Enamel lead biomarker for prenatal exposure assessment.

The development of the enamel biomarker for heavy metal exposure assessment is designed to improve studies of dose-effect relationships to embryonic anomalies, particularly neurotoxic dysfunction. This report documents initial demonstrations of ambient lead (Pb) relative to calcium (Ca) in histological cross sections of deciduous tooth enamel of three human subjects, by use of ion mass spectrometry. The goal of this research was to measure Pb and Ca in tooth enamel for use as a temporal biomarker in assessing prenatal and postnatal exposure. This involves measurement of these heavy metals in enamel at high spatial resolution along histological transects following the temporal pattern of enamel growth. The technique may be applied when completely developed to cross-sectional and longitudinal research.     

Reduced intellectual development in children with prenatal lead exposure

OBJECTIVE: Low-level postnatal lead exposure is associated with poor intellectual development in children, although effects of prenatal exposure are less well studied. We hypothesized that prenatal lead exposure would have a more powerful and lasting impact on child development than postnatal exposure. DESIGN: We used generalized linear mixed models with random intercept and slope to analyze the pattern of lead effect of the cohort from pregnancy through 10 years of age on child IQ from 6 to 10 years. We statistically evaluated dose-response nonlinearity. PARTICIPANTS: A cohort of 175 children, 150 of whom had complete data for all included covariates, attended the National Institute of Perinatology in Mexico City from 1987 through 2002. EVALUATIONS/MEASUREMENTS: We used the Wechsler Intelligence Scale for Children-Revised, Spanish version, to measure IQ. Blood lead (BPb) was measured by a reference laboratory of the Centers for Disease Control and Prevention (CDC) quality assurance program for BPb. RESULTS: Geometric mean BPb during pregnancy was 8.0 microg/dL (range, 1-33 microg/dL), from 1 through 5 years was 9.8 microg/dL (2.8-36.4 microg/dL), and from 6 through 10 years was 6.2 microg/dL (2.2-18.6 microg/dL). IQ at 6-10 years decreased significantly only with increasing natural-log third-trimester BPb (beta=-3.90; 95% confidence interval, -6.45 to -1.36), controlling for other BPb and covariates. The dose-response BPb-IQ function was log-linear, not linear-linear. CONCLUSIONS: Lead exposure around 28 weeks gestation is a critical period for later child intellectual development, with lasting and possibly permanent effects. There was no evidence of a threshold; the strongest lead effects on IQ occurred within the first few micrograms of BPb. RELEVANCE TO CLINICAL PRACTICE: Current CDC action limits for children applied to pregnant women permit most lead-associated child IQ decreases measured over the studied BPb range.     

南方某地16～60岁人群环境铅暴露现况调查

目的 了解南方某地16～60周岁人群环境铅暴露情况,分析影响血铅水平升高的危险因素以及铅暴露所致的健康损害.方法 随机选取居住于当地>5年,食用当地自产食物的人群,石墨炉原子吸收法检测血、尿、头发、趾/指甲样本中铅浓度.自制调查问卷面询.采用SPSS软件进行分析.结果 412名调查对象血铅水平为(64.1±1.8)μg/L,尿铅、发铅、指(趾)甲铅分别为(11.0±1.7),(11.7±3.4),(12.1±3.4)μg/g.对数变换的尿铅、发铅、甲铅与血铅呈正相关,对应Pearson相关系数分别为0.485,0.317,0.350;居住于D村、饮酒、男性是血铅升高的危险因素;发铅、指(趾)甲铅与失眠、记忆力减退、手脚麻木、视力模糊等自觉症状的发生有关.结论 A村铅暴露最严重,男性、饮酒是血铅增高的危险因素.     

