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. 2021 May;129(5):57006.
doi: 10.1289/EHP7502. Epub 2021 May 14.

Umbilical Cord Blood Metal Mixtures and Birth Size in Bangladeshi Children

Mi-Sun Lee  1 , Ki-Do Eum  2 , Mostofa Golam  3 , Quazi Quamruzzaman  3 , Molly L Kile  4 , Maitreyi Mazumdar  1   5 , David C Christiani  1   6
Affiliations

Umbilical Cord Blood Metal Mixtures and Birth Size in Bangladeshi Children

Mi-Sun Lee et al. Environ Health Perspect. 2021 May.

Abstract

Background: Studies have evaluated environmental exposure to toxic metals such as arsenic (As), cadmium (Cd), manganese (Mn), or lead (Pb) on birth size; however, information on potential effects of exposures to metal mixtures is limited.

Objectives: We assessed the association between metal mixtures (As, Cd, Mn, Pb) in umbilical cord blood and neonate size in Bangladeshi children.

Methods: In this birth cohort study, pregnant women who were ≥18 years of age with an ultrasound-confirmed singleton pregnancy of ≤16wk gestation were recruited from two Bangladesh clinics between 2008 and 2011. Neonate size metrics were measured at the time of delivery. Metals in cord blood were measured using inductively coupled plasma mass spectrometry. We employed multivariable linear regression and Bayesian kernel machine regression (BKMR) to estimate associations of individual metals and metal mixtures with birth size parameters.

Results: Data from 1,088 participants was assessed. We found a significant negative association between metal mixture and birth length and head circumference when all metal concentrations were above the 60th and 55th percentiles, respectively, compared with the median. An interquartile range (IQR) increase in log Cd concentration {log[Cd (in micrograms per deciliter)] IQR=2.51} was associated with a 0.13-standard deviation (SD) decrease in mean birth length (95% CI: -0.25, -0.02) and a 0.17-SD decrease in mean head circumference (95% CI: -0.28, -0.05), based on linear regression models adjusted for covariates and the other metals. An IQR increase in log Mn concentration {log[Mn (in micrograms per deciliter)] IQR=0.69} was associated with a 0.07-SD decrease in mean birth weight (95% CI: -0.15, 0.002).

Discussion: Metal mixtures in cord blood were associated with reduced birth size in Bangladeshi children. Results from linear regression models adjusted and the BKMR mixtures analyses suggest adverse effects of Cd and Mn, as individual metal exposures, on birth size outcomes. https://doi.org/10.1289/EHP7502.

