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1.  Maternal Blood, Plasma, and Breast Milk Lead: Lactational Transfer and Contribution to Infant Exposure 
Background: Human milk is a potential source of lead exposure. Yet lactational transfer of lead from maternal blood into breast milk and its contribution to infant lead burden remains poorly understood.
Objectives: We explored the dose–response relationships between maternal blood, plasma, and breast milk to better understand lactational transfer of lead from blood and plasma into milk and, ultimately, to the breastfeeding infant.
Methods: We measured lead in 81 maternal blood, plasma, and breast milk samples at 1 month postpartum and in 60 infant blood samples at 3 months of age. Milk-to-plasma (M/P) lead ratios were calculated. Multivariate linear, piecewise, and generalized additive models were used to examine dose–response relationships between blood, plasma, and milk lead levels.
Results: Maternal lead levels (mean ± SD) were as follows: blood: 7.7 ± 4.0 μg/dL; plasma: 0.1 ± 0.1 μg/L; milk: 0.8 ± 0.7 μg/L. The average M/P lead ratio was 7.7 (range, 0.6–39.8) with 97% of the ratios being > 1. The dose–response relationship between plasma lead and M/P ratio was nonlinear (empirical distribution function = 6.5, p = 0.0006) with the M/P ratio decreasing by 16.6 and 0.6 per 0.1 μg/L of plasma lead, respectively, below and above 0.1 μg/L plasma lead. Infant blood lead level (3.4 ± 2.2 μg/dL) increased by 1.8 μg/dL per 1 μg/L milk lead (p < 0.0001, R2 = 0.3).
Conclusions: The M/P ratio for lead in humans is substantially higher than previously reported, and transfer of lead from plasma to milk may be higher at lower levels of plasma lead. Breast milk is an important determinant of lead burden among breastfeeding infants.
Citation: Ettinger AS, Roy A, Amarasiriwardena CJ, Smith DR, Lupoli N, Mercado-García A, Lamadrid-Figueroa H, Tellez-Rojo MM, Hu H, Hernández-Avila M. 2014. Maternal blood, plasma, and breast milk lead: lactational transfer and contribution to infant exposure. Environ Health Perspect 122:87–92;
PMCID: PMC3888576  PMID: 24184948
2.  Windows of lead exposure sensitivity, attained height, and BMI at 48 months 
The Journal of Pediatrics  2012;160(6):1044-1049.
To examine longitudinal association of prenatal, infancy, and early childhood lead exposure during sensitive periods with height and BMI.
Study design
The 773 participants were recruited between 1994 and 2005 in Mexico City. We constructed lead exposure history categories for prenatal (maternal patella lead), infancy and childhood periods (mean child blood lead between birth to 24 months and 30 to 48 months, respectively). Linear regression models were used to study lead exposure history with height and BMI at 48 months.
Children with blood lead levels higher than the median during infancy attained a mean height at 48 months that was significantly shorter (−0.84 cm, 95% CI= −1.42 to −0.25) than children with levels lower than the median. Prenatal lead exposure was not associated with height at 48 months. Results for attained BMI were in general in the same direction as for height.
Our study suggests an effect of early life lead exposure on height attainment at 48 months with an exposure window of greatest sensitivity occurring in infancy.
PMCID: PMC3360798  PMID: 22284921
3.  A dopamine receptor (DRD2) but not dopamine transporter (DAT1) gene polymorphism is associated with neurocognitive development of Mexican preschool children with lead exposure 
The Journal of pediatrics  2011;159(4):638-643.
To investigate the effects of pre- and postnatal lead exposure and polymorphisms in dopamine metabolism genes on neurocognitive development of Mexican children at 24 (n=220) and 48 months (n=186) of age.
Study design
We genotyped the dopamine transporter gene (DAT1; SLC6A3) variable nucleotide tandem repeat, and the dopamine receptor D2 (DRD2) Taq 1A single nucleotide polymorphism. Children were assessed at 24 mo with Bayley Scales of Infant Development (MDI, PDI) and at 48 mo with McCarthy Scales of Children’s Abilities.
