Maternal Blood Pb Research Articles

Exposure to manganese and lead disrupt the human placental serotonergic system

Objectives: Serotonin is crucial for placental function and fetal development. Maternal exposure to metals can interfere with the placenta functioning and fetal development. The aim of this study is to determine if low concentrations of manganese (Mn) and lead (Pb) alter placental serotonin system. Methods and results: Birth biological samples from a cohort of pregnant women were collected and Mn and Pb levels were measured in maternal and cord blood, and placenta. Expression of placental serotonin 5-HT2A receptor mRNA is lower in high-level groups of Pb and Mn in maternal blood compared to low-level groups. Placental expression of the serotonin transporter (SERT) protein is lower in high-level group of Pb in cord blood compared to low-level group. To better understand the effect of metals on the placental serotonin system, BeWo cell line (trophoblast model) was exposed to increasing concentrations of Mn and Pb. Exposure to 1 nM of Pb reduced SERT expression by 64% in BeWo cells. SERT activity in BeWo cells exposed to Mn (1000 nM) and Pb (0.01 nM) was decreased by 30% and 52%, respectively, and was accompanied by a decrease in serotonin cell level. Conclusion: This study shows that low concentrations of Mn and Pb affect placental serotonin system, which could disturb the proper course of pregnancy and fetal development.

Maternal and fetal exposure to cadmium, lead, manganese and mercury: The MIREC study

Given the susceptibility of the fetus to toxicants, it is important to estimate their exposure. Approximately 2000 pregnant women were recruited in 2008–2011 from 10 cities across Canada. Cd, Pb, Mn and total Hg were measured in maternal blood from the 1st and 3rd trimesters, umbilical cord blood, and infant meconium. Nutrient intakes of vitamin D, iron, and calcium (Ca) were assessed using a food frequency questionnaire and a dietary supplement questionnaire.Median concentrations in 1st trimester maternal blood (n = 1938) were 0.20, 8.79 and 0.70 μg/L for Cd, Mn and Hg, respectively, and 0.60 μg/dL for Pb. While the median difference between the paired 1st and 3rd trimester concentrations of Cd was 0, there was a significant decrease in Pb (0.04 μg/dL) and Hg (0.12 μg/L) and an increase in Mn (3.30 μg/L) concentrations over the course of the pregnancy. While Cd was rarely detected in cord blood (19%) or meconium (3%), median Pb (0.77 μg/dL), Mn (31.87 μg/L) and Hg (0.80 μg/L) concentrations in cord blood were significantly higher than in maternal blood. Significant negative associations were observed between estimated Ca intake and maternal Cd, Pb, Mn and Hg, as well as cord blood Pb. Vitamin D intake was associated with lower maternal Cd, Pb, and Mn as well as Pb in cord blood.Even at current metal exposure levels, increasing dietary Ca and vitamin D intake during pregnancy may be associated with lower maternal blood Pb and Cd concentrations and lower Pb in cord blood.

Use of human milk in the assessment of toxic metal exposure and essential element status in breastfeeding women and their infants in coastal Croatia

Pregnant and lactating women and infants are vulnerable population groups for adverse effects of toxic metals due to their high nutritional needs and the resultant increased gastrointestinal absorption of both, essential and toxic elements. Although breastfeeding is recommended for infants worldwide, as human milk is the best source of nutrients and other required bioactive factors, it is also a pathway of maternal excretion of toxic substances including toxic metals and thus a source of infant exposure. The aim of this research was to assess health risks in breastfeeding women in the coastal area of the Republic of Croatia and their infants (N=107) due to maternal exposure to Cd and Pb via cigarette smoking, and Hg via seafood and dental amalgam fillings, and their interaction with essential elements. Biological markers of exposure were the concentrations of main toxic metals Pb, Cd and Hg in maternal blood and three types of breast milk throughout lactation stages. Biological markers of effects were the levels of essential elements Ca, Fe, Cu, Zn and Se in maternal serum and breast milk. With regard to cigarette smoking as a source of exposure to Cd and Pb, there were effects of smoking on Cd concentration in blood and correlations between the smoking index and Cd concentrations in maternal blood (Ͽ=0.593; P<0.001) and mature milk (Ͽ=0.271; P=0.011) and Pb concentration in transitional milk (Ͽ=0.280; P=0.042). Regarding fish, we found correlations between weekly consumption frequency and total Hg concentrations in maternal blood (Ͽ=0.292; P=0.003) and mature milk (Ͽ=0.303; P=0.003). The number of dental amalgam fillings correlated with total Hg concentrations in colostrum (Ͽ=0.489; P=0.005) and transitional milk (Ͽ=0.309; P=0.018). As for the essential element status, only Se levels in maternal serum decreased by 10% in persons who continued smoking during pregnancy compared to non-smokers. In conclusion, the levels of main toxic metals Cd, Pb and Hg and essential elements Ca, Fe, Cu, Zn and Se in maternal blood and three types of breast milk samples in the studied area of coastal Croatia showed no risk of disrupted essential element levels with regard of toxic metal exposure in both breastfeeding women and their infants.

