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1.  A process evaluation of PRONTO simulation training for obstetric and neonatal emergency response teams in Guatemala 
BMC Medical Education  2015;15:117.
Despite expanding access to institutional birth in Guatemala, maternal mortality remains largely unchanged over the last ten years. Enhancing the quality of emergency obstetric and neonatal care is one important strategy to decrease mortality. An innovative, low-tech, simulation-based team training program (PRONTO) aims to optimize care provided during obstetric and neonatal emergencies in low-resource settings.
We conducted PRONTO simulation training between July 2012 and December 2012 in 15 clinics in Alta Verapaz, Huehuetenango, San Marcos, and Quiche, Guatemala. These clinics received PRONTO as part of a larger pair-matched cluster randomized trial of a comprehensive intervention package. Training participants were obstetric and neonatal care providers that completed pre- and post- training assessments for the two PRONTO training modules, which evaluated knowledge of evidence-based practice and self-efficacy in obstetric and neonatal topics. Part of the training included a session for trained teams to establish strategic goals to improve clinical practice. We utilized a pre/post-test design to evaluate the impact of the course on both knowledge and self-efficacy with longitudinal fixed effects linear regression with robust standard errors. Pearson correlation coefficients were used to assess the correlation between knowledge and self-efficacy. Poisson regression was used to assess the association between the number of goals achieved and knowledge, self-efficacy, and identified facility-level factors.
Knowledge and self-efficacy scores improved significantly in all areas of teaching. Scores were correlated for all topics overall at training completion. More than 60 % of goals set to improve clinic functioning and emergency care were achieved. No predictors of goal achievement were identified.
PRONTO training is effective at improving provider knowledge and self-efficacy in training areas. Further research is needed to evaluate the impact of the training on provider use of evidence-based practices and on maternal and neonatal health outcomes.
Trial registration
PMCID: PMC4513701  PMID: 26206373
In-situ simulation; Continuing medical education; Emergency obstetric care; Inter-professional training
2.  Effect of calcium supplementation on bone resorption in pregnancy and the early postpartum: a randomized controlled trial in Mexican Women 
Nutrition Journal  2014;13:116.
Calcium needs are physiologically upregulated during pregnancy and lactation to meet demands of the developing fetus and breastfeeding infant. Maternal calcium homeostasis is maintained by hormonal adaptive mechanisms, thus, the role of dietary calcium supplementation in altering maternal responses to fetal-infant demand for calcium is thought to be limited. However, increased calcium absorption is directly related to maternal calcium intake and dietary supplementation has been suggested to prevent transient bone loss associated with childbearing.
In a double-blind, randomized placebo-controlled trial, we randomly assigned 670 women in their first trimester of pregnancy to 1,200 mg/day calcium (N = 334) or placebo (N = 336). Subjects were followed through 1-month postpartum and the effect on urinary cross-linked N-telopeptides (NTx) of type I collagen, a specific marker of bone resorption, was evaluated using an intent-to-treat analysis. Women with a baseline and at least one follow-up measurement (N = 563; 84%) were included. Subsequent analyses were conducted stratifying subjects by compliance assessed using pill counts. In random subsets of participants, bone-specific alkaline phosphatase (BAP) (N = 100) and quantitative ultrasound (QUS) (N = 290) were also measured.
Calcium was associated with an overall reduction of 15.8% in urinary NTx relative to placebo (p < 0.001). Among those who consumed ≥50%, ≥67%, and ≥75% of pills, respectively, the effect was associated with 17.3%, 21.3%, and 22.1% reductions in bone resorption (all p < 0.001). There was no significant effect of calcium on bone formation measured by BAP. However, by 1-month postpartum, those in the calcium group had significantly lower NTx/BAP ratios than those in the placebo group (p = 0.04) indicating a net reduction in bone loss in the supplement group by the end of follow-up. Among subjects who consumed ≥50% and ≥75% of pills, respectively, calcium was also associated with an increase of 26.3 m/s (p = 0.03) and 59.0 m/s (p = 0.009) in radial SOS relative to placebo by 1-month postpartum.
Calcium administered during pregnancy and the early postpartum period, to women with intakes around adequacy, was associated with reduced bone resorption and, thus, may constitute a practical intervention to prevent transient skeletal loss associated with childbearing.
Trial registration Identifier NCT00558623
PMCID: PMC4289552  PMID: 25511814
Bone-specific alkaline phosphatase; Calcium; Clinical trials; Lactation; Pregnancy; Quantitative ultrasound bone speed of sound; Urinary N-telopeptide of type I collagen
4.  Bias correction by use of errors-in-variables regression models in studies with K-X ray fluorescence bone lead measurements1 
Environmental research  2010;111(1):17-20.