Lead concentration (BLL) in umbilical cord was 6.6±3.3 μg/dL (measured in 1995-96), 8.1±4.4 μg/dL at 24, and 8.1±3.6 μg/dL at 48 months. Cord BLL was negatively associated with MDI (p<0.01) and PDI (p<0.1) but not McCarthy scores. The 48- but not 24-month BLL was negatively associated with children’s scores. Children with DRD2 TT genotype (variant) scored higher than those with CC genotype (wild type) on MDI and McCarthy memory scale. Neither polymorphism modified the relationship between BLL (either pre or post-natal) and neurocognitive development.
Lead exposure was adversely, whereas the DRD2 Taq 1A TT variant was positively associated with neurocognitive measures. We found no evidence of gene-environment interactions on developmental outcomes in early childhood.
PMCID: PMC3158955  PMID: 21592505
Cord blood lead; postnatal lead exposure; DAT1; DRD2; gene polymorphisms; Mexico; child development
4.  Associations of Early Childhood Manganese and Lead Coexposure with Neurodevelopment 
Environmental Health Perspectives  2011;120(1):126-131.
Background: Most toxicologic studies focus on a single agent, although this does not reflect real-world scenarios in which humans are exposed to multiple chemicals.
Objectives: We prospectively studied manganese–lead interactions in early childhood to examine whether manganese–lead coexposure is associated with neurodevelopmental deficiencies that are more severe than expected based on effects of exposure to each metal alone.
Methods: Four hundred fifty-five children were enrolled at birth in an longitudinal cohort study in Mexico City, provided blood samples, and were followed until 36 months of age. We measured lead and manganese at 12 and 24 months and assessed neurodevelopment at 6-month intervals from 12 to 36 months of age using Bayley Scales of Infant Development–II.
Results: Mean (± SD) blood concentrations at 12 and 24 months were, respectively, 24.7 ± 5.9 μg/L and 21.5 ± 7.4 μg/L for manganese and 5.1 ± 2.6 μg/dL and 5.0 ± 2.9 μg/dL for lead. Mixed-effects models, including Bayley scores at five time points, showed a significant interaction over time: highest manganese quintile × continuous lead; mental development score, β = –1.27 [95% confidence interval (CI): –2.18, –0.37]; psychomotor development score, β = –0.92 (95% CI: –1.76, –0.09). Slopes for the estimated 12-month lead effect on 18-month mental development and 24- through 36-month psychomotor development scores were steeper for children with high manganese than for children with midrange manganese levels.
Conclusions: We observed evidence of synergism between lead and manganese, whereby lead toxicity was increased among children with high manganese coexposure. Findings highlight the importance of understanding health effects of mixed exposures, particularly during potentially sensitive developmental stages such as early childhood.
PMCID: PMC3261931  PMID: 21885384
coexposure; early childhood; lead; manganese; metals; neurodevelopment
5.  Associations of iron metabolism genes with blood manganese levels: a population-based study with validation data from animal models 
Environmental Health  2011;10:97.
Given mounting evidence for adverse effects from excess manganese exposure, it is critical to understand host factors, such as genetics, that affect manganese metabolism.
Archived blood samples, collected from 332 Mexican women at delivery, were analyzed for manganese. We evaluated associations of manganese with functional variants in three candidate iron metabolism genes: HFE [hemochromatosis], TF [transferrin], and ALAD [δ-aminolevulinic acid dehydratase]. We used a knockout mouse model to parallel our significant results as a novel method of validating the observed associations between genotype and blood manganese in our epidemiologic data.
Percentage of participants carrying at least one copy of HFE C282Y, HFE H63D, TF P570S, and ALAD K59N variant alleles was 2.4%, 17.7%, 20.1%, and 6.4%, respectively. Percentage carrying at least one copy of either C282Y or H63D allele in HFE gene was 19.6%. Geometric mean (geometric standard deviation) manganese concentrations were 17.0 (1.5) μg/l. Women with any HFE variant allele had 12% lower blood manganese concentrations than women with no variant alleles (β = -0.12 [95% CI = -0.23 to -0.01]). TF and ALAD variants were not significant predictors of blood manganese. In animal models, Hfe-/- mice displayed a significant reduction in blood manganese compared with Hfe+/+ mice, replicating the altered manganese metabolism found in our human research.
Our study suggests that genetic variants in iron metabolism genes may contribute to variability in manganese exposure by affecting manganese absorption, distribution, or excretion. Genetic background may be critical to consider in studies that rely on environmental manganese measurements.
