Bulletin of the World Health Organization

Global methylmercury exposure from seafood consumption and risk of developmental neurotoxicity: a systematic review

Mary C Sheehan a, Thomas A Burke b, Ana Navas-Acien c, Patrick N Breysse c, John McGready d & Mary A Fox b

a. Risk Sciences and Public Policy Institute, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, United States of America (USA).
b. Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA.
c. Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA.
d. Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA.

Correspondence to Mary C Sheehan (e-mail: msheehan@jhsph.edu).

(Submitted: 05 December 2012 – Revised version received: 15 October 2013 – Accepted: 12 November 2013 – Published online: 10 January 2014.)

Bulletin of the World Health Organization 2014;92:254-269F. doi: http://dx.doi.org/10.2471/BLT.12.116152


The World Health Organization (WHO) considers mercury (Hg) among the top 10 chemicals of “major public health concern”.1 Evidence of ubiquitous Hg contamination globally led to the recent Minamata Mercury Convention, a binding international treaty to control anthropogenic Hg emissions.2 A principal form of Hg to which general populations are exposed is methylmercury (MeHg). Transformation of Hg emissions to organic MeHg takes place in the aquatic environment, where MeHg bioaccumulates in food webs. In human beings MeHg exposure occurs predominantly through the consumption of seafood (including freshwater and marine varieties, shellfish and marine mammals).36 MeHg is a neurotoxin particularly harmful to the developing fetal brain.36 A large body of research has demonstrated an association of exposure in utero with developmental neurotoxicity (e.g. deficits in fine motor skills, language and memory) among populations that consume seafood regularly.3,79 Such studies have been used to develop health-based reference doses below which no appreciable risk of harm is thought to occur, including the provisional tolerable weekly intake (PTWI), established by the Joint Expert Committee on Food Additivies (JECFA) of the Food and Agriculture Organization (FAO) and WHO.6,10 Recent research suggests harm at doses associated with relatively infrequent seafood consumption.11

Seafood species vary in MeHg content depending on contamination source, trophic level and other factors.1214 Seafood, on the other hand, is an important source of nutrients, including neuroprotective omega-3 polyunsaturated fatty acids.15 Research on the benefits and harms of seafood highlights the importance of choosing species low in MeHg and high in these polyunsaturated fatty acids and of ensuring that consumers have sufficient information to make such choices.15,16 Well-designed seafood advisories can be helpful to this end,17,18 but they exist in a small number of countries, most of which are high-income.19 An estimated 400 million women of reproductive age in the world rely on seafood for at least 20% of their intake of animal protein; a large share of them live in low- and middle-income countries where access to information on MeHg content in seafood is not widely available.2022 Although the research conducted in the last two decades has highlighted the risk in subsistence fishing communities that practise artisanal and small-scale gold mining23 and among Arctic peoples whose diet consists of apex marine predators such as the pilot whale,24 few researchers have compared MeHg exposures globally in women who consume seafood.

Human exposure to chemical contaminants can be characterized by examining biomarkers.25 Total Hg in hair (THHg) and total Hg in blood (TBHg) are both validated biomarkers of MeHg intake correlated with seafood consumption in general human populations.4,26 Our goal was to review and synthesize the evidence from published studies reporting THHg and TBHg biomarkers to systematically compare global MeHg exposure among women and their infants from seafood-consuming populations. By identifying populations at higher risk, we aim to provide policy-makers with scientific evidence for the prioritization of risk reduction messages and targeted population surveillance.


Based on a pre-defined study protocol,27 we performed a systematic electronic search of the peer-reviewed scientific literature (Box 1). Studies were selected in two stages: title and abstract screening, followed by full text review after application of exclusion criteria. We excluded studies not involving women or infants from general populations and not reporting a central THHg or TBHg biomarker estimate. When multiple articles reported on a single sample, we chose the most recent one with complete data. To ensure robust summary statistics, we excluded studies with less than 40 participants.

