Low-level Prenatal Lead Exposure Research Articles

Prenatal exposure to mixtures of environmental chemicals and adolescent internalizing behaviors in the New Bedford Cohort

Background/Aim: Exposure to combinations of chemical neurotoxicants has not been well explored as a risk factor for mental health difficulties. We evaluated associations of prenatal exposure to mixtures of organochlorines and metals with adolescent internalizing behaviors.Methods: Participants were 397 socioeconomically (32% household income <$20,000) and racially (31% non-White) diverse children from a prospective birth cohort recruited at birth (1993-1998) in New Bedford, Massachusetts. Organochlorines [hexachlorobenzene, p,p'-dichlorodiphenyl dichloroethylene, polychlorinated biphenyls] and metals [manganese, lead] were analyzed in cord blood. Internalizing behaviors (anxiety, depression, somatization) at age ~15 years were assessed via teacher, parent, and self-report using the Behavior Assessment System for Children, 2nd Edition (BASC-2). Adjusted for sociodemographic predictors of exposures and internalizing behaviors, multi-chemical linear regression and Bayesian Kernel Machine Regression (BKMR) were used to explore overall and sex-specific associations between prenatal chemical exposures and BASC-2 T-scores [standardized to mean (standard deviation) of 50 (10)].Results: Chemical concentrations were consistent with background exposure levels [e.g., mean (range) cord blood lead: 1.50 (0-17.45) g/dL]. Although there was some variability in magnitude and precision, across all three reporters, lead was associated with higher anxiety, depression, and somatization behaviors in adolescents of both sexes. For example, in linear regression, a doubling of lead was associated with a 1.6-point higher (95% confidence interval: 0.6, 2.7) parent-reported anxiety T-score. There was suggestive evidence of increased susceptibility to lead among boys for parent-reported behaviors. The direction of associations of organochlorines and manganese with internalizing behaviors varied, depending on the reporter. BKMR analysis supported linear regression results, with no evidence of interactions between chemicals or non-linear associations.Conclusions: Low-level prenatal lead exposure was consistently associated with adolescent internalizing behaviors. In utero chemical exposures, particularly lead, may contribute to the emergence of anxiety and depression symptoms during this vulnerable developmental stage.[Funding: NIEHS/NIH P42ES005947, R01ES014864; CDC/NIOSH T42OH008416].

Prenatal lead exposure: associations with growth and anthropometry in early childhood in a UK observational birth cohort study

Background:Lead is a neurotoxic metal that crosses the placenta freely. It has adverse effects on a range of birth outcomes. The few studies reporting on the associations of prenatal exposure to lead and child growth have had conflicting results. This study aimed to examine the effect of low-level prenatal exposure to lead on children’s growth from 4 to 61 months old.Methods:Pregnant women were enrolled in the UK Avon Longitudinal Study of Parents and Children (ALSPAC). Whole blood samples for pregnancies with a live birth were analysed for lead (n=4140). A 10% subsample of the offspring cohort (Children in Focus) were invited to clinics at 10 time points (4–61 months) at which anthropometric measurements were carried out; z-scores for height, weight and BMI were calculated using the 1990 British Growth Reference Standards. Associations between prenatal log10-lead concentrations and z-scores and other anthropometric measures were modelled using adjusted linear regression models in an imputed dataset for children who attended at least one clinic (n=574).Results:The mean prenatal blood lead concentration was 3.59±1.50 (range 1.22–14.70) µg/dl. There was no evidence for any associations of low-level prenatal lead exposure with z-scores for BMI, height or weight in adjusted models from age 4 to 61 months. There were no associations for other anthropometric measures including mid-upper arm circumference, head circumference and waist circumference. There was some evidence for a weakly positive effect of prenatal lead exposure on head circumference in girls at age 43 and 61 months (at 61 months unstandardised B coefficient 1.59 (95% CI 0.12, 3.16) cm, p=0.048) but not at other ages.Conclusions:There was no consistent evidence of associations between prenatal exposure to lead and measures of growth and anthropometry from age 4 to 61 months in this cohort of children in the UK.

