Environmental exposure to metals and children's growth to age 5 years: a prospective cohort study

Abstract

In this prospective cohort study, based on 1,505 mother-infant pairs in rural Bangladesh, we evaluated the associations between early-life exposure to arsenic, cadmium, and lead, assessed via concentrations in maternal and child urine, and children's weights and heights up to age 5 years, during the period 2001-2009. Concurrent and prenatal exposures were evaluated using linear regression analysis, while longitudinal exposure was assessed using mixed-effects linear regression. An inverse association was found between children's weight and height, age-adjusted z scores, and growth velocity at age 5 years and concurrent exposure to cadmium and arsenic. In the longitudinal analysis, multivariable-adjusted attributable differences in children's weight at age 5 years were -0.33 kg (95% confidence interval (CI): -0.60, -0.06) for high (≥95th percentile) arsenic exposure and -0.57 kg (95% CI: -0.88, -0.26) for high cadmium exposure, in comparison with children with the lowest exposure (≤5th percentile). Multivariable-adjusted attributable differences in height were -0.50 cm (95% CI: -1.20, 0.21) for high arsenic exposure and -1.6 cm (95% CI: -2.4, -0.77) for high cadmium exposure. The associations were apparent primarily among girls. The negative effects on children's growth at age 5 years attributable to arsenic and cadmium were of similar magnitude to the difference between girls and boys in terms of weight (-0.67 kg, 95% CI: -0.82, -0.53) and height (-1.3 cm, 95% CI: -1.7, -0.89).

Keywords: arsenic; body height; body weight; cadmium; child, preschool; growth; lead; prenatal exposure delayed effects.

Figure 1.

Loss to follow-up and exclusion of mother-child pairs within the MINIMat Study, Matlab, Bangladesh, 2007–2009. MINIMat, Maternal and Infant Nutrition Interventions in Matlab.

Figure 2.

The relationship between log₂-transformed urinary biomarkers of metals exposure and children's weight (left-hand panels) and height (right-hand panels) at age 5 years, Matlab, Bangladesh, 2007–2009. Top row, urinary arsenic; middle row, urinary cadmium; bottom row, urinary lead. In all cases, the solid line represents a LoWeSS (locally weighted scatterplot smoothing) moving-average curve for the raw data represented in the scatterplot. The dashed line represents the fitted curve following log₂-transformation of urinary concentration, adjusted for child's sex, family socioeconomic status, season of birth, gestational age at birth, maternal education, maternal height or body mass index (weight (kg)/height (m)²) (as appropriate), maternal tobacco-chewing, indoor cooking without ventilation, and birth order (model 2).

Figure 3.

Relationship between urinary arsenic (As), urinary cadmium (Cd), and urinary lead (Pb) concentrations and anthropometric outcomes according to tertiles of exposure, measured in children at age 5 years in Matlab, Bangladesh, 2007–2009. Weight (A), height (B), weight-for-age z score (WAZ) (C), height-for-age z score (HAZ) (D), peak weight velocity (E), and peak height velocity (F) were considered as outcomes. Crude (unadjusted) model estimates are shown as squares. Estimates adjusted for child's sex, family socioeconomic status, season of birth, gestational age at birth, maternal education, maternal height or body mass index (weight (kg)/height (m)²) (as appropriate), maternal tobacco-chewing, indoor cooking without ventilation, and birth order (model 2) are presented as diamonds. Δ indicates “change,” and tertiles are labeled along the x-axis. Vertical lines represent 95% confidence intervals.

Figure 4.

Relationship between children's log₂-transformed urinary arsenic (As), urinary cadmium (Cd), and urinary lead (Pb) concentrations and anthropometric outcomes at age 5 years (linear regression analysis) in Matlab, Bangladesh, 2007–2009. Weight (A), height (B), weight-for-age z score (WAZ) (C), height-for-age z score (HAZ) (D), peak weight velocity (E), and peak height velocity (F) were considered as outcomes. Crude (unadjusted) associations, as described for model 1 in the Materials and Methods section, are shown as diamonds. Estimates adjusted for child's sex, family socioeconomic status, season of birth, gestational age at birth, maternal education, maternal height or body mass index (weight (kg)/height (m)²) (as appropriate), maternal tobacco-chewing, indoor cooking without ventilation, and birth order (model 2) are shown as squares. Estimates additionally adjusted for log₂-transformed maternal urinary As, Cd, or Pb as appropriate (model 3) are shown as triangles. Results from a model jointly estimating the combined effects of urinary As, Cd, and Pb (model 4) are shown as circles. Δ indicates “change.” Vertical lines represent 95% confidence intervals.

Figure 5.

Differences in children's weights and heights at age 5 years attributable to lifelong arsenic (As), cadmium (Cd), and lead (Pb) exposure, assessed in Matlab, Bangladesh, 2001–2009. The relationship between combined exposure to arsenic, cadmium, and lead over time and the child's weight and length/height from birth to age 5 years was assessed using mixed-effects linear regression and was adjusted for child's sex, family socioeconomic status (SES), season of birth, gestational age at birth, maternal education, maternal height or body mass index (weight (kg)/height (m)²) (as appropriate), maternal tobacco-chewing, indoor cooking without ventilation, and birth order. Multivariable-adjusted attributable differences were calculated by comparing the model-predicted weight (A) or height (B) of children with urinary arsenic, urinary cadmium, and urinary lead levels at or above the 95th percentile at age 5 years with those of children at or below the 5th percentile (shown as squares). The analysis was repeated after stratification for sex and SES, and multivariable-adjusted differences are also shown for boys (triangles), girls (circles), low SES (diamonds), and high SES (X's). Δ indicates “change.” Vertical lines represent 95% confidence intervals.