Association between prenatal lead exposure and blood pressure in children

Background: Lead exposure in adults is associated with hypertension. Altered prenatal nutrition is associated with subsequent risks of adult hypertension, but little is known about whether prenatal exposure to toxicants, such as lead, may also confer such risks.Objectives: We investigated the relationship of prenatal lead exposure and blood pressure (BP) in 7- to 15-year-old boys and girls.Methods: We evaluated 457 mother–child pairs, originally recruited for an environmental birth cohort study between 1994 and 2003 in Mexico City, at a follow-up visit in 2008–2010. Prenatal lead exposure was assessed by measurement of maternal tibia and patella lead using in vivo K-shell X-ray fluorescence and cord blood lead using atomic absorption spectrometry. BP was measured by mercury sphygmomanometer with appropriate-size cuffs.Results: Adjusting for relevant covariates, maternal tibia lead was significantly associated with increases in systolic BP (SBP) and diastolic BP (DBP) in girls but not in boys (p-interaction with sex = 0.025 and 0.007 for SBP and DBP, respectively). Among girls, an interquartile range increase in tibia lead (13 μg/g) was associated with 2.11-mmHg [95% confidence interval (CI): 0.69, 3.52] and 1.60-mmHg (95% CI: 0.28, 2.91) increases in SBP and DBP, respectively. Neither patella nor cord lead was associated with child BP.Conclusions: Maternal tibia lead, which reflects cumulative environmental lead exposure and a source of exposure to the fetus, is a predisposing factor to higher BP in girls but not boys. Sex-specific adaptive responses to lead toxicity during early-life development may explain these differences.     

Fetal lead exposure: antenatal factors

It was hypothesized that maternal blood lead level at delivery and cord blood lead level of the neonate would be affected by maternal use of alcohol, history of alcohol abuse, and smoking. The possibility that iron status, as reflected in maternal serum ferritin, would be related to lead level was also explored. The maternal history of alcohol abuse was unrelated to lead level in 208 samples of maternal blood and 178 samples of cord blood. However, alcohol use during pregnancy was related in a dose-response fashion to maternal and to cord blood lead level. This effect was significant with and without control of maternal smoking. The effect of maternal smoking and serum thiocyanate on maternal and cord blood lead level were also highly significant with and without control of the maternal drinking variable. Serum ferritin was marginally related to lead level for white women and for black infants, but tests of the dichotomized maternal ferritin variable did not yield a significant linkage with maternal or cord blood lead level. The results further support recommendations that women abstain from alcohol consumption and cigarette smoking in pregnancy.     

Low-level lead exposure in the prenatal and early preschool periods: language development

Inconsistent results continue to be reported from studies linking low-level lead exposure and child development. This inconsistency is seen for both prenatal exposure and exposure in the preschool years. The primary outcome measures in most reports are indices of cognitive development, including IQ. Verbal skills may be particularly vulnerable to toxic insult. The fact that 2 y of age is both a time of peak exposure and also a time of rapid language development suggests that this may be a critical period for such an effect. The later prenatal and early infancy period, at which time the nervous system is developing rapidly, may also be critical exposure period. We examined the relationship of maternal and cord blood lead (PbB) at birth and venous PbB at 6 mo, 2 y, and 3 y with language measures at 1, 2, and 3 y of age. The sample consisted of disadvantaged urban children. Multivariate analyses revealed no statistically significant relationship of either prenatal PbB or early preschool PbB with language measures after control of cofactors. Supplementary partial correlations revealed a marginal relationship of cord PbB and mean length of utterance (MLU), which describes a child's ability to form meaningful word combinations. Because this analysis was one of a large number of analyses with both positive and negative regression coefficients, the possibility that this was a chance effect was considered. If there is an effect of low-level lead exposure on language development, that effect is not robust.     

出生前后铅暴露对婴幼儿生长发育的影响

对妊娠 3个月左右的孕妇开始进行追踪观察 ,并随访其子女至 2岁。在此期间分别采集孕妇和婴幼儿的血样做血铅分析。并对孕妇家庭的一般情况及分娩、婴幼儿喂养和发育情况进行调查。分析出生前后铅暴露水平对婴幼儿体格发育的影响。结果显示 :妊娠 9个月血铅和脐带血铅水平与出生后婴幼儿的身长、体重均呈负相关。多元回归分析显示幼儿于 1岁和 2岁时的身长和体重分别与同期血铅水平呈负相关 (P<0 .0 5 )     