PMCID: PMC3248860  PMID: 22074419
Iron; Manganese; Genes; Iron metabolism genes
6.  Critical Windows of Fetal Lead Exposure: Adverse Impacts on Length of Gestation and Risk of Premature Delivery 
Research on the role of environmental lead exposure in the complex etiology of premature birth has yielded inconsistent results. We assessed the trimester-specific effect of prenatal lead exposure on gestational age and risk of premature delivery.
We used linear and logistic regression to identify critical windows of susceptibility to lead exposure upon gestational length.
In single-trimester models, decreases in gestational length were most strongly associated with first and second trimester blood lead. In adjusted logistic regression models a one-standard deviation increase in second trimester blood lead was associated with an odds ratio of prematurity of 1.75 (95%CI: 1.02, 3.02).
Maternal whole blood lead levels measured during first and second trimesters yielded the most prominent inverse association with length of gestation and increased the risk of prematurity. .
PMCID: PMC3003442  PMID: 21063188
7.  Prenatal Lead Exposure and Weight of 0- to 5-Year-Old Children in Mexico City 
Environmental Health Perspectives  2011;119(10):1436-1441.
Background: Cumulative prenatal lead exposure, as measured by maternal bone lead burden, has been associated with smaller weight of offspring at birth and 1 month of age, but no study has examined whether this effect persists into early childhood.
Objective: We investigated the association of perinatal maternal bone lead, a biomarker of cumulative prenatal lead exposure, with children’s attained weight over time from birth to 5 years of age.
Methods: Children were weighed at birth and at several intervals up until 60 months. Maternal tibia and patella lead were measured at 1 month postpartum using in vivo K-shell X-ray fluorescence. We used varying coefficient models with random effects to assess the association of maternal bone lead with weight trajectories of 522 boys and 477 girls born between 1994 and 2005 in Mexico City.
Results: After controlling for breast-feeding duration, maternal anthropometry, and sociodemographic characteristics, a 1-SD increase in maternal patella lead (micrograms per gram) was associated with a 130.9-g decrease in weight [95% confidence interval (CI), –227.4 to –34.4 g] among females and a 13.0-g nonsignificant increase in weight among males (95% CI, –73.7 to 99.9 g) at 5 years of age. These associations were similar after controlling for concurrent blood lead levels between birth and 5 years.
Conclusions: Maternal bone lead was associated with lower weight over time among female but not male children up to 5 years of age. Given that the association was evident for patellar but not tibial lead levels, and was limited to females, results need to be confirmed in other studies.
PMCID: PMC3230436  PMID: 21715242
bone lead; growth; weight
8.  Early Postnatal Blood Manganese Levels and Children’s Neurodevelopment 
Epidemiology (Cambridge, Mass.)  2010;21(4):433-439.
Recent evidence suggests that low-level environmental exposure to manganese adversely affects child growth and neurodevelopment. Previous studies have addressed the effects of prenatal exposure, but little is known about developmental effects of early postnatal exposure.
We studied 448 children born in Mexico City from 1997 through 2000, using a longitudinal study to investigate neurotoxic effects of early life manganese exposure. Archived blood samples, collected from children at 12 and 24 months of age, were analyzed for manganese levels using inductively-coupled plasma mass spectrometry. Mental and psychomotor development were scored using Bayley Scales of Infant Development at 6-month intervals between 12 and 36 months of age.
At 12 months of age, the mean (SD) blood manganese level was 24.3 (4.5) μg/l and the median was 23.7 μg/l; at 24 months, these values were 21.1 (6.2) μg/l and 20.3 μg/l, respectively. Twelve- and 24-month manganese concentrations were correlated (Spearman correlation = 0.55) and levels declined over time (β = −5.7 [95% CI = −6.2 to −5.1]). We observed an inverted U-shaped association between 12-month blood manganese and concurrent mental development scores (compared with the middle 3 manganese quintiles, for the lowest manganese quintile, β = −3.3 [−6.0 to −0.7] and for the highest manganese quintile, β = −2.8 [−5.5 to −0.2]). This 12-month manganese effect was apparent but diminished with mental development scores at later ages. The 24-month manganese levels were not associated with neurodevelopment.
These results suggest a possible biphasic dose-response relationship between early-life manganese exposure at lower exposure levels and infant neurodevelopment. The data are consistent with manganese as both an essential nutrient and a toxicant.
