Interaction between cadmium (Cd), selenium (Se) and oxidative stress biomarkers in healthy mothers and its impact on birth anthropometric measures.

To our knowledge, this study may be the first to examine the antagonistic role of selenium (Se) on oxidative stress induced by cadmium (Cd) and its impact on birth measures. Cd and Se levels were measured in umbilical-cord blood and the placentas of a subsample of 250 healthy mothers who participated between 2005 and 2006 in the project "Prenatal Exposure to Pollutants". The median Cd levels in cord and maternal blood and placental tissue were 0.78µg/l, 0.976µg/l and 0.037µg/g dry wt., respectively. The median levels of Se in cord serum and placental tissue were 65.68µg/l and 1.052µg/g dry wt., respectively. Se was more than 100-fold in molar excess over Cd in both cord serum and placental tissue. The median molar Cd/Se ratios in cord serum and placental tissue were 0.008 and 0.024, respectively, which were much lower than unity. This study suggests that both Cd and Se play a role in the mechanism of oxidative stress, but, the process underlying this mechanism remains unclear. Nevertheless, three biomarkers of oxidative stress had inconsistent relationships with Cd and/or Se in various matrices, perhaps due to potential untested confounders. Our results generally support an association between low in utero exposure to Cd and the anthropometric development of the fetus. Adjusted regression models indicated a negative association of cord blood Cd levels ≥0.78µg/l with Apgar 5-min scores and birth height. Maternal Cd levels ≥0.976µg/l were associated with a 5.94-fold increased risk of small-for-gestational-age births, which increased to 7.48-fold after excluding preterm births. Placenta weight decreased with increasing placental Cd levels ≥0.037µg/g dry wt. (p=0.045), an association that became stronger after excluding preterm births or adjusting for birth weight. Cord Se levels ≥65.68µg/l were positively associated with placenta weight (p=0.041) and thickness (p=0.031), an association that remained unchanged after excluding preterm births. Cord Se levels, however, were negatively associated with cephalization index, but only after excluding preterm births (p=0.017). Each birth measure was again modeled as a function of the Cd/Se ratios in cord blood and placenta tissue. Interestingly cord ratios ≥0.008 were negatively associated with Apgar-5min score (p=0.047), birth weight (p=0.034) and placenta thickness (p=0.022). After excluding preterm births, only the association with placenta thickness remained significant (p=0.021), while birth weight (p=0.053) was marginally significant. In contrast, cephalization index increased with Cd/Se ratios ≥0.008 (p=0.033), an association that became marginally significant after excluding preterm births (p=0.058). For placental Cd/Se ratios ≥0.024, only placenta weight was reduced with (p=0.037) and without (p=0.009) the inclusion of preterm births. These findings do not support an antagonistic mechanism between Cd and Se. The role of oxidative mechanisms either induced by Cd exposure or alleviated by Se on these birth anthropometric measures was examined by principal component analysis. Se did not have a clear protective role against Cd-induced adverse effects despite its substantial excess over Cd, and its role in alleviating oxidative stress by reducing malondialdehyde levels. The results may suggest that the extent of the Se beneficial effects is not governed only by its concentration but also by the chemical forms of Se that interact with various proteins. Consequently, the speciation of Se in such studies is essential for understanding and predicting Se availability for absorption.

Mercury (Hg) and oxidative stress status in healthy mothers and its effect on birth anthropometric measures.