Box 1. Literature search strategy for global systematic review of methylmercury exposure from seafood in women and infants

1. “fetus” OR “infant” OR “newborn” OR “maternal” OR “mother” OR “pregnant” OR “women”

2. “fish” OR “marine” OR “shellfish” OR “seafood”

3. “mercury” OR “methylmercury” OR “methyl AND mercury” OR “biomonitoring”

Combined terms: 1 AND 2 AND 3.

Note: The following databases were searched for studies published from January 1991 to September 2013: PubMed, Embase, SCOPUS, Web of Science, TOXNET and LILACS. References were hand-checked and there were no restrictions on language or study design.

We extracted data on study design, population characteristics, measures of average (geometric mean or median) and high-end (90th or 95th percentile or maximum) biomarkers, exposure conditions and main covariates examined. Extracted biomarkers were organized into three subpopulation groups: non-pregnant women; pregnant women and mothers who had recently given birth; and infants (up to 12 months of age). Because biomarkers for more than one subpopulation with different levels of exposure were often reported in the same study, the subpopulation was our main level of analysis.

We stratified subpopulations into six mutually exclusive categories based on predictors of the body burden of MeHg. The most important of these predictors are seafood consumption frequency and seafood MeHg content. In most seafood species MeHg represents the largest fraction of total Hg (inorganic Hg representing a much smaller share). Thus, seafood MeHg concentration is commonly measured as total Hg in tissue.3,4 Seafood consumption estimates were reported in some studies; data on total Hg concentrations were rarely provided. Research suggests the following general hierarchy: marine mammals, other apex marine predators and some industrially-contaminated fish [containing several parts per million (ppm)]; large marine fish [containing up to 1 or more ppm]; most commercially purchased marine and freshwater fish [often containing less than 0.5 ppm] and  most shellfish [often containing less than 0.2 ppm].23,24,2831 Seafood intake is generally higher in coastal regions than inland30,32 and seafood from globalized commercial sources predominates in many urban areas.14 We therefore generated six categories based on the following proxy predictors, reported in most studies: seafood source; seafood type; likely Hg contamination pathway; and residential context. Four categories included populations consuming seafood that was mainly self-caught and two included populations consuming seafood that was commercially purchased primarily (Table 1).

As recommended in guidelines for the systematic review of observational studies,27 we evaluated study quality by examining the risk of bias in three areas: selection of participants (selection methods and reporting of exposure characteristics); exposure measurement (laboratory methods and quality control); and statistical methods and covariate analysis (evaluation of distribution shape, reporting of seafood intake and exposure to non-seafood sources of Hg).

We derived two summary distributions – central and upper bound – for each exposure category by pooling average and high-end biomarkers. For comparability, all TBHg biomarkers were converted to THHg-equivalent at a hair-to-blood ratio of 250:1.3,5 We summarized resulting statistical distributions using medians and percentiles. To interpret results, we compared distribution medians with the THHg-equivalent value of the PTWI dose (approximately 2.2 μg/g) established by the JECFA.10 We also determined the share of subpopulations with average and high-end biomarkers over this reference. In sensitivity analysis we evaluated the impact on pooled biomarkers taking into account differences in participant selection, exposure measurement and statistical methods identified in the quality review. Given substantial heterogeneity in population exposure conditions, study designs and reporting, we did not undertake a meta-analysis. All data analysis was performed in Stata10 (StataCorp, College Station, United States of America).


Selected studies

Of 3042 articles identified in the published literature, we screened 1402 non-duplicates (1379 were identified by electronic search and 23 by hand search); we excluded 1120 and we reviewed the full texts of the remaining 282, from which we excluded 118 (Fig. 1). The remaining 164 articles, which reported total Hg biomarkers for 239 distinct subpopulations, were included in this review. Selected articles report biomarker concentrations for 63 943 women and infants from 43 countries (Table 2). Most (73%) studies were cross-sectional and over half (56%) reported THHg measures; the majority (79%) were published after 2001. Studies published in 1991–2001 were conducted primarily in populations consuming self-caught seafood; since 2001, the number of studies in consumers of seafood that is predominantly commercially purchased has increased notably in both absolute and relative terms (Fig. 2). The characteristics of the selected studies are provided in Table 3 and Table 4 (both available at: http://www.who.int/bulletin/volumes/92/04/13-116152).