Low level lead exposure and pregnancy outcomes in an observational birth cohort study: dose-response relationships.

BackgroundNational and international guidelines on safe levels for blood Pb in pregnancy focus on a threshold above which exposure is of concern. However, it has recently been suggested that the decrease in birth weight per unit increase in blood Pb is actually greater at lower than at higher concentrations of Pb without evidence of a lower threshold of effect. Our aim was to investigate whether there was evidence for a differential effect of maternal Pb levels on birth outcomes and/or a threshold value for effects.MethodsBlood samples from pregnant women enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) were analysed. Data collected on the infants included anthropometric variables. We fitted adjusted multivariable fractional polynomial models for birth outcomes.ResultsAdjusted models that assumed a linear relationship between untransformed blood Pb and the outcomes provided the best fit: an increase of 1 µg/dl was associated with changes in birth weight of −9.93 (95 % CI −20.27, 0.41) g, head circumference −0.03 (95 % CI −0.06, 0.00) cm and crown–heel length −0.05 (95 % CI −0.10, 0.00) cm.ConclusionThere was no evidence in this study to suggest a supralinear dose–response relationship or a lower threshold for the effect of maternal blood Pb on birth outcomes. This has implications for consideration of national and international guidelines on levels of concern in pregnancy. Exposure to Pb should be kept as low as possible during pregnancy to minimise adverse outcomes.

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.

Mirna Expression in the Cervix Is Associated with Lead and Mercury Exposure during Pregnancy