PMCID: PMC3127440  PMID: 20549838
9.  Oseltamivir-Resistant Pandemic (H1N1) 2009 Virus, Mexico 
Emerging Infectious Diseases  2011;17(2):283-286.
During May 2009–April 2010, we analyzed 692 samples of pandemic (H1N1) 2009 virus from patients in Mexico. We detected the H275Y substitution of the neuraminidase gene in a specimen from an infant with pandemic (H1N1) 2009 who was treated with oseltamivir. This virus was susceptible to zanamivir and resistant to adamantanes and oseltamivir.
PMCID: PMC3204764  PMID: 21291607
Oseltamivir; influenza; neuraminidase; G1N1; pandemic; viruses; Mexico; expedited; dispatch
10.  HFE Gene Variants Modify the Association between Maternal Lead Burden and Infant Birthweight: A Prospective Birth Cohort Study in Mexico City, Mexico 
Environmental Health  2010;9:43.
Neonatal growth is a complex process involving genetic and environmental factors. Polymorphisms in the hemochromatosis (HFE) iron regulatory genes have been shown to modify transport and toxicity of lead which is known to affect birth weight.
We investigated the role of HFE C282Y, HFE H63 D, and transferrin (TF) P570 S gene variants in modifying the association of lead and infant birthweight in a cohort of Mexican mother-infant pairs. Subjects were initially recruited between 1994-1995 from three maternity hospitals in Mexico City and 411 infants/565 mothers had archived blood available for genotyping. Multiple linear regression models, stratified by either maternal/infant HFE or TF genotype and then combined with interaction terms, were constructed examining the association of lead and birthweight after controlling for covariates.
3.1%, 16.8% and 17.5% of infants (N = 390) and 1.9%, 14.5% and 18.9% of mothers (N = 533) carried the HFE C282Y, HFE H63D, and TF P570 S variants, respectively. The presence of infant HFE H63 D variants predicted 110.3 g (95% CI -216.1, -4.6) decreases in birthweight while maternal HFE H63 D variants predicted reductions of 52.0 g (95% CI -147.3 to 43.2). Interaction models suggest that both maternal and infant HFE H63 D genotype may modify tibia lead's effect on infant birthweight in opposing ways. In our interaction models, maternal HFE H63 D variant carriers had a negative association between tibia lead and birthweight.
These results suggest that the HFE H63 D genotype modifies lead's effects on infant birthweight in a complex fashion that may reflect maternal-fetal interactions with respect to the metabolism and transport of metals.
PMCID: PMC2916893  PMID: 20659343
11.  Influence of Prenatal Lead Exposure on Genomic Methylation of Cord Blood DNA 
Environmental Health Perspectives  2009;117(9):1466-1471.
Fetal lead exposure is associated with adverse pregnancy outcomes and developmental and cognitive deficits; however, the mechanism(s) by which lead-induced toxicity occurs remains unknown. Epigenetic fetal programming via DNA methylation may provide a pathway by which environmental lead exposure can influence disease susceptibility.
This study was designed to determine whether prenatal lead exposure is associated with alterations in genomic methylation of leukocyte DNA levels from umbilical cord samples.
We measured genomic DNA methylation, as assessed by Alu and LINE-1 (long interspersed nuclear element-1) methylation via pyrosequencing, on 103 umbilical cord blood samples from the biorepository of the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) study group. Prenatal lead exposure had been assessed by measuring maternal bone lead levels at the mid-tibial shaft and the patella using a spot-source 109Cd K-shell X-ray fluorescence instrument.
We found an inverse dose–response relationship in which quartiles of patella lead correlated with cord LINE-1 methylation (p for trend = 0.01) and and tibia lead correlated with Alu methylation (p for trend = 0.05). In mixed effects regression models, maternal tibia lead was negatively associated with umbilical cord genomic DNA methylation of Alu (β= −0.027; p = 0.01). We found no associations between cord blood lead and cord genomic DNA methylation.
Prenatal lead exposure is inversely associated with genomic DNA methylation in cord blood. These data suggest that the epigenome of the developing fetus can be influenced by maternal cumulative lead burden, which may influence long-term epigenetic programming and disease susceptibility throughout the life course.