Fig. 1. Selection of articles for the review of studies on methylmercury exposure in women and infants from seafood-consuming populations
Fig. 1. Selection of articles for the review of studies on methylmercury exposure in women and infants from seafood-consuming populations
Fig. 2. Number of selected studies reporting total mercury in hair (THHg) or total mercury in blood (TBHg) in women and infants from seafood-consuming populations, by predominant seafood type (local self-caught or commercially purchased) and year of publication
Fig. 2. Number of selected studies reporting total mercury in hair (THHg) or total mercury in blood (TBHg) in women and infants from seafood-consuming populations, by predominant seafood type (local self-caught or commercially purchased) and year of publication

Pooled biomarker concentrations

For 43 subpopulations of women and infants living near small-scale gold mining sites in Bolivia (Plurinational State of),33,34 Brazil,3553,59,60 Colombia,54 French Guiana,5557 Indonesia58 and Surinam61 the pooled central distribution median THHg biomarker concentration was 5.4 µg/g (upper bound median: 23.1) (Table 5). Values were higher (8.2 µg/g; upper bound: 27.5) in the subgroup of rural riverine dwellers reliant on local freshwater fish and lower (1.4 µg/g; upper bound: 11.8) among urban dwellers consuming less fish. For 21 subpopulations from Arctic regions, including in Canada,6266 Denmark (Greenland and the Faroe Islands),6769 Norway,70,71 the Russian Federation72 and the United States (state of Alaska),73 the pooled central distribution median result was 2.1 µg/g (upper bound: 9.8); values were higher (3.6 µg/g; upper bound: 24.3) for marine mammal and other self-caught seafood consumers and lower (0.4 µg/g; upper bound: 1.4) among those with a diet including less seafood and less reliant on these traditional foods.

For 25 subpopulations whose self-caught fish from local waterways is affected by Hg-emitting industries in Brazil,74,75 Chile,76 China,7781 Colombia,82 Italy,83,84 Kazakhstan,85 Mexico,87 Morocco,88 Nicaragua,89 Norway,115 the Republic of Korea,86 Romania,90 Slovakia,81,91 Sweden,92 Taiwan, China,93 the United States94 and Venezuela (Bolivarian Republic of),95 the pooled central THHg median biomarker was 0.8 µg/g (upper bound: 4.6). In 14 subpopulations consuming fish periodically from non-industry-contaminated waters in Botswana,96 Canada,97102 Norway,103 Sweden104 and the United States,105107 the value was 0.4 µg/g (upper bound: 2.8).

For 102 coastal or island-dwelling subpopulations consuming seafood that is predominantly commercially purchased, the combined central median THHg concentration was 0.8 µg/g (upper bound: 6.8). On the Atlantic coast, the pooled result for 35 subpopulations in Brazil,108 Canada,99,109 France,110,111 Norway,115 Portugal,117 Spain,118 Sweden,81,92,112114,119 the United Kingdom of Great Britain and Northern Ireland120,121 and the United States122131 was 0.4 µg/g (upper bound: 2.9). For 27 subpopulations from the Mediterranean, Persian Gulf and Indian Ocean (combined because of similar THHg ranges and referred to as “Mediterranean”) in Albania,132 Croatia,133 Greece,133,135 the Islamic Republic of Iran,136139 Italy,83,133,140 Kuwait,141 Morocco,142 Seychelles,143 South Africa,144,145 Spain146 and Turkey,147 the pooled central THHg concentration was 0.7 µg/g (upper bound: 8.5). For 40 Pacific coast subpopulations in China,148151 Japan,153160 Peru,172 the Republic of Korea,161171 Taiwan, China174 and the United States,175,176 the pooled result was 1.3 µg/g (upper bound: 6.0).