Mirna Expression in the Cervix Is Associated with Lead and Mercury Exposure during PregnancyAbstract Number:2550 Alison Sanders*, Heather Burris, Allan Just, Katherine Svensson, Chitra Amarasiriwardena, Valeria Motta, Adriana Mercado-Garcia, Joel Schwartz, Martha Tellez-Rojo, Robert Wright, and Andrea Baccarelli Alison Sanders* Icahn School of Medicine at Mount Sinai, United States, E-mail Address: [email protected] Search for more papers by this author , Heather Burris Beth Isreal Deaconess Medical Center, Harvard Medical School, United States, E-mail Address: [email protected] Search for more papers by this author , Allan Just Harvard School of Public Health, United States, E-mail Address: [email protected] Search for more papers by this author , Katherine Svensson Icahn School of Medicine at Mount Sinai, United States, E-mail Address: [email protected] Search for more papers by this author , Chitra Amarasiriwardena Icahn School of Medicine at Mount Sinai, United States, E-mail Address: [email protected] Search for more papers by this author , Valeria Motta Harvard School of Public Health, United States, E-mail Address: [email protected] Search for more papers by this author , Adriana Mercado-Garcia National Institute of Public Health , Mexico, E-mail Address: [email protected] Search for more papers by this author , Joel Schwartz Harvard School of Public Health, United States, E-mail Address: [email protected] Search for more papers by this author , Martha Tellez-Rojo National Institute of Public Health , Mexico, E-mail Address: [email protected] Search for more papers by this author , Robert Wright Icahn School of Medicine at Mount Sinai, United States, E-mail Address: [email protected] Search for more papers by this author , and Andrea Baccarelli Harvard School of Public Health, United States, E-mail Address: [email protected] Search for more papers by this author AbstractToxic metals including lead (Pb) and mercury (Hg) are associated with adverse pregnancy outcomes. miRNAs are small non-coding RNAs that post-transcriptionally control gene expression. miRNAs are particularly susceptible to environmental exposures, and no previous studies have examined environmentally-associated alterations in cervix miRNA expression during pregnancy. This study aimed to analyze the association between miRNA expression in the cervix with Pb and Hg levels biomonitored during pregnancy. We obtained cervical swabs from 80 women between 18 to 20 weeks gestation in a cohort from Mexico City, Mexico. Cervical RNA was extracted and miRNA expression was quantified in a subset of 60 samples using the nCounter Analysis System from Nanostring. Women’s blood Pb was analyzed via ICP-MS and toenail Hg levels were analyzed with a direct Hg analyzer. We performed linear regression to examine the associations between expression of thirty-five miRNAs and metal exposures adjusting for women’s age, education, and environmental tobacco smoke. Expression of miR-188 was positively associated with maternal blood Pb levels (ß=0.3, p=0.04). Expression of let-7b (ß=-1.9, p=0.02), miR-205 (ß=-2.9, p=0.02), and miR-203 (ß=-2.3, p=0.03) were negatively associated with toenail Hg levels, whereas expression of miR-1283 (ß=1.4, p=0.01) and miR-888 (ß=1.0, p=0.03) were positively associated. Pathway analysis of the five Hg-associated miRNAs revealed enrichment for genes involved in cell cycle, cancer, and organismal injury and abnormalities (p=1x10-11). Notably, let-7, miR-205, and miR-203 are known to play a role in reproductive system diseases. We showed altered miRNA expression in the human cervix during pregnancy associated with biomonitored toxic metal levels. These findings highlight miRNAs as novel responders to maternal chemical exposure in specific tissues relevant to labor. The role of metals and cervical miRNA expression in pregnancy outcomes deserves further study.

Early Life Lead Exposure and DNA Methylation: Birth through Adolescence

Epigenetic modification is a plausible mechanism linking early life exposures to adult disease susceptibility. Evidence suggests lead (Pb) exposure during sensitive periods in child development may modify the epigenome. We assessed whether early life Pb exposures altered DNA methylation levels (globally at repetitive elements and at candidate genes) in blood samples at birth and peripuberty and evaluated epigenetic drift between these two life stages. Mothers were recruited during pregnancy and children followed for 7-15 years. Exposures were estimated at three time points: 1) prenatal (average of trimester-specific maternal blood Pb levels), 2) birth (cord blood Pb), and 3) early childhood (average of multiple child blood Pb, sampled 3-48 months). DNA was isolated and bisulfite converted from peripubertal blood leukocytes and cord blood samples (n=79). Percent methylation was quantified via bisulfite sequencing at long interspersed nuclear elements (LINE-1) and growth-related genes (HSD11B2, IGF2, H19). Multivariable linear regression was used to evaluate the influence of Pb exposures on DNA methylation and epigenetic drift (peripubertal minus cord blood DNA methylation) adjusting for sex and age (when applicable). Prenatal and/or cord blood Pb were associated with higher LINE-1 and HSD11B2 methylation at birth (p&lt;0.05). Each µg/dL of mean blood Pb 3-48 months was associated with a 0.2% decrease in peripubertal DNA methylation of HSD11B2 (p=0.01). Hypomethylation of H19 and hypermethylation of IGF2 occurred between birth and peri-puberty over time regardless of Pb exposure (p&lt;0.05). Epigenetic drift was significantly altered by Pb exposure at LINE-1 and HSD11B2. Results suggest early life Pb exposure modifies DNA methylation at birth and impacts epigenetic drift from birth to peri-puberty. Future work will examine DNA methylation change as a mediator of Pb-induced impacts on childhood growth.

Relationships between lead biomarkers and diurnal salivary cortisol indices in pregnant women from Mexico City: a cross-sectional study.

