Maternal Hair Concentrations Research Articles

Associations between hair levels of trace elements and the risk of preterm birth among pregnant women: A prospective nested case-control study in Beijing Birth Cohort (BBC), China

Trace elements have various physiochemical functions in humans and are associated with the occurrence of preterm birth (PB). However, their mixed effects on PB risk have rarely been studied. We aimed to investigate the associations between hair levels of trace elements and PB risk among pregnant women. A nested case-control study with a prospective cohort was conducted in Beijing City, China. We included 82 women who had a PB [total PB (tPB)] as cases [including 40 with a spontaneous PB (SPB)] and 415 who had a term delivery as controls. Hair levels of the concerned trace elements were measured including endocrine disrupting metal(loid)s [EDMs; lead, mercury (Hg), arsenic, and cadmium] and nutritional trace metal(loid)s [NTMs; zinc (Zn), iron (Fe), copper, and selenium]. Logistic regression analysis was performed to estimate the odds ratios (ORs) for PB. Bayesian kernel machine regression (BKMR) was used to assess the associations between mixed exposure to the trace elements and PB risk. Significantly lower maternal hair concentrations of Zn and Fe were observed in the SPB cases than in the controls, whereas no differences for the other trace elements. Single-element modeling results suggested second-quartile Hg maternal hair concentrations, third-quartile Zn concentrations, and fourth-quartile Fe concentrations were associated with a reduced risk of tPB with adjusted ORs of 0.43 [95% confidence interval (CI): 0.21–0.87], 0.38 (95% CI: 0.18–0.82), and 0.48 (95% CI: 0.24–0.98), respectively, compared to first-quartile values. Similar results were obtained for SPB. According to the BKMR models, hair NTMs were significantly, monotonously, and inversely associated with the risk of SPB, after controlling for covariates and levels of the four EDMs. Fe and Zn contributed the most strongly to the association. We concluded that maternal higher levels of NTMs, especially Fe and Zn, may reduce the risk of PB.

Multiple pesticides in mothers' hair samples and children's measurements at birth: Results from the French national birth cohort (ELFE).

A growing body of studies now suggests that the general population is continuously and ubiquitously exposed to numerous pesticides. However, studies investigating the possible role of environmental exposure to pesticides on fetal growth have focused on a limited set of substances, despite the hundreds of modern pesticides currently available. To explore the relation between maternal hair concentrations of 64 pesticides and metabolites and their newborns' measurements at birth, with data from the ELFE French nationwide birth cohort. We measured 64 compounds (10-100% detection) in bundles of hair 9 cm long collected at birth from 311 women who gave birth in France in 2011. We assessed their associations with birth weight, length, and head circumference, adjusted for potential confounders, and used elastic net regularization to simultaneously select the strongest predictors of measurements at birth. Selected variables were multiply imputed for missing values, and unpenalized estimators were assessed by standard linear regression. We observed statistically significant associations between maternal hair concentrations of seven pesticides or pesticide metabolites and birth measurements (weight: fipronil sulfone; length: TCPy, bitertanol, DEP, and isoproturon; head circumference: tebuconazole and prochloraz). Analyses restricted to boys identified 12 additional compounds: 8 independently associated with birth weight (3Me4NP, DCPMU, DMST, fipronil, mecoprop, propoxur, fenhexamid, and thiabendazole), 2 with birth length (dieldrin and β-endosulfan), and 6 with head circumference (β-endosulfan, β-HCH, fenuron, DCPMU, propoxur, and thiabendazole). Our results suggest that prenatal exposure to 19 pesticides or metabolites from various chemical families may influence measurements at birth. As with any exploratory research findings, results should be interpreted cautiously, until they are replicated or verified by further epidemiological or mechanistic studies.

Bioanalysis for cocaine, opiates, methadone, and amphetamines exposure detection during pregnancy.

