Mercury is a naturally-occurring element that is widespread in the environment and exists as elemental, inorganic, and organic mercury (methylmercury) ¹. Inorganic and elemental mercury, measured in urine, are usually associated with dental amalgams, occupational exposures, and herbs and medicines adulterated with inorganic mercury ². Methylmercury (MeHg) exposure, which can be estimated by measuring concentrations in blood and hair comes almost exclusively from consumption of fish or shellfish ^1,3–5. Studies have consistently reported that increasing frequency of seafood intake is the single most influential predictor of blood MeHg concentrations ^6–9.

Fetuses are a high-risk group for MeHg exposure because of the increased susceptibility of the developing brain to environmental insults ^1,10. Three long-term studies, the Seychelles Island study ^11–13, the Faroe Islands study ^14–16, and a third study conducted in New Zealand^17–19, have investigated MeHg in children who were prenatally exposed to MeHg through maternal seafood consumption. MeHg dose-related deficits in tests of memory, attention, and language were observed in children of different ages ^13–16,19. Given that permanent damage to the developing brain can occur, MeHg exposure in pregnant women is a source for concern ¹⁰. The US Environmental Protection Agency (EPA) set the reference dose (RfD) - a dose which is unlikely to have deleterious effects - for MeHg at 0.1 μg/Kg/day ²⁰.

Total blood mercury (BHg) includes all form of mercury and is used in biomonitoring as a proxy for MeHg, although the distribution of mercury types in blood can vary ^6,21,22. Although the RfD varies by body weight, the value 5.8 μg/L (ppb) for BHg has been widely used in place of a weight-specific value in studies of mercury concentrations and health outcomes ²³. Originally, it was thought that cord blood and maternal blood mercury levels were equivalent when calculating the RfD ²⁰; however, studies comparing maternal and cord blood concentrations of MeHg have found that cord-blood mercury is higher than maternal blood mercury. According to the EPA, a review of the literature identified 21 studies that reported cord-blood mercury and maternal blood mercury data; these data indicated that cord-blood mercury concentrations are higher than maternal mercury concentrations, with a ratio of approximately 1.7 ^20,24–26. Studies have therefore suggested and used a lower RfD reflecting exposures equivalent to RfD of 3.5 μg/L total blood mercury concentration ^24–26.

Two previous studies have examined and compared BHg concentrations in pregnant and non-pregnant women; one reported no significant differences between the two groups using hair total mercury concentrations from NHANES 1999–2000 ²⁷, and the other found significantly lower concentrations of total BHg in pregnant women aged 17–39 years using NHANES 2003–2010 ²⁸. The objective of our study was to assess whether predictors of BHg concentrations were the same in pregnant and non-pregnant women.

We analyzed data on 6,770 women: 1,183 pregnant and 5,587 non-pregnant women from 1999 to 2006 who had completed interviews, exams, and valid pregnancy data. Geometric mean BHg concentrations were significantly lower in pregnant women compared to non-pregnant women (0.71 and 0.92 μg/L, respectively; p<0.0001). After adjustment for age and race/ethnicity, the difference in geometric mean BHg concentration between the groups was smaller, 0.81 and 0.93μg/L, respectively, although still statistically significant (Table 1). We also examined geometric mean BHg concentrations by trimester of pregnancy alone as well as adjusting for age and found no significant differences by trimester of pregnancy (p=0.88). There were statistically significant differences between pregnant and non-pregnant women by age (p=<0.0001) and race/ethnicity (p=<0.0001). Among pregnant women, 91% were younger than 35 years of age, compared to approximately 53% of non-pregnant women; and a greater percentage of pregnant women were Mexican American compared to non-pregnant women, approximately 16% and 9%, respectively (Table 1). Pregnant women were less likely to have reported consuming any seafood (fish or shellfish) compared to non-pregnant (73.0% and 78.1%, respectively; p=0.05), and fish specifically (62.5% and 68.8%, respectively; p=0.03) in the last 30 days but not shellfish. There were no significant differences observed between pregnant and non-pregnant women in education level or family income to poverty ratio (Table 1).

In examining the factors associated with having a high BHg concentration (at or above 3.5 μg/L), we observed that pregnancy status was not a strong predictor after adjusting for other factors (Odds Ratio [OR] for pregnant vs. non-pregnant: 0.7; 95% CI: 0.5, 1.0). Reported seafood consumption was the strongest predictor of high BHg concentrations for both pregnant (OR: 18.7; 95% CI: 4.9, 71.1) and non-pregnant (OR: 15.5; 95% CI: 7.5, 32.1) women. Among non-pregnant women, other factors significantly associated with high BHg concentrations were increasing age (OR for 26–35 vs. 16–25 years: 1.8; 95% CI: 1.3, 2.5; OR for 36–49 vs. 16–25 years: 2.0; 95% CI: 1.5, 2.7), other/multiracial ethnicity (OR compared to non-Hispanic white: 2.2; 95% CI: 1.4, 3.4), greater than high school education (OR compared to less than high school: 1.4; 95% CI: 1.0, 1.9), and higher family income to poverty ratio (OR for FIPR>3.5 compared to FIPR≤1.3: 95% CI: 2.1; 1.4, 3.3) for non-pregnant women. Similar, but non-significant patterns were observed for pregnant women, for whom the sample size was smaller (Table 2).