For 34 subpopulations living in inland regions of Austria,177 Brazil,178 Canada,179 Croatia,81 the Czech Republic,81,180,181 France,142,182 Italy,84 Morocco,81 Pakistan,183 Poland,184 the Republic of Korea,169 Saudi Arabia,186188 Slovenia,81,189 Spain,190,191 Sweden192 and the United States,193196 the pooled central TTHg median was 0.4 µg/g (upper bound: 2.9).

Comparison with provisional tolerable weekly intake

The median of the pooled central THHg biomarker distribution for women and infants in rural riverine communities near tropical gold mining sites reached nearly four times the FAO/WHO PTWI reference level of 2.2 ug/g (Fig. 3), while the upper-bound median reached more than 10 times this reference. Some individual high-end biomarkers exceeded 50 µg/g, the lower end of the range found in the neurological syndrome known as Minamata disease,4 associated with accidental industrial Hg poisoning in Japan in the 1950s and 1960s (Fig. 4). The median of the central THHg biomarker distribution in Arctic traditional food consumers exceeded the reference by 63%, while the upper bound median was over 10 times the value. For women and infants in the industry and fishing categories, central estimate medians were below the international reference, although the industry central median was twice that of the fishing category; most high-end biomarkers were above it. For those in the Pacific coastal subcategory, the 75th percentile approached the reference value; the upper bound median was nearly three times this value and nearly all high-end biomarkers exceeded it. Central biomarkers were below the PTWI in the Atlantic. However in many subpopulations in the Mediterranean they exceeded this reference, while the upper bound median was nearly four times the reference and most high-end biomarkers exceeded it. For the inland category, the central estimate median was well below the reference, but nearly 80% of the high-end biomarkers exceeded it.

Fig. 3. Distributions of central estimate for total mercury in hair (THHg) reported in selected studies of women and infants from seafood-consuming populations, by exposure category
Fig. 3. Distributions of central estimate for total mercury in hair (THHg) reported in selected studies of women and infants from seafood-consuming populations, by exposure category
PTWI, provisional tolerable weekly intake.
Fig. 4. Distributions of upper-bound total mercury in hair (THHg) reported in selected studies of women and infants from seafood-consuming populations, by exposure category
Fig. 4. Distributions of upper-bound total mercury in hair (THHg) reported in selected studies of women and infants from seafood-consuming populations, by exposure category
PTWI, provisional tolerable weekly intake.
Note: High-end biomarkers in the gold mining, Arctic and coastal categories reach into the range associated with observable neurological damage.

Study quality

A majority (78%) of selected studies were based on convenience samples taken from seafood-consuming populations. Some details of the seafood context were provided in most (71%) studies, but in the others this information was sparse. Laboratory protocols for THHg and TBHg detection were nearly universally reported (91%). Most (82%) protocols were based on cold vapour atomic absorption spectrometry (CV-AAS) or inductively-coupled plasma mass spectrometry (ICP-MS) and a majority (74%) reported laboratory quality control procedures. In 86% of studies, distributions were transformed to lognormal scale and summarized using geometric means or medians. More than half (55%) of the studies reported maximums as high-end estimates, while the remainder reported 90th or 95th percentiles. Only 51% of studies reported some seafood intake data and 25% evaluated non-seafood sources of Hg.


We found that biomarkers of MeHg intake were of greatest health concern among three categories of seafood-consuming women and their infants: (i) rural riverside dwellers living near tropical small-scale gold mining with diets dependent on locally-caught freshwater fish; (ii) those in Arctic regions for whom apex food-chain marine mammals are a dietary staple; and (iii) coastal inhabitants, particularly in the Pacific and Mediterranean, who probably consume seafood that is primarily commercially sourced. In the first group, average Hg biomarkers suggest MeHg intake exceeds by several fold the level considered by WHO and FAO to pose no substantial risk of developmental neurotoxicity. In the second group, average biomarkers suggest MeHg intake well over the reference value. In the third group, biomarkers suggest an important share of the population approach or exceed the reference level. High-end biomarkers in all three groups indicate body burdens of MeHg in the range associated in epidemiological studies with observable neurological damage. While average biomarkers in other groups suggest that MeHg intake is below the recommended level, most upper bound biomarkers in these categories exceed the reference, which shows that even in groups with lower average exposure certain populations are at risk.