BackgroundLead (Pb) exposure during pregnancy may increase the risk of adverse maternal, infant, or childhood health outcomes by interfering with hypothalamic-pituitary-adrenal-axis function. We examined relationships between maternal blood or bone Pb concentrations and features of diurnal cortisol profiles in 936 pregnant women from Mexico City.MethodsFrom 2007–11 we recruited women from hospitals/clinics affiliated with the Mexican Social Security System. Pb was measured in blood (BPb) during the second trimester and in mothers’ tibia and patella 1-month postpartum. We characterized maternal HPA-axis function using 10 timed salivary cortisol measurements collected over 2-days (mean: 19.7, range: 14–35 weeks gestation). We used linear mixed models to examine the relationship between Pb biomarkers and cortisol area under the curve (AUC), awakening response (CAR), and diurnal slope.ResultsAfter adjustment for confounders, women in the highest quintile of BPb concentrations had a reduced CAR (Ratio: −13%; Confidence Interval [CI]: −24, 1, p-value for trend < 0.05) compared to women in the lowest quintile. Tibia/patella Pb concentrations were not associated with CAR, but diurnal cortisol slopes were suggestively flatter among women in the highest patella Pb quantile compared to women in the lowest quantile (Ratio: 14%; CI: −2, 33). BPb and bone Pb concentrations were not associated with cortisol AUC.ConclusionsConcurrent blood Pb levels were associated with cortisol awakening response in these pregnant women and this might explain adverse health outcomes associated with Pb. Further research is needed to confirm these results and determine if other environmental chemicals disrupt hypothalamic-pituitary-adrenal-axis function during pregnancy.

Early-Life Lead Exposure Results in Dose- and Sex-Specific Effects on Weight and Epigenetic Gene Regulation in Weanling Mice

Epidemiological and animal data suggest that the development of adult chronic conditions is influenced by early-life exposure-induced changes to the epigenome. This study investigates the effects of perinatal lead (Pb) exposure on DNA methylation and bodyweight in weanling mice. Viable yellow agouti (A(vy)) mouse dams were exposed to 0, 2.1, 16 and 32 ppm Pb acetate before conception through weaning. Epigenetic effects were evaluated by scoring coat color of A(vy)/a offspring and quantitative bisulfite sequencing of two retrotransposon-driven (A(vy) and CDK5 activator-binding protein intracisternal A particle element) and two imprinted (Igf2 and Igf2r) loci in tail DNA. Maternal blood Pb levels were below the limit of detection in controls, and 4.1, 25.1 and 32.1 µg/dl for each dose, respectively. Pb exposure was associated with a trend of increased wean bodyweight in males (p = 0.03) and altered coat color in A(vy)/a offspring. DNA methylation at A(vy) and the CDK5 activator-binding protein intracisternal A-particle element was significantly different from controls following a cubic trend (p = 0.04; p = 0.01), with male-specific effects at the A(vy) locus. Imprinted genes did not shift in methylation across exposures. Dose- and sex-specific responses in bodyweight and DNA methylation indicate that Pb acts on the epigenome in a locus-specific fashion, dependent on the genomic feature hosting the CpG site of interest, and that sex is a factor in epigenetic response.

Perinatal lead and mercury exposure in Austria

Objective The heavy metals lead (Pb) and mercury (Hg) are ubiquitous environmental pollutants with high neurotoxic potential. We aimed to compare perinatal Pb and Hg concentrations and to explore the potential association between Pb and Hg exposure and newborn anthropometry. Study design Pregnant women were recruited in 2005 at the General Hospital Vienna for participation in this longitudinal study. Pb and Hg concentrations were measured in maternal blood and hair, placenta, cord blood, meconium, and breast milk of 53 mother-child pairs by CV-AAS, GF-AAS, and HPLC-CV-ICPMS. We conducted bivariate analyses and categorical regression analysis (CATREG) to evaluate the determinants of Pb and Hg exposure, and of infant anthropometry. Results Median Pb and total Hg contents were low, i.e., 25 μg/L (maternal blood-Pb), 13 μg/L (cord blood-Pb), 0.7 μg/L (maternal blood-Hg), and 1.1 μg/L (cord blood-Hg). Hg levels in maternal and fetal tissues were frequently correlated ( r > 0.3, P < 0.05, respectively). Regarding Pb, only maternal blood and cord blood concentrations correlated ( P = 0.043). Cord blood levels indicated higher Hg exposure but lower Pb exposure relative to maternal blood contents. Adjusted CATREG models indicated the significant predictors of birth length (placenta-Pb, gestational length, meconium-Pb), birth weight (placenta-Pb, gestational length, maternal blood-Pb), and head circumference (maternal education, maternal height). Besides one significant correlation between maternal hair Hg and birth length, the mercury levels were not associated with newborn anthropometry. Conclusions Our data implicate that different modes of action may exist for placentar transfer of Pb and Hg as well as that low Pb exposure levels can result in lower birth weight. The findings related to newborn anthropometry need to be confirmed by the examination of larger study groups. Further research is needed to clarify the mechanisms of Pb and Hg transfer via the placenta, and to explore how prenatal Pb exposure is related to intrauterine growth.