Drug exposure during pregnancy constitutes a major legal issue and a public health concern. Drug and metabolite determination in biological matrices from mother and newborn is an objective indication of prenatal drug exposure. However, limited data are available regarding the interpretation of these analytical results in terms of window of detection and degree of exposure. We collected paired maternal hair, meconium, placenta, and umbilical cord from 727 mother-newborn dyads. We analyzed these specimens by liquid chromatography-tandem mass spectrometry for the determination of cocaine, opioids, methadone, and amphetamines, and compared the analytical results from the four different matrices. The cases were divided in non-exposure, low, and frequent exposure, based on maternal hair concentrations and segmental analysis by trimesters. For cocaine, 62 cases tested positive in hair, 9 in meconium, 6 in placenta and 7 in umbilical cord. In the case of opioids, 14 maternal hair cases were positive, 11 meconium and umbilical cord and 9 placenta samples. For methadone, 11 cases were positive in hair, 9 in meconium and 6 in placenta and umbilical cord. For amphetamines, 18 cases were positive according to maternal hair, but all meconium, placenta, and umbilical cord tested negative. Maternal hair was the most sensitive specimen to detect drug exposure during pregnancy. Meconium, placenta, and umbilical cord tested positive if hair concentrations showed frequent drug use during the whole pregnancy, especially during the third trimester. Meconium, placenta, and umbilical cord also tested positive for morphine and metabolites, if this drug was administered during labour and delivery. Copyright © 2016 John Wiley & Sons, Ltd.

Maternal-infant biomarkers of prenatal exposure to arsenic and manganese.

Because arsenic (As) and manganese (Mn) are able to pass the placenta, infants among exposed populations may be exposed to considerable levels in utero. The main objective of this paper is to evaluate infant toenails, hair, and cord blood as biomarkers of prenatal exposure to As and Mn and determine the relationship between maternal and infant As and Mn concentrations in these biomarkers. Of the 1196 pregnant women in Bangladesh who were monitored throughout pregnancy until 1 month post-partum and completed all study visits, we included 711 mother-infant pairs who had at least one maternal and one infant biomarker of exposure available for analysis. Toenail and hair samples were collected from the women during the first trimester and 1 month post-partum and from the infants at the age of 1 month. Cord blood was collected at the time of delivery. Maternal toenail concentrations were correlated with infant toenail concentrations for As and Mn (n=258, r=0.52, 95% CI: 0.43-0.60, P<0.0001 and r=0.39, 95% CI: 0.28-0.49, P<0.0001), respectively. Similarly, maternal hair concentrations were correlated with infant hair As (n=685, r=0.61, 95% CI: 0.56-0.65, P<0.0001) and infant hair Mn (n=686, r=0.21, 95% CI: 0.14-0.28, P<0.0001). Cord blood As was correlated with infant toenail and hair As, although cord blood Mn was only correlated with infant toenail. Toenails and cord blood appear to be valid biomarkers of maternal-fetal transfer of As and Mn, whereas hair may not be a suitable biomarker for in utero exposure to Mn.

Effect of hemoglobin adjustment on the precision of mercury concentrations in maternal and cord blood

The cord-blood mercury concentration is usually considered the best biomarker in regard to developmental methylmercury neurotoxicity. However, the mercury concentration may be affected by the binding of methylmercury to hemoglobin and perhaps also selenium. As cord-blood mercury analyses appear to be less precise than suggested by laboratory quality data, we studied the interrelationships of mercury concentrations with hemoglobin in paired maternal and cord blood samples from a Faroese birth cohort (N=514) and the Mothers and Children׳s Environmental Health study in Korea (n=797). Linear regression and structural equation model (SEM) analyses were used to ascertain interrelationships between the exposure biomarkers and the possible impact of hemoglobin as well as selenium. Both methods showed a significant dependence of the cord-blood concentration on hemoglobin, also after adjustment for other exposure biomarkers. In the SEM, the cord blood measurement was a less imprecise indicator of the latent methylmercury exposure variable than other exposure biomarkers available, and the maternal hair concentration had the largest imprecision. Adjustment of mercury concentrations both in maternal and cord blood for hemoglobin improved their precision, while no significant effect of the selenium concentration in maternal blood was found. Adjustment of blood–mercury concentrations for hemoglobin is therefore recommended.

