Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Jun 26;125(6):067015.
doi: 10.1289/EHP614.

The Joint Effect of Prenatal Exposure to Metal Mixtures on Neurodevelopmental Outcomes at 20-40 Months of Age: Evidence from Rural Bangladesh

Linda Valeri  1   2 , Maitreyi M Mazumdar  3   4 , Jennifer F Bobb  5 , Birgit Claus Henn  6 , Ema Rodrigues  3   4 , Omar I A Sharif  7 , Molly L Kile  8 , Quazi Quamruzzaman  7 , Sakila Afroz  7 , Mostafa Golam  7 , Citra Amarasiriwardena  9 , David C Bellinger  3   4 , David C Christiani  4 , Brent A Coull  4 , Robert O Wright  9
Affiliations

The Joint Effect of Prenatal Exposure to Metal Mixtures on Neurodevelopmental Outcomes at 20-40 Months of Age: Evidence from Rural Bangladesh

Linda Valeri et al. Environ Health Perspect. .

Abstract

Background: Exposure to chemical mixtures is recognized as the real-life scenario in all populations, needing new statistical methods that can assess their complex effects.

Objectives: We aimed to assess the joint effect of in utero exposure to arsenic, manganese, and lead on children's neurodevelopment.

Methods: We employed a novel statistical approach, Bayesian kernel machine regression (BKMR), to study the joint effect of coexposure to arsenic, manganese, and lead on neurodevelopment using an adapted Bayley Scale of Infant and Toddler Development™. Third Edition, in 825 mother-child pairs recruited into a prospective birth cohort from two clinics in the Pabna and Sirajdikhan districts of Bangladesh. Metals were measured in cord blood using inductively coupled plasma-mass spectrometry.

Results: Analyses were stratified by clinic due to differences in exposure profiles. In the Pabna district, which displayed high manganese levels [interquartile range (IQR): 4.8, 18 μg/dl], we found a statistically significant negative effect of the mixture of arsenic, lead, and manganese on cognitive score when cord blood metals concentrations were all above the 60th percentile (As≥0.7 μg/dl, Mn≥6.6 μg/dl, Pb≥4.2 μg/dl) compared to the median (As=0.5 μg/dl, Mn=5.8 μg/dl, Pb=3.1 μg/dl). Evidence of a nonlinear effect of manganese was found. A change in log manganese from the 25th to the 75th percentile when arsenic and manganese were at the median was associated with a decrease in cognitive score of −0.3 (−0.5, −0.1) standard deviations. Our study suggests that arsenic might be a potentiator of manganese toxicity.

Conclusions: Employing a novel statistical method for the study of the health effects of chemical mixtures, we found evidence of neurotoxicity of the mixture, as well as potential synergism between arsenic and manganese. https://doi.org/10.1289/EHP614.

PubMed Disclaimer

Figures

Two grids indicating concentrations of arsenic, manganese, and lead.
Figure 1.
Correlation (Pearson) matrix for maternal and cord blood metals. (A) Pabna (B) Sirajdikhan.
Two graphs indicate changes in neurodevelopment score according to percentile metal exposure; and two graphs depict univariate and bivariate exposure–response functions according to concentrations of other two metals by using the data from Pabna clinic.
Figure 2.
Joint effect of the mixture on cognitive score (CS) in Pabna clinic estimated by Bayesian Kernel Machine Regression (BKMR). Model adjusted for child gender, maternal IQ, maternal education, maternal protein intake, smoking environment, age at testing, and maternal age. (A) Overall effect of the mixture (estimates and 95% credible intervals). This figure plots the estimated change in neurodevelopment score when exposures are at a particular percentile (x-axis) compared to when exposure are all at the 50th percentile. (B) Single pollutant association (estimates and 95% credible intervals, gray dashed line at the null). This plot compares the neurodevelopment score when a single pollutant is at the 75th vs. 25th percentile, when all the other exposures are fixed at either the 25th, 50th, or 75th percentile. (C) Univariate exposure–response functions and 95% confidence bands for each metal with the other pollutants fixed at the median. (D) Bivariate exposure–response functions for: arsenic when manganese is fixed at either the 25th, 50th, or 75th percentile and lead is fixed at the median (top left panel); arsenic when lead is fixed at either the 25th, 50th or 75th percentile and manganese is fixed at the median (top right panel); manganese when arsenic is fixed at either 25th, 50th, or 75th percentile and lead is fixed at the median (bottom left panel); manganese when lead is fixed at either the 25th, 50th, or 75th percentile and arsenic is fixed at the median (bottom right panel). [percentiles: (0.25,0.5,0.75); As=(0.56,0.88,1.60), Mn=(4.80,7.12,17.5), Pb=(1.15, 1.63, 2.42)].
Two graphs indicate changes in neurodevelopment score according to percentile metal exposures; and two graphs depict univariate and bivariate exposure–response functions according to concentrations of other two metals by using data from Sirajdikhan clinic.
Figure 3.
Joint effect of the mixture on cognitive score in Sirajdikhan clinic estimated by Bayesian Kernel Machine Regression (BKMR). Model adjusted for child gender, maternal IQ, maternal education, maternal protein intake, smoking environment, age at testing, and maternal age. (A) Overall effect of the mixture (estimates and 95% credible intervals). This plot compares the neurodevelopment score when all exposures are at a particular quantile to when all are at the 50th percentile. (B) Single pollutant association (estimates and 95% credible intervals, gray dashed line at the null). This plot compares the neurodevelopment score when a single pollutant is at the 75th vs. 25th percentile, when all the other exposures are fixed at either the 25th, 50th, or 75th percentile. (C) Univariate exposure–response functions and 95% confidence bands for each metal with the other pollutants fixed at the median (D) Bivariate exposure–response functions for: arsenic when manganese is fixed at either the 25th, 50th, or 75th percentile and lead is fixed at the median (top left panel); arsenic when lead is fixed at either the 25th, 50th, or 75th percentile and manganese is fixed at the median (top right panel); manganese when arsenic is fixed at either 25th, 50th, or 75th percentile and lead is fixed at the median (bottom left panel); manganese when lead is fixed at either the 25th, 50th, or 75th percentile and arsenic is fixed at the median (bottom right panel). [percentiles: (0.25,0.5,0.75); As=(0.26,0.40,0.60), Mn=(3.93,5.14,6.66), Pb=(3.87,6.12,9.67)].
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bayley N. 1993. Bayley Scales of Infant Development, II. San Antonio, TX:Harcourt Brace & Co.
    1. Bayley N. 2006. Bayley Scales of Infant and Toddler Development. 3rd Edition San Antonio, TX:Harcourt Assessment Inc. - PubMed
    1. Black MM, Baqui AH, Zaman K, Persson L, El Arifeen S, Le K, et al. . 2004. Iron and zinc supplementation promote motor development and exploratory behavior among Bangladeshi infants. Am J Clin Nutr 80(4): 903–910, PMID: 15447897. - PubMed
    1. Bobb JF, Valeri L, Claus Henn B, Christiani DC, Wright RO, Mazumdar M, et al. . 2015. Bayesian kernel machine regression for estimating the health effects of multi-pollutant mixtures. Biostatistics 16(3):493–508. - PMC - PubMed
    1. Bressler J, Kim KA, Chakraborti T, Goldstein G. 1999. Molecular mechanisms of lead neurotoxicity. Neurochem Res 24(4):595–600, PMID: 10227691. - PubMed

Publication types

-