Cord Blood Methylmercury and Fetal Growth Outcomes in Baltimore Newborns: Potential Confounding and Effect Modification by Omega-3 Fatty Acids, Selenium, and Sex

Abstract

BackgroundMethylmercury (MeHg) may affect fetal growth; however, prior research often lacked assessment of mercury speciation, confounders, and interactions.ObjectiveOur objective was to assess the relationship between MeHg and fetal growth as well as the potential for confounding or interaction of this relationship from speciated mercury, fatty acids, selenium, and sex.MethodsThis cross-sectional study includes 271 singletons born in Baltimore, Maryland, 2004–2005. Umbilical cord blood was analyzed for speciated mercury, serum omega-3 highly unsaturated fatty acids (n-3 HUFAs), and selenium. Multivariable linear regression models controlled for gestational age, birth weight, maternal age, parity, prepregnancy body mass index, smoking, hypertension, diabetes, selenium, n-3 HUFAs, and inorganic mercury (IHg).ResultsGeometric mean cord blood MeHg was 0.94 μg/L (95% CI: 0.84, 1.07). In adjusted models for ponderal index, βln(MeHg) = –0.045 (g/cm3) × 100 (95% CI: –0.084, –0.005). There was no evidence of a MeHg × sex interaction with ponderal index. Contrastingly, there was evidence of a MeHg × n-3 HUFAs interaction with birth length [among low n-3 HUFAs, βln(MeHg) = 0.40 cm, 95% CI: –0.02, 0.81; among high n-3 HUFAs, βln(MeHg) = –0.15, 95% CI: –0.54, 0.25; p-interaction = 0.048] and head circumference [among low n-3 HUFAs, βln(MeHg) = 0.01 cm, 95% CI: –0.27, 0.29; among high n-3 HUFAs, βln(MeHg) = –0.37, 95% CI: –0.63, –0.10; p-interaction = 0.042]. The association of MeHg with birth weight and ponderal index was affected by n-3 HUFAs, selenium, and IHg. For birth weight, βln(MeHg) without these variables was –16.8 g (95% CI: –75.0, 41.3) versus –29.7 (95% CI: –93.9, 34.6) with all covariates. Corresponding values for ponderal index were –0.030 (g/cm3) × 100 (95% CI: –0.065, 0.005) and –0.045 (95% CI: –0.084, –0005).ConclusionWe observed an association of increased MeHg with decreased ponderal index. There is evidence for interaction between MeHg and n-3 HUFAs; infants with higher MeHg and n-3 HUFAs had lower birth length and head circumference. These results should be verified with additional studies.CitationWells EM, Herbstman JB, Lin YH, Jarrett J, Verdon CP, Ward C, Caldwell KL, Hibbeln JR, Witter FR, Halden RU, Goldman LR. 2016. Cord blood methylmercury and fetal growth outcomes in Baltimore newborns: potential confounding and effect modification by omega-3 fatty acids, selenium, and sex. Environ Health Perspect 124:373–379; http://dx.doi.org/10.1289/ehp.1408596

Development and application of a novel method to characterize methylmercury exposure in newborns using dried blood spots

“…For example, median total Hg levels in cord blood taken from participants of the MIREC cohort (n=2,001 pregnant women from across 10 Canadian cities; Arbuckle et al, 2016) was 0.80 μg/L with a 95 th percentile value of 3.61 μg/L. In more targeted studies across the U.S., average cord blood Hg measurements were 0.59 μg/L in San Francisco (Morello-Frosch et al, 2016), 0.94 μg/L in Baltimore (Wells et al, 2016), and 2.14 μg/L in New York (Geer et al, 2012). In other jurisdictions worldwide, the cord blood Hg levels are even higher with average values of 3.6 μg/L in Nigeria (Obi et al, 2015), 4.7 μg/L in Mexico (Basu et al, 2015b), and 8.2 μg/L in Spain (Ramon et al, 2011).…”

Blood mercury levels and fish consumption in pregnancy: Risks and benefits for birth outcomes in a prospective observational birth cohort

“…This difference may reflect the detrimental presence of pollutants such as organochlorine compounds that accumulate in the fat tissues of large oily fish accounting for differences in the effects of oily and lean fish, and a combination thereof. Many studies on maternal Hg exposure and birth outcomes do not report fish intake at all ( Al-Saleh et al, 2014b ; Hu et al, 2015 , Lucas et al, 2004 , Ramirez et al, 2000 , Wells et al, 2016 ), while others have reported fish intake but have not used the data for adjustment in the models or stratification ( Ding et al, 2013 ; Gundacker et al, 2010 , Lee et al, 2010 ). Lack of adjustment for fish intake is likely to result in an underestimation of the toxic effects of Hg as well as the nutritional benefits of eating fish.…”

“…There are relatively few studies on the effect of moderate or low levels of maternal blood or cord blood/tissue mercury levels on birth outcomes such as birth weight, birth length, head circumference or gestational age ( Karagas et al, 2012 ) (Supplementary Table A1). Such studies have generally found no associations of maternal blood mercury with these outcomes ( Al-Saleh et al, 2014b ; Ding et al, 2013 ; Gundacker et al, 2010 , Lederman et al, 2008 , Lucas et al, 2004 , Wells et al, 2016 ), with a few exceptions, mainly negative associations with birthweight ( Lee et al, 2010 , Ramon et al, 2009 ). Some studies have also included data on maternal fish consumption in addition to maternal or cord blood mercury levels during pregnancy ( Al-Saleh et al, 2014a , Ding et al, 2013 ; Gundacker et al, 2010 , Lederman et al, 2008 , Lee et al, 2010 , Ramon et al, 2009 ), but few of these have stratified or adjusted for fish consumption ( Al-Saleh et al, 2014a , Lederman et al, 2008 , Ramon et al, 2009 ).…”

Development of a Cumulative Exposure Index (CEI) for Manganese and Comparison with Bone Manganese and Other Biomarkers of Manganese Exposure

“…Replacement of values <DL is a common method to account for the uncertainty of these samples; however, this is an unbiased method only when a small percentage of values are <DL. Instead, we chose to retain the values which were detected but <DL instead of replacing them with a constant, as has been done previously [ 49 , 50 ]. While these values likely have a greater variability and uncertainty compared to values >DL, this approach is likely to reduce the potential for left-censoring to induce bias in our results.…”