子宫内铅暴露对仔鼠学习能力的影响及预防

目的 研讨子宫内铅暴露致仔鼠学习能力影响，维生素C、锌和硒对其保护作用。方法 Wistar-性成熟雌鼠40只，随机均分5组，自妊娠之日起，各组饮下列成分加双蒸水，各成分为：0．1mol／L醋酸铅(Pb2 )、0．1mol／L葡萄糖酸锌(Zn2 )、0．5％维生素C(VC)及亚硒酸钠(Se)强化饲料(0．5μg／kg)。对照组A：(双蒸水)，铅对照组B：( Pb2 )，C组：Pb2 VC，D组：Pb2 VC Zn2 ，各组喂基础饲料。E组：饮水(Pb2 VC Zn2 )，喂se强化饲料。各组分娩后，分笼喂养，由母鼠哺乳，21d断乳，每组仔鼠随机选10只，进行学习记忆力的测试(跳台和水迷宫试验)。测试结束后，处死动物，测试仔鼠血、海马脑Pb、Zn和Se水平、大脑皮层单胺类神经递质和乙酰胆碱。结果 染铅B组仔鼠学习记忆力受损，其大脑皮层5-HT、Ach下降，多巴胺(DA)、去甲肾上腺素(NE)升高。C、D和E组学习记忆力有改善，5-HT、Ach、DA及NE水平有所恢复，以E组效果较好。孕鼠补锌、硒能提高仔鼠血Zn、Se水平；VC降血Pb，锌、硒降血Pb和抗Pb蓄积，E组驱铅明显。结论 子宫内铅暴露损害仔鼠学习记忆能力，维生素C、锌和硒对其智力损害均有保护作用，三联用，效果较理想。     

Results of lead research: prenatal exposure and neurological consequences.

The history of advances in the understanding of the toxic effects of lead over the past 20 years is an outstanding example of how knowledge learned from research can impact public health. Measures that have had the greatest impact on reducing exposure to lead are reduction of lead from gasoline, elimination of lead solder from canned food, removal of lead from paint, and abatement of housing containing lead-based paint. Nevertheless, continuing factors that enhance risk to lead exposure, particularly during fetal life, are low socioeconomic status, old housing with lead-containing paint, and less than ideal nutrition, particularly low dietary intake of calcium, iron, and zinc. Prenatal exposure may result from endogenous sources such as lead in the maternal skeletal system or maternal exposures from diet and the environment. Experimental studies have shown that the developing nervous system is particularly sensitive to the toxic effects of lead and that a large number of the effects in the nervous system are due to interference of lead with biochemical functions dependent on calcium ions and impairment of neuronal connections dependent on dendritic pruning. There is need for more study to determine whether these effects are a continuum of prenatal lead exposure or whether prenatal exposure to lead produces unique effects.     

The behavioral effects of prenatal and early postnatal lead exposure in the primate Macaca fascicularis

Female Macaca fascicularis monkeys were given daily oral doses of 3.0 and 4.25 mg/kg lead, as lead nitrate, prior to breeding, and exposure was maintained throughout gestation and terminated at parturition. No overt signs of lead toxicity were observed in the maternal monkeys. The offspring were tested at 6 to 18 months of age on a three-choice non-spatial form discrimination paradigm, and at 19 to 26 months of age on a response inhibition task. When compared to controls, the lead-exposed infants showed a deficit in form discrimination performance which continued during the entire period of testing. A deficit in response inhibition performance was also observed in exposed infants when compared to controls. However, the deficit was temporary, as the performance of all groups was similar at the termination of testing. The observation of a persistent deficit in form discrimination up to 18 months following the termination of exposure suggests that lead-induced behavioral changes may be permanent. These findings are cause for concern since behavioral deficits in the offspring were observed at maternal gestational whole blood lead levels within a concentration range (30 to 70 micrograms/dl) associated with occupational exposure.     

A prospective study of prenatal and childhood lead exposure and erythropoietin production

We test the hypothesis that chronic lead (Pb) exposure may be associated with an inability to maintain an adequate serum erythropoietin (EPO) concentration. From a longitudinal study of Pb exposure and infant and childhood development, we measured blood Pb (BPb) and serum EPO concentrations serially at ages 4.5, 6.5, 9.5, and 12 and tibia (cortical) Pb concentration at age 12. Pb-exposed children aged 4.5 and 6.5 produced increased concentrations of EPO to maintain normal Hgb concentrations. EPO production declined between ages 4.5 and 6.5. At ages 9.5 and 12, further diminution of the association was found. No association was found between tibia Pb and EPO. The continued decline in the slope of the relationship between EPO and BPb with age, after adjustment for hemoglobin, implies a gradually decreasing capacity to produce EPO.     

