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. 2013 Nov;36(3):1266-75.
doi: 10.1016/j.etap.2013.10.006. Epub 2013 Oct 19.

A pilot study: the importance of inter-individual differences in inorganic arsenic metabolism for birth weight outcome

Elyssa R Gelmann  1 , Eugen Gurzau  2   3 , Anca Gurzau  2 , Walter Goessler  4 , Julie Kunrath  1 , Catherine W Yeckel #  1   5 , Kathleen M McCarty #  1   6   7
Affiliations

A pilot study: the importance of inter-individual differences in inorganic arsenic metabolism for birth weight outcome

Elyssa R Gelmann et al. Environ Toxicol Pharmacol. 2013 Nov.

Abstract

Inorganic arsenic (iAs) exposure is detrimental to birth outcome. We lack information regarding the potential for iAs metabolism to affect fetal growth. Our pilot study evaluated postpartum Romanian women with known birth weight outcome for differences in iAs metabolism. Subjects were chronically exposed to low-to-moderate drinking water iAs. We analyzed well water, arsenic metabolites in urine, and toenail arsenic. Urine iAs and metabolites, toenail iAs, and secondary methylation efficiency increased as an effect of exposure (p<0.001). Urine iAs and metabolites showed a significant interaction effect between exposure and birth weight. Moderately exposed women with low compared to normal birth weight outcome had greater metabolite excretion (p<0.03); 67% with low compared to 10% with normal birth weight outcome presented urine iAs >9 μg/L (p=0.019). Metabolic partitioning of iAs toward excretion may impair fetal growth. Prospective studies on iAs excretion before and during pregnancy may provide a biomarker for poor fetal growth risk.

Keywords: ANOVA; ASHRAM; Arsenic; Arsenic Health Risk Assessment and Molecular Epidemiology; Biomarker; Birth weight; DMA; EU; European Union; MMA; Methylation ratio; Romania; analysis of variance; dimethylarsinic acid; iAs; inorganic arsenic; monomethylarsonic acid.

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Figures

Figure 1
Figure 1
Multivariate ANOVA showing main effects (*) (p<0.05) of exposure and birth weight outcome (normal or low): (A) inorganic arsenic (iAs) drinking water exposure, methylation efficiency, (B) primary methylation index (PMI), (C) secondary methylation index (SMI), and (D) peripheral (toenail) storage. Main effects of exposure were observed for all parameters (p<0.05), except for PMI. There were neither significant main effects of birth weight nor significant interaction effects for these variables. Within the exposed and unexposed groups, the total ingested arsenic dose from drinking water showed no significant difference.
Figure 2
Figure 2
Multivariate ANOVAs showing main effects (*) and interactive effects (†) (p<0.05) of exposure and birth weight outcome (normal or low) with all urine variables in the models: (A) inorganic arsenic, (B) monomethylarsonic acid (MMA), and (C) dimethylarsinic acid (DMA), and (D) % inorganic arsenic, (E) % MMA, and (F) % DMA. This analysis revealed significance of all factors as a main effect of exposure (p<0.001). Significant interaction effects between exposure and birth weight were seen for all absolute urine metabolites: DMA (p=0.015), MMA (p=0.018), and iAs (p=0.020) that demonstrated increased excretion for the exposed, low birth weight group. When percentages of the metabolites were used, the only significant increases were for the main effect of exposure for MMA(%) (p<0.001) and iAs(%) (p=0.043).
Figure 3
Figure 3
Graphs showing (A) breakdown of subjects with urinary iAs > 9.0 μg/L by exposure and birth weight outcome (UN: unexposed; E: exposed; NBW: normal birth weight; LBW: low birth weight) and (B) percent of subjects by exposure and birth weight outcome (normal or low) with > 9.0 μg/L urinary iAs. Sixty-seven percent of exposed women in the low birth weight group compared to only 10% of exposed women in the normal birth weight group (p=0.019) had urinary iAs concentrations > 9.0 μg/L.
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