Systematic review of studies on exposure to arsenic in drinking water and cognitive and neurobehavioral effects

Figures & data

Figure 1. Flowchart of the study selection process.

Table 1. Distribution of studies selected for review, by source of arsenic exposure.

Source of exposure	N studies
Urine	44
Blood, serum, and plasma	30
Hair	22
Nail	8
Water	23
Soil	4
Other	7

Table 2. Main characteristics of the studies included in detailed review.

First author, year (ref)	Parent study	Year(s) of data collection/ recruitment	Country	Study base	Sex, male (%)	Age mean, years median (m), range	Sample size	As concentration (μg/L), mean, and median (m)	Water As assessment	Data collection	Adjustment factors	Tier	Outcome domain
Studies in adults
Liu et al. (2017)			China	CB	43.3	58.7	483	74	IH	I	A, S, E, T, Al, B, M	1	1
Karim et al. (2019)			Bangladesh	CB	49.4	36.2	693	Exp 183, controls 2.5	IH	I	A, S, E, B, T, In	1	1
O’Bryant et al. (2011)	FRONTIER		USA	CB	30.6	62.1	434	6.3	GIS	IBS	A, S, E, L, Se, APOE	2	1,2,3,4,5,6
Edwards, Hall, et al. (2014a)	FRONTIER		USA	CB	NA	61.5	527	6.4	GIS	IBS	A, S, E, L, Se, APOE	2	1,2,3,5,6
Edwards, Johnson, et al. (2014)	TARCC		USA	HB	59.4	73.6	1390*	3.9	GIS	IBS	A, S, E, B, Lip, Hyp, D, Se	2	1,2,3,4,5,6
Gong et al. (2011)	FRONTIER		USA	CB	32.8	61.6	299	6.5	GIS	IBS		3	1
Studies in children
Wasserman et al. (2004)	Araihazar study		Bangladesh	CB	48.8	10.0	201	118	IHP	I	ME, MIQ, HT, AT, H, HC	1	1
von Ehrenstein et al. (2007)		2001–2003	India	CB	54	9m	351	59	VW	IP	A, S, B, ME, PE, PO, MA, HT, NR	1	1
Wasserman et al. (2007)	Araihazar study	2003–2005	Bangladesh	CB	49.8	6.1	301	120	IHP	IP	ME, MIQ, HS, Sch, H, HC, Mn	1	1, 2
Parvez et al. (2011)	HEALS		Bangladesh	CB	50.0	9.6	303	Exp 83, controls 3	IH	IBS	S, Sch, HC, MIQ, Mn, Se, Pb, BAs	1	8
Rodrigues et al. (2016)	Sirajdikhan and Pabna Birth Cohort	2008–2011	Bangladesh	CB	50.7	2.3m	524	Exp 27 m, controls 1.3 m	IH^†	IBS	MA, S, ME, SHS, HT, MIQ, Htc	1	1, 8
Tsai et al. (2003)		1991–1994	Taiwan	SB	48.6	13.4	109	High 185, low 131, controls NA	IH	I	S, E	2	2, 6
Rocha-Amador et al. (2007)			Mexico	SB	50	8	132	Exp1 169, exp2 194, controls 6	IH	NA	Pb, ME, SES, H, TS	2	1
Asadullah and Chaudhury (2011)		2005	Bangladesh	SB	39	13	7710	NA	SR	I	A, S, ME, PE, SES	2	3
Khan et al. (2011)	Araihazar study	2009	Bangladesh	CB	50.3	9.6	201	44	IH	IP	S, ME, B, AC, Mn	2	3, 7
Khan et al. (2012)	Araihazar study		Bangladesh	SB	47.1	9.3	840	119	IH	IP	A, ME, PE, HC, Mn	2	3, 4
Wasserman et al. (2014)			USA	SB	53.31	9.67	272	9.9	IH	I	ME, MIQ, HT, Sch, Sib	2	1, 2, 3, 4, 6
Nahar et al. (2014a)			Bangladesh	CB	44.2	14-15	312	72	IH	IP	SES	2	1, 7
Wang et al. (2007)		2003	China	CB	54.2	8-12	720	Exp 172, controls 3	IH(30%)	IP		3	1
Abbas et al. (2012)			Pakistan	CB	NA	12	NA	NA	VW	Q		3	1
Ghosh et al. (2017)			India	SB	NA	9-11	142	Exp 51, controls 6	IH exposed; NA controls	IP	S, B, HC, Mn, Fe	3	1, 6
Manju et al. (2017)			India	SB	30	12	40	Exp 90, controls 'negligible’	IH	None		3	1