Maternal blood metal and metalloid concentrations in association with birth outcomes in Northern Puerto Rico

BackgroundIn previous studies, exposures to heavy metals such as Pb and Cd have been associated with adverse birth outcomes; however, knowledge on effects at low levels of exposure and of other elements remain limited. MethodWe examined individual and mixture effects of metals and metalloids on birth outcomes among 812 pregnant women in the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) cohort. We measured 16 essential and non-essential metal(loid)s in maternal blood collected at 16–20 and 24–28 weeks gestation. We used linear and logistic regression to independently examine associations between geometric mean (GM) concentrations of each metal across visits and gestational age, birthweight z-scores, preterm birth, small for gestational age (SGA), and large for gestational age (LGA). We evaluated effect modification with infant sex*metal interaction terms. To identify critical windows of susceptibility, birth outcomes were regressed on visit-specific metal concentrations. Furthermore, average metal concentrations were divided into tertiles to examine the potential for non-linear relationships. We used elastic net (ENET) regularization to construct Environmental Risk Score (ERS) as a metal risk score and Bayesian Kernel Machine Regression (BKMR) to identify individual metals most critical to each outcome, accounting for correlated exposures. ResultsIn adjusted models, an interquartile range (IQR) increase in GM lead (Pb) was associated with 1.63 higher odds of preterm birth (95%CI = 1.17, 2.28) and 2 days shorter gestational age (95% CI = −3.1, −0.5). Manganese (Mn) and zinc (Zn) were also associated with higher odds of preterm birth and shorter gestational age; the associations were strongest among the highest tertile for Mn and among females for Zn. Mercury (Hg) was associated with higher risk of preterm birth at the later window of pregnancy. Ni measured later in pregnancy was associated with lower odds of SGA. ENET and BKMR models selected similar metals as “important” predictors of birth outcomes. The association between ERS and preterm birth was assessed and the third tertile of ERS was significantly associated with an elevated odds ratio of 2.13 (95% CI = 1.12, 5.49) for preterm birth compared to the first tertile. ConclusionAs the PROTECT cohort has lower Pb concentrations (GM = 0.33 μg/dL) compared to the mainland US, our findings suggest that low-level prenatal lead exposure, as well as elevated Mn and Zn exposure, may adversely affect birth outcomes. Improved understanding on environmental factors contributing to preterm birth, together with sustainable technologies to remove contamination, will have a direct impact in Puerto Rico and elsewhere.

Maternal Blood Metal levels in Association with Birth Outcomes in Northern Puerto Rico

PDS 74: Pregnancy outcomes, Exhibition Hall (PDS), Ground floor, August 26, 2019, 1:30 PM - 3:00 PM Background: In previous studies exposures to heavy metals such as Pb and Cd have been associated with adverse birth outcomes; however, knowledge of effects at low levels of exposure and of other elements remain limited. Methods: We examined individual and mixture effects of 10 metals on birth outcomes among 810 pregnant women in the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) cohort. We measured As, Cd, Co, Cs, Cu, Mn, Hg, Ni, Pb, and Zn in maternal blood collected at 16–20 and 24–28 weeks gestation. We used linear and logistic regression to independently examine associations between geometric mean (GM) concentrations of each metal across visits and 1) gestational age and birthweight z-scores; and 2) preterm birth and small for gestational age (SGA). We evaluated effect modification with infant sex*metal interaction terms. To identify critical windows of susceptibility, birth outcomes were regressed on visit-specific metal concentrations. We used elastic net (ENET) regularization to identify individual metals most critical to each outcome, accounting for correlated exposures. Results: In adjusted models, an interquartile range increase in GM Pb was associated with 1.70 higher odds of preterm birth (95%CI: 1.24, 2.34) and 24% shorter gestational age (95%CI:-36.7%, -8.6). Mn and Zn were also associated with higher odds of preterm birth and shorter gestational age, although only significant among the highest tertile and females, respectively. Co, Cs, and Ni measured later in pregnancy were positively associated with birthweight z-score, and Ni was associated with decreased odds of SGA. ENET yielded similar results. Conclusions: As the PROTECT cohort has lower Pb concentrations (GM=0.33 ug/dL) compared to the mainland US, our findings suggest that low-level prenatal lead exposure, as well as higher Mn and Zn exposure, may adversely affect birth outcomes. Higher concentrations of certain essential metals later in pregnancy were associated with increased size at birth.