Underestimation of Risk Due to Exposure Misclassification

ABSTRACT Aim. Exposure misclassification constitutes a major obstacle when developing dose-response relationships for risk assessment. A non-differentional error results in underestimation of the risk. If the degree of misclassification is known, adjustment may be achieved by sensitivity analysis. The purpose of this study was to examine the full magnitude of measurement error in determining the prenatal exposure to methylmercury. Materials and methods. We used data from a prospective study of a Faroese birth cohort. Two biomarkers of methylmercury exposure were available, i.e., the mercury concentrations in cord blood and in maternal hair (sampled at the time of parturition). The laboratory imprecision on both chemical analyses was thought to be below 5% (coefficient of variation, CV). As a third exposure parameter, we used the dietary questionnaire response on frequency of whale meat dinners. Factor analysis and structural equation analysis were applied to assess the full extent of the imprecision. Results. The calculated total imprecision much exceeded the known laboratory variation: the CV was 28–30% for the cord-blood concentration and 52–55% for the maternal hair concentration. The dietary questionnaire response was even more imprecise. Conclusions. These findings illustrate that measurement error may be greatly underestimated if judged solely from reproducibility or laboratory quality data. Adjustment by sensitivity analysis is meaningful only if realistic measurement errors are applied. When exposure measurement errors are overlooked or underestimated, decisions based on the precautionary principle will not appropriately reflect the degree of precaution that was intended.

Association between mercury concentrations in blood and hair in methylmercury-exposed subjects at different ages

Mercury concentrations were measured in paired hair and blood samples from a cohort of about 1000 children examined at birth and at 7 and 14 years of age. The ratio between concentrations in maternal hair (in μg/g) and in cord blood (μg/L) was approximately 200, but samples from the children at age 14 years showed a ratio of about 250. These findings are in accordance with previous data from smaller studies. However, an even higher ratio of about 360 was seen at 7 years of age, suggesting that hair strands at this age retain more mercury. The 95th percentile of the hair-to-blood ratio was between five-fold and nine-fold greater than the 5th percentile. The results were examined in structural equation models to estimate the total imprecision of the individual biomarker results and the possibility that the ratio may not be constant. The hair-to-blood ratio was found to increase at lower mercury concentrations, a tendency that could not be explained by potential confounders, such as alcohol intake or number of amalgam fillings. The total imprecision (coefficient of variation) for the blood determinations averaged about 30%, thereby substantially exceeding normal laboratory imprecision. Yet hair-mercury results had an even greater imprecision, which suggested that preanalytical factors, such as variable sample characteristics, impacted the results. These findings are in accordance with other evidence that the cord blood concentration is a better predictor of neurobehavioral toxicity than is the maternal hair concentration. Although practical for field studies and monitoring purposes, hair-mercury concentration results, therefore, need to be calibrated and interpreted in regard to each specific study setting.

Determination of a site-specific reference dose for methylmercury for fish-eating populations.

Determination of a site-specific reference dose for methylmercury for fish-eating populations.

Site-specific reference dose for methylmercury for fish-eating populations

The purpose of the analysis reported here was to derive a site-specific reference dose (RfD) for methylmercury, specifically for a population exposed through the chronic ingestion of contaminated fish. A study of the neurodevelopmental toxicity of methylmercury conducted on a fish-eating population in the Seychelles Islands was determined to be the most applicable for the development of the site-specific RfD. The analysis, which made use of the benchmark dose approach as an alternative to the traditional no-observed-adverse effect-level (NOAEL) approach, physiologically based pharmacokinetic (PBPK) modeling, and Monte Carlo uncertainty analysis, was designed to provide information on the distribution of acceptable ingestion rates across the population, rather than a single point estimate. Benchmark dose modeling over the wide range of neurodevelopmental endpoints reported in the Seychelles study yielded a BMDL (95% lower confidence limit) tolerable concentration of methylmercury in maternal hair of 21 ppm. This hair concentration was then converted to an expected distribution of daily ingestion rates across a population of U.S. women of childbearing age using Monte Carlo analysis with a PBPK model to evaluate the impact of interindividual variability. An uncertainty factor of 3 was applied in consideration of results from similar studies in New Zealand and the Faroe Islands that could be construed to suggest the possibility of effects at maternal hair concentrations below 10 ppm. Based on the analysis described above, the distribution of acceptable daily ingestion rates (RfDs) ranges from approximately 0.3–1.1 μg/kg/day, with a population median (50th percentile) of 0.5 μg/kg/day.