PMCID: PMC2737027  PMID: 19750115
blood lead; bone lead; DNA methylation; early life; epigenetics; fetal programming; genomic DNA methylation; intergenerational; lead exposure; life course; Mexico
12.  Susceptibility to Smoking among Adolescents and Its Implications for Mexico’s Tobacco Control Programs. Analysis of the Global Youth Tobacco Survey 2003–2004 and 2006–2007 
Smoking prevention efforts should either prevent target groups from becoming susceptible to smoking or prevent susceptible adolescents from progressing to becoming regular smokers. To describe the prevalence of susceptibility to smoking among never smoker students from cities that applied the GYTS in 2003 and 2006. The GYTS uses a two-stage cluster sample survey design that produces representative samples of students aged 12–15 years enrolled in public, private, and technical schools. The survey was undertaken at 399 schools in 9 cities. The GYTS surveyed 33,297 students during the academic years 2003–04 and 2006–07. Among never smokers, about 25% are likely to initiate smoking in the next 12 months. There are no differences in susceptibility to smoking by gender. When comparing results from 2003 and 2006, the susceptibility index has not changed, but for one city. The GYTS results are useful for monitoring susceptibility to smoking among adolescents and provide evidence for strengthening the efforts of tobacco control programs in Mexico.
PMCID: PMC2672381  PMID: 19440444
Susceptibility to smoking; adolescents; GYTS; tobacco control and prevention; Mexico
13.  Maternal Dietary Intake of Polyunsaturated Fatty Acids Modifies the Relationship between Lead Levels in Bone and Breast Milk1,2 
The Journal of nutrition  2008;138(1):73-79.
Whereas dietary fats are known to influence bone mineral density, little is known about their effect on the skeletal stores of lead that are a pervasive source of fetal and infant lead exposure from heightened mobilization during pregnancy and lactation. This cross-sectional study examined the potential influence of maternal dietary intake of saturated and unsaturated fats on the relationship of lead levels in bone and breast milk during lactation. Lead was measured in blood, breast milk, and bone (patella and tibia) at 1 mo postpartum in 310 women in Mexico City. Dietary nutrient intake was assessed using a validated FFQ. Multivariate linear regression analyses were used to study the influence of dietary saturated and unsaturated fats on the association between bone and breast milk lead. In multivariate models that included both the dietary intake of SFA and PUFA, an interquartile range increase in patella lead [~20 µg/g (0.097 µmol/g)] was associated with a 24% (95% CI = 5–43) higher increase in breast milk lead in women in the lowest tertile of PUFA intake compared with those in the highest tertile of PUFA intake. Monounsaturated fatty acids did not modify the relationship between lead levels in patella and breast milk. In conclusion, higher maternal dietary intake of PUFA may limit the transfer of lead from bone to breast milk.
PMCID: PMC2628754  PMID: 18156407
14.  Effect of Calcium Supplementation on Blood Lead Levels in Pregnancy: A Randomized Placebo-Controlled Trial 
Prenatal lead exposure is associated with deficits in fetal growth and neurodevelopment. Calcium supplementation may attenuate fetal exposure by inhibiting mobilization of maternal bone lead and/or intestinal absorption of ingested lead.
Our goal was to evaluate the effect of 1,200 mg dietary calcium supplementation on maternal blood lead levels during pregnancy.
In a double-blind, randomized, placebo-controlled trial conducted from 2001 through 2003 in Mexico City, we randomly assigned 670 women in their first trimester of pregnancy to ingest calcium (n = 334) or placebo (n = 336). We followed subjects through pregnancy and evaluated the effect of supplementation on maternal blood lead, using an intent-to-treat analysis by a mixed-effects regression model with random intercept, in 557 participants (83%) who completed follow-up. We then conducted as-treated analyses using similar models stratified by treatment compliance.
Adjusting for baseline lead level, age, trimester of pregnancy, and dietary energy and calcium intake, calcium was associated with an average 11% reduction (0.4 μg/dL) in blood lead level relative to placebo (p = 0.004). This reduction was more evident in the second trimester (−14%, p < 0.001) than in the third (−8%, p = 0.107) and was strongest in women who were most compliant (those who consumed ≥ 75% calcium pills; −24%, p < 0.001), had baseline blood lead > 5 μg/dL (−17%, p < 0.01), or reported use of lead-glazed ceramics and high bone lead (−31%, p < 0.01).