Family environmental and dietary implications for low-level prenatal lead exposure in Wujiang City, China.

To explore the potential environmental and dietary factors during pregnancy affecting low-level prenatal lead exposure, we conducted a longitudinal study in Wujiang City, China. A total of 1976 mother-infant pairs were included from 2009 to 2010. An interviewed questionnaire was conducted and cord blood samples were collected. The geometric means of cord blood lead level was 30.3μg/L (95% CI, 29.8-30.8) with 99.24% below 100μg/L. Maternal age, passive smoking, and living in the countryside were significantly associated with cord blood lead concentrations. Multiple logistic models showed that some family environmental factors including using firewood and electricity as kitchen fuel were positively correlated with increased cord blood lead levels. Among dietary sources recorded in this study, meat consumption (> 3 times/week), fish consumption (1-3 times/week), vegetables consumption (> 1 times/day), and fruit intake (> 1 times/day) had inverse relationship with cord blood lead levels. In general, our findings may have important implications for family environmental and dietary direction during pregnancy to decrease prenatal lead exposure.

Effects of low-level prenatal lead exposure on child IQ at 4 and 8 years in a UK birth cohort study

BackgroundThe association between childhood exposure to lead (Pb) and deficits in cognitive function is well established. The association with prenatal exposure, however, is not well understood, even though the potential adverse effects are equally important. ObjectivesTo evaluate the association between low prenatal exposure to lead and IQ in children, to determine whether there were sex differences in the associations, and to evaluate the moderation effect of prenatal Pb exposure on child IQ. MethodsWhole blood samples from pregnant women enrolled in ALSPAC (n=4285) and from offspring at age 30 months (n=235) were analysed for Pb. Associations between prenatal blood lead concentrations (B-Pb) and child IQ at age 4 and 8 years (WPPSI and WISC-III, respectively) were examined in adjusted regression models. ResultsThere was no association of prenatal lead exposure with child IQ at 4 or 8 years old in adjusted regression models, and no moderation of the association between child B-Pb and IQ. However, there was a positive association for IQ at age 8 years in girls with a predicted increase in IQ (points) per 1μg/dl of: verbal 0.71, performance 0.57, total 0.73. In boys, the coefficients tended to be negative (−0.15, −0.42 and −0.29 points, respectively). ConclusionPrenatal lead exposure was not associated with adverse effects on child IQ at age 4 or 8 years in this study. There was, however, some evidence to suggest that boys are more susceptible than girls to prenatal exposure to lead. Further investigation in other cohorts is required.

Low-level prenatal lead exposure and infant sensory function.

