Howard Hu

Maternal Fish Consumption, Hair Mercury, and Infant Cognition in a U.S. Cohort.

Fish and other seafood may contain organic mercury but also beneficial nutrients such as n-3 polyunsaturated fatty acids. We endeavored to study whether maternal fish consumption during pregnancy harms or benefits fetal brain development. We examined associations of maternal fish intake during pregnancy and maternal hair mercury at delivery with infant cognition among 135 mother–infant pairs in Project Viva, a prospective U.S. pregnancy and child cohort study. We assessed infant cognition by the percent novelty preference on visual recognition memory (VRM) testing at 6 months of age. Mothers consumed an average of 1.2 fish servings per week during the second trimester. Mean maternal hair mercury was 0.55 ppm, with 10% of samples > 1.2 ppm. Mean VRM score was 59.8 (range, 10.9–92.5). After adjusting for participant characteristics using linear regression, higher fish intake was associated with higher infant cognition. This association strengthened after adjustment for hair mercury level: For each additional weekly fish serving, offspring VRM score was 4.0 points higher [95% confidence interval (CI), 1.3 to 6.7]. However, an increase of 1 ppm in mercury was associated with a decrement in VRM score of 7.5 (95% CI, –13.7 to –1.2) points. VRM scores were highest among infants of women who consumed > 2 weekly fish servings but had mercury levels ≤1.2 ppm. Higher fish consumption in pregnancy was associated with better infant cognition, but higher mercury levels were associated with lower cognition. Women should continue to eat fish during pregnancy but choose varieties with lower mercury contamination.

Maternal Fish Intake during Pregnancy, Blood Mercury Levels, and Child Cognition at Age 3 Years in a US Cohort

The balance of contaminant risk and nutritional benefit from maternal prenatal fish consumption for child cognitive development is not known. Using data from a prospective cohort study of 341 mother-child pairs in Massachusetts enrolled in 1999-2002, the authors studied associations of maternal second-trimester fish intake and erythrocyte mercury levels with childrens scores on the Peabody Picture Vocabulary Test (PPVT) and Wide Range Assessment of Visual Motor Abilities (WRAVMA) at age 3 years. Mean maternal total fish intake was 1.5 (standard deviation, 1.4) servings/week, and 40 (12%) mothers consumed >2 servings/week. Mean maternal mercury level was 3.8 (standard deviation, 3.8) ng/g. After adjustment using multivariable linear regression, higher fish intake was associated with better child cognitive test performance, and higher mercury levels with poorer test scores. Associations strengthened with inclusion of both fish and mercury: effect estimates for fish intake of >2 servings/week versus never were 2.2 (95% confidence interval (CI): -2.6, 7.0) for the PPVT and 6.4 (95% CI: 2.0, 10.8) for the WRAVMA; for mercury in the top decile, they were -4.5 (95% CI: -8.5, -0.4) for the PPVT and -4.6 (95% CI: -8.3, -0.9) for the WRAVMA. Fish consumption of < or =2 servings/week was not associated with a benefit. Dietary recommendations for pregnant women should incorporate the nutritional benefits as well as the risks of fish intake.

Fetal Lead Exposure at Each Stage of Pregnancy as a Predictor of Infant Mental Development

Background 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. Objective 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. Methods 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. Results 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. Conclusions 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.

