Heavy metals and neurodevelopment of children in low and middle-income countries: A systematic review

Abstract

Background The presence of harmful environmental exposures, which disproportionately affects low-and-middle income countries (LMICs), contributes to >25% of deaths and diseases worldwide and detrimentally affects child neurodevelopment. Few resources succinctly summarize the existing literature on this topic. Our objective is to systematically review and characterize the evidence regarding the relationship between heavy metals and neurodevelopment of children in LMICs. Methods We conducted a medical librarian-curated search on multiple online databases to identify articles that included individuals <18 years living in a LMIC, quantitatively measured exposure to a heavy metal (either prenatal or postnatal), and used a standardized measurement of neurodevelopment (i.e. cognitive, language, motor, and behavior). Reviews, editorials, or case studies were excluded. Results were analyzed qualitatively, and quality was assessed. Results Of the 18,043 screened articles, 298 full-text articles were reviewed, and 100 articles met inclusion criteria. The included studies represented data from 19 LMICs, only one of which was classified as a low-income country. Ninety-four percent of postnatal lead and all postnatal manganese studies showed a negative association with metal exposure and neurodevelopment, which were the strongest relationships among the metals studied. Postnatal exposure of mercury was associated with poor neurodevelopment in only half of studies. Limited data on postnatal arsenic and cadmium suggests an association with worse neurodevelopment. Findings were mixed for prenatal arsenic and lead, although some evidence supports that the neurotoxicity of lead was amplified in the presence of manganese. Conclusions and potential impact We found that lead and manganese appear to consistently have a detrimental effect on the neurodevelopment of children, and more evidence is needed for mercury, arsenic, and cadmium. Better characterization of these effects can motivate and inform prioritization of much needed international policies and programs to reduce heavy metal exposures for young children within LMICs.

Topological network properties of resting-state functional connectivity patterns are associated with metal mixture exposure in adolescents

“…Few studies investigated the neural mechanisms of metal neurotoxicity throughout this extended window of vulnerability. Findings from these studies have linked metal exposure with alterations in regional brain volume ( Claus et al, 2012 , 2014 ; Horton et al, 2014 , 2018 ; Levin-Schwartz et al, 2021 ; Heng et al, 2022 ; Migneron-Foisy et al, 2022 ), and brain metabolite concentrations ( Trope et al, 2001 ; Meng et al, 2005 ; Thomason et al, 2019 , 2021 ; Cecil, 2022 ) during this period. This heightened vulnerability may be due to rapid growth and differentiation of the brain throughout childhood.…”

“…This heightened vulnerability may be due to rapid growth and differentiation of the brain throughout childhood. Neurotoxic exposures during this critical period can also disrupt behavioral, cognitive, and motor development ( Claus et al, 2012 , 2014 ; Horton et al, 2018 ; Rechtman et al, 2020 ; Levin-Schwartz et al, 2021 ; Heng et al, 2022 ). Despite the breadth of research on the developmental effects of childhood metal exposure, the underlying brain mechanisms behind these observed metal-associated outcomes are still not clear.…”

Exposure of metal toxicity in Alzheimer’s disease: An extensive review

“…Around 25% of global fatalities and disorders are caused by harmful environmental exposures ( Heng et al, 2022 ). Metals are a common source of dangerous environmental exposure, with levels regularly exceeding the recommended limits.…”

Determinants of Exposure to Potentially Toxic Metals in Pregnant Women of the DSAN-12M Cohort in the Recôncavo Baiano, Brazil

“…Exposure to a high level of PTM such as lead (Pb), arsenic (As), cadmium (Cd) and the micronutrient manganese (Mn) have been the subject of several investigations in workers from the industrial and mining sector and in populations living in risk zones [ 2 , 3 , 4 , 5 , 6 ]. Over time, however, the neurotoxic potential of these metals, even at low exposure levels in children have been reported, [ 7 , 8 , 9 , 10 ] and there is a gap of knowledge regarding the toxicity of such contaminants in women [ 2 ]. In pregnant women, there is also a growing concern due to their vulnerability and the possibility of transferring PMT to the fetus; thus, compromising the child’s development [ 10 , 11 ].…”