Biomonitoring of populations in Western New York at risk for exposure to Great Lakes contaminants.

The New York State Department of Health conducted the Healthy Fishing Communities Program in collaboration with the Agency for Toxic Substances and Disease Registry to assess human exposure to contaminants common to Lake Ontario, Lake Erie and surrounding rivers and waterways among populations in western New York State who eat locally caught fish. The program enrolled licensed anglers and Burmese refugees and immigrants, living near four designated Great Lakes Areas of Concern: Buffalo River, Niagara River, Eighteenmile Creek, and the Rochester Embayment. These target populations were sampled and enrolled independently into the program between February and October of 2013. A core set of contaminants were measured in blood and urine of 409 licensed anglers and 206 Burmese refugees and immigrants which included lead, cadmium, mercury, PCBs, PBDEs, organochlorine pesticides (hexachlorobenzene, mirex, DDT, DDE, and chlordane and its metabolites oxychlordane and trans-Nonachlor), and PFOS and PFOA. Biomonitoring results showed that both groups had higher geometric means for blood lead, total blood mercury, and serum PFOS compared to the 2013-2014 NHANES reference levels. The Burmese refugee group also showed higher geometric means for creatinine-adjusted urine mercury and lipid-adjusted serum DDE compared to national levels. Licensed angler participants reported eating a median of 16 locally caught fish meals in the past year. Burmese participants consumed local fish throughout the year, and most frequently in the summer (median 39 fish meals or 3 times a week). The study results provide valuable information on populations at high risk of exposure to contaminants in the Great Lakes Basin of western New York. The results provide the foundation for developing and implementing public health actions to reduce potential exposures to Great Lakes pollutants.

Tracking Declines in Mercury Exposure in the New York City Adult Population, 2004-2014.

Mercury is a toxic metal that can be measured in human blood and urine. Population-based biomonitoring from 2004 guided New York City (NYC) Department of Health and Mental Hygiene (DOHMH) efforts to reduce exposures by educating the public about risks and benefits of fish consumption-a predominant source of exposure in the general population-and removing mercury-containing skin-lightening creams and other consumer products from the marketplace. We describe changes in exposures over the past decade in relation to these local public health actions and in the context of national changes by comparing mercury concentrations measured in blood (1201 specimens) and urine (1408 specimens) from the NYC Health and Nutrition Examination Survey (NYC HANES) 2013-2014 with measurements from NYC HANES 2004 and National Health and Nutrition Examination Surveys (NHANES) 2003-2004 and 2013-2014. We found that NYC adult blood and urine geometric mean mercury concentrations decreased 46% and 45%, respectively. Adult New Yorkers with blood mercury concentration ≥ 5 µg/L (the New York State reportable level) declined from 24.8% (95% CL = 22.2%, 27.7%) to 12.0% (95% CL = 10.1%, 14.3%). The decline in blood mercury in NYC was greater than the national decline, while the decline in urine mercury was similar. As in 2004, Asian New Yorkers had higher blood mercury concentrations than other racial/ethnic groups. Foreign-born adults of East or Southeast Asian origin had the highest prevalence of reportable levels (29.7%; 95% CL = 21.0%, 40.1%) across sociodemographic groups, and Asians generally were the most frequent fish consumers, eating on average 11 fish meals in the past month compared with 7 among other groups (p < 0.001). Fish consumption patterns were similar over time, and fish continues to be consumed more frequently in NYC than nationwide (24.7% of NYC adults ate fish ten or more times in the past 30 days vs. 14.7% nationally, p < 0.001). The findings are consistent with the hypothesis that blood mercury levels have declined in part because of local and national efforts to promote consumption of lower mercury fish. Local NYC efforts may have accelerated the reduction in exposure. Having "silver-colored fillings" on five or more teeth was associated with the highest 95th percentile for urine mercury (4.06 µg/L; 95% CL = 3.1, 5.9). An estimated 5.5% of the adult population (95% CL = 4.3%, 7.0%) reported using a skin-lightening cream in the past 30 days, but there was little evidence that use was associated with elevated urine mercury in 2013-14.

Associations between IVF outcomes and essential trace elements measured in follicular fluid and urine: a pilot study.