Effect Modification of Levels of Heavy Metals by Hemochromatosis Genotype among Mother-Infant Pairs: The Tar Creek Birth Cohort

ISEE-0323 Background and Objective: Exposure to heavy metals during windows of increased susceptibility such as fetal development can cause adverse growth and neurodevelopmental effects. Hemochromatosis (gene = HFE) is the most common form of excess adult onset iron accumulation disease and the presence of its gene variants can potentially modify the levels of other metals. The study objective was to assess potential effect modification of the association between maternal and fetal exposure to manganese (Mn) and lead (Pb) by two variants of the HFE gene (H63D and C282Y). Methods: A birth cohort of mothers (304) and infants (278) residing around the Tar Creek Superfund Site in Oklahoma (USA) was studied. Maternal and umbilical cord blood Mn and Pb were measured at delivery and blood metal levels were examined in linear regression models stratified by genotype. Results: Prevalence of the HFE C282Y and HFE H63D variants among mothers was approximately 13% and 30%, respectively, while 4% carried both variants. The corresponding values for infants were: 11%, 34% and 4%. Maternal blood Mn was a significant predictor of cord blood Mn among infants carrying at least one copy of either the C282Y or H63D allele (N = 113, β = 0.77; 95% CI: 0.40, 1.14) but not among wild-type infants (N = 165, β = 0.26; 95% CI: −10.01, 0.53). Conversely, wild-type mothers (N = 186) had a higher effect of maternal blood on cord blood Mn (β = 0.62; 95% CI: 0.33, 0.92) and Pb (β = 0.68; 95% CI: 0.60, 0.77) versus those with any HFE variant (N = 118) for Mn (β = 0.13; 95% CI, −0.18, 0.43) and Pb (β = 0.37; 95% CI: 0.23, 0.50). These observations did not change significantly after adjusting for maternal age and parity. Conclusion: Among this population of mother-infant pairs, HFE variants modified the association between maternal and cord blood metal levels. Identifying susceptibility factors for increased metal exposure during pregnancy is important for protecting children from potential exposures.

Methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C and G1793A genotypes, and the relationship between maternal folate intake, tibia lead and infant size at birth

Small size at birth continues to be a problem worldwide and many factors, including reduced folate intake and Pb exposure, are associated with it. However, single factors rarely explain the variability in birth weight, suggesting a need for more complex explanatory models. We investigated environment-gene interactions to understand whether folate intake and maternal Pb exposure were associated with smaller newborn size in 474 women with uncomplicated pregnancies delivering term infants in Mexico City. We examined if folate intake modified the negative effects of maternal Pb burden on birth size. We also asked if maternal and infant methylenetetrahydrofolate reductase (MTHFR) genotypes (C677T, A1298C and G1793A) modified the effects of folate intake or Pb exposure on birth size. Women were aged 24.6 (sd 5.1) years; 43.5 % were primiparous. Maternal blood Pb at delivery was 86 (sd 42) microg/l, with 26.7 % having levels > or = 100 microg/l. Tibia Pb level was 9.9 (SD 9.8) microg/g. Of the women, 35.3 % had folate intakes < 400 microg/d. Birth weight was 3170 (SD 422) g. In covariate-adjusted regressions, higher folate intake was associated with higher birth weight (beta 0.04; P < 0.05). Higher bone Pb was associated with lower birth weight (beta - 4.9; P < 0.05). Folate intake did not modify the effects of Pb on birth size, nor did MTHFR modify the association between Pb or folate intake on birth size. Although modest, the relationship between maternal nutrition, Pb burden and birth size does underscore the importance of environmental exposures to child health because patterns of fetal growth may affect health outcomes well into adulthood.