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Figures

Figures 1A to 1C are error bar graphs plotting Estimate for Birth Weight uppercase z score, Estimate for Birth length uppercase z score, and Estimate for Head Circumference uppercase z score, respectively, ranging from negative 0.3 to 0.2 in increments of 0.1 (y-axis) across Quantile, ranging from 0.3 to 0.7 in increments of 0.1 (x-axis).
Figure 1.
Estimated effects (with 95% credible intervals) of cord blood metal mixtures on birth size z-scores estimated by BKMR. Estimates represent the mean difference in each outcome when all log-transformed metal concentrations are at one percentile compared with the outcome when all log-transformed metal concentrations are at the 50th percentile. All models are adjusted for maternal age, infant sex, maternal enrollment BMI, income, daily tea intake, study site, and secondhand smoke exposure. Concentrations <LOD (n=12 for As and 520 for Cd) were replaced with the LOD divided by 2. (A) Birth weight z-score; (B) birth length z-score; (C) head circumference z-score. Note: As, arsenic; BKMR, Bayesian kernel machine regression; BMI, body mass index; Cd, cadmium; LOD, limit of detection.
Figures 2A to 2C are horizontal error bar graphs plotting Arsenic, Cadmium, Manganese, and Lead (y-axis) across Estimate for Birth Weight uppercase z score, Estimate for Birth length uppercase z score, and Estimate for Head Circumference uppercase z score, respectively, ranging from negative 0.4 to 0.2 in increments of 0.2 (x-axis) for the following Quantiles: 0.25, 0.5, and 0.75.
Figure 2.
Estimated differences (95% credible intervals) in birth size z-scores for individual metals at their 75th vs. 25th percentile and all other metals are fixed at their 25th, 50th, or 75th percentiles. Estimates are from BKMR models adjusted for maternal age, infant sex, maternal enrollment BMI, income, daily tea intake, study site, and secondhand smoke exposure. Concentrations <LOD (n=12 for As and 520 for Cd) were replaced with the LOD divided by 2. (A) Birth weight z-score; (B) birth length z-score; (C) head circumference z-score. Note: As, arsenic; BKMR, Bayesian kernel machine regression; BMI, body mass index; Cd, cadmium; LOD, limit of detection; Mn, manganese; Pb, lead.
Figures 3A to 3C are exposure–response plots, each comprising four plots, namely, Arsenic, Cadmium, Manganese, and Lead, plotting Estimate for Birth Weight uppercase z score, Estimate for Birth length uppercase z score, and Estimate for Head Circumference uppercase z score, respectively, ranging from negative 1.5 to 1.0 in increments of 0.5 (y-axis) across Log of concentrations, ranging from negative 2 to 4, negative 4 to 4, 0 to 4, and negative 2 to 2 in increments of 2 (x-axis).
Figure 3.
Exposure–response plots (95% credible intervals) for associations between birth outcome z-scores and log-transformed concentrations of individual metals when all other metals are fixed at their median concentrations. Estimates are from BKMR models adjusted for maternal age, infant sex, maternal enrollment BMI, income, daily tea intake, study site, and secondhand smoke. Concentrations <LOD (n=12 for As and 520 for Cd) were replaced with the LOD divided by 2. Each metal was natural log-transformed and centered at the median. (A) Birth weight z-score; (B) birth length z-score; (C) Head circumference z-score. Note: As, arsenic; BKMR, Bayesian kernel machine regression; BMI, body mass index; Cd, cadmium; LOD, limit of detection; Mn, manganese; Pb, lead.
Figures 4A to 4C are exposure–response plots, each comprising 6 plots for birth outcome z scores in association with the log-transformed concentrations of two metals, plotting log of concentrations, ranging from negative 2 to 2, 0 to 4, and negative 2 to 4 in increments of 2 (y-axis) across log of concentrations, ranging from negative 2 to 4, negative 4 to 4, and 0 to 4 in increments of 2 (x-axis) for Arsenic and Lead, Cadmium and Lead, and Manganese and Lead; plotting log of concentrations, ranging from 0 to 4 in increments of 2 (y-axis) across log of concentrations, ranging from negative 2 to 4 and negative 4 to 4 in increments of 2 (x-axis) for Arsenic and Manganese and Cadmium and Manganese; and plotting log of concentrations, ranging from negative 2 to 4 in increments of 2 (y-axis) across log of concentrations, ranging from negative 2 to 4 in increments of 2 (x-axis) for Arsenic and Cadmium for color-coded estimates ranging from negative 0.4 to 0.2.
Figure 4.
Exposure–response plots for birth outcome z-scores in association with the log-transformed concentrations of two metals when the two other metals in the mixture are fixed at their median concentrations. Estimates are from BKMR models adjusted for maternal age, infant sex, maternal enrollment BMI, income, daily tea intake, study site, and secondhand smoke. Concentrations <LOD (n=12 for As and 520 for Cd) were replaced with the LOD divided by 2. Each metal was natural log-transformed and centered at the median. (A) Birth weight z-score; (B) birth length z-score; (C) head circumference z-score. Note: As, arsenic; BKMR, Bayesian kernel machine regression; BMI, body mass index; Cd, cadmium; LOD, limit of detection; Mn, manganese; Pb, lead.
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