Calcium supplementation was associated with modest reductions in blood lead when administered during pregnancy and may constitute an important secondary prevention effort to reduce circulating maternal lead and, consequently, fetal exposure.
PMCID: PMC2627861  PMID: 19165383
calcium; diet; lead; pregnancy; randomized trial; supplementation
15.  Variants in Iron Metabolism Genes Predict Higher Blood Lead Levels in Young Children 
Environmental Health Perspectives  2008;116(9):1261-1266.
Given the association between iron deficiency and lead absorption, we hypothesized that variants in iron metabolism genes would predict higher blood lead levels in young children.
We examined the association between common missense variants in the hemochromatosis (HFE) and transferrin (TF) genes and blood lead levels in 422 Mexican children.
Archived umbilical cord blood samples were genotyped for HFE (H63D and C282Y) and TF (P570S) variants. Blood lead was measured at 24, 30, 36, 42, and 48 months of age. A total of 341 subjects had at least one follow-up blood lead level available and data available on covariates of interest for inclusion in the longitudinal analyses. We used random-effects models to examine the associations between genotype (HFE, TF, and combined HFE + TF) and repeated measures of blood lead, adjusting for maternal blood lead at delivery and child’s concurrent anemia status.
Of 422 children genotyped, 17.7, 3.3, and 18.9% carried the HFE H63D, HFE C282Y, and TF P570S variants, respectively. One percent of children carried both the HFE C282Y and TF P570S variants, and 3% of children carried both the HFE H63D and TF P570S variants. On average, carriers of either the HFE (β = 0.11, p = 0.04) or TF (β = 0.10, p = 0.08) variant had blood lead levels that were 11% and 10% higher, respectively, than wild-type subjects. In models examining the dose effect, subjects carrying both variants (β = 0.41, p = 0.006) had blood lead 50% higher than wild-type subjects and a significantly higher odds of having a blood lead level > 10 μg/dL (odds ratio = 18.3; 95% confidence interval, 1.9–177.1).
Iron metabolism gene variants modify lead metabolism such that HFE variants are associated with increased blood lead levels in young children. The joint presence of variant alleles in the HFE and TF genes showed the greatest effect, suggesting a gene-by-gene-by-environment interaction.
PMCID: PMC2535632  PMID: 18795173
C282Y; children; H63D; hemochromatosis; iron; lead; P570S; polymorphism; transferrin
16.  Association between the plasma/whole blood lead ratio and history of spontaneous abortion: a nested cross-sectional study 
Blood lead has been associated with an elevated risk of miscarriage. The plasmatic fraction of lead represents the toxicologically active fraction of lead. Women with a tendency to have a higher plasma/whole blood Pb ratio could tend towards an elevated risk of miscarriage due to a higher plasma Pb for a given whole blood Pb and would consequently have a history of spontaneous abortion.
We studied 207 pregnant Mexico City residents during the 1st trimester of pregnancy, originally recruited for two cohorts between 1997 and 2004. Criteria for inclusion in this study were having had at least one previous pregnancy, and having valid plasma and blood Pb measurements. Pb was measured in whole blood and plasma by inductively coupled plasma mass spectrometry using ultra-clean techniques. History of miscarriage in previous pregnancies was obtained by interview. The incidence rate of spontaneous abortion was defined as the proportion of previous pregnancies that resulted in miscarriage. Data were analyzed by means of Poisson regression models featuring the incidence rate of spontaneous abortion as the outcome and continuous or categorized plasma/blood Pb ratios as predictor variables. All models were adjusted for age and schooling. Additionally, logistic regression models featuring inclusion in the study sample as the outcome were fitted to assess potential selection bias.
The mean number of miscarriages was 0.42 (range 0 to 4); mean Pb concentrations were 62.4 and 0.14 μg/L in whole blood and plasma respectively. Mean plasma/blood Pb ratio was 0.22%. We estimated that a 0.1% increment in the plasma/blood Pb ratio lead was associated to a 12% greater incidence of spontaneous abortion (p = 0.02). Women in the upper tertile of the plasma/blood Pb ratio had twice the incidence rate of those in the lower tertile (p = 0.02). Conditional on recruitment cohort, inclusion in the study sample was unrelated to observable characteristics such as number of abortions, number of pregnancies, blood Pb levels, age schooling, weight and height.