PURPOSE: A hypothesis-generating pilot study exploring associations between essential trace elements measured in follicular fluid (FF) and urine and in vitro fertilization (IVF) endpoints. METHODS: We recruited 58 women undergoing IVF between 2007 and 2008, and measured cobalt, chromium, copper, manganese, molybdenum, and zinc in FF (n = 46) and urine (n = 45) by inductively coupled plasma mass spectrometry (ICP-MS). We used multivariable regression models to assess the impact of FF and urine trace elements on IVF outcomes, adjusted for age, body mass index, race, and cigarette smoking. RESULTS: Trace elements were mostly present at lower concentrations in FF than in urine. The average number of oocytes retrieved was positively associated with higher urine cobalt, chromium, copper, and molybdenum concentrations. FF chromium and manganese were negatively associated with the proportion of mature oocytes, yet urine manganese had a positive association. FF zinc was inversely associated with average oocyte fertilization. Urine trace elements were significant positive predictors for the total number of embryos generated. FF copper predicted lower embryo fragmentation while urine copper was associated with higher embryo cell number and urine manganese with higher embryo fragmentation. No associations were detected for implantation, pregnancy, or live birth. CONCLUSIONS: Our results suggest the importance of trace elements in both FF and urine for intermediate, although not necessarily clinical, IVF endpoints. The results differed using FF or urine biomarkers of exposure, which may have implications for the design of clinical and epidemiologic investigations. These initial findings will form the basis of a more definitive future study.

Birth outcomes and background exposures to select elements, the Longitudinal Investigation of Fertility and the Environment (LIFE).

Evidence suggests that trace exposures to select elements may increase the risk for adverse birth outcomes. To investigate further, we used multiple regression to assess associations between preconception parental exposures to Pb, Cd, and total Hg in blood, and 21 elements in urine, with n=235 singleton birth outcomes, adjusted for confounders and partner's exposure. Earlier gestational age at delivery (GA) was associated with higher tertiles of urine maternal W (-1.22 days) and paternal U (-1.07 days), but GA was later for higher tertiles of maternal (+1.11 days) and paternal (+1.30 days) blood Hg. Additional analysis indicated shorter GA associated with higher paternal urine Ba, W, and U, and with higher maternal blood Pb for boys, but GA was longer in association with higher maternal urine Cr. Birth weight (BW) was lower for higher tertiles of paternal urine Cs (-237.85g), U (-187.34g), and Zn (-209.08g), and for higher continuous Cr (P=0.021). In contrast, BW was higher for higher tertiles of paternal urine As (+194.71g) and counterintuitively for maternal blood Cd (+178.52g). Birth length (BL) was shorter for higher tertiles of urine maternal W (-1.22cm) and paternal U (-1.10cm). Yet, higher tertiles of maternal (+1.11cm) and paternal (+1.30) blood Hg were associated with longer BL. Head circumference at delivery was lower for higher tertiles of paternal urine U (-0.83cm), and for higher continuous Mo in boys (-0.57cm). Overall, associations were most consistently indicated for GA and measures of birth size with urine W and U, and paternal exposures were more frequently associated than maternal. Though limited by several factors, ours is the largest multi-element investigation of prospective couple-level trace exposures and birth outcomes to date; the novel observations for W and U merit further investigation.

Impact of urine concentration adjustment method on associations between urine metals and estimated glomerular filtration rates (eGFR) in adolescents.

Positive associations between urine toxicant levels and measures of glomerular filtration rate (GFR) have been reported recently in a range of populations. The explanation for these associations, in a direction opposite that of traditional nephrotoxicity, is uncertain. Variation in associations by urine concentration adjustment approach has also been observed. Associations of urine cadmium, thallium and uranium in models of serum creatinine- and cystatin-C-based estimated GFR (eGFR) were examined using multiple linear regression in a cross-sectional study of adolescents residing near a lead smelter complex. Urine concentration adjustment approaches compared included urine creatinine, urine osmolality and no adjustment. Median age, blood lead and urine cadmium, thallium and uranium were 13.9 years, 4.0 µg/dL, 0.22, 0.27 and 0.04 g/g creatinine, respectively, in 512 adolescents. Urine cadmium and thallium were positively associated with serum creatinine-based eGFR only when urine creatinine was used to adjust for urine concentration (ß coefficient=3.1 mL/min/1.73 m(2); 95% confidence interval=1.4, 4.8 per each doubling of urine cadmium). Weaker positive associations, also only with urine creatinine adjustment, were observed between these metals and serum cystatin-C-based eGFR and between urine uranium and serum creatinine-based eGFR. Additional research using non-creatinine-based methods of adjustment for urine concentration is necessary.

