Editorial Mercury and Pregnancy The recent Minamata Convention on Mercury will eventually result in less mercury being dispersed into the environment. Because this will take some years, however, it will remain necessary to provide guidance to women seeking to reduce their exposure to mercury and, in particular, the exposure of their fetuses to methylmercury. This editorial discusses the challenges that risk communicators have had in realizing this goal. In October, 2013, more than 90 countries signed the Minamata Convention on Mercury, an initiative begun in 2009 by the Governing Council of the United Nations Environment Program (UNEP) (http://www..mercuryconvention.org/Portals/11/documents/conventionText/Minamata%2 0Convention%20on%20Mercury_e.pdf). The goal of this pact is to, “. . .protect the human health and the environment from anthropogenic emissions and releases of mercury and mercury compounds.” It requires state-of-the-art emission-control technologies on new coal-fired power plants, boilers, and smelters and bans the use of mercury in the production of chlor-alkali and acetaldehyde. It also bans certain products containing mercury, including compact fluorescent light bulbs, batteries, switches and relays, and soaps and cosmetics. Some controversial uses of mercury were exempted, however. Its use as an amalgamator in artisanal gold mining, which has been associated with high exposures both to miners and to residents of nearby communities, can continue, as can the use of mercury in dental amalgams, religious activities, and vaccines (as a preservative). The Convention will enter into force 90 days after it is ratified by 50 nations, which likely will take some years. The years of effort devoted to crafting and negotiating the Convention reflects the continued concern worldwide about the potential health impacts of mercury on human health. Of greatest concern with regard to pregnant women and their fetuses is exposure to methylmercury, which occurs primarily through the consumption of contaminated seafood (Mahaffey et al., 2009) and, in some areas of the world, rice grown in contaminated waters (Zhang et al., 2010). Mercury is actively transported across the placenta, and impaired neurodevelopment as a result of fetal exposure is widely considered to be the most sensitive endpoint. It served, for instance, as the basis for deriving the U.S. Environmental Protection Agency’s (EPA)

*Correspondence to: David C. Bellinger, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA, 02115 Email: [email protected]. Published online in Wiley Online Library (wileyonlinelibrary.com). Doi: 10.1002/bdra.23219

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mercury reference dose (RfD) (Rice et al., 2003), the European Food Safety Authority Tolerable Weekly Intake (TWI) (EFSA, 2012), and the FAO/WHO Joint Expert Committee on Food Additives’ Provisional Tolerance Weekly Intake (PTWI) (FAO/WHO JECFA, 2004). These standards were based primarily on the findings of birth cohort studies of relatively high seafood consumers (Faroe Islands, Seychelles Islands, New Zealand). They are expressed as mercury intakes (RfD: 0.1 mg Hg/kg body weight/day; TWI 1.3 mg Hg/kg body weight/week; PTWI 1.6 mg Hg/kg body weight/week) that, over a lifetime, will not produce a level of concern for a specific biomarker (e.g., for the RfD, a blood mercury 5.8 mg/L). Some have suggested that these guidance values are not sufficiently protective and should be reevaluated in light of several considerations. First, imprecision in the measurement of the critical biomarkers was not considered, which will tend to result in risk being underestimated (Grandjean and BudtzJorgensen, 2010). Second, in addition to methylmercury, seafood contains nutrients that benefit a child’s neurodevelopment. Failure to account for this introduces negative confounding, resulting in an underestimate of methylmercury’s neurotoxicity (Choi et al., 2008). Third, in the EPA assessment, fetal risk was determined based on cord blood mercury level, but the RfD specifies a maternal blood mercury level that should not be exceeded. The EPA assumed a cord to maternal blood mercury ratio of 1:1, but recent data suggest that this ratio is closer to 1.7:1 across a wide range of exposures (Jedrychowski et al., 2007a; Santos et al., 2007; Fok et al., 2007). Assuming this new ratio would produce a lower RfD. Finally, several recent epidemiological studies have demonstrated adverse effects at lower mercury biomarker levels than those identified in the studies on which the EPA, EFSA, and JECFA assessments were based (Oken et al., 2005, 2008; Jedrychowski et al., 2007b; Lederman et al., 2008; Freire et al., 2010; Sagiv et al., 2012; Lam et al., 2013). Few nationally representative surveys of mercury biomarker levels are available. In the United States (Schober et al., 2003), Germany (Seifert et al., 2000), and South Korea (Lee et al., 2012), such surveys indicate that the vast majority of people have a mercury burden below the levels of concern. However, in regions or subgroups in which seafood is a prominent component of the diet, the prevalence of mercury burdens consistent with an intake that exceeds these guidance values can be substantial (Bjornberg et al., 2005; Yaginuma-Sakurai et al., 2009). In one U.S. study, individuals who frequently consumed large predatory fish, such as swordfish, had blood mercury