Recommendations for medical management of adult lead exposure

Research conducted in recent years has increased public health concern about the toxicity of lead at low dose and has supported a reappraisal of the levels of lead exposure that may be safely tolerated in the workplace. In this article, which appears as part of a mini-monograph on adult lead exposure, we summarize a body of published literature that establishes the potential for hypertension, effects on renal function, cognitive dysfunction, and adverse female reproductive outcome in adults with whole-blood lead concentrations < 40 μg/dL. Based on this literature, and our collective experience in evaluating lead-exposed adults, we recommend that individuals be removed from occupational lead exposure if a single blood lead concentration exceeds 30 μg/dL or if two successive blood lead concentrations measured over a 4-week interval are ≥ 20 μg/dL. Removal of individuals from lead exposure should be considered to avoid long-term risk to health if exposure control measures over an extended period do not decrease blood lead concentrations to < 10 μg/dL or if selected medical conditions exist that would increase the risk of continued exposure. Recommended medical surveillance for all lead-exposed workers should include quarterly blood lead measurements for individuals with blood lead concentrations between 10 and 19 μg/dL, and semiannual blood lead measurements when sustained blood lead concentrations are < 10 μg/dL. It is advisable for pregnant women to avoid occupational or avocational lead exposure that would result in blood lead concentrations > 5 μg/dL. Chelation may have an adjunctive role in the medical management of highly exposed adults with symptomatic lead intoxication but is not recommended for asymptomatic individuals with low blood lead concentrations.

Longitudinal Associations Between Blood Lead Concentrations Lower Than 10 μg/dL and Neurobehavioral Development in Environmentally Exposed Children in Mexico City

OBJECTIVE. Increasing evidence suggests that 10 μg/dL, the current Centers for Disease Control and Prevention screening guideline for childrens blood lead level, should not be interpreted as a level at which adverse effects do not occur. Using data from a prospective study conducted in Mexico City, Mexico, we evaluated the dose-effect relationship between blood lead levels and neurodevelopment at 12 and 24 months of age. METHODS. The study population consisted of 294 children whose blood lead levels at both 12 and 24 months of age were <10 μg/dL; blood lead levels were measured by graphite furnace atomic absorption spectroscopy; Bayley Scales of Infant Development II were administered at these ages. The outcomes of interest were the Mental Development Index and the Psychomotor Development Index. RESULTS. Adjusting for covariates, childrens blood lead levels at 24 months were significantly associated, in an inverse direction, with both Mental Development Index and Psychomotor Development Index scores at 24 months. Blood lead level at 12 months of age was not associated with concurrent Mental Development Index or Psychomotor Development Index scores or with Mental Development Index at 24 months of age but was significantly associated with Psychomotor Development Index score at 24 months. The relationships were not altered by adjustment for cord blood lead level or, in the analyses of 24-month Mental Development Index and Psychomotor Development Index scores, for the 12-month Mental Development Index and Psychomotor Development Index scores. For both Mental Development Index and Psychomotor Development Index at 24 months of age, the coefficients that were associated with concurrent blood lead level were significantly larger among children with blood lead levels <10 μg/dL than it was among children with levels >10 μg/dL. CONCLUSIONS. These analyses indicate that childrens neurodevelopment is inversely related to their blood lead levels even in the range of <10 μg/dL. Our findings were consistent with a supralinear relationship between blood lead levels and neurobehavioral outcomes.

Influence of prenatal lead exposure on genomic methylation of cord blood DNA.

Background 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. Objective 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. Methods 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. Results 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. Conclusions 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.

The epidemiology of lead toxicity in adults: measuring dose and consideration of other methodologic issues.

We review several issues of broad relevance to the interpretation of epidemiologic evidence concerning the toxicity of lead in adults, particularly regarding cognitive function and the cardiovascular system, which are the subjects of two systematic reviews that are also part of this mini-monograph. Chief among the recent developments in methodologic advances has been the refinement of concepts and methods for measuring individual lead dose in terms of appreciating distinctions between recent versus cumulative doses and the use of biological markers to measure these parameters in epidemiologic studies of chronic disease. Attention is focused particularly on bone lead levels measured by K-shell X-ray fluorescence as a relatively new biological marker of cumulative dose that has been used in many recent epidemiologic studies to generate insights into lead’s impact on cognition and risk of hypertension, as well as the alternative method of estimating cumulative dose using available repeated measures of blood lead to calculate an individual’s cumulative blood lead index. We review the relevance and interpretation of these lead biomarkers in the context of the toxico-kinetics of lead. In addition, we also discuss methodologic challenges that arise in studies of occupationally and environmentally exposed subjects and those concerning race/ethnicity and socioeconomic status and other important covariates.