Regional distribution and accumulation of lead in caprine brain tissues following a long-term oral dosing regimen.

It is well known that the brain is a key target organ for lead (Pb)-induced toxicity, with exposure potentially resulting in numerous adverse neurological effects. However, information on the distribution and accumulation of Pb within different brain regions is scarce. In this study, Pb uptake and accumulation were characterized in brain and related tissues obtained from a convenience sample of goats dosed with Pb. Tissues were harvested postmortem from 10 animals (9 dosed and 1 undosed) that are used to produce blood Pb pools for the New York State Department of Health's Proficiency Testing program. Whole brains were subdivided into 14 distinct anatomical regions to explore interregional differences. Related tissues included the olfactory epithelium and spinal cord. Where sufficient tissue mass permitted, further subdivision into smaller sections was carried out to examine intraregional Pb variability. Determination of Pb content in these tissues was accomplished using inductively coupled plasma mass spectrometry (ICP-MS), with accuracy assessed using reference materials certified for Pb. Lead content (dry weight) varied from <10 ng/g, that is, below the method detection limit, to as much as 4.45 × 10(4) ng/g Pb. Olfactory epithelium Pb content was several orders of magnitude greater than found in other regions analyzed. Enrichment of Pb was also observed in the olfactory bulb and choroid plexus. Data for each region analyzed were pooled from all goats to identify regions with the greatest propensity for Pb accumulation. Data related to Pb content were also assessed individually within each goat and significant differences in Pb content between regions were determined.

Urine cortisol concentration as a biomarker of stress is unrelated to IVF outcomes in women and men.

PURPOSE: Our primary objective was to assess associations between urine cortisol as a biomarker of psychological stress and in vitro fertilization (IVF) outcomes. A secondary objective was to assess associations between toxic metals and cortisol. METHODS: Urine and blood specimens were collected from 52 women and 28 male partners completing a first IVF procedure, on the day of oocyte retrieval. Urine cortisol was measured with an enzyme-linked immunosorbent assay. Mercury (Hg), cadmium (Cd), and lead (Pb) were determined in blood and Cd in urine by inductively coupled plasma-mass spectrometry. RESULTS: No associations were indicated for cortisol with IVF outcomes in multivariable regression models adjusted for covariates. However, we detected positive linear associations for cortisol and urine Cd (ß = 9.96, 95%CI 1.52, 21.44) and blood Hg (ß = 1.44, 95%CI 0.31, 3.18). An exploratory stratified analysis suggested a potential inverse association between urine cortisol and oocyte fertilization among women with low, but not high blood Hg. CONCLUSION: While limited, these preliminary data suggest that psychological stress may not play a major role in IVF outcomes, which therefore could be one less concern for couples and their clinicians. Our data also raise the possibility for toxic metals to modify associations between cortisol and IVF outcomes among women. However, these preliminary results require corroboration in an experimental animal model and confirmation in a larger, more definitive observational study.

Trace element analysis of human urine collected after administration of Gd-based MRI contrast agents: characterizing spectral interferences using inorganic mass spectrometry.

Analysis of human urine is commonly used in biomonitoring studies to assess exposure to essential (e.g., Cu, Zn, Se) and non-essential (Pb, Cd, Pt) trace elements. These data are also used in epidemiological studies to evaluate potential associations between trace element exposure and various health outcomes within a population. Today most trace element analyses are typically performed using quadrupole-based inductively coupled plasma mass spectrometry (Q-ICP-MS). However, there is always the potential for spectral interferences with Q-ICP-MS instrumentation, especially when analyzing human specimens that may contain medications and other exogenous substances. Moreover, such xenobiotics may be unknown to the investigators. In a recent study focusing on environmental exposures and endometriosis: Endometriosis: Natural History, Diagnosis, and Outcomes (ENDO Study), urine specimens (n=619) were collected from participating women upon enrollment into the study or prior to surgery or pelvic magnetic resonance imaging (MRI), and analyzed for 21 trace elements by Q-ICP-MS. Here we report on some anomalous results observed for Se and Pt with elevated concentrations up to several orders of magnitude greater than what might be expected based on established reference intervals. Further investigations using Sector Field (SF-) ICP-MS instrumentation led to identification of doubly charged and polyatomic gadolinium (Gd) species traced to a Gd-based contrast agent that was administered to some subjects just prior to urine collection. Specifically, interferences from Gd2+ and several minor polyatomics were identified as interferences on all of the major isotopes of Se including 74Se, 76Se, 77Se, 78Se, 80Se, and 82Se. While trace amounts of Pt were present in the urine, a number of Gd-containing polyatomic species were also evident as major interferences on all isotopes of Pt (190Pt, 192Pt, 194Pt, 195Pt, 196Pt, and 198Pt), including Gd-chlorides, Gd-argides, and Gd-oxides. These observations underscore the importance of considering potential isobaric interferences when interpreting unusual trace element results for clinical specimens.

