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

BACKGROUND: Methylmercury (MeHg) may affect fetal growth; however, prior research often lacked assessment of mercury speciation, confounders, and interactions. OBJECTIVE: Our 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. METHODS: This 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). RESULTS: Geometric mean cord blood MeHg was 0.94 µg/L (95% CI: 0.84, 1.07). In adjusted models for ponderal index, ßln(MeHg) = -0.045 (g/cm(3)) × 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, ßln(MeHg) = 0.40 cm, 95% CI: -0.02, 0.81; among high n-3 HUFAs, ßln(MeHg) = -0.15, 95% CI: -0.54, 0.25; p-interaction = 0.048] and head circumference [among low n-3 HUFAs, ßln(MeHg) = 0.01 cm, 95% CI: -0.27, 0.29; among high n-3 HUFAs, ßln(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, ßln(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/cm(3)) × 100 (95% CI: -0.065, 0.005) and -0.045 (95% CI: -0.084, -0005). CONCLUSION: We 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.

Measurement of mercury species in human blood using triple spike isotope dilution with SPME-GC-ICP-DRC-MS.

The measurement of different mercury compounds in human blood can provide valuable information about the type of mercury exposure. To this end, our laboratory developed a biomonitoring method for the quantification of inorganic (iHg), methyl (MeHg), and ethyl (EtHg) mercury in whole blood using a triple-spike isotope dilution (TSID) quantification method employing capillary gas chromatography (GC) and inductively coupled dynamic reaction cell mass spectrometry (ICP-DRC-MS). We used a robotic CombiPAL(®) sample handling station featuring twin fiber-based solid-phase microextraction (SPME) injector heads. The use of two SPME fibers significantly reduces sample analysis cycle times making this method very suitable for high sample throughput, which is a requirement for large public health biomonitoring studies. Our sample preparation procedure involved solubilization of blood samples with tetramethylammonium hydroxide (TMAH) followed by the derivatization with sodium tetra(n-propyl)borate (NaBPr(4)) to promote volatility of mercury species. We thoroughly investigated mercury species stability in the blood matrix during the course of sample treatment and analysis. The method accuracy for quantifying iHg, MeHg, and EtHg was validated using NIST standard reference materials (SRM 955c level 3) and the Centre de Toxicologie du Québec (CTQ) proficiency testing (PT) samples. The limit of detection (LOD) for iHg, MeHg, and EtHg in human blood was determined to be 0.27, 0.12, and 0.16 µg/L, respectively.

Levels of urinary total and speciated arsenic in the US population: National Health and Nutrition Examination Survey 2003-2004.

OBJECTIVE: To provide levels of total and speciated urinary arsenic in a representative sample of the US population. METHODS: For the first time, total arsenic and seven inorganic and organic arsenic species were measured in the urine of participants (n=2557) for the 2003-2004 National Health and Nutrition Examination Survey (NHANES). Data were compiled as geometric means and selected percentiles of urinary arsenic concentrations (microg/l) and creatinine-corrected urinary arsenic (microg/g creatinine) for total arsenic, dimethylarsinic acid, arsenobetaine, and a sum of the inorganic related species. RESULTS: Arsenic acid, arsenous acid, arsenocholine, and trimethylarsine oxide were detected in 7.6%, 4.6%, 1.8%, and 0.3% of the participants, respectively (the limits of detection of 0.6-1.2 microg/l). Monomethylarsonic acid was detected in 35% of the overall population. For all participants aged > or =6 years, dimethylarsinic acid (geometric mean of 3.71 microg/l) and arsenobetaine (geometric mean of 1.55 microg/l) had the greatest contribution to the total urinary arsenic levels. A relatively greater percentage contribution from arsenobetaine is seen at higher total urinary arsenic levels and from dimethylarsinic acid at lower total urinary arsenic levels. For all participants aged > or =6 years, the 95th percentiles for total urinary arsenic and the sum of inorganic-related arsenic (arsenic acid, arsenous acid, dimethylarsinic acid, and monomethylarsonic acid) were 65.4 and 18.9 microg/l, respectively. For total arsenic and dimethylarsinic acid, covariate-adjusted geometric means demonstrated several slight differences due to age, gender, and race/ethnicity. CONCLUSIONS: The data reflect relative background contributions of inorganic and seafood-related arsenic exposures in the US population. Arsenobetaine and dimethylarsinic acid are the major arsenic species present with arsenobetaine, accounting for a greater proportion of total arsenic as total arsenic levels increase.

Determination of seven arsenic compounds in urine by HPLC-ICP-DRC-MS: a CDC population biomonitoring method.

A robust analytical method has been developed and validated by use of high-performance liquid chromatography inductively coupled plasma mass spectrometry with Dynamic Reaction Cell (DRC) technology that separates seven arsenic (As) species in human urine: arsenobetaine (AB), arsenocholine, trimethylarsine oxide (TMAO), arsenate (As(V)), arsenite (As(III)), monomethylarsonate, and dimethylarsinate. A polymeric anion-exchange (Hamilton PRP X-100) column was used for separation of the species that were detected at m/z 75 by ICP-DRC-MS (PerkinElmer SCIEX ELAN DRCII) using 10% hydrogen-90% argon as the DRC gas. The internal standard (As) is added postcolumn via an external injector with a sample loop. All analyte peaks were baseline-separated except AB and TMAO. Analytical method limits of detection for the various species ranged from 0.4 to 1.7 microg L(-1) as elemental As. As(III) conversion to As(V) was avoided by adjusting the urine sample to