A: age; AC: arm circumference; Al: alcohol drinking; As: arsenic; AT: access to television; B: body mass index/obesity; BAs: blood arsenic; CB: community-based; D: diabetes; E: education; exp: exposed; Fe: iron; FRONTIER: Facing Rural Obstacles Now through Intervention, Education & Research; GIS: geographic information system; H: height; HB: hospital-based; HC: head circumference; HEALS: Health Effects of Arsenic Longitudinal Study; HS: home stimulation; HT: house type; Htc: hematocrit; Hyp: hypertension; I: interview; IBS: interview before study; IH: individual household; IHP: individual household of parent; In: income; IP: interview to parents; L: language of administration of the test; Lip: blood lipids; M: marital status; MA: mother’s age; ME: maternal education; MIQ: maternal intellectual quotient; Mn: manganese; NA: not available; NR: number of rooms in the house; Pb: lead; PE: paternal education; PO: paternal occupation; Q: questionnaire; S: sex; SB: school-based; Sch: school attendance; Se: selenium; SES: socioeconomic status; SHS: exposure to secondhand smoke; Sib: number of siblings; SR: survey response based on screening for arsenic contamination of home tube wells carried out by the government; T: tobacco smoking; TARCC: Texas Alzheimer’s Research and Care Consortium; TS: transferrin saturation; VW: village wells

^†Assessment performed at different points in time.

Table A1. Preferred reporting Items for systematic reviews and meta-analyses (PRISMA) checklist.

Section and Topic	Item #	Checklist item	Location where item is reported
TITLE
Title	1	Identify the report as a systematic review.	1
ABSTRACT
Abstract	2	See the PRISMA 2020 for Abstracts checklist.	1
INTRODUCTION
Rationale	3	Describe the rationale for the review in the context of existing knowledge.	2
Objectives	4	Provide an explicit statement of the objective(s) or question(s) the review addresses.	2
METHODS
Eligibility criteria	5	Specify the inclusion and exclusion criteria for the review and how studies were grouped for the syntheses.	2
Information sources	6	Specify all databases, registers, websites, organizations, reference lists, and other sources searched or consulted to identify studies. Specify the date when each source was last searched or consulted.	2
Search strategy	7	Present the full search strategies for all databases, registers, and websites, including any filters and limits used.	2
Selection process	8	Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process.	2
Data collection process	9	Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process.	2,3
Data items	10a	List and define all outcomes for which data were sought. Specify whether all results that were compatible with each outcome domain in each study were sought (e.g. for all measures, time points, analyses), and if not, the methods used to decide which results to collect.	2–4
	10b	List and define all other variables for which data were sought (e.g. participant and intervention characteristics, funding sources). Describe any assumptions made about any missing or unclear information.	2–4
Study risk of bias assessment	11	Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) used, how many reviewers assessed each study and whether they worked independently, and if applicable, details of automation tools used in the process.	NA
Effect measures	12	Specify for each outcome the effect measure(s) (e.g. risk ratio, mean difference) used in the synthesis or presentation of results.	2,3
Synthesis methods	13a	Describe the processes used to decide which studies were eligible for each synthesis (e.g. tabulating the study intervention characteristics and comparing against the planned groups for each synthesis (item #5)).	3,4
	13b	Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data conversions.	NA
	13c	Describe any methods used to tabulate or visually display results of individual studies and syntheses.	3,4
	13d	Describe any methods used to synthesize results and provide a rationale for the choice(s). If meta-analysis was performed, describe the model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used.	3,4
	13e	Describe any methods used to explore possible causes of heterogeneity among study results (e.g. subgroup analysis, meta-regression).	NA
	13f	Describe any sensitivity analyses conducted to assess robustness of the synthesized results.	NA
Reporting bias assessment	14	Describe any methods used to assess risk of bias due to missing results in a synthesis (arising from reporting biases).	NA
Certainty assessment	15	Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome.	3,4
RESULTS
Study selection	16a	Describe the results of the search and selection process, from the number of records identified in the search to the number of studies included in the review, ideally using a flow diagram.	2
	16b	Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded.	4, Figure 1
Study characteristics	17	Cite each included study and present its characteristics.	4, Table 2
Risk of bias in studies	18	Present assessments of risk of bias for each included study.	4–9
Results of individual studies	19	For all outcomes, present, for each study: (a) summary statistics for each group (where appropriate) and (b) an effect estimate and its precision (e.g. confidence/credible interval), ideally using structured tables or plots.	4–9, Table 2
Results of syntheses	20a	For each synthesis, briefly summarize the characteristics and risk of bias among contributing studies.	4–9
	20b	Present results of all statistical syntheses conducted. If meta-analysis was done, present for each the summary estimate and its precision (e.g. confidence/credible interval) and measures of statistical heterogeneity. If comparing groups, describe the direction of the effect.	4–9
	20c	Present results of all investigations of possible causes of heterogeneity among study results.	NA
	20d	Present results of all sensitivity analyses conducted to assess the robustness of the synthesized results.	NA
Reporting biases	21	Present assessments of risk of bias due to missing results (arising from reporting biases) for each synthesis assessed.	NA
Certainty of evidence	22	Present assessments of certainty (or confidence) in the body of evidence for each outcome assessed.	9
DISCUSSION
Discussion	23a	Provide a general interpretation of the results in the context of other evidence.	9,10
	23b	Discuss any limitations of the evidence included in the review.	9,10
	23c	Discuss any limitations of the review processes used.	11
	23d	Discuss implications of the results for practice, policy, and future research.	11
OTHER INFORMATION
Registration and protocol	24a	Provide registration information for the review, including register name and registration number, or state that the review was not registered.	Not registered
	24b	Indicate where the review protocol can be accessed, or state that a protocol was not prepared.	NA
	24c	Describe and explain any amendments to information provided at registration or in the protocol.	NA
Support	25	Describe sources of financial or non-financial support for the review, and the role of the funders or sponsors in the review.	11
Competing interests	26	Declare any competing interests of review authors.	11
Availability of data, code, and other materials	27	Report which of the following are publicly available and where they can be found: template data collection forms; data extracted from included studies; data used for all analyses; analytic code; any other materials used in the review.	11