DNA methylation changes in whole blood is associated with exposure to the environmental contaminants, mercury, lead, cadmium and bisphenol A, in women undergoing ovarian stimulation for IVF.

BACKGROUND: Changes in DNA methylation may play an important role in the deleterious reproductive effects reported in association with exposure to environmental pollutants. In this pilot study, we identify candidate methylation changes associated with exposure to pollutants in women undergoing in vitro fertilization (IVF). METHODS: Blood and urine were collected from women on the day of oocyte retrieval. Whole blood was analyzed for mercury and lead, and urine for cadmium using inductively coupled plasma mass spectrometry. Unconjugated bisphenol A (BPA) was analyzed in serum using high-performance liquid chromatography with Coularray detection. Participants were dichotomized as higher or lower exposure groups by median concentrations. Using the Illumina GoldenGate Methylation Cancer Panel I, DNA methylation in whole blood from 43 women was assessed at 1505 CpG sites for association with exposure levels of each pollutant. Candidate CpG sites were identified using a Diff Score >|13| (P< 0.05) and an absolute difference >10% which were confirmed using bisulfite pyrosequencing. RESULTS: Methylation of the GSTM1/5 promoter was increased for women with higher mercury exposure (P= 0.04); however, no correlation was observed (r= 0.17, P= 0.27). Reduced methylation was detected in the COL1A2 promoter in women with higher exposure to lead (P= 0.004), and an inverse correlation was observed (r = - 0.45, P= 0.03). Lower methylation of a promoter CpG site at the TSP50 gene was detected in women with higher BPA exposure (P= 0.005), and again an inverse correlation was identified (r = - 0.51, P= 0.001). CONCLUSIONS: Altered DNA methylation at various CpG sites was associated with exposure to mercury, lead or BPA, providing candidates to be investigated using a larger study sample, as the results may reflect an independently associated predictor (e.g. socioeconomic status, diet, genetic variants, altered blood cell composition). Further studies accommodating variations in these factors will be needed to confirm these associations and identify their underlying causes.

Associations between toxic metals in follicular fluid and in vitro fertilization (IVF) outcomes.

PURPOSE: We previously reported associations between trace concentrations of Hg, Cd and Pb in blood and urine and reproductive outcomes for women undergoing in-vitro fertilization (IVF). Here we assess measurements in single follicular fluid (FF) specimens from 46 women as a presumably more relevant marker of dose for reproductive toxicity. METHODS: FF specimens were analyzed for Hg, Cd and Pb using sector field-inductively coupled plasma-mass spectrometry (SF-ICP-MS). Variability sources were assessed by nested ANOVA. Multivariable regression was used to evaluate associations for square root transformed metals with IVF outcomes, adjusting for confounders. RESULTS: An inverse association is detected for FF Pb and fertilization (relative risk (RR) = 0.68, P = 0.026), although positive for Cd (RR = 9.05, P = 0.025). While no other statistically significant associations are detected, odds ratios (OR) are increased for embryo cleavage with Hg (OR = 3.83, P = 0.264) and Cd (OR = 3.18, P = 0.644), and for embryo fragmentation with Cd (OR = 4.08, P = 0.586) and Pb (OR = 2.22, P = 0.220). Positive estimates are observed for Cd with biochemical (RR = 19.02, P = 0.286) and clinical pregnancies (RR = 38.80, P = 0.212), yet with very low precision. CONCLUSIONS: We have identified associations between trace amounts of Pb and Cd in FF from a single follicle, and oocyte fertilization. Yet, the likelihood of biological variation in trace element concentrations within and between follicles, coupled with levels that are near the limits of detection suggest that future work should examine multiple follicles using a 'one follicle-one oocyte/embryo' approach. A larger study is merited to assess more definitively the role that these environmental factors could play with respect to egg quality in IVF programs.

