Maternal Cd Levels Research Articles

Maternal urinary cadmium concentrations in early pregnancy in relation to prenatal and postpartum size of offspring

BackgroundThe impacts of environmental cadmium (Cd) exposure on birth size parameters including weight, length and head circumference (HC) have been reported in multiple studies. However, little remains known of the impacts of maternal Cd exposure during pregnancy on size during in utero development and during early childhood. The aim of this study was to comprehensively investigate impacts of maternal Cd exposure during pregnancy on the size of offspring in utero (from 24 weeks pregnancy) until six months of age. MethodsPregnant mothers were recruited as part of an ongoing prospective birth cohort study based in Guangdong, China. Maternal urine samples were collected in the first and third trimesters of pregnancy, in which Cd concentrations were measured by inductively couple plasma mass spectrometry (ICPMS). In utero size indicators at 24 and 32 week of gestation, including biparietal diameter (BPD), abdominal circumference (AC), femur length (FL) and HC were derived from ultrasound examinations. Anthropometric measures of weight, height and HC at birth and one, three and six months of age were also collected. Associations of size measures at the various time points with maternal urinary Cd concentrations were assessed using linear regression models. ResultsThe median urinary Cd concentration was 1.00 and 0.98 μg/g creatinine in the first and third trimesters respectively. In univariate analysis, increased maternal Cd levels in the first trimester were associated with decreased HC (-0.17 cm/ug/g urinary Cd) at birth, and the association was particularly pronounced among males (-0.30 cm/ug/g urinary Cd). First trimester Cd exposure was also found to be significantly associated with decreased infant weight at three and six months of age among girls (−101 g/ug/g and −97 g/ug/g urinary Cd, respectively). Associations of similar magnitude were observed after adjustment for various maternal factors. No significant associations were observed with infant size measures or with measures of Cd in the third trimester. ConclusionsOur detailed study suggests that the first trimester is particularly critical window of susceptibility to sex-specific effects of Cd on size parameters at birth, with some effects persisting to six months of age. These compelling sex-dependent effects on HC and body weight warrant future studies examining longer-term health effects of pregnancy-related Cd exposures.

The association between prenatal cadmium exposure and birth weight: A systematic review and meta-analysis of available evidence

We conducted a meta-analysis to evaluate the association between prenatal cadmium (Cd) exposure and birth weight. PubMed, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched for studies published before March 2019. We used a model-based method, standardizing effect size from linear regression models to include a maximum number of studies during our quantitative evaluations. As a result, 11 articles from the general population, containing 10 birth cohorts and one cross-sectional study, were included. Our meta-analysis demonstrated that a 50% increase of maternal urine Cd (UCd) would be associated with a 6.15 g decrease in neonatal birth weight (β = −6.15 g, 95% CI: −10.81, −1.49) as well as a 50% increase of maternal blood Cd (BCd) would be associated with an 11.57 g decrease (β = −11.57 g; 95% CI: −18.85, −4.30). Stratified analysis of UCd data indicated that the results of female newborns were statistically significant (β = −8.92 g, 95% CI: −17.51, −0.34), as was the first trimester (β = −11.34 g, 95% CI: −19.54, −3.14). Furthermore, increased UCd levels were associated with a higher rate of low birth weight (LBW) risk (OR = 1.12, 95% CI: 1.03, 1.22). This meta-analysis demonstrated that elevated maternal Cd levels are associated with decreased birth weight and higher LBW risk.

Cadmium Body Burden and Gestational Diabetes Mellitus: A Prospective Study.

Background:Several studies have reported that cadmium (Cd) is associated with type 2 diabetes. However, little is known about Cd exposure and the risk of gestational diabetes mellitus (GDM).Objective:We examined the association between Cd body burden in early pregnancy and the risk of GDM.Methods:We conducted a prospective study of 2,026 pregnant women from a single tertiary medical center between 2013 and 2016 in Wuhan, China. Cd body burden was reflected by Cd concentrations in urine samples collected between gestational weeks 8 and 14. GDM was diagnosed according to International Association of Diabetes and Pregnancy Study Groups Consensus Panel (IADPSG) recommendations.Results:The geometric mean of Cd concentrations in maternal urine of all pregnant women was . A total of 198 (9.8%) women were diagnosed with GDM. After adjustment for potential confounders, the risk ratios (RRs) of GDM were 1.04 (95% CI: 0.74, 1.44) for the middle tertile of Cd levels and 1.36 (95%: CI: 0.98, 1.90) for the top tertile compared with the bottom tertile. In addition, we found a significant interaction between fetal sex and maternal Cd levels on the risk of GDM (). Among women carrying male fetuses, the RR of GDM was 1.86 (95% CI: 1.14, 2.93) for the top tertile of Cd levels compared with the bottom tertile.Conclusions:To our knowledge, this is the first report of an association between urinary Cd levels in early pregnancy and GDM. Our findings suggest that Cd body burden increases the risk of GDM and that the association may be modified by fetal sex. https://doi.org/10.1289/EHP2716

Critical Windows of Prenatal Exposure to Cadmium and Size at Birth.

Prenatal cadmium (Cd) exposure has been associated with adverse birth outcomes, but the findings of previous studies are inconsistent. We measured Cd concentrations in urine samples at or near 13, 24, and 35 gestational weeks from 282 women in Wuhan, China. We used generalized estimating equation models to assess the associations between maternal creatinine adjusted urinary Cd concentrations at each trimester and birth size. A significant inverse association was observed between higher maternal Cd levels measured during the 1st trimester and birth size in girls. For each log unit increase in Cd (µg/g creatinine) levels from the 1st trimester, there was a decrease in birth weight by 116.99 g (95% confidence interval (CI): −208.87, −25.11 g). The Cd levels from the 1st and 2nd trimesters were also borderline significantly associated with ponderal index in girls. Joint estimation of trimester-specific effects suggested that associations with Cd levels for ponderal index (pint = 0.02) were significantly different across trimesters, and differences for effects across trimesters for birth weight were marginally significant (pint = 0.08) in girls. No significant associations were observed between Cd levels from any trimester and birth size in boys. Maternal Cd exposure during earlier periods of pregnancy may have a larger impact on delayed fetal growth.