Study on maternal-fetal status of Pb, As, Cd, Mn and Zn elements and the influence factors

Trace and toxic elements have great influences on the fetus growth during the pregnancy. The status of Pb, As, Cd, Mn and Zn in maternal and umbilical cord blood and influence factors were analyzed. From September 2006 to April 2007, 130 pairs of maternal blood and cord blood in total were collected at the time of spontaneous delivery or cesarean section. At the same time, the development of newborn was measured immediately. The concentrations of elements were determined by inductively coupled plasma mass spectrometry, the relationship of these elements between maternal and cord blood were also analyzed. The median (microg/L) concentration of blood Pb, As, Cd, Mn and Zn in maternal blood were 64.32, 3.81, 0.84, 54.26 and 6312.50. And the median (microg/L) of those elements in cord blood were 35.72, 2.84, 0.32, 78.99 and 2250. The levels of Cd (r=0.341, P=0.000) and As (r=0.552, P=0.000) in maternal blood were positively correlated with the elements in the cord blood. From the questionnaire we conclude that the occupational hazardous factors and room decorated were the risk factors for the blood As and Zn levels. After multilinear regression analysis we also found mother weight, occupational hazardous factors and mother systolic pressure might affect the levels of blood Mn, Zn, As and Cd. The levels of these elements were affected by environmental and maternal factors. In this study, although the levels of all heavy metals in pregnant women were below those considered hazardous, however, they were still higher than those in the developed countries. The effects of heavy metals of maternal exposure on developing fetuses should deserve attention further.

Biological Markers of Fetal Lead Exposure at Each Stage of Pregnancy

It has been suggested that plasma lead (Pb) represents the fraction of circulating Pb that crosses the placenta. Whole-blood Pb levels, the conventional method for measuring circulating Pb, may not adequately reflect plasma Pb levels. The objective of this study was to assess the relationship between whole-blood and plasma Pb in a cohort of pregnant women. A group of 237 pregnant women, recruited in Mexico City from 1997 to 1999, was studied. whole-blood and plasma lead concentrations were evaluated at 12, 24, and 34 wk of gestation by inductively coupled plasma–mass spectrometry. Data were analyzed using a mixed-effects regression model. An exponential relationship was found between plasma and whole-blood Pb levels and significant modification of the association by stage of pregnancy. The association was stronger in the second trimester relative to the first, and it further increased in the third trimester. The model predicts increased plasma Pb levels for a given whole-blood Pb value as pregnancy advances for whole-blood Pb levels greater than ∼110 µg/L, but not for blood Pb levels less than 100 µg/L. These findings could be due to physiologic changes during pregnancy, such as decreasing hematocrit, saturation of red cell Pb binding capacity, and increased bone resorption or intestinal absorption. Collectively, these data suggest that at elevated maternal blood Pb levels the developing fetus may be at greater risk of Pb exposure from increased maternal plasma Pb than otherwise predicted from whole-blood Pb levels.

Genderbasic: Promoting attention to sex and gender differences in life sciences research in Europe

The heavy metals lead (Pb) and mercury (Hg) are ubiquitous environmental pollutants with high neurotoxic potential. We aimed to compare perinatal Pb and Hg concentrations and to explore the potential association between Pb and Hg exposure and newborn anthropometry.Pregnant women were recruited in 2005 at the General Hospital Vienna for participation in this longitudinal study. Pb and Hg concentrations were measured in maternal blood and hair, placenta, cord blood, meconium, and breast milk of 53 mother-child pairs by CV-AAS, GF-AAS, and HPLC-CV-ICPMS. We conducted bivariate analyses and categorical regression analysis (CATREG) to evaluate the determinants of Pb and Hg exposure, and of infant anthropometry.Median Pb and total Hg contents were low, i.e., 25 μg/L (maternal blood-Pb), 13 μg/L (cord blood-Pb), 0.7 μg/L (maternal blood-Hg), and 1.1 μg/L (cord blood-Hg). Hg levels in maternal and fetal tissues were frequently correlated (r > 0.3, P < 0.05, respectively). Regarding Pb, only maternal blood and cord blood concentrations correlated (P = 0.043). Cord blood levels indicated higher Hg exposure but lower Pb exposure relative to maternal blood contents. Adjusted CATREG models indicated the significant predictors of birth length (placenta-Pb, gestational length, meconium-Pb), birth weight (placenta-Pb, gestational length, maternal blood-Pb), and head circumference (maternal education, maternal height). Besides one significant correlation between maternal hair Hg and birth length, the mercury levels were not associated with newborn anthropometry.Our data implicate that different modes of action may exist for placentar transfer of Pb and Hg as well as that low Pb exposure levels can result in lower birth weight. The findings related to newborn anthropometry need to be confirmed by the examination of larger study groups. Further research is needed to clarify the mechanisms of Pb and Hg transfer via the placenta, and to explore how prenatal Pb exposure is related to intrauterine growth.