Before this study, few researchers had systematically compared the global exposures and risks linked to MeHg intake from seafood. Brune et al. reviewed Hg biomarker studies – published from 1976 to 1990 – of general populations exposed through various sources and found the highest values among seafood consumers in Greenland and Japan.197 Sioen et al. estimated contaminant and nutrient intake in general populations based on global seafood availability data and found the estimated MeHg intake to be highest in Japan and the Pacific islands, followed by the Nordic and Mediterranean regions.198 A recent European regional study examining biomarkers showed the highest MeHg exposure to be in Mediterranean countries.199 Our findings are broadly consistent with these studies and with the literature describing MeHg exposure and risk in specific subsistence fishing communities. This review adds to the evidence by synthesizing the findings from the two most recent decades of published international Hg biomarker data specifically for women and infants and by examining, in a single study, MeHg exposure in populations consuming self-caught and commercially purchased seafood.

Several limitations affect the interpretation of our results. Our goal was to compare MeHg exposure across various international groups of women and infants from seafood-consuming populations. However, incomplete reporting prevented us from evaluating the share of non-consumers of seafood in each study. Furthermore, most studies used convenience samples that may not have been representative of the populations from which they were taken. In sensitivity analysis we pooled biomarkers excluding the several large representative population surveys (which have a higher share of non-consumers of seafood than other studies). However, this did not alter our findings. Physiological differences in MeHg metabolism and elimination by life stage are well known200 and the FAO/WHO reference dose was established based on maternal biomarkers. Thus, in sensitivity analysis we also combined biomarkers excluding infants. This resulted in slightly lower medians for the Arctic and gold mining categories and higher ones for the coastal and inland categories.

TBHg is a better indicator of recent MeHg exposure than THHg, which is a better measure of longer-term MeHg exposure.3,4,6 Although this difference may be important among sporadic seafood consumers, the majority of our subpopulations were regular seafood consumers. Conversion of TBHg biomarkers to THHg equivalents is likely to have resulted in some measurement error. However, the range of hair-to-blood ratios reported in our studies was similar to the range on which the standard conversion ratio is based, which minimizes this bias.5 When we pooled only THHg biomarkers, medians were slightly higher across most categories (although some categories had few observations). Despite the use of laboratory methods that relied on commonly employed protocols, detection techniques are subject to variation3,11 and quality control practices were not uniformly reported. Sensitivity analysis examining only studies using CV-AAS or similar procedures resulted in slightly higher biomarkers for the Arctic category.

Population Hg biomarker distributions are often skewed to the right, so that central tendency is best captured by geometric means or medians.3 Thus, in reporting our main results we chose to exclude the small number of studies reporting only arithmetic means. Including arithmetic means yielded higher results for the inland category. To give greater weight to estimates from larger samples, we pooled biomarkers using sample-size weighting. Doing so yielded higher summary biomarkers in the Arctic and coastal categories. Variations in the share of MeHg in total Hg have been reported, both among frequent and infrequent seafood consumers,23,201 depending in part on exposure to Hg sources other than seafood (such as elemental Hg in dental amalgams or inorganic Hg compounds in skin-lightening creams).3,29 Most of the one quarter of selected studies examining non-seafood sources of Hg assessed the presence of dental amalgams, mainly in infrequent consumers of seafood; while this inorganic Hg source is best measured with urinary biomarkers, in cases where this exposure is important TBHg biomarkers may overestimate MeHg.26 We eliminated high outlier biomarkers due to suspected non-seafood sources wherever these were noted by authors (most were in subpopulations where skin-lightening creams were used). Nevertheless, other sources of Hg exposure influencing high-end measures cannot be excluded. These limitations in the underlying data suggest that our findings should be interpreted cautiously. However, most sensitivity analyses resulted in higher biomarker summary statistics than the main findings we report; we chose conservative assumptions for our main results.