BackgroundLead is a pervasive neurotoxicant that has been associated with poorer cognitive, behavioral, and motor outcomes in children. The effects of lead on sensory function have not been well characterized. The aim of this study was to assess the effects of prenatal lead exposure on infant sensory function, as measured by auditory brainstem response (ABR) and grating visual acuity (VA).MethodsLead was measured in maternal blood in mid- and late-pregnancy (mean gestational age = 15.5 and 39.0 weeks, respectively) and umbilical cord blood in a cohort of full-term infants in rural northeastern China. ABR latencies (peaks I, III, V) were measured in newborns during unsedated sleep (n = 315). The ABR central-to-peripheral (C-P) ratio was calculated as the ratio between the III-V and I-III interpeak intervals. VA was measured in 6-week-olds using Teller Acuity Cards (n = 1019) and assigned as the narrowest grid the infant fixated on. Multivariate linear regression was used to evaluate relationships between tertiles of mid-pregnancy, late-pregnancy, or cord lead and newborn ABR or 6-week VA.ResultsHigher late-pregnancy lead levels were associated with higher ABR C-P ratios and lower VA. In covariate-adjusted analyses, mean C-P ratios were 4.6 and 3.2 % higher in infants whose mothers had lead > 3.8 μg/dL and lead = 2–3.8 μg/dL, respectively, than for infants whose mothers had lead < 2 μg/dL (p-trend =0.002). In adjusted analyses for VA, mean scores were 8.5 and 7.2 % lower for maternal lead > 3.8 μg/dL and lead = 2–3.8 μg/dL, respectively, compared to lead < 2 μg/dL (p-trend =0.009).ConclusionAuditory and visual systems maturation appears delayed in infants with higher prenatal lead exposure during late-pregnancy, even at relatively low levels. Both systems start myelinating in late gestation and mature rapidly in infancy. Higher ABR C-P ratio and lower grating VA scores suggest effects of low-level lead exposure on sensory system myelination.Electronic supplementary materialThe online version of this article (doi:10.1186/s12940-016-0148-6) contains supplementary material, which is available to authorized users.

Association of cord blood levels of lead, arsenic, and zinc and home environment with children neurodevelopment at 36 months living in Chitwan Valley, Nepal.

BackgroundInconsistent results continue to be reported from studies linking low-level prenatal lead exposure and child development. Because of limited earlier epidemiological studies with birth cohort follow up design, it still remains inconclusive that either the associations of cord blood level of toxic, and essential elements, and postnatal raising environment on neurodevelopment of children remains constant throughout childhood or change over time.AimsThis study aims to investigate the influence of in utero toxic [lead (Pb) and arsenic (As)] and essential elements [zinc (Zn)] levels on neurodevelopment of 36 months children in Chitwan valley, Nepal taking the postnatal environment into account.Study Designs and SubjectsIn this birth cohort study, participants (N=100 mother-infants’ pairs) were recruited in Chitwan district, Nepal. We measured Pb, As and Zn concentrations in cord blood. Postnatal raising environment (i.e., Home score or home environment hereafter) was evaluated using Home Observation for Measurement of Environment (HOME) scale. Neurodevelopment of children at 36 months of age (n=70) were assessed using Bayley Scale of Infant Development, Second Edition (BSID II). Multivariate regression was performed (n=70) to see the association of in utero toxic and essential elements level and home environment with neurodevelopment score adjusted for covariates.ResultsCord blood levels of Pb, As and Zn were not associated with any BSID II cluster scores of 36 months children. The children with relatively superior HOME score and concurrent nutritional status (weight at 36 months) showed better cognitive development (i.e., MDI scores) and motor functions than their counterparts, respectively.ConclusionIn this general population in Nepal, prenatal Pb, As and Zn levels are not important determinants of the neurodevelopment of 36- month-old children while a consistent beneficial effect of a stimulating home environment on neurodevelopmental indicators is continued.

Changes in low levels of lead over the course of pregnancy and the association with birth outcomes.

Data are lacking on the effect of low level prenatal lead exposure. We examined the change in blood lead from the second trimester until delivery and the association between maternal and cord blood lead and birth outcomes in 98 participants of the CANDLE birth cohort study. Mixed effects models were constructed to assess blood lead change over pregnancy and regression models were used to explore the relationship with cord blood lead, characteristics effecting maternal lead, birth weight and gestational age. Overall, the geometric mean maternal blood level was 0.43 μg/dL. Maternal blood lead at each time point was predictive of cord blood lead level. A 0.1 μg/dL increase in second trimester lead was associated with lower birth weight and pre-term birth. Maternal blood lead below 1 μg/dL behaves in a manner similar to lead at higher levels and is associated with a small decrease in birth weight and gestational age.