Women with a large plasma/whole blood Pb ratio may be at higher risk of miscarriage, which could be due to a greater availability of placental barrier-crossing Pb.
PMCID: PMC2148053  PMID: 17900368
18.  Fetal Lead Exposure at Each Stage of Pregnancy as a Predictor of Infant Mental Development 
Environmental Health Perspectives  2006;114(11):1730-1735.
The impact of prenatal lead exposure on neurodevelopment remains unclear in terms of consistency, the trimester of greatest vulnerability, and the best method for estimating fetal lead exposure.
We studied prenatal lead exposure’s impact on neurodevelopment using repeated measures of fetal dose as reflected by maternal whole blood and plasma lead levels.
We measured lead in maternal plasma and whole blood during each trimester in 146 pregnant women in Mexico City. We then measured umbilical cord blood lead at delivery and, when offspring were 12 and 24 months of age, measured blood lead and administered the Bayley Scales of Infant Development. We used multivariate regression, adjusting for covariates and 24-month blood lead, to compare the impacts of our pregnancy measures of fetal lead dose.
Maternal lead levels were moderately high with a first-trimester blood lead mean (± SD) value of 7.1 ± 5.1 μg/dL and 14% of values ≥10 μg/dL. Both maternal plasma and whole blood lead during the first trimester (but not in the second or third trimester) were significant predictors (p < 0.05) of poorer Mental Development Index (MDI) scores. In models combining all three trimester measures and using standardized coefficients, the effect of first-trimester maternal plasma lead was somewhat greater than the effect of first-trimester maternal whole blood lead and substantially greater than the effects of second- or third-trimester plasma lead, and values averaged over all three trimesters. A 1-SD change in first-trimester plasma lead was associated with a reduction in MDI score of 3.5 points. Postnatal blood lead levels in the offspring were less strongly correlated with MDI scores.
Fetal lead exposure has an adverse effect on neurodevelopment, with an effect that may be most pronounced during the first trimester and best captured by measuring lead in either maternal plasma or whole blood.
PMCID: PMC1665421  PMID: 17107860
bone; IQ; lead; plasma; pregnancy; neurodevelopment
19.  Effect of Breast Milk Lead on Infant Blood Lead Levels at 1 Month of Age 
Environmental Health Perspectives  2004;112(14):1381-1385.
Nursing infants may be exposed to lead from breast milk, but relatively few data exist with which to evaluate and quantify this relationship. This route of exposure constitutes a potential infant hazard from mothers with current ongoing exposure to lead as well as from mothers who have been exposed previously due to the redistribution of cumulative maternal bone lead stores. We studied the relationship between maternal breast milk lead and infant blood lead levels among 255 mother–infant pairs exclusively or partially breast-feeding through 1 month of age in Mexico City. A rigorous, well-validated technique was used to collect, prepare, and analyze the samples of breast milk to minimize the potential for environmental contamination and maximize the percent recovery of lead. Umbilical cord and maternal blood lead were measured at delivery; 1 month after delivery (± 5 days) maternal blood, bone, and breast milk and infant blood lead levels were obtained. Levels of lead at 1 month postpartum were, for breast milk, 0.3–8.0 μg/L (mean ± SD, 1.5 ± 1.2); maternal blood lead, 2.9–29.9 μg/dL (mean ± SD, 9.4 ± 4.5); and infant blood lead, 1.0–23.1 μg/dL (mean ± SD, 5.5 ± 3.0). Infant blood lead at 1 month postpartum was significantly correlated with umbilical cord (Spearman correlation coefficient rS = 0.40, p < 0.0001) and maternal (rS = 0.42, p < 0.0001) blood lead at delivery and with maternal blood (rS = 0.67, p < 0.0001), patella (rS = 0.19, p = 0.004), and breast milk (rS = 0.32, p < 0.0001) lead at 1 month postpartum. Adjusting for cord blood lead, infant weight change, and reported breast-feeding status, a difference of approximately 2 μg/L (ppb; from the midpoint of the lowest quartile to the midpoint of the highest quartile) breast milk lead was associated with a 0.82 μg/dL increase in blood lead for breast-feeding infants at 1 month of age. Breast milk lead accounted for 12% of the variance of infant blood lead levels, whereas maternal blood lead accounted for 30%. Although these levels of lead in breast milk were low, they clearly have a strong influence on infant blood lead levels over and above the influence of maternal blood lead. Additional information on the lead content of dietary alternatives and interactions with other nutritional factors should be considered. However, because human milk is the best and most complete nutritional source for young infants, breast-feeding should be encouraged because the absolute values of the effects are small within this range of lead concentrations.
