Association between sickle cell disease and dental caries: a systematic review and meta-analysis

Figures & data

Figure 1. Flow diagram of the study selection process.

Table 1. Characteristics of the studies included.

(Study, year); Country	Study design	SCD diagnosis	Setting		Sample total (cases AND controls)	Mean age (SD or range)	Measures for dental caries and calibration	Data (mean ± SD)			Statistic	P-value	Study quality
			SCD	Non-SCD				SCD		Non-SCD
(Laurence, Reid et al. 2002) USA	Retrospective cohort	Medical records	Howard University’s College of Dentistry	Howard University’s College of Dentistry	175: 35 SCA; 140 controls	30.4 (19.4) y 30.4(19.0) y	DMFS DMFT K = no definition	33.0(32.3) 12.0(8.3)		26.2(27.7) 9.9(6.9)	t-tests	0.21 0.12	High
(Laurence, George et al. 2006) USA	Retrospective cohort	Medical history	Howard University Hospital in Washington, D.C and Johns Hopkins Hospital in Baltimore	The same University College of Dentistry with SCD	152: 102 SCD; 50 controls	30.4 (19.4) y 30.4(19.0) y	DMFS Number of examiners; K = 0.90	28.01 (1.35)		28.26 ± 1.34	chi-square tests	-	High
(Passos, Santos et al. 2012) Brazil	Cross-section	Electrophoresis	Laboratory of Genetics of Professor Edgar Santos University Hospital or the School of Pharmacy of Federal University of Bahia	The same University with SCD	180: 51 HbSS; 48 HbSC; 91 controls	31.51(10.16) y 34.19(13.02) y 34.05(11.89) y	Decayed Teeth Missing Teeth Filled Teeth DMFT Intra-examiner; K = 0.82	HbSS 4.23(4.19) 4.52(5.74) 3.13(3.59) 11.8(6.16)	HbSC 3.27(2.98) 4.47(4.72) 3.47(3.22) 11.22(6.57)	2.91(3.07) 4.79(5.76) 3.68(3.93) 11.3(6.93)	Chi-square or Fisher’s Exact test	0.07 0.93 0.64 0.63	Moderate
(Ralstrom, da Fonseca et al. 2014) USA	Cross-section	Medical history	the sickle cell and the adolescent medicine clinics	no definition	106: 54 SCD; 52 controls	14(6)y 16(4)y	DMFT; Intra-examiner; K = no definition	1.94 (2.70)		2.96 (4.10)	chi-square test or Fisher’s exact test	0.10	Moderate
(Al-Alawi, Al-Jawad et al. 2015) Saudi Arabia	Cross-section	Medical history	Al-Qatif Central Hospital	general population	66: 33 SCD; 33 controls	24.52(4.611)y 24.58(6.124)y	Decayed teeth Missing teeth Filled teeth DMFT; one examiner; K = no definition	5.30 (3.861) 0.85 (0.972) 1.70 (1.403) 7.85 (4.071)		3.33 (3.594) 0.67(1.08) 2.97 (2.568) 6.97 (3.729)	Chi-square test	0.036 0.475 0.015 0.364	Moderate
(Fernandes, Kawachi et al. 2015a) Brazil	Cross-section	Medical history	Referral Center for Hematology and Transfusion Services in the State of Minas Gerais	100 schools	261: 56 SCD; 205 controls	8.9 (0.87)y 8.9 (0.8)y	Decayed teeth Missing teeth Filled teeth DMFT Intra- examiner; K = 0.87	0.9 (1.8) 0 0.4 (1.2) 1.3 (2.1)		1.1 (1.5 ) 0.2 (0.6) 0.5 (1.0) 1.8 (2.0)	Mann Whitney U test	- - - -	High
(Fernandes, Kawachi et al. 2015b) Brazil	Cross-section	Medical history	Referral Center for Hematology and Transfusion Services in the State of Minas Gerais	100 schools	261: 50 SCD; 180 controls	12.0 (1.08)y 11.9 (1.0) y	Decayed teeth Missing teeth Filled teeth DMFT; Intra- examiner; K = 0.87	1.0 (1.4) 0.1 (0.6) 0.4 (0.8) 1.5 (1.9)		1.0 (1.7) 0.2 (0.7) 0.8 (1.7) 2.1 (2.8)	Mann Whitney U test	- - - -	High
(Brandao, Oliveira et al. 2018) Brazil	Cross-section	Hb electrophoresis and/or high-performance liquid chromatography	Hematology and Hem-therapy Foundation in Bahia	State School Francisco da ConceiçãoMenezes	124: 61 SCD; 63 controls	12.4 (2.9)y 11.1 (2.9)y	Decayed teeth Missing teeth Filled teeth DMFT; dmft two examiner; K = 0.71	1.5 ( 2.38) 0.8 ( 0.33) 0.5 (1.0) 2 (2.7) 2.3(2.6)		0.8 ( 1.23) 0.98 (0.3) 0.24 ( 0.7) 1.1 (1.7) 0.88(1.2)	Student’s t-test	0.003 0.620 0.004 0.013 0.018	High
(Kalbassi, Younesi et al. 2018) Iran	Cross-section	Medical history	Tehran, Mashhad, Isfahan and Tabriz cities, central hospitals	private offices	155: 55 SCA; 100 controls	19.2 (2.91)y 19.3 (3.211)y	Decayed teeth three examiner; K = no definition	6.10 ( 3.620)		2.33 (1.221)	Chi-squared test	<0.05	High