Low-Level Prenatal Lead Exposure Alters Auditory Recognition Memory in 2-Month-Old Infants: An Event-Related Potentials (ERPs) Study

This study used event-related potentials (ERPs) to assess effects of low-level prenatal lead exposure on auditory recognition memory in 2-month-old infants. Infants were divided into four groups according to cord-blood lead concentration: (1) <2.00 μg/dL, (2) 2.00–2.99 μg/dL, (3) 3.0–3.7 μg/dL, and (4) ≥3.7 μg/dL. The first group showed the normally expected differences in P2, P750, and late slow wave (LSW) amplitudes elicited by mothers’ and strangers’ voices. These differences were not observed for one or more ERP components in the other groups. Thus, there was electrophysiological evidence of poorer auditory recognition memory at 2 months with cord-blood lead ≥2.00 μg/dL.

The effects of low-level prenatal lead exposure on birth outcomes

Exposure to lead early in life may be a risk factor for fetal growth, but little is known about the effects of low-level prenatal lead exposure on birth outcomes. We measured maternal and cord blood lead levels and examined their associations with birth outcomes. Mother–infant pairs (n = 252) were recruited from a rural area located on the south coast of Laizhou Bay between 2010 and 2011. The median levels of maternal and cord blood lead were 3.20 and 2.52 μg/dL, respectively. Increasing maternal blood lead exposure was associated with decreasing birth weight (β = −148.99; 95% CI, −286.33 to −11.66), and a significant negative relationship was found between cord blood lead levels and birth length (β = −0.84; 95% CI, −1.52 to −0.16). Low-level prenatal lead exposure may adversely affect fetal growth. These results may be important for public health and have implications regarding the recommended blood lead levels.

Prenatal Lead Exposure in Mice: Age-Related, Sex-Specific Effects Observed

Children with low-level prenatal lead exposure may suffer reduced cognitive function, impaired motor ability, and visual and auditory processing problems. Other effects, such as accelerated age-related functional decline or delayed neurotoxicity, may become apparent in adulthood, though few studies have examined the long-term consequences of exposure. A novel animal model now reveals age-related, male-specific, and nonmonotonic dose–response effects associated with low-level prenatal lead exposure [EHP 116:355–361; Leasure et al.]. To model gestational lead exposure (GLE), one group of dams received tap water or drinking solutions containing low (27 ppm), moderate (55 ppm), or high (109 ppm) concentrations of lead beginning 2 weeks before mating and continuing until postnatal day 10. To measure postnatal lead exposure (PLE), another group of dams received tap water or water that contained low or moderate levels of lead from birth to weaning. The offspring of both groups were measured at birth and several times throughout the following year for weight and blood lead concentrations. Blood lead levels ranged from 10 μg/dL or less in low-exposure GLE offspring to 42 μg/dL in the high-exposure GLE group at post-natal day 10, and from 10 μg/dL in low-exposure PLE offspring to 27 μg/dL in the high-exposure PLE group at postnatal day 21. By postnatal day 30 for GLE offspring and postnatal day 60 for PLE offspring, blood lead levels were no different than in controls. At 1 year of age, male and female offspring were assessed for exploratory activity and interlimb balance and coordination. Because human developmental studies have demonstrated that males are at higher risk of deficits related to early lead exposure, additional testing of male offspring included measuring fore-brain and striatal levels of dopamine and its major metabolite, 3,4-dihydroxyphenylacetic acid. Lead exposure did not affect body weight of any PLE mice or of female GLE mice, but there was a significant inverse relationship between lead exposure and body weight for male low-exposure and high-exposure GLE mice (26% and 13% heavier than controls, respectively). Male GLE mice also exhibited significantly less exploratory activity, with a greater effect again seen in the low-exposure group. This group also had significantly poorer balance and coordination, lower forebrain levels of dopamine, and higher forebrain and striatal levels of 3,4-dihydroxyphenylacetic acid. Multiple endocrine or metabolic mechanisms that occurred during gestational development could explain the late-onset obesity observed at 1 year of age. The diminished exploratory activity may reflect an altered stress response arising from lead-related changes in the hypothalamic–pituitary–adrenal axis and dopaminergic systems. Changes in the forebrain may also have implications for attention deficit/hyperactivity disorder, as abnormalities in the prefrontal cortex appear to underlie the disorder. Multidisciplinary behavioral, biochemical, and molecular studies are needed to test and explain the reported novel findings, which highlight the need for realistic lifetime dose–response assessment of toxicants.