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levels that ranged up to 89.5 mg/L and, in women, averaged 15 mg/L, well above the RfD (Hightower and Moore, 2004). Individuals living in regions impacted by the downstream contamination associated with artisanal gold mining, which is currently practiced in dozens of countries, mostly in South America, Africa, and Asia, are at particular risk (UNEP, 2013). When the Minamata Convention goes into force, the steps it mandates will reduce the dispersion of mercury into the environment but given the complex biogeochemistry of methylmercury, its global transport, and the primary pathways of exposure, it is unlikely to have a large impact on human biomarker levels in the short-term. Therefore, it will continue to be necessary to provide guidance to help people reduce their exposures. Technical standards such as the RfD, TWI, and PTWI are clearly not very useful to a member of the general population trying to manage mercury exposure. Instead, guidance must be framed in terms of seafood choices, but doing this in a way that is accurate, comprehensible, and easy to implement has proven challenging. Estimating one’s methylmercury intake in relation to an intake standard requires information about the amounts of different commodities consumed (e.g., fish species, rice cultivars), the methylmercury concentrations in these commodities, and the individual’s body weight. Furthermore, with regard to seafood, the message needs to be crafted in such a way that not only does one reduce methylmercury exposure, but, at the same time, maintains the nutritional benefits associated with seafood consumption (e.g., long chain polyunsaturated omega-3 fatty acids (e.g., docosahexanoic acid and eicosapentanoic acid), and contributes to the sustainability of fish stocks (i.e., by consuming seafood that is abundant, well-managed, and fished or farmed in environmentally friendly ways). The problem for consumers is that the lists of seafood that satisfy the different criteria sometimes conflict. For instance, while farmed salmon is often recommended as a good source of omega-3 fatty acids and is low in mercury, farmed Atlantic salmon is on the Monterey Bay Aquarium Seafood Watch’s list of fish that are not sustainable (http://www.seafoodwatch. org/cr/seafoodwatch.aspx). While albacore/white canned tuna (from Canada or the US, harvested by troll or pole) is on the Seafood Watch “best choices” list and is a good source of omega-3s, certain species of tuna usually classified as albacore, including Bigeye and Ahi, are on the National Resources Defense Council’s list of fish to avoid altogether because of high mercury concentrations (http://www.nrdc.org/health/ effects/mercury/guide.asp). It is a lot to expect that a consumer will be able to identify the small subset of fish that are low in mercury, high in omega-3s, and sustainable, while also factoring in personal tastes and cost. In 2004, the U.S. EPA and FDA issued a joint advisory regarding seafood consumption (http://water.epa.gov/ scitech/swguidance/fishshellfish/outreach/factsheet.cfm) that makes recommendations for total seafood consumption per week and identifies seafood with low methylmercury levels. The advisory does not address the issues of beneficial nutrients or sustainability, however. Further-

MERCURY AND PREGNANCY

more, many have expressed concerns about both the complexity of the advisory and the possibility that women (and, especially, children) following the recommendations might still have intakes exceeding the RfD. Furthermore, following the recommendations of no more than two fish servings per week would result in a failure to reach the suggested intake recommended by other organizations, such as the American Heart Association’s (AHA) suggestion that adults consume ”at least two fish servings per week”) to promote heart health (http://www.heart.org/HEARTOR G/GettingHealthy/NutritionCenter/HealthyDietGoals/Fishand-Omega-3-Fatty-Acids_UCM_303248_Article.jsp#). The FDA began to consider revisions of the advisory in 2009, but, as of the turn of 2014, it has not been released. There is evidence that seafood advisories can be effective. In Bermuda, the blood mercury level of pregnant women was reduced several-fold following the provision of local fish consumption guidelines (Dewailly et al., 2012). Given the relatively long whole body half-life of mercury of 70 to 80 days (NRC, 2000), consumption advice should have a relatively long time horizon. Recognizing this, public health authorities in the Faroe Islands recommended that females not consume pilot whale meat, an important source of mercury exposure in this population, until they had completed child-bearing, which resulted in a reduction in women’s mercury biomarker levels (Weihe et al., 2005). In the U.S., an NHANES analysis revealed a reduction in the 90th percentile of women’s blood mercury levels over the period of 1999 to 2004 without a concomitant decrease in total fish consumption, consistent with a shift in the species consumed by frequent fish consumers (Mahaffey et al., 2009). There is not a simple solution to the challenge of counseling pregnant women about how to limit methylmercury exposure to their fetuses. Seafood is a complex exposure, involving nutrients other than omega-3s as well as toxicants other than methylmercury. Women can preserve the benefits of consuming seafood while minimizing methylmercury exposure by avoiding the seafoods that have the highest methylmercury levels and by consuming, in moderation and in accordance with health-based guidelines such as those of the AHA, a wide variety of fish with lower methylmercury levels. This might be the best guidance we can offer them at the moment.

David C. Bellinger* Boston Children’s Hospital, Harvard Medical School, Harvard School of Public Health, Boston, Massachusetts

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Mercury and pregnancy.

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