某铅高暴露地区居民经饮食途径铅暴露的调查

目的探讨某铅高暴露地区居民从饮食(饮用水和食物)途径获得的铅暴露水平,并评价该暴露导致的健康风险。方法随机选择某矿区居民和对照组居民2组人群共65人作为调查对象,测定其饮用水、自产蔬菜中铅含量以及血铅、尿铅含量,并结合膳食调查数据,估算调查对象饮食铅暴露量和饮食铅暴露导致的健康风险值,并评价饮食对人体铅含量的影响。结果该矿区饮用水和自产蔬菜铅含量(几何均数分别为20.6μg/L和1.61mg/kg)均高于对照地区(几何均数分别为6.0μg/L和0.56 mg/kg)(P<0.01)。矿区居民每日经饮食途径摄入的铅,男性为16.88μg/kg,女性为16.09μg/kg,高于对照组(P<0.01),但性别差异无显著性(P>0.05)。暴露导致的健康风险值分别为4.73和4.51,矿区居民的血铅、尿铅均显著高于对照组。结论该矿区由于饮食(饮用水和食物)导致的铅暴露具有较高的健康风险,长期暴露将会导致人体内的铅含量增高。     

铅对胎鼠脑组织中蛋白激酶C和钙调蛋白M表达的影响

目的 研究铅对不同发育时期胎鼠脑组织中蛋白激酶C(PKC)与钙调蛋白(CaM)mRNA和蛋白表达的影响.方法 孕鼠随机分为去离子水对照组、0.2%醋酸铅组和1.0%醋酸铅组,从妊娠第0天起开始通过自由饮水染铅.分别于孕12、18 d处死孕鼠,取胎鼠脑组织,原子吸收光谱法测定脑铅含量,反转录-聚合酶链反应(RT-PCR)和免疫印迹(Westen blotting)法分别观察各组PKC与CaM mRNA及蛋白的表达情况.结果 同一发育时期的染铅组胎鼠脑铅含量高于对照组,同一剂量染铅组孕18 d时胎鼠脑铅含量高于孕12 d时,差异均有统计学意义(P<0.01,P<0.05).孕12 d时,与相应的对照组(mRNA:PKC:1.03±0.01、CaM:0.80±0.01,蛋白:PKC:0.70±0.05、CaM:0.75±0.05)相比,1.0%醋酸铅组胎鼠脑内PKC与CaM的mRNA(0.86±0.03、0.71±0.02)和蛋白表达(0.49±0.03、0.46±0.03)均降低;孕18 d时,0.2%和1.0%醋酸组胎鼠脑内PKC与CaM的mRNA和蛋白表达均较对照组降低,差异均有统计学意义(P<0.05,P<0.01).结论 孕期母鼠染铅可使胎鼠脑组织铅含量升高,并引起PKC与CaM mRNA和蛋白表达水平的下降.     

胎儿期铅暴露水平与脐带血钙、铁、锌含量的相关研究

【目的】研究胎儿期铅暴露水平与胎儿体内钙、铁、锌等矿物元素含量的相关关系。【方法】以脐血血铅含量作为胎儿期铅暴露的指标,脐血钙、铁、锌含量作为胎儿体内相应元素含量的指标,采用BUCK-210型原子吸收光谱仪石磨炉原子吸收光谱法和分光光度法检测100份脐带血标本四种元素的含量。【结果】胎儿体内血铅水平处于在CDC标准的Ⅰ级(<0.483μmol/L)、Ⅱ-A(0.483-0.676μmol/L)水平时,即与二价元素钙、铁含量呈显著负相关(P<0.05);血铅≥0.247μmol/L者,其脐血钙、铁含量明显低于血铅水平<0.247μmol/L者,差异有显著性(P<0.05)。【结论】在认为相对安全的铅暴露水平,随着胎儿体内血铅水平的上升,二价元素钙、铁含量有下降趋势,亦即铅作为一种外来毒素,有可能干扰胎儿体内的正常矿物元素代谢。     

Environmental lead exposure in a population of children in northern France: factors affecting lead burden

BACKGROUND: This study is part of the assessment of a site in northern France polluted by lead from industrial emissions. Our objectives were to look for the factors that influence lead burden in children aged 8-11 years. METHODS: A cross-sectional population-based study took place in 1996-97 and included 400 children (200 of whom lived on the metal-polluted site). RESULTS: The geometric mean of the blood-lead levels of children living on the polluted site was 39.5 microg/l (95% CI = 36.3-43.1); that of the non-exposed children was 30.6 microg/l (95% CI = 27.8-33.6) (P < 0.0001). Analysis of the variations in the mean blood-lead levels showed associations with: distance from the smelting plants (mean blood-lead level fell by a factor of 1/1.3 (95% CI = 1/1.2-1/1.4) for each km from the smelter over the range of 1-3 km and was constant thereafter) and consumption of tap water (when the water pipes were made of lead, the mean blood-lead level of children who drank tap water was twice as high (95% CI = 1.2-3.4) as that of children who did not). CONCLUSIONS: The children's blood-lead levels were essentially linked to two factors: proximity to the smelters and drinking tap rather than bottled water.     

