Heavy metals and neurodevelopment of

Overview

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Key numbers

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and-middle income countries (LMICs), contributes to >25% of deaths and diseases world-
Harmful environmental exposures contribute to approximately 25% of deaths and diseases
levels of manganese exceeding 400 μg/L in their drinking water. Although the World Health
lated limit of 10 μg/L (9). Many of these heavy metals result from poorly regulated use in agri-
of this review. However, full summaries of all mixed metal articles are included in S1 Table.
3.2.1. General characteristics. The majority of the studies (n = 64) were conducted in
The studies within this review addressed 5 heavy metals, lead (n = 34), mercury (n = 19),
arsenic (n = 11), manganese (n = 11), and cadmium (n = 3), In this review, twenty-two studies
(n = 62); 34 were prospective cohort studies, and 4 were case-control studies. Of the 100 publi-
(WISC) (n = 33), the Bayley Scales of Infant Development (BSID) (n = 18), the Gesell Develop-
mental Scale (GDS) (n = 8), the Raven’s Progressive Matrices (n = 10), and the Child Behavior
Checklist (CBCL) (n = 5). These neurodevelopment assessments were performed at a variety
total of 18,582 participants that ranged from 132 to 7479 participants per study. Two of the
were rated “good.” Additional details about these studies can be found in Tables 1–3, and S1.
arsenic levels between 122 and 246 μg/L at early pregnancy had lower FSIQ scores compared
to those with maternal urinary levels between 3.2 and 32.4 μg/L. However, there was no signifi-
score in children with arsenic levels > 163 μg/L (37).
arsenic, those with urinary arsenic levels > 82.6 μg/dL had a decline of 12% on the vocabu-
lary, 21% on the object assembly, and 13% in the picture completion subtests of the WISC
total of 1708 participants that ranged from 106 to 1453 participants per study. One of the stud-
Table 1. Studies that found a negative association between heavy metal exposure and various domains of neurodevelopment.
lower in children with cord cadmium � 6 μg/L compared with <0.6 μg/L (45); the other study
Table 2. Studies that found no association between heavy metal exposure and various domains of neurodevelopment.
Table 3. Studies that found positive associations between heavy metal exposures and various domains of neurodevelopment.
Costa Rica (n = 1), Democratic Republic of the Congo (n = 1), Ecuador (n = 3), Arab Republic
(n = 7), Pakistan (n = 1), Peru (n = 1), Philippines (n = 1), and the country formerly known as
Additional details about these studies can be found in Tables 1–3, and S1.
sure, nearly all (n = 32) studies measured lead levels in blood. Of these, a few studies concur-
levels (geometric mean of 1.75 μg/dL (95% CI: 1.68–1.84)) were associated with a higher BSID
quality. Additional details about these studies can be found in Tables 1–3, and S1.
levels prenatally. These studies involved a total of 5595 participants that ranged from 70 to
mercury levels > 5 μg/L had significantly worse visuospatial ability than did children with
including Bangladesh (n = 9), Brazil (n = 4), China (n = 1), Democratic Republic of the Congo
(n = 1), Arab Republic of Egypt (n = 2) Mexico (n = 4) (114–134), and Tanzania (n = 1) (135).
nese, and 4 included mercury. Additional details about these studies can be found in S1 Table.
were arsenic, manganese, and lead (n = 3) (128, 129, 136) and manganese and arsenic (n = 3)
deaths per capita that are attributable to the environmental exposures (137). Toxicity from
those with median levels (129), and another showed that arsenic and lead individually potenti-

Methods (brief)

sample size, age at outcome measurement, whether the study was conducted in utero, exposure
Prenatal Vigeh et al. (2014) (47) Wasserman et al. (1998) (48) Schnaas et al. (2000) (49)
(2011) (52), Schnaas et al. (2000) (56), Olympio et al. (2010) (57), et al. (1998) (62), Counter et al. (2005) Liu et al. (2013) (65), Rahman et al.
et al. (2012) (67), Schnaas et al. (2006) Nascimento et al. (2014) (76)
1. de Water E, Proal E, Wang V, Medina SM, Schnaas L, Téllez-Rojo MM, et al. Prenatal Manganese
1. Schnaas L, Rothenberg SJ, Perroni E, Martı́nez S, Hernández C, Hernández RM. Temporal pattern in
1. Braun JM, Hoffman E, Schwartz J, Sanchez B, Schnaas L, Mercado-Garcia A, et al. Assessing win-
1. Kordas K, Ettinger AS, Bellinger DC, Schnaas L, Téllez Rojo MM, Hernández-Avila M, et al. A dopa-
1. Téllez-Rojo MM, Bellinger DC, Arroyo-Quiroz C, Lamadrid-Figueroa H, Mercado-Garcı́a A, Schnaas-
1. Schnaas L, Rothenberg SJ, Flores M-F, Martinez S, Hernandez C, Osorio E, et al. Reduced Intellec-
1. Claus Henn B, Schnaas L, Ettinger AS, Schwartz J, Lamadrid-Figueroa H, Hernández-Avila M, et al.
of Hair Aluminum, Lead, and Mercury in a Sample of Autistic Egyptian Children: Environmental Risk

Implications

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Update history

The five most recent substantive edits to this page, classified major (evidence or structure moved), correction (a published value or statement was wrong and has been fixed), or minor (narrative rewritten without changing the underlying evidence). Each description is derived from what the edit did to this page; the linked commit is the authoritative record, routine regeneration passes are excluded, and the full version history lives in git. When DOI minting comes online (see schema docs), each entry below will also link to a version-pinned DataCite DOI.

Commit	Date	Change	Description
b01ec52c	2026-08-04	major	2 sections added
d49e450f	2026-08-03	major	5 sections added; narrative text revised