The Faroes statement: Human Health effects of developmental exposure to chemicals in our environment

The periods of embryonic, foetal and infant developmentare remarkably susceptible to environmental hazards. Toxicexposures to chemical pollutants during these windows ofincreased susceptibility can cause disease and disability ininfants, children and across the entire span of human life.Among the effects of toxic exposures recognized in the pasthave been spontaneous abortion, congenital malformations,lowered birthweight and other adverse effects. These outcomesmay be readily apparent. However, even subtle changes causedby chemical exposures during early development may leadto important functional deficits and increased risks ofdisease later in life. The timing of exposure during early lifehas therefore become a crucial factor to be considered intoxicological assessments.During 20–24 May 2007, researchers in the fields of environmentalhealth, environmental chemistry, developmentalbiology, toxicology, epidemiology, nutrition and paediatricsgathered at the International Conference on Fetal Programmingand Developmental Toxicity, in Torshavn, FaroeIslands. The conference goal was to highlight new insightsinto the effects of prenatal and early postnatal exposure tochemical agents, and their sustained effects on the individualthroughout the lifespan. The conference brought togetherresearchers to focus on human data and the translationof laboratory results to elucidate the environmental risks tohuman health.

Use of Di(2-ethylhexyl) Phthalate-Containing Medical Products and Urinary Levels of Mono(2-ethylhexyl) Phthalate in Neonatal Intensive Care Unit Infants

Objective: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in medical products made with polyvinyl chloride (PVC) plastic and may be toxic to humans. DEHP is lipophilic and binds non-covalently to PVC, allowing it to leach from these products. Medical devices containing DEHP are used extensively in neonatal intensive care units (NICUs). Among neonates in NICUs, we studied exposure to DEHP-containing medical devices in relation to urinary levels of mono(2-ethylhexyl) phthalate (MEHP), a metabolite of DEHP. Design: We used a cross-sectional design for this study. Participants: We studied 54 neonates admitted to either of two level III hospital NICUs for at least 3 days between 1 March and 30 April 2003. Measurements: A priori, we classified the infants’ exposures to DEHP based on medical products used: The low-DEHP exposure group included infants receiving primarily bottle and/or gavage feedings; the medium exposure group included infants receiving enteral feedings, intravenous hyperalimentation, and/or nasal continuous positive airway pressure; and the high exposure group included infants receiving umbilical vessel catheterization, endotracheal intubation, intravenous hyperalimentation, and indwelling gavage tube. We measured MEHP in the infants’ urine using automated solid-phase extraction/isotope dilution/high-performance liquid chromatography/ tandem mass spectrometry. Results: Urinary MEHP levels increased monotonically with DEHP exposure. For the low-, medium-, and high-DEHP exposure groups, median (interquartile range) MEHP levels were 4 (18), 28 (58), and 86 ng/mL (150), respectively (p = 0.004). After adjustment for institution and sex, urinary MEHP levels among infants in the high exposure group were 5.1 times those among infants in the low exposure group (p = 0.03). Conclusion: Intensive use of DEHP-containing medical devices in NICU infants results in higher exposure to DEHP as reflected by elevated urinary levels of MEHP.

Attentional Correlates of Dentin and Bone Lead Levels in Adolescents

In an effort to determine whether specific aspects of attention are impaired by lead, the performance of 79 subjects (aged 19 and 20 y) on a neuropsychologically based battery of tests of attention was examined in relation to lead levels in deciduous teeth (dentin), current blood, and tibia and patella bones measured by K-X-ray fluorescence. Dentin lead levels averaged 14 micrograms/g. Most bone lead levels were less than 10 micrograms/g. Dentin lead levels were related inversely to scores on two of four attention factors: focus-execute (ability to select and respond to critical information) and shift (ability to shift focus adaptively). Few significant associations were observed between bone lead levels and performance. Five individuals with the ALA-D 1-2 isozyme phenotype tended to achieve more optimal scores. Executive and self-regulation functions may be among the cognitive skills targeted by lead.