Assessment of prenatal mercury exposure in a predominately Caribbean immigrant community in Brooklyn, NY.

Prenatal mercury exposure and its fetotoxic effects may be of particular concern in urban immigrant communities as a result of possible contributing cultural factors. The most common source of exposure in these communities is ingestion of fish and shellfish contaminated with methylmercury. Other sources of exposure may occur in ritualistic practices associated with Hispanic and Caribbean-based religions. This study 1) assessed total mercury levels in both random urine specimens from pregnant women, and in cord blood; and 2) examined environmental sources of exposure from a convenience sample in a predominantly Caribbean immigrant population in Brooklyn, New York. A questionnaire designed in collaboration with health professionals from the Caribbean community assessed the frequency of fish consumption, ritualistic practices, occupational exposures, and use of dental amalgams and mercury-containing skin and household products. The geometric mean for total mercury in cord blood was 2.14 µg L(-1) (95%CI: 1.76-2.60) (n = 78), and 0.45 µg L(-1) (95%CI: 0.37-0.55) (n = 183) in maternal urine corrected for creatinine (µg g(-1)). Sixteen percent of cord blood mercury levels exceeded the estimated equivalent of U.S. Environmental Protection Agency's Reference Dose (5.8 µg L(-1) blood). Predictors of cord blood mercury included maternal fish consumption and foreign birth of the mother. Predictors of urine mercury included foreign birth of the mother, number of dental amalgams, and special product use. There were no reports of mercury use in ritualistic practices or in cosmetics; however some women reported use of religious medals and charms. This study characterized risk factors for mercury exposure in a sample of urban, predominantly Caribbean-born blacks. Findings may help target interventions in this population, which might include appropriate fish selection and consumption frequency during pregnancy, and safe handling of mercury-containing products in the home.

Associations of low-level urine cadmium with kidney function in lead workers.

OBJECTIVES: Low-level cadmium exposure, resulting in, for example, urinary cadmium <2.0 µg/g creatinine, is widespread; recent data suggest nephrotoxicity even at these low levels. Few studies have examined the impact of low-level cadmium exposure in workers who are occupationally exposed to other nephrotoxicants such as lead. METHODS: We evaluated associations of urine cadmium, a measure of cumulative dose, with four glomerular filtration measures and N-acetyl-ß-D-glucosaminidase (NAG) in lead workers. Recent and cumulative lead doses were assessed via blood and tibia lead, respectively. RESULTS: In 712 lead workers, mean (SD) blood and tibia lead values, urine cadmium values and estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation were 23.1 (14.1) µg/dl, 26.6 (28.9) µg Pb/g bone mineral, 1.15 (0.66) µg/g creatinine and 97.4 (19.2) ml/min/1.73 m(2), respectively. After adjustment for age, sex, body mass index, urine creatinine, smoking, alcohol, education, annual income, diastolic blood pressure, current or former lead worker job status, new or returning study participant, and blood and tibia lead, higher ln-urine cadmium was associated with higher calculated creatinine clearance, eGFR (ß = 8.7 ml/min/1.73 m(2); 95% CI 5.4 to 12.1) and ln-NAG but lower serum creatinine. CONCLUSIONS: Potential explanations for these results include a normal physiological response in which urine cadmium levels reflect renal filtration, the impact of adjustment for urine dilution with creatinine in models of kidney outcomes, and cadmium-related hyperfiltration.

Differences in urine cadmium associations with kidney outcomes based on serum creatinine and cystatin C.

Cadmium is a well-known nephrotoxicant; chronic exposure increases risk for chronic kidney disease. Recently, however, associations between urine cadmium and higher creatinine-based estimated glomerular filtration rate (eGFR) have been reported. Analyses utilizing alternate biomarkers of kidney function allow evaluation of potential mechanisms for these observations. We compared associations of urine cadmium with kidney function measures based on serum cystatin C to those with serum creatinine in 712 lead workers. Mean (standard deviation) molybdenum-corrected urine cadmium, Modification of Diet in Renal Disease (MDRD) eGFR and multi-variable cystatin C eGFR were 1.02 (0.65) µg/g creatinine, and 97.4 (19.2) and 112.0 (17.7) mL/min/1.73 m2, respectively. The eGFR measures were moderately correlated (rs=0.5; p<0.001). After adjustment, ln (urine cadmium) was not associated with serum cystatin-C-based measures. However, higher ln (urine cadmium) was associated with higher creatinine-based eGFRs including the MDRD and an equation incorporating serum cystatin C and creatinine (beta-coefficient=4.1 mL/min/1.73 m2; 95% confidence interval=1.6, 6.6). Urine creatinine was associated with serum creatinine-based but not cystatin-C-based eGFRs. These results support a biomarker-specific, rather than a kidney function, effect underlying the associations observed between higher urine cadmium and creatinine-based kidney function measures. Given the routine use of serum and urine creatinine in kidney and biomarker research, additional research to elucidate the mechanism(s) for these associations is essential.

