the gel with your finger, gently massaging the inflamed gum; if necessary, reapply at intervals of at least 20min, but no more than 6 times / day, for 3 days. The main components: lidocaine hydrochloride and cetylpyridinium chloride					«Dantinorm Baby» drug, which is designed on the basis of plant substances, in a liquid dosage form. It has no contraindications, does not cause side effects, does not increase the pharmacological load on the growing organism, and can be recommended for wide use in pediatric practice.
Memarpour et al. / 2015 / Iran	Non randomized clinical trial	n = 254	8 to 36 months	Cuddle therapy (n=53)	Hug or cuddle the child. Activities to distract the child.	Drooling, Diarrhea, lethargy, Loss of appetite, Lack of sleep, Gum irritation, chewing objects, Finger sucking, Irritability, Red and inflamed gums, Gingival pain, Crying.	Questionnaire contained 27 items. Body temperature was measured; Body temperature was measured; and Intraoral examination (palpation).	4 days before eruption, On the day of eruption and 3 days after eruption.	Cuddle therapy (frequency of successful cases) Drooling (n=47), Lethargy (n=13), Loss of appetite (n= 21); Lack of sleep (n=41); Gum irritation (n=36); Chewing objects (n= 29); Finger sucking (n=26); Irritability(n=6); Red and inflamed gum(n=11); Gingival pain (n= 18); Crying (n=41). Pieces of ice (frequency of successful cases)	Teething rings, cuddle therapy and rubbing the gums were the most effective methods to reduce symptoms.	Vice Chancellory of Research of Shiraz University of Medical Science, Shiraz, Iran.	No competing interests.
Memarpour et al. / 2015 / Iran	Non randomized clinical trial	n = 254	8 to 36 months	Pieces of ice (n=50)	Pieces of ice wrapped in a towel were placed on the gums and mucous membrane overlying the erupting teeth for 1 to 2 min.
Memarpour et al. / 2015 / Iran	Non randomized clinical trial	n = 254	8 to 36 months			Drooling, Diarrhea, lethargy, Loss of appetite, Lack of sleep, Gum irritation, chewing objects, Finger sucking, Irritability, Red and inflamed gums, Gingival pain, Crying.			Drooling (n=29); Lethargy (n=17); Loss of appetite (n=22); Lack of sleep (n=41); Gum irritation (n=36); Chewing objects (n= 39); Finger sucking (n=37); Irritability(n=6); Red and inflamed gum (n=29); Gengival pain(n=16); Crying (n=38). Teething rings (frequency of successful cases)	Teething rings, cuddle therapy and rubbing the gums were the most effective methods to reduce symptoms.
				Rubbing the child's gums (n=50)	Massage for 1 to 2 min.				Drooling (n=47); Lethargy(n=11); Loss of appetite (n=17); Lack of sleep (n=40); Gum irritation (n=29); Chewing objects (n= 33); Finger sucking (n=40); Irritability (n=16); Red and inflamed gum(n=21); Gingival pain (n= 18); Crying (n=34). Food for chewing (frequency of successful cases)
				Teething rings (n=51)	Give the ring to the child to chew or bite on.				Drooling (n= 37); Lethargy (n=9); Loss of appetite (n= 31); Lack of sleep(n=32); Gum irritation (n=29); Finger sucking (n=23); Chewing objects(n=21); Irritability(n=16); Red and inflamed gum(n=15); Gengival pain(n=14); Crying (n=32).
				Food for chewing (n=50)	Pieces of a frozen fruit or vegetable.

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[1] Corresponding Author: Matheus Melo Pithon, E-mail: matheuspithon@gmail.com