This study was conducted to: (a) investigate the antagonistic interaction between selenium (Se) and mercury (Hg) in mothers and their newborns, (b) delineate the role of oxidative mechanisms induced by Hg exposure and (c) examine the protective effect of Se on Hg-induced oxidative stress and birth outcomes. Levels of Hg and Se were measured in umbilical cord blood and the placentas of 250 healthy mothers who participated in a study between 2006 and 2006 assessing prenatal exposure various pollutants. Levels of malondialdehyde (MDA) in cord and maternal blood and of 8-hydroxy-2-deoxyguanosine in urine were measured for assessing oxidative stress. Tail moment (TM) in the comet assay, as a biomarker of DNA damage was measured in samples of cord and maternal blood. The mean Se levels in umbilical cord blood (67.618±12.897µg/l) were lower than those reported in many countries, but none of the newborns had Se levels <20µg/l (the threshold limit of Keshan disease). More than 80% of the newborns, though, had Se levels below the 80µg/l needed for maximum glutathione peroxidase activity. Even though 18.6% of the newborns had levels of Hg ≥5.8µg/l (the reference dose of the Environmental Protection Agency), no relationship was observed with the biomarkers of oxidative stress. The mean placental Hg levels (0.056±0.075µg/g dry wt.) were higher than those reported for newborns with abnormal fetal development. Our study also documented significant placental transfer of Hg and Se to the fetus. The Hg/Se molar ratio in both cord blood and placental tissue was well below 1. The average amount of Se in both matrices was approximately 50-fold in molar excess over Hg. The molar excess of Se in the umbilical cord (0.843µmol/l), however, was lower than in placental tissues (13.098µmol/kg dry wt.). In further support of the relationships of Hg and Se on oxidative stress, we observed significantly lower levels of maternal MDA associated with Se levels in both cord blood and placental tissues and significantly higher TM levels associated with placental Hg in both newborns and their mothers. In contrast, Se/Hg molar ratios in placental tissues were positively associated with MDA and negatively with TM. The disproportion between Hg and Se might be influenced by the length of Hg exposure that in turn might affect Se bioavailability. Each birth anthropometric outcome was modeled as a function of Hg, Se and their interactions. After an adjustment for confounding variables, Hg in cord blood had a significantly positive rather than the expected negative association with crown-heel length. Placental Hg was associated with reduced birth height. Both associations were independent of prematurity. The status of Se in newborns was positively associated with crown-heel length and placental weight, with and without preterm births, and with birth weight, but only without preterm births. In contrast, a lower cephalization index was correlated with Se levels in cord blood, which may be an indicator of a detrimental effect on health. Our study, however, revealed associations between significantly lower levels of placental Se and several birth anthropometric measures (head circumference, birth weight and birth height) but the significance disappeared after excluding preterm births. Regression analyses generally indicated either significant or marginally significant Hg-Se antagonistic interactions that may have moderated the toxic effect of Hg on head circumference and birth weight. This finding may be due to chance or residual confounding and so may not be clinically relevant, but it may also suggest that Hg, Se and Hg-Se interactions are important factors for understanding Hg-induced adverse birth outcomes. Additional research will be necessary to evaluate the biological impact of combined metals in the assessment of fetal growth and development.

Polycyclic aromatic hydrocarbons (PAHs) as determinants of various anthropometric measures of birth outcome.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants that are known to induce oxidative stress. There have been several reports about the link between PAH exposure and complications in pregnancy. This cross-sectional study was conducted to: (1) measure the levels of benzo(a)anthracene (BaA), chrysene (Ch), benzo(b)fluoranthene (BbF), benzo(a)pyrene (BaP), and dibenzo(a,h)anthracene (DBahA) in placentas and maternal and -umbilical cord blood obtained at delivery from 1578 women between June 2005 and 2006 in the area of Al-Kharj, Saudi Arabia; (2) assess their influence on various anthropometric measures of birth outcome taking into consideration the carcinogenic properties of these PAHs; and (3) determine the degree of PAH-related oxidative DNA damage and birth outcome. Among the five tested PAHs, only BaP was carcinogenic; therefore, the levels of the other four probable or possible carcinogenic PAHs (BaA, Ch, BaF, and DBahA) were summed as ∑4-PAHs. Levels of 1-hydroxypyrene (1-HP) were determined in maternal urine samples as a biomarker of PAH internal dose. Urinary cotinine (COT) was measured as an index of smoking. The following markers of oxidative stress were selected: malondialdehyde (MDA) in cord (C-MDA) and maternal (M-MDA) serum and 8-hydroxy-2-deoxyguanosine (8-OHdG) in maternal urine. None of the tested PAHs was found in maternal or cord blood. However, all five PAH compounds were detected in placentas; Ch was the highest (6.582 µg/kg dry wt.), and BaA was the lowest (0.236 µg/kg dry wt.). The mean concentration of urinary 1-HP found in this study was 0.216 ± 0.856 µg/g Cr. After adjusting for gestational age and other confounding variables, regression models revealed an inverse relationship between placental weight, cord length and placental BaP. A similar trend was observed between cord length and ∑4-PAHs in placental tissues. Urinary 1-HP, though, cannot be used as an unequivocal biomarker of PAH exposure, but it can be an appropriate indicator of exposure to environmental tobacco smoke (ETS). The data demonstrate that ETS exposure (as measured by urinary COT) may adversely affect birth outcome as shown by reduced head circumference, birth weight, and birth length, as well as increased cephalization index. The positive relationship between 8-OHdG levels and 1-HP in urine provides evidence of an oxidative stress mechanism. Although this study provides no direct evidence of an association between PAH exposure and DNA damage, increased oxidative stress in the form of lipid peroxidation significantly affected various birth measures. Therefore, there is a need for studies regarding PAH exposure and its associated biological effects to determine the extent of potential fetal damage as well as possible long-term effects, such as cancer.