The Conquest of Lead Poisoning: A Pyrrhic Victory

The Conquest of Lead Poisoning: A Pyrrhic Victory

The relation of low-level prenatal lead exposure to behavioral indicators of attention in Inuit infants in Arctic Quebec

The aim of this study was to investigate the association between prenatal exposure to lead (Pb) and several aspects of behavioral function during infancy through examiner ratings and behavioral coding of video recordings. The sample consisted of 169 11-month-old Inuit infants from Arctic Quebec. Umbilical cord and maternal blood samples were used to document prenatal exposure to Pb. Average blood Pb levels were 4.6 μg/dL and 5.9 μg/dL in cord and maternal samples respectively. The Behavior Rating Scales (BRS) from the Bayley Scales of Infant Development (BSID-II) were used to assess behavior. Attention was assessed through the BRS and behavioral coding of video recordings taken during the administration of the BSID-II. Whereas the examiner ratings of behaviors detected very few associations with prenatal Pb exposure, cord blood Pb concentrations were significantly related to the direct observational measures of infant attention, after adjustment for confounding variables. These data provide evidence that increasing the specificity and the precision of the behavioral assessment has considerable potential for improving our ability to detect low-to-moderate associations between neurotoxicants, such Pb and infant behavior.

Neurobehavioral effects of low-level lead exposure in human neonates

In a clinically healthy sample of 103 African American neonates maternal blood lead levels <10 μg/dL were related to discrete aspects of neonatal behavior but not to a priori cluster scores of the Brazelton Neonatal Behavior Assessment Scale. In statistical tests modest detrimental effects on motor control and attention were found for neonatal subjects whose mothers had slightly higher blood lead levels in the sixth and seventh prenatal months. Correlation and dose-effect trends reveal slightly poorer attention and motor control performance among neonatal offspring of mothers with higher maternal blood lead levels. These results are in agreement with those of previous studies, which have consistently reported modest statistical relationships between low-level prenatal lead exposure and neonatal behavior. (Am J Obstet Gynecol 1999;181:S2-S11.)

Low-Level Prenatal Lead Exposure and Neurobehavioral Development of Children in the First Year of Life: A Prospective Study in Shanghai

We used a prospective study design to assess the effects of prenatal low-level lead exposure on the development of urban, inner-city children in Shanghai. Umbilical cord blood samples were consecutively collected from 605 live newborns. Two hundred and fifty-seven samples were excluded from the study due to clotting. Lead levels were determined on 348 cord blood samples. The geometric mean was 9.2 μg/dl. Based on their cord blood lead levels, infants were classified into two exposure groups: 104 in a relatively low lead group (lead levels ≤30 percentile), and 104 in a relatively high lead group (lead levels ≥70 percentile). Seventy-five subjects failed to complete the study, and 133 babies were included in the final cohort: 69 babies in the high lead group and 64 in the low lead group. At 3, 6, and 12 months, the Bayley Scales of Infant Development were administered and capillary blood lead levels were measured. Detailed information was obtained on a wide range of variables relevant to infant development. At all three ages, the Mental Development Index (MDI) scores, adjusted for confounders, were inversely related to the infants' cord blood lead levels. The difference of the mean adjusted MDI scores between low and high lead groups was 3.4 at 3 months, 6.3 at 6 months, and 5.2 at 12 months of age. These differences were statistically significant at all time points. No significant association between cord blood lead levels and the Psychomotor Development Index (PDI) scores was detected at all three visits after adjustment for confounders. Postnatal lead levels were unrelated to concurrent developmental status. We conclude that prenatal low-level lead exposure, which is relatively common in Shanghai, is associated with an adverse developmental impact on children through the first year of life.