The Relationship Between the Level of Copper, Lead, Mercury and Autism Disorders: A Meta-Analysis

Figures & data

Figure 1 Flowchart for inclusion of the studies in the systematic review and meta-analysis.

Table 1 Overall Data of the Selected Studies in This Meta-Analysis

Author References	Year	Country	Autism					Healthy Controls					Type of Sample	Type of Measurement
			Age (Mean)	N	Cu (m±SD)	Hg (m±SD)	Pb (m±SD)	Age (Mean)	N	Cu (m±SD)	Hg (m±SD)	Pb (m±SD)
Wecker.L^Citation5	1985	USA	2–11	12	12.3±1.9	15.2±0.6	12.6±1.6	2–11	21	26.3±2.7	15.2±0.3	10.7±1.2	Hair	Atomic Absorption
Elsheshtaway.E^Citation18	2011	Egypt	4	32	26.5±1.9	0.55±0.06	9.75±1.8	4.1	32	19.1±4.4	3.2±0.2	6.8±0.86	Hair	Atomic Absorption
De Palma.G^Citation24	2012	Italy	9	44	10.2	0.5	1.3	8.4	61	9.4	0.25	0.8	Hair	ICP-MS
Adams.J^Citation13	2006	USA	7.1	51	34.6	0.29	0.62	7.5	40	33.4	0.29	0.81	Hair	ICP-MS
Blaurockbusch.E^Citation14	2012	KSA	3–9	44	133.8±115.4	3.35±4.8	4.56±1.4	3–9	146				Hair	ICP-MS
Adams.J^Citation25	2011	USA	5–16	55	0.76±0.08			5–16	44	0.72±0.09			Plasma	ICP-MS
Lakshmi. M.D^Citation16	2011	India	4–12	45	18.4±2.3	4.02±0.47	20.18±2.36	4–12	50	9.62±1.15	2.87±0.34	16.2±1.94	Nail	Atomic Absorption
Lakshmi. M.D^Citation16	2011	India	4–12	45	24.04±2.88	1.61±0.19	7.72±0.92	4–12	50	12.31±1.4	0.37±0.04	1.56±0.18	Hair	Atomic Absorption
Blaurockbusch.E^Citation23	2011	KSA	3–9	25	21.94±21.7	0.47±0.42	0.01±0.02	3–9	25	19.69±9.95	0.3±0.31	0.01±0.01	Hair	ICP-MS
AL-Farsi. Y.M^Citation26	2012	Oman	1–14	27	1.2±0.1		12.2±1.1	3–14	27	6.6±0.7		6.3±0.8	Hair	ICP-MS
Shearer.T.R^Citation27	1982	American	8	12	11±22		3.5±3.3	8.4	12	10±4		4.7±3.4	Hair	Atomic Absorption
El BazMohamed.F^Citation28	2015	Egypt	6.2	100		0.39±0.37	3.31±3.92	6.8	100		0.25±0.16	2.06±2.45	Hair	Atomic Absorption
Geier.D.A^Citation29	2010	USA	7.3	83		22.2±12.1		11.4	89		10.7±4.3		Plasma	Cold Vapor Analysis
Torsdottir.G^Citation30	2005	Iceland	18–35	13	16.8					17.1			Plasma	Atomic Absorption
Jeff Brad.M.D^Citation31	2003	USA	3–15	221		4.06±8.59	18.2±43.3	3–16	18		1.29±1.54	11.8±8.6	Plasma	ICP-MS
Holms.A.S^Citation12	2003	USA	2–15	94		0.47±0.28		2–15	45		3.63±3.56		Hair	ICP-MS
Yassa.H.A^Citation32	2014	Egypt	2–10	45		4.02±0.54	55.24±10.02	2–10	45		0±0.02	9.75±0.58	Blood	Atomic Absorption
Yassa.H.A^Citation19	2014	Egypt	2–10	45		5.21±0.08	60.04±9.75	2–10	45		0.11±0.05	12.03±0.45	Hair	Atomic Absorption
Macedoni.M^Citation33	2014	Slovenia	6.2	52	20.57±3.29	1.9±0.97	30.8±34.33	6.6	22	19.87±4.12	1.55±0.56	18.6±7.24	Blood	FAAS&EAAS &VAAS
Obrenvich.ME^Citation17	2011		<6	26		0.25	0.6	<6	39		0.6	0.66	Hair

Table 2 The Relationship Between the Concentrations of Copper, Lead, and Mercury and Autism in Terms of Number and Type of Studies Included in the Meta-Analysis

Element	Subgroup	NO. of Date from Studies	I^2	SMD(95% CI)	P value for Significant	Z
Sample CU	Serum and plasma	1	0.000%	0.47(0.07,0.87)	0.021	2.31
	Blood	1	0.000%	0.20(−0.30,0.70)	0.439	0.77
	Hair	8	97.8%	−0.75(−2.29,0.80)	0.344	0.95
	Nail	1	0.000%	4.91(4.10,5.72)	0.000	11.84
Sample Hg	Serum and Plasma	2	90.2%	0.83(−0.10,1.76)	0.082	1.74
	Blood	2	99.3%	5.43(−4.48,15.35)	0.283	1.07
	Hair	7	98.9%	1.74(−0.64,4.12)	0.152	1.43
	Nail	1	0.000%	2.83(2.26,3.40)	0.000	9.69
Sample Pb	Serum and Plasma	1	0.00%	0.15(−0.33,0.63)	0.532	0.62
	Blood	2	99.0%	3.40(−2.47,9.27)	1.13	0.257
	Hair	8	98.1%	3.18(1.47,4.89)	3.65	0.000
	Nail	1	0.000%	1.85(1.37,2.33)	7.52	0.000

Figure 2 (A) cu Forest plots for the studies Cu concentration statuses combination difference between autistic patients and healthy individuals. The area of each square is proportional to the percentage weight of each individual study in the meta-analysis (CI 95%). In this chart, studies are stored in order of year publication and author’s names, based on a random effects model. (B) cu. Sensitivity analysis for studies in overall study copper for autism patients versus healthy controls. (C) cu. Begg’s funnel plot for publication bias in the risk difference (RD) analysis. The diameter of each circle represents the weight in the meta-analysis.

Figure 3 (A) Hg, Forest plots for the studies Hg statuses combination difference between autistic patients and healthy individuals. The area of each square is proportional to the percentage weight of each individual study in the meta-analysis (CI 95%). In this chart, studies are stored in order of year publication and author’s names, based on a random effects model. (B) Hg. Sensitivity analysis for studies in overall study for autism patients versus healthy controls.

Figure 4 (A) Pb. Forest plots for the studies Pb statuses combination difference between autistic patients and healthy individuals. The area of each square is proportional to the percentage weight of each individual study in the meta-analysis (CI 95%). In this chart, studies are stored in order of year publication and author’s names, based on a random effects model. (B) Pb. Sensitivity analysis for studies in overall study for autism patients versus healthy controls.

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