Very low level environmental exposure to lead and prolactin levels during pregnancy

Lead (Pb) is a well-known poison interfering with calcium homeostasis and dopaminergic pathway. We hypothesized that environmental Pb exposure can interact with prolactin (PRL) secretion, regulated by calcium and dopamine, during pregnancy and in fetus. The objective of this longitudinal study was to determine the relationships between blood Pb concentration and serum PRL levels in 101 pregnant women recruited during pregnancy and their fetuses exposed to low environmental levels of Pb. We observed a significant negative relationship between maternal blood Pb concentrations and maternal serum PRL levels. Cord blood PRL was weakly correlated with blood Pb levels. Our results suggest that maternal physiological parameters in pregnancy can be modulated by low level of Pb exposure and indicate a particular susceptibility of pregnant women to its toxic effects.

Low Environmental Contamination by Lead in Pregnant Women: Effect on Calcium Transfer in Human Placental Syncytiotrophoblasts

There is an extensive literature on the neurotoxic effects of lead (Pb) on the developing fetus; however, little is known about the mechanisms of action at low levels. Heavy metals are known to affect calcium (Ca2 + ) homeostasis through perturbation of Ca2 + channels and pumps and interference with protein kinase C (PKC) and Ca2 + binding protein (CaBP). During pregnancy, placental Ca2 + exchange is one of the most important mechanisms for fetal survival. This ion is an essential element for healthy fetal growth and development. The aim of the present study was to determine the influence of low maternal blood Pb levels on Ca2 + levels in serum and placenta and placental Ca2 + transfer. Blood samples (maternal and cord) and placental tissue were obtained at birth from 30 women residing in southwest Quebec. Total 2+and Pb levels were measured in maternal and umbilical cord samples and placental tissue at term. The placentas were taken for trophoblast cell isolation and Ca2 + incorporation kinetic experiments. Data showed that Ca2 + in maternal blood did not influence Ca2 + uptake by syncytiotrophoblast. However, although maternal and cord blood Pb levels were low, maternal blood Pb concentration was significantly linked to a decrease in Ca2 + uptake by syncytiotrophoblast. This suggests that exposure to very levels of Pb significantly modifies Ca2 + transfer in syncytiotrophoblasts.

BIOLOGICAL MARKERS OF FETAL LEAD EXPOSURE AT EACH STAGE OF PREGNANCY

ISEE-348 Introduction: It has been suggested that plasma lead (Pb) represents the fraction of circulating Pb that crosses the placental barrier with consequent exposure to the fetus. Evidence indicates that whole blood Pb levels, the conventional method for measuring circulating Pb, may not adequately reflect plasma Pb levels. The objective of this study was to longitudinally assess the relationship between whole blood and plasma Pb in a cohort of environmentally exposed pregnant women in Mexico City. Methods: We studied 237 pregnant women. Whole blood and plasma lead concentrations were evaluated at 12th, 24th and 34th weeks of gestation by inductively coupled plasma mass spectrometry. Data were analyzed in a longitudinal fashion using a mixed-effects regression model. Results: We found an exponential relationship between plasma and whole blood Pb levels and sign ificant modification of the association by the stage of pregnancy. The association was stronger in the 2nd trimester relative to the 1st, and it further increased in the 3rd trimester. The fitted model, which accounts for 60% of the variability in plasma Pb levels, predicts increased plasma Pb levels for a given whole blood Pb value as pregnancy advances for whole blood Pb levels greater than ∼110 μg/L, but not for blood Pb levels less than 100 μg/L. Discussion: These findings could be due to a combination of physiologic changes that occur as pregnancy progresses such as decreasing hematocrit, saturation of red cell Pb binding capacity at higher Pb levels, and increased input of Pb to plasma from increased bone resorption and/or intestinal absorption. Collectively, these data suggest that at elevated maternal blood Pb levels the developing fetus may be at greater risk of Pb exposure and toxicity from increased maternal plasma Pb than otherwise predicted from whole blood Pb levels.