Estimated IQ losses in infants born to seafood consuming mothers serve as an alternative means of characterizing the public health impact of MeHg exposure. As an illustration, we applied a dose–response relationship (0.18 infant IQ point lost for every ppm increase in maternal THHg)202 that has been used to estimate the economic costs associated with Hg contamination203,204 to our pooled upper bound biomarkers. The resulting interquartile range of estimated IQ loss spanned from 1 to 13 points for the gold mining, Arctic and coastal subpopulation categories. IQ losses at the higher end of this range may be sufficient to contribute to mild mental retardation, defined as an IQ between 50 and 69 points. Among subsistence fishing populations in the Amazon, an assessment of global burden of disease showed an incidence of mild mental retardation of up to 17.4 cases per 1000 infants205 and separate research identified MeHg-associated deficits in memory and learning in adults.206 IQ losses in the lower end of the range may contribute to borderline intellectual functioning, characterized by memory and executive function deficits.207 Although such minor losses in IQ may go unnoticed in an individual, they can cause an important shift in intellectual capacity at the population level, as documented in the case of lead.208 IQ loss represents only one facet of the neurological harm resulting from MeHg; our analysis did not include recent research suggesting neurological effects at lower dose11 or other documented effects, such as adverse cardiovascular outcomes.209

Systematic reviews provide an opportunity to identify gaps in a body of research. Small-scale gold mining is practiced in 70 countries,210 but we found Hg biomarker studies meeting our criteria in only six. We identified studies in 23 coastal countries, although per capita seafood consumption data suggest that many other such countries warrant study.20 Although reviews of subsistence fishing populations in the Amazon and Arctic are available, few have been conducted for coast-dwelling frequent seafood consumers (e.g. in south-eastern Asia or the Mediterranean) or for fishing populations near abandoned chloralkali plants and other aquatic sources of Hg contamination. We found population-based Hg biomonitoring surveys in only a handful of countries; most are high-income and have relatively low per capita seafood consumption.

It was beyond the scope of this review to assess time trends in Hg biomarkers. Without major policy changes, projections indicate that global anthropogenic Hg emissions are likely to increase.211 Moreover, modelling suggests that any reduction in Hg emissions is likely to take time to translate into reduced MeHg in seafood.212 Declines in Hg biomarkers in humans have been observed in association with changes in seafood consumption habits in various populations. This finding reinforces the importance of carefully designed public health messages intended to reduce MeHg exposure.199,212 In subsistence fishing populations, the cultural importance of seafood harvesting and the scarcity of alternative animal protein sources suggest the existence of complex tradeoffs in guiding seafood consumption and the need for well-targeted messages. In predominantly urban seafood-consuming coastal populations, commercial seafood advisories may be an appropriate choice for reaching at-risk populations.19 Because of seafood’s important nutritional benefits, all such messages should aim to encourage a shift away from large apex predator species and towards those with lower MeHg and higher polyunsaturated fatty acid content, rather than to reduce seafood intake.


In this review of biomarkers of MeHg intake in women and infants from 164 studies across 43 countries, we found a very high risk in tropical riverine populations near gold mining sites and in traditional Arctic populations. In both groups, biomarkers suggest average MeHg intake exceeds the FAO/WHO recommendation, although their share of the global total of seafood-consuming women and infants is likely to be fairly small. We also found an elevated risk among seafood consumers in the coastal regions of south-eastern Asia, the western Pacific and the Mediterranean; a large share of the world’s seafood-consuming women and their infants is likely to be found in this group because of its large population. In other populations for whom data were available, average indicators of risk were lower and generally within international intake recommendations. However, women and infants with high exposure to MeHg were evident across all exposure categories. Although sources of bias were present, these results should help to set broad priorities for preventive policy and research.

The findings of this review underscore the importance of WHO’s call for enhanced population monitoring and risk communication to women of reproductive age regarding healthful seafood choices.1 One of the provisions of the Minamata Convention aims to protect vulnerable populations from Hg exposure through public education and other measures.213 The Convention is a potentially important strategic tool to reach the populations at highest risk through development of seafood advisory risk messages for commercial seafood consumers, targeted community-based interventions for subsistence fishing groups and regular population surveillance.

Competing interests:

None declared.