PMCID: PMC1247564  PMID: 15471729
blood lead; breast milk lead; breast-feeding; KXRF bone lead; lactation
20.  Levels of lead in breast milk and their relation to maternal blood and bone lead levels at one month postpartum. 
Environmental Health Perspectives  2004;112(8):926-931.
Despite the many well-recognized benefits of breast-feeding for both mothers and infants, detectable levels of lead in breast milk have been documented in population studies of women with no current environmental or occupational exposures. Mobilization of maternal bone lead stores has been suggested as a potential endogenous source of lead in breast milk. We measured lead in breast milk to quantify the relation between maternal blood and bone lead levels and breast-feeding status (exclusive vs. partial) among 310 lactating women in Mexico City, Mexico, at 1 month postpartum. Umbilical cord and maternal blood samples were collected at delivery. Maternal breast milk, blood, and bone lead levels were obtained at 1 month postpartum. Levels of lead in breast milk ranged from 0.21 to 8.02 microg/L (ppb), with a geometric mean (GM) of 1.1 microg/L; blood lead ranged from 1.8 to 29.9 microg/dL (GM = 8.4 microg/dL); bone lead ranged from < 1 to 67.2 microg/g bone mineral (patella) and from < 1 to 76.6 microg/g bone mineral (tibia) at 1 month postpartum. Breast milk lead was significantly correlated with umbilical cord lead [Spearman correlation coefficient (rS) = 0.36, p < 0.0001] and maternal blood lead (rS= 0.38, p < 0.0001) at delivery and with maternal blood lead (rS = 0.42, p < 0.0001) and patella lead (rS= 0.15, p < 0.01) at 1 month postpartum. Mother's age, years living in Mexico City, and use of lead-glazed ceramics, all predictive of cumulative lead exposure, were not significant predictors of breast milk lead levels. Adjusting for parity, daily dietary calcium intake (milligrams), infant weight change (grams), and breast-feeding status (exclusive or partial lactation), the estimated effect of an interquartile range (IQR) increase in blood lead (5.0 microg/dL) was associated with a 33% increase in breast milk lead [95% confidence interval (CI), 24 to 43%], whereas an IQR increase in patella lead (20 microg/g) was associated with a 14% increase in breast milk lead (95% CI, 5 to 25%). An IQR increase in tibia lead (12.0 microg/g) was associated with a 5% increase in breast milk lead (95% CI, -3% to 14%). Our results indicate that even among a population of women with relatively high lifetime exposure to lead, levels of lead in breast milk are low, influenced both by current lead exposure and by redistribution of bone lead accumulated from past environmental exposures.
PMCID: PMC1242024  PMID: 15175184
21.  Relationship of blood and bone lead to menopause and bone mineral density among middle-age women in Mexico City. 
Environmental Health Perspectives  2003;111(4):631-636.
To describe the relationship of blood lead levels to menopause and bone lead levels, we conducted a cross-sectional study on 232 pre- or perimenopausal (PreM) and postmenopausal (PosM) women who participated in an osteoporosis-screening program in Mexico City during the first quarter of 1995. Information regarding reproductive characteristics and known risk factors for blood lead was obtained using a standard questionnaire by direct interview. The mean age of the population was 54.7 years (SD = 9.8), with a mean blood lead level of 9.2 microg/dL (SD = 4.7/dL) and a range from 2.1 to 32.1 microg/dL. After adjusting for age and bone lead levels, the mean blood lead level was 1.98 microg/dL higher in PosM women than in PreM women (p = 0.024). The increase in mean blood lead levels peaked during the second year of amenorrhea with a level (10.35 microg/dL) that was 3.51 microg/dL higher than that of PreM women. Other important predictors of blood lead levels were use of lead-glazed ceramics, schooling, trabecular bone lead, body mass index, time of living in Mexico City, and use of hormone replacement therapy. Bone density was not associated with blood lead levels. These results support the hypothesis that release of bone lead stores increases during menopause and constitutes an internal source of exposure possibly associated with health effects in women in menopause transition.
PMCID: PMC1241456  PMID: 12676627

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