Table 2. Methodological quality scores of the selected articles.

	Selection*				Comparability**		Exposure***
Study	Is the case definition adequate?	Representativeness of the cases	Selection of controls	Definition of controls	Comparability of cases and controls on the basis of the design or analysis		Ascertainment of exposure	Same method of ascertainment for cases and controls	Non-response rate	Total	quality
Laurence and Colleagues, 2002	*	*	*	*	*	–	*	*	*	8	High
Laurence and Colleagues, 2006	*	*	*	*	*	–	*	*	*	8	High

*a maximum of 1 point for each item; **a maximum of 2 points for each item; ***a maximum of 1 point for each item****a maximum of 9 points.

*1 point.

1 (a) yes, with independent validation*, (b) yes, egrecord linkage or based on self-reports*, (c) no description.

2 (a) consecutive or obviously representative series of cases *, (b) potential for selection biases or not stated.

3 (a) community controls or school controls *, (b) hospitalor dental clinical controls, (c) no description.

4 (a) no history of disease (endpoint) *, (b) no description of source.

5 (a) the exposures of interest (dental caries and periodontal diseases) were adjusted for one confounder (demographic confounder: sex or age) *, (b) the exposures of interest (dentalcaries and periodontal diseases) were adjusted for two or more confounders (demographic confounder: sex or age and socioeconomic confounder: hygiene or income) **, (c) nodescription related to the adjustment analysis for confounding factors.

6 (a) secure record (e.g. surgical records) *, (b) structured interview where blind to case/control status*, (c) interview not blinded to case/control status (d) written self-report or medical record only, (e) no description.

7 (a) yes *, (b) no.

8 (a) same rate for both groups *, (b) non respondents described, (c) rate different and no definition.

Table 3. Methodological quality scores of the selected articles.

Study, year	a	b	c	d	e	f	g	h	i	j	k	Total	Quality
Al-Alawi and colleagues, 2015	√	√	×	–	×	?	?	√	?	√	–	5	Moderate
Brandão and colleagues, 2018	√	√	×	–	×	√	?	√	?	√	–	6	High
Fernandes and colleagues, 2015	√	√	√	–	×	√	?	√	?	√	–	6	High
Kalbassi and colleagues, 2018	√	√	√	–	×	√	?	√	?	√	–	7	High
Passos and colleagues, 2012	√	√	×	–	×	√	?	√	?	√	–	5	Moderate
Ralstrom and colleagues, 2014	√	√	×	–	×	√	?	√	?	√	–	5	Moderate

Notes: Item a–k represents the 11 items of the AHRQ recommended criteria. ‘√’ means ‘YES’, ‘×’ means ‘NO’, ‘?’ means ‘UCLEAR’, ‘–’ means ‘not suitable’.

Figure 2. Forest plot presenting weighted mean differences (WMD) of the permanent decayed, missing and filled teeth (DMFT) between patients with SCD and non-SCD participants. CI: Confidence interval. SCD: Sickle cell disease. Non-SCD: participants without sickle cell disease.

Figure 3. Forest plot presenting weighted mean differences (WMD) of the permanent decayed, missing and filled surface (DMFS) between patients with SCD and non-SCD participants. CI: Confidence interval. SCD: Sickle cell disease. Non-SCD: participants without sickle cell disease.

Table 4. Results of subgroup analyses.

Character		No. of trails	Heterogeneity		Meta-analysis
			p	I^2 (%)	WMD (95% CI)	p
Components	Decayed teeth	5	<0.001	93%	1.14(−0.04, 2.33)	0.06
	Missing teeth	3	0.33	10%	−0.14(−0.25, −0.03)	0.01
	Filled teeth	4	0.003	78%	−0.22(−0.66, 0.21)	0.31
Age	Children/Adolescents	4	0.01	73%	−0.26(−0.64, 0.12)	0.17
	Adults	2	0.50	0%	−0.18(−0.55, 0.18)	0.13
Genotypes	HbSS	5	0.41	0%	−0.42(−0.84, 0.00)	0.05
	HbSC	2	0.27	17%	−1.17(−2.47, 0.13)	0.08

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