Maternal cadmium, iron and zinc levels, DNA methylation and birth weight.

BackgroundCadmium (Cd) is a ubiquitous and environmentally persistent toxic metal that has been implicated in neurotoxicity, carcinogenesis and obesity and essential metals including zinc (Zn) and iron (Fe) may alter these outcomes. However mechanisms underlying these relationships remain limited.MethodsWe examined whether maternal Cd levels during early pregnancy were associated with offspring DNA methylation at regulatory sequences of genomically imprinted genes and weight at birth, and whether Fe and Zn altered these associations. Cd, Fe and Zn were measured in maternal blood of 319 women ≤12 weeks gestation. Offspring umbilical cord blood leukocyte DNA methylation at regulatory differentially methylated regions (DMRs) of 8 imprinted genes was measured using bisulfite pyrosequencing. Regression models were used to examine the relationships among Cd, Fe, Zn, and DMR methylation and birth weight.ResultsElevated maternal blood Cd levels were associated with lower birth weight (p = 0.03). Higher maternal blood Cd levels were also associated with lower offspring methylation at the PEG3 DMR in females (β = 0.55, se = 0.17, p = 0.05), and at the MEG3 DMR in males (β = 0.72, se = 0.3, p = 0.08), however the latter association was not statistically significant. Associations between Cd and PEG3 and PLAGL1 DNA methylation were stronger in infants born to women with low concentrations of Fe (p < 0.05).ConclusionsOur data suggest the association between pre-natal Cd and offspring DNA methylation at regulatory sequences of imprinted genes may be sex- and gene-specific. Essential metals such as Zn may mitigate DNA methylation response to Cd exposure. Larger studies are required.

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.

Association between maternal blood cadmium during pregnancy and birth weight and the risk of fetal growth restriction: The EDEN mother–child cohort study

The objective of this study is to investigate the potential effect of maternal environmental cadmium (Cd) exposure on birth weight and fetal growth restriction (FGR). A total of 901 pregnant women from the EDEN cohort study were enrolled from two maternity units. Blood Cd was measured at mid-pregnancy and associations with birth weight and FGR were analyzed. Maternal Cd levels were associated with reduced birth weight in the offspring of women who smoked during pregnancy (b=−113.7; p=0.001). Smoking during pregnancy and maternal blood Cd concentrations had comparable effects on FGR incidence (OR 1.89; 95% CI: 1.00–3.58 and OR=1.41; 95% CI: 1.00–1.99, respectively). This study highlights the effect of Cd toxicity on fetal growth through the probable accumulation and transmission of this metal through the placenta. The close relationship between blood Cd levels and smoking habits indicates that Cd may be a relevant biomarker for smoking toxicity on fetal development.

Maternal and Fetal Exposure to Four Carcinogenic Environmental Metals

To examine maternal and fetal exposure levels to four carcinogenic metals, arsenic (As), cadmium (Cd), nickel (Ni), and beryllium (Be), and to investigate their environmental influences. Metal concentrations in maternal and umbilical cord blood were measured by inductively coupled plasma-mass spectrometry (ICP-MS). Environmental factors that might play a role in exposure were analyzed using Mann-Whitney nonparametric U-tests and multiple linear regression. The concentrations of As, Cd, and Ni in umbilical cord blood (5.41, 0.87, and 139.54 μg/L) were significantly lower than those in maternal blood (6.91, 1.93, and 165.93 μg/L). There were significant positive correlations between the maternal and cord concentrations of each carcinogen. Our results showed that: (i) exposures to potentially harmful occupational factors during pregnancy were associated with high levels of maternal As, Cd, and Ni; (ii) living close to major transportation routes (<500 m) or exposure to second-hand smoke during pregnancy increased the maternal Cd levels and (iii) living close to industrial chimneys induced high maternal Ni levels. Multiple linear regression analysis showed that these environmental factors remained significant in models of the influences of these four carcinogens. Both mothers and fetuses had been exposed to As, Cd, Ni, and Be. The increased levels of these carcinogens in pregnant women were associated with some detrimental environmental factors, such as occupational exposure, contact with second-hand smoke and living close to major transportation routes or industrial chimneys.

Smoking, cereal consumption, and supplementation affect cadmium content in breast milk

Breast milk might be a source of potentially toxic metals such as cadmium (Cd). The purpose of the present study is to provide data pertaining to the influence of maternal lifestyles on Cd concentrations in breast milk in the Austrian setting. Breast milk was obtained from 124 Austrian women. Each participant provided 10 ml of milk. A second group of eight mothers were recruited to investigate changes in their milk cadmium levels at 1, 3, 5, 7 and 9 weeks post partum. The study participants filled a questionnaire concerning nutrition, supplementation, and smoking habits. The samples were analyzed using GF-Atomic Absorption Spectrophotometer (AAS). The mean Cd content in breast milk was among the lowest in Europe (0.086 +/- 0.085 microg/l, 95% CI: 0.07-0.10; n = 124). Increased Cd levels in breast milk were found to be significantly associated with frequent cereal consumption and smoking. Smokers had a two-fold higher concentration than did non-smokers (0.15 versus 0.07 microg/l; P = 0.000). In contrast, low Cd levels in breast milk were associated with the intake of supplements containing trace elements or vitamins and trace elements (P < 0.05). This protective effect of supplements on Cd levels was only observed in non-