Benchmark dose calculations of methylmercury-associated neurobehavioural deficits

Prenatal methylmercury exposure is associated with neuropsychological deficits in Faroese children at age 7 years. Lower confidence bounds of benchmark doses (BMDLs) have now been calculated. With the cord-blood mercury concentration as the dose parameter, a logarithmic dose-response model tended to show a better fit than a linear dose model for the attention, language and verbal memory tests. The lowest BMDLs averaged ≈5 μg/l cord blood, which corresponds to a maternal hair concentration of ≈1 μg/g. However, most BMDLs for hair mercury concentrations were higher. Thus, the results of the benchmark calculations depend on the assumed dose-response model.

Development of a single-meal fish consumption advisory for methyl mercury.

Methyl mercury (meHg) contamination of fish is the leading cause of fish consumption advisories in the United States. These advisories have focused upon repeated or chronic exposure, whereas risks during pregnancy may also exist from a single-meal exposure if the fish tissue concentration is high enough. In this study, acute exposure to meHg from a single fish meal was analyzed by using the one-compartment meHg biokinetic model to predict maternal hair concentrations. These concentrations were evaluated against the mercury hair concentration corresponding to the U.S. Environmental Protection Agency's reference dose (RfD), which is intended to protect against neurodevelopmental effects. The one-compartment model was validated against blood concentrations from three datasets in which human subjects ingested meHg in fish, either as a single meal or multiple meals. Model simulations of the single-meal scenario at different fish meHg concentrations found that concentrations of 2.0 ppm or higher can be associated with maternal hair concentrations elevated above the RfD level for days to weeks during gestation. A single-meal fish concentration cutoff of > or = 2.0 ppm is an important consideration, especially because this single high exposure event might be in addition to a baseline meHg body burden from other types of fish consumption. This type of single-meal advisory requires that fish sampling programs provide data for individual rather than composited fish, and take into account seasonal differences that may exist in fish concentrations.

Delayed evoked potentials in children exposed to methylmercury from seafood.

Methylmercury poisoning may cause constriction of visual fields and deafness, especially if exposure occurs prenatally. However, the risks associated with exposure from contaminated seafood is unclear. We examined 149 children attending first grade in a Madeiran fishing community. As maternal dietary habits were relatively unchanged, current maternal hair concentrations were used as indicator of the child's prenatal exposure to methylmercury (geometric average, 9.64 microg/g [48.2 nmol/g]). After adjustment for age and sex, the mean (+/-SD) latency of peak III of the brainstem auditory evoked potentials at 40 Hz was increased by 0.128+/-0.047 ms when maternal hair-mercury concentrations exceeded 10 microg/g (50 nmol/g) (p for association, 0.002), and the increase of the N145 pattern-reversal visual evoked potential latency at 15 minutes of arc was 3.16+/-1.57 ms (p for association, 0.002). No such relationships were seen with the child's own hair-mercury concentration, and other clinical examinations revealed no mercury-associated deficits. Neurophysiological evidence of adverse effects on brain function are relatively independent of confounders, and should be considered in the risk assessment of this seafood pollutant.

Fetal methylmercury poisoning: clinical and toxicological data on 29 cases.

This report describes psychomotor retardation in infants caused by prenatal exposure to methylmercury. A study of 29 mother-infant pairs established a relationship between maximum maternal hair mercury concentration during pregnancy and the frequency of neurological effects in the infants. The latter included delayed achievement of developmental milestones with or without neurological signs. The infants were 4 1/2 to 5 years of age on last examination. Ten infants of mothers who had maximum hair concentrations in the range of 99 to 384 pars per million (ppm) had a significantly higher frequency of abnormal findings than those in two groups having lower maternal hair mercury concentrations (12 to 85 and 0 to 11 ppm). The group sizes were too small to allow identification of a specific "threshold" maternal hair concentration above which such effects can be expected. Transient paresthesias during pregnancy occurred in 80% of the mothers in the higher concentration group (99 to 384 ppm) as compared with 30% and 22% in the lower groups. Neurological abnormalities were found in some children whose mothers had been asymptomatic during pregnancy.