We assessed trends in BHg concentrations stratified by several factors among both pregnant and non-pregnant women, for which similar patterns were seen. Overall, 94% of pregnant and 89% of non-pregnant women had BHg concentrations below 3.5 μg/L. BHg concentrations increased with increasing age for both pregnant and non-pregnant women (Figure 1). There was little difference in the distribution of BHg concentrations by race/ethnicity (Figure 2), except among those in the highest 20% of the distribution, for whom non-Hispanic whites and those classified in the “other” race/ethnicity group had higher BHg concentrations than non-Hispanic blacks or Mexican Americans; Mexican Americans had the lowest BHg concentrations across the entire distribution for both groups. BHg concentrations also increased with increasing educational attainment (Figure 3) and FIPR (Figure 4), with both pregnant and non-pregnant women with highest education and FIPR having markedly higher BHg concentrations. Increasing seafood consumption was associated with higher BHg concentrations for both pregnant and non-pregnant women (Figure 5), with over 10% of women in each group who consumed seafood on 3 or more occasions in the past 30 days having BHg above 3.5μg/L.

To assess whether differences in the types of seafood consumed could explain the small but statistically significant difference in the adjusted geometric mean BHg concentrations observed among pregnant and non-pregnant women, we estimated the geometric mean BHg concentrations for pregnant and non-pregnant women stratified by seafood intake. After adjusting for age group and race/ethnicity, the geometric mean BHg concentration among those who reported consumption of seafood in the past 30 days was 0.93μg/L (95% CI: 0.89, 0.98) for pregnant women and 1.10μg/L (95% CI: 1.07, 1.13) for non-pregnant women (p=0.004). Among those who reported no consumption of seafood in the past 30 days, the adjusted geometric mean BHg among pregnant women was 0.45 (95% CI: 0.38, 0.52) μg/L and among non-pregnant women was 0.47 (95% CI: 0.43, 0.50) μg/L (p=0.64).

We observed that geometric mean BHg concentrations were slightly, but statistically significantly, lower in pregnant women compared to non-pregnant women after adjusting for age and race/ethnicity. Given that the most significant driver of high BHg concentrations was seafood consumption for both pregnant and non-pregnant women, the lower concentrations of BHg in pregnant women may be due to fewer pregnant women consuming any seafood at all (a finding supported by this analysis), consuming fewer servings of seafood, and/or properly avoiding high risk seafood species. Our findings complement the findings of the only other study of which we are aware using BHg concentrations where they also found lower levels of BHg concentrations in pregnant women ²⁸.

The United States Food and Drug Administration (FDA) as well as the EPA have issued warnings recommending that pregnant women and women of childbearing age who may become pregnant avoid consumption of certain types of fish that have high concentrations of mercury including shark, swordfish, king mackerel, and tile fish ^32,33. Many local and state agencies issue additional fish advisories and bans relating to locally caught fish ^33,34. Although the FDA and EPA also advise consumption of two servings per week of seafood with low mercury levels, such as shrimp and salmon ^32,33, these messages may not be as well-understood by pregnant women and their health care providers. A qualitative study of fish consumption during pregnancy reported that many pregnant women knew that fish might contain mercury and had received advice on limiting fish consumption but had not received advice on the types of fish that are safer to consume or contain less mercury. As such, they reported that they avoided fish consumption altogether ³⁵. Our finding of lower BHg concentrations among pregnant women could also be partially due to the fact that pregnant women who consume seafood are consuming seafood less often than non-pregnant women or that they are consuming fish low in mercury as observed in related analysis conducted by our research group (data unpublished). These potential explanations are supported by the geometric mean BHg estimates stratified by seafood consumption and could possibly be due to pregnant women adhering to recommendations put forth by the FDA ³² and EPA ³⁴ about which fish to eat during pregnancy.

Although there are concerns with MeHg exposure during pregnancy because of the high susceptibility of the developing brain ^1,10; fish and shellfish are also the primary dietary sources of long-chain Omega 3 (N-3) polyunsaturated fatty acids, specifically docosahexaenoic acid (DHA) and eicosapentaenoic acid, which are essential for optimal neurodevelopment of the fetus during pregnancy and infancy through breastmilk exposure ^33,36–40. The Dietary Guidelines for Americans 2010, from the U.S. Department of Agriculture (USDA) and the U.S. Department of Health and Human Services (HHS), recommends consumption of at least 8 ounces of variety of seafood per week for the general public corresponding to intake of an average of 250 mg/d of fatty acids, including DHA. These Guidelines also include the recommendation for pregnant and breastfeeding women to consume 8 to 12 ounces of variety of seafood per week to receive the benefits from fatty acids with the onus on the obstetricians to discuss the types of seafood and servings that are appropriate⁴¹.

Strengths of our study include its large sample size; oversampling of pregnant women during the 1999–2006 NHANES allowed us sufficient power to stratify our analysis and make comparisons between pregnant and non-pregnant women. One limitation is that as the reference doses for mercury are based on total blood mercury, therefor total blood mercury was used as a proxy for methylmercury. There are also several limitations of the NHANES data on seafood consumption. Self-reported data on fish and shellfish consumption in the past 30 days is subject to misreporting. Not all types of higher mercury fish were specifically queried, and even among those that were queried we did not have power to examine BHg concentrations by the type of seafood that was consumed. In addition, the data did not contain information about serving size or cooking methods for seafood.

While it is reassuring that the majority of pregnant women did not have BHg levels above the reference dose (≥3.5 μg/L), our observation that almost 1 out of 4 pregnant women consumed no seafood in the past 30 days is of concern given the important nutrients contained in seafood. Additional measures may be needed to increase awareness of how to balance the benefits and risks of seafood consumption during pregnancy and breastfeeding.