The epidemic research of Pb exposure of 1151 pregnant women in Beijing

目的 了解目前北京城区孕妇血铅水平、脐带血铅水平及产妇乳汁铅水平,探讨三者之间的关系,并分析孕妇铅暴露的影响因素. 方法将孕妇按不同孕周分为早孕、中孕和晚孕三组,收集孕妇静脉血,于胎儿娩出时收集脐带血,于产后3 d收集产妇乳汁.所有样本采用石墨炉原子吸收法进行铅含量的测定.采用自行编制的问卷对调查对象进行有关环境、生活方式、膳食情况的调查以分析孕妇铅暴露的影响因素. 结果共收集孕产妇静脉血1151例,孕期血铅中位数为43.40 μg/L.孕期血铅呈动态变化,孕中期最低为37.40 μg/L,孕早、晚期较高,分别为44.50 μg/L和45.10 μg/L,差异有显著性,P<0.001.文化程度、家用燃料、乳制品摄入量这三个因素对血铅的影响具有统计学意义.收集脐带血434例,铅中位数为26.40 μg/L,与母体血铅呈正相关,r=0.365,P<0.001.收集乳汁276例,铅水平4.48 μg/L,与母血铅无明显相关性. 结论目前北京城区孕妇血铅水平处于可接受范围.铅易于通过胎盘进入胎儿体内,但产妇早期乳汁中铅含量很低.另外,加强健康教育,大力治理环境,适当增加饮食中乳制品比例,采用天然气为家用燃料,是减少铅暴露的有效措施。

Impact on blood Pb levels of maternal and early infant feeding practices of First Nation Cree in the Mushkegowuk Territory of northern Ontario, Canada.

Exposure to Pb in-utero and in infancy has been associated with cognitive risk, even at low blood Pb levels of 0.48-0.96 micromol L(-1). Based on the hypothesis that wild game consumed by First Nation women of Mushkegowuk Territory contains Pb that might be transferred through blood or breast-milk to the fetus or infant, the study's objectives were to describe: (1) Pb in maternal and cord blood at birth and infant blood at 4 months, and (2) dietary influence on Pb status. Cord and maternal Pb were 0.10 +/- 0.08 and 0.11 +/- 0.06 micromol L(-1) (x +/- SD), respectively, and were significantly correlated (r = 0.77, p < 0.0001, n = 70), as was infant blood Pb (0.08 +/- 0.05 micromol L(-1)) with matched cord blood (r = 0.65, p < 0.0001, n = 30). Two cord blood samples (3%) were above 0.48 micromol L(-1). Pb in breast-milk at 0.010 +/- 0.008 micromol L(-1) (n = 25), was significantly lower than Pb in commercial formula or evaporated milk-based feedings (range 0.02-0.05 micromol L(-1), p < 0.05), and correlated with matched maternal blood Pb (r = 0.55, p < 0.005). However, in a sub-sample of infants (n = 31), blood Pb was similar for breastfed and formula-fed groups, though above the evaporated milk-fed group (p < 0.05). Maternal consumption of wild fowl, mammals and fish, estimated from the previous year, provided, respectively, 128 +/- 124, 46 +/- 68 and 8 +/- 13 MJ annum(-1). Traditional animal food intake, especially wild fowl, correlated significantly with cord blood Pb (Spearman rank correlation, p = 0.017). Although blood and milk Pb levels were largely within acceptable ranges, the presence of some elevated levels and association between blood Pb and traditional game consumption may reflect the legacy of using lead-containing ammunition.