In-vivo measurement of bone lead by means of K-X ray fluorescence (KXRF) is the preferred biological marker of chronic exposure to lead. Unfortunately, considerable measurement error associated with KXRF estimations can introduce bias in estimates of the effect of bone lead when this variable is included as the exposure in a regression model. Estimates of uncertainty reported by the KXRF instrument reflect the variance of the measurement error and, although they can be used to correct the measurement error bias, they are seldom used in epidemiological statistical analyses. Errors-in-variables regression (EIV) allows for correction of bias caused by measurement error in predictor variables, based on the knowledge of the reliability of such variables. The authors propose a way to obtain reliability coefficients for bone lead measurements from uncertainty data reported by the KXRF instrument and compare, by use of Monte Carlo simulations, results obtained using EIV regression models versus those obtained by the standard procedures. Results of the simulations show that Ordinary Least Square (OLS) regression models provide severely biased estimates of effect, and that EIV provides nearly unbiased estimates. Although EIV effect estimates are more imprecise, their mean squared error is much smaller than that of OLS estimates. In conclusion, EIV is a better alternative than OLS to estimate the effect of bone lead when measured by KXRF.
PMCID: PMC3026095  PMID: 21092947
Lead; KXRF; measurement error; errors-in-variables model; simulations
5.  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
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.  Methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C and G1793A genotypes, and the relationship between maternal folate intake, tibia lead and infant size at birth 
The British journal of nutrition  2009;102(6):907-914.
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) μg/l, with 26·7 % having levels ≥100 μg/l. Tibia Pb level was 9·9 (SD 9·8) μg/g. Of the women, 35·3 % had folate intakes <400 μg/d. Birth weight was 3170 (SD 422) g. In covariate-adjusted regressions, higher folate intake was associated with higher birth weight (β 0·04; P<0·05). Higher bone Pb was associated with lower birth weight (β −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.
PMCID: PMC3098451  PMID: 19338708
Dietary folate; Lead exposure; Pregnancy; Birth weight; Mexico
10.  Bisphenol a exposure in Mexico City and risk of prematurity: a pilot nested case control study 
Environmental Health  2010;9:62.
Presence of Bisphenol A (BPA) has been documented worldwide in a variety of human biological samples. There is growing evidence that low level BPA exposure may impact placental tissue development and thyroid function in humans. The aim of this present pilot study was to determine urinary concentrations of BPA during the last trimester of pregnancy among a small subset of women in Mexico City, Mexico and relate these concentrations to risk of delivering prematurely.
A nested case-control subset of 60 participants in the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) study in Mexico City, Mexico were selected based on delivering less than or equal to 37 weeks of gestation and greater than 37 weeks of gestation. Third trimester archived spot urine samples were analyzed by online solid phase extraction coupled with high performance liquid chromatography isotope dilution tandem mass spectrometry.
BPA was detected in 80.0% (N = 48) of the urine samples; total concentrations ranged from < 0.4 μg/L to 6.7 μg/L; uncorrected geometric mean was 1.52 μg/L. The adjusted odds ratio of delivering less than or equal to 37 weeks in relation to specific gravity adjusted third trimester BPA concentration was 1.91 (95%CI 0.93, 3.91, p-value = 0.08). When cases were further restricted to births occurring prior to the 37th week (n = 12), the odds ratio for specific-gravity adjusted BPA was larger and statistically significant (p < 0.05).
This is the first study to document measurable levels of BPA in the urine of a population of Mexican women. This study also provides preliminary evidence, based on a single spot urine sample collected during the third trimester, that pregnant women who delivered less than or equal to 37 weeks of gestation and prematurely (< 37 weeks) had higher urinary concentrations of BPA compared to women delivering after 37 weeks.
PMCID: PMC2965706  PMID: 20955576
11.  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
12.  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
Neurotoxicology  2007;29(2):278-285.
The notion that maternal personality characteristics influence cognitive development in their children has been grounded in stress moderation theory. Maternal personality traits, such as self-esteem, may buffer maternal stressors or lead to improved maternal-child interactions that directly impact neurodevelopment. This can be extended to suggest that maternal personality may serve to attenuate or exacerbate the effects of other neurotoxicants, although this has not been studied directly. We examined whether mothers’ self-esteem had a direct or main effect on their children's cognitive outcomes. We also explored the modifying effects of maternal self-esteem on the association between exposure to lead and neurodevelopment in these children. Study participants included 379 mother-child pairs from Mexico City. Data included the Coopersmith self-esteem scale in mothers, children's Bayley's Scale of Infant Development (BSID) scores, and sociodemographic information. Linear regression was used to model the relationship between maternal self-esteem and the Bayley's Mental Development Index (MDI) and Psychomotor Development Index (PDI) scores at age 24 months using regression models stratified by levels of maternal self-esteem. In adjusted models, each point increase in maternal self-esteem was associated with children having 0.2 higher score on the Bayley's MDI (p=0.04). Similar results were observed using the PDI outcome. Moreover, there was evidence that maternal self-esteem attenuated the negative effects of lead exposure, although the interaction fell short of conventional levels of statistical significance.
PMCID: PMC2495770  PMID: 18261800
child; cognition; lead; neurotoxicology; mother-child relations
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

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