Table A2. List of studies selected for review.

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Table A3. Outcome categories included in the studies retained in the systematic review.

Outcome	Category
Academic achievement in languages	4
Academic achievement in mathematics	3
Anxiety/depression and withdrawn	7
Attention	2
Attention problems and aggressive behavior	3
Attention, processing speed, and verbal function	3
Behavior problems	7
Categorical verbal fluency	4
Cognitive development	1
Cognitive function	1
Cognitive impairment	1
Cognitive performance	1
Confrontational naming	4
Continuous performance test	2
Delayed memory	6
Dementia and cognitive function defects	1
Disease severity	1
Executive control	3
Executive control (including sequencing)	3
Executive function	3
Fine and gross motor abilities	8
Fine motor skills	8
General cognitive development	1
Global cognition	1
Gross motor skills	8
Immediate memory	6
Intellectual function	1
Intellectual function (WISC-IV full scale)	1
Intellectual function (WISC-IV perception)	3
Intellectual function (WISC-IV processing)	2
Intellectual function (WISC-IV verbal function)	4
Intellectual function (WISC-IV working function)	6
Intelligence quotient	1
Language function	4
Marks obtained – memory, attention, problem solving, and motor-visual perception	1
Memory power	6
Mental distress	7
Motor development	8
Motor function	8
Motor function, coordination of the hands, and fingers	8
Motor function, coordination of arms and hands, especially for object manipulation	8
Motor function, locomotion	8
Motor function, posture, and balance	8
Non-verbal intelligence quotient	1
Numerical abilities	3
Pattern memory	6
Perceptual information processing	2
Performance intelligence quotient	1
Phonemic verbal fluency	4
Processing of verbal information	4
Processing speed	2
Processing speed, verbal fluency	4
Semantic fluency	4
Short-term retention of information (verbal, visual, or numerical)	6
Social competence	7
Switching attention	2
Symbol digit	2
Time taken to fill the questionnaire – memory, attention, problem solving, and motor-visual perception	2
Verbal intelligence quotient	1
Verbal memory delayed	6
Visual attention ability and motor skills	2
Visual memory delayed	6
Visual memory immediate	6
Visuospatial abilities	5
Visuospatial functioning	5
Visuospatial praxis to overall clock drawing performance	5
Working memory	6

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Data availability

The work was performed on publicly available data retrieved from the studies included in the review and which are available upon request from the authors.