孕期低水平铅暴露对子代大鼠海马肾母细胞瘤过度表达基因的影响

目的 观察孕鼠低水平铅暴露对子代大鼠海马组织肾母细胞瘤过度表达基因(NOV)蛋白及mRNA表达的影响,探讨铅影响学习记忆的分子机制.方法 孕鼠随机分为对照组及低剂量(125 mg/L)、中剂量(250 mg/L)、高剂量(500 mg/L)3个染铅组,每组8只.母鼠自受孕1d起分别给予蒸馏水和不同剂量的醋酸铅饮水,直到仔鼠出生.分别在胚胎18 d及仔鼠出生后1、21、60 d时,采用氢化物-原子吸收光谱法测定仔鼠血铅、海马铅含量,免疫组化和原位杂交方法 检测海马NOV蛋白及mRNA的变化.结果 低、中、高剂量染铅组胚胎18d及仔鼠出生后1、21 d时,血铅[(312.46±43.55)、(419.35±62.25)、(541.45±47.90)μg/L、海马铅[(2.10±0.18)、(2.58±0.12)、(3.41±0.23)μg/L]明显高于对照组[分别为(214.31±40.77)、(0.76±0.13)μg/L伽,差异有统计学意义(P<0.05),至60 d龄时,染铅组仔鼠血铅、海马铅含量与对照组无明显差异.免疫组化结果 显示,中、高剂量染铅组在仔鼠出生后1、21 d时,NOV蛋白表达量明显低于对照组,差异有统计学意义(P<0.05,P<0.01),60 d龄时无明显差异.原位杂交结果 显示,各染铅组在胚胎18 d及仔鼠出生后1、21 d时,NOV mRNA表达量明显低于对照组,差异有统计学意义(P<0.05,P<0.01),60d龄时,仅高剂量组NOV mRNA表达量(0.0355±0.0100)与对照组(0.0900±0.0200)的差异有统计学意义(P<0.01).结论 孕期低水平铅暴露可使子代海马组织中NOV蛋白及其mRNA表达降低,这可能是铅影响学习记忆能力的分子机制之一.     

母鼠围产期铅暴露对仔鼠不同脑区POU域蛋白表达的影响

目的探讨POU域蛋白在铅的神经毒性机制中的作用。方法受孕雌性大鼠从妊娠第15天开始经饮水染铅(对照饮蒸馏水,试验组醋酸铅低0.5g L、中1.0g L、高2.0g L),至仔鼠出生后21日断乳为止。分别取21日龄仔鼠大脑皮层、海马、小脑部位组织制作冰冻切片,采用免疫组织化学方法测定不同脑区的Oct2和Brn3a蛋白表达水平。结果显微图像分析表明,染铅组脑组织皮层、海马及小脑的Oct2和Brn3a蛋白表达的阳性面积比[Aa(%)]、平均灰度与对照组相比其差异有不同程度的显著性(P<0.05或P<0.01),并呈剂量依赖性的变化。染铅组Oct2表达高于对照组,而Brn3a表达低于对照组。结论POU域蛋白作为转录调节因子参与了铅对学习记忆损害的神经毒性过程。     

Low-level prenatal and postnatal blood lead exposure and adrenocortical responses to acute stress in children

BACKGROUND: A few recent studies have demonstrated heightened hypothalamic-pituitary-adrenal (HPA) axis reactivity to acute stress in animals exposed to heavy metal contaminants, particularly lead. However, Pb-induced dysregulation of the HPA axis has not yet been studied in humans. OBJECTIVE: In this study, we examined children's cortisol response to acute stress (the glucocorticoid product of HPA activation) in relation to low-level prenatal and postnatal Pb exposure. METHODS: Children's prenatal blood Pb levels were determined from cord blood specimens, and postnatal lead levels were abstracted from pediatrician and state records. Children's adrenocortical responses to an acute stressor were measured using assays of salivary cortisol before and after administration of a standard cold pressor task. RESULTS: Pb exposure was not associated with initial salivary cortisol levels. After an acute stressor, however, increasing prenatal and postnatal blood Pb levels were independently associated with significantly heightened salivary cortisol responses. CONCLUSIONS: Our results suggest that relatively low prenatal and postnatal blood lead levels--notably those below the 10 microg/dL blood lead level identified by the Centers for Disease Control and Prevention for public health purposes--can alter children's adrenocortical responses to acute stress. The behavioral and health consequences of this Pb-induced HPA dysregulation in children have yet to be determined.