Biomonitoring for exposure to multiple trace elements via analysis of urine from participants in the study of metals and assisted reproductive technologies (SMART).

Humans are exposed to concentrations of multiple trace elements through a variety of background sources; many are suspected reproductive toxicants. Prior to investigating associations between trace elements and human reproductive health, potential biomarkers of exposure should be characterized by sources of variability in the population at risk. Factors influencing elemental exposure should also be identified to ensure their consideration as potential confounding variables. The principal aim of this study is to characterize sources of variability for 19 trace elements measured in urine specimens collected from 55 women and 36 male partners completing a 1st cycle of in vitro fertilization (IVF). Urine specimens were analyzed using a biomonitoring method based on inductively coupled plasma-mass spectrometry (ICP-MS). Randomly selected urine specimens (∼6%) were analyzed in duplicate, and these data were used to characterize sources of variability. Nine trace elements including As, Ba, Cd, Cs, Co, Cu, Mn, Mo, and Zn, were quantified in most specimens, indicating their utility in future epidemiologic studies of trace elements exposure and IVF outcomes. With few exceptions, normalizing urine using the traditional creatinine-correction procedure, or an alternative approach based on a linear regression model, increased residual variability only slightly. Sex and race appear to be important factors to consider in epidemiologic studies conducted in this population. Urine concentrations for most elements are similar to those reported in the 2005-2006 National Health and Nutrition Examination Survey (NHANES); however, differences in others may indicate regional trends or a unique exposure history for this infertile study population.

Recent cadmium exposure among male partners may affect oocyte fertilization during in vitro fertilization (IVF).

PURPOSE: We recently reported evidence suggesting associations between urine cadmium concentrations, reflecting long-term exposure, measured in 25 female patients (relative risk = 1.41, P = 0.412) and 15 of their male partners (relative risk = 0.19, P = 0.097) and oocyte fertilization in vitro. Blood cadmium concentrations reflect more recent exposure. METHODS: We here incorporate those measures into our prior data set and employ multivariable log-binomial regression models to generate hypotheses concerning the relative effects of long-term and recent cadmium exposure on oocyte fertilization in vitro. RESULTS: No association is indicated for blood cadmium from women and oocyte fertilization, adjusted for urine cadmium and creatinine, blood lead and mercury, age, race/ethnicity and cigarette smoking (relative risk = 0.88, P = 0.828). However, we suggest an inverse adjusted association between blood cadmium from men and oocyte fertilization (relative risk = 0.66, P = 0.143). CONCLUSIONS: These results suggest that consideration of long-term and recent exposures are both important for assessing the effect of partner cadmium levels on oocyte fertilization in vitro.

Low-level environmental metals and metalloids and incident pregnancy loss.

Environmental exposure to metals and metalloids is associated with pregnancy loss in some but not all studies. We assessed arsenic, cadmium, mercury, and lead concentrations in 501 couples upon trying for pregnancy and followed them throughout pregnancy to estimate the risk of incident pregnancy loss. Using Cox proportional hazard models, we estimated hazard ratios (HR) and 95% confidence intervals (CIs) for pregnancy loss after covariate adjustment for each partner modeled individually then we jointly modeled both partners' concentrations. Incidence of pregnancy loss was 28%. In individual partner models, the highest adjusted HRs were observed for female and male blood cadmium (HR=1.08; CI 0.81, 1.44; HR=1.09; 95% CI 0.84, 1.41, respectively). In couple based models, neither partner's blood cadmium concentrations were associated with loss (HR=1.01; 95% CI 0.75, 1.37; HR=0.92; CI 0.68, 1.25, respectively). We observed no evidence of a significant relation between metal(loids) at these environmentally relevant concentrations and pregnancy loss.

In vitro characterization of an in situ microdialysis sampling assay for elastase activity detection.

A microdialysis sampling method has been developed to detect the in vitro presence of a proteolytic enzyme, porcine elastase, external to a microdialysis probe. Elastase converts the substrate, succinyl(Ala)(3)-p-nitroanilide (suc(Ala)(3)-p-NA), to p-nitroaniline (p-NA). The substrate, suc(Ala)(3)-p-NA, was locally delivered through the microdialysis probe to external solutions containing different elastase activities (0.025-0.5 units/mL). The product, p-NA, was recovered back into the probe. Dialysates containing both suc(Ala)(3)-p-NA and p-NA were quantified using HPLC-UV. Different microdialysis suc(Ala)(3)-p-NA extraction efficiencies (EE) were observed among different elastase-containing solutions (buffer and 0.3% agar solutions). The p-NA concentrations recovered back into the microdialysis probe correlated with the elastase activity external to the microdialysis probe. The greatest fraction of p-NA recovered as compared to substrate lost occurred with the highest flow rate used (5.0 microL/min). However, the highest concentrations of p-NA recovered occurred at the lowest flow rates. This method may allow for microdialysis sampling to be used as a means to study localized enzyme activity.

Maternal mercury exposure, season of conception and adverse birth outcomes in an urban immigrant community in Brooklyn, New York, U.S.A.

Adverse birth outcomes including preterm birth (PTB: <37 weeks gestation) and low birth weight (LBW: <2500 g) can result in severe infant morbidity and mortality. In the United States, there are racial and ethnic differences in the prevalence of PTB and LBW. We investigated the association between PTB and LBW with prenatal mercury (Hg) exposure and season of conception in an urban immigrant community in Brooklyn, New York. We recruited 191 pregnant women aged 18-45 in a Brooklyn Prenatal Clinic and followed them until delivery. Urine specimens were collected from the participants during the 6th to 9th month of pregnancy. Cord blood specimens and neonate anthropometric data were collected at birth. We used multivariate logistic regression models to investigate the odds of LBW or PTB with either maternal urinary mercury or neonate cord blood mercury. We used linear regression models to investigate the association between continuous anthropometric outcomes and maternal urinary mercury or neonate cord blood mercury. We also examined the association between LBW and PTB and the season that pregnancy began. Results showed higher rates of PTB and LBW in this cohort of women compared to other studies. Pregnancies beginning in winter (December, January, February) were at increased odds of LBW births compared with births from pregnancies that began in all other months (OR7.52 [95% CI 1.65, 34.29]). We observed no association between maternal exposure to Hg, and either LBW or PTB. The apparent lack of association is consistent with other studies. Further examination of seasonal association with LBW is warranted.

Spatial clustering of toxic trace elements in adolescents around the Torreón, Mexico lead-zinc smelter.

High blood lead (BPb) levels in children and elevated soil and dust arsenic, cadmium, and lead were previously found in Torreón, northern Mexico, host to the world's fourth largest lead-zinc metal smelter. The objectives of this study were to determine spatial distributions of adolescents with higher BPb and creatinine-corrected urine total arsenic, cadmium, molybdenum, thallium, and uranium around the smelter. Cross-sectional study of 512 male and female subjects 12-15 years of age was conducted. We measured BPb by graphite furnace atomic absorption spectrometry and urine trace elements by inductively coupled plasma-mass spectrometry, with dynamic reaction cell mode for arsenic. We constructed multiple regression models including sociodemographic variables and adjusted for subject residence spatial correlation with spatial lag or error terms. We applied local indicators of spatial association statistics to model residuals to identify hot spots of significant spatial clusters of subjects with higher trace elements. We found spatial clusters of subjects with elevated BPb (range 3.6-14.7 µg/dl) and urine cadmium (0.18-1.14 µg/g creatinine) adjacent to and downwind of the smelter and elevated urine thallium (0.28-0.93 µg/g creatinine) and uranium (0.07-0.13 µg/g creatinine) near ore transport routes, former waste, and industrial discharge sites. The conclusion derived from this study was that spatial clustering of adolescents with high BPb and urine cadmium adjacent to and downwind of the smelter and residual waste pile, areas identified over a decade ago with high lead and cadmium in soil and dust, suggests that past and/or present plant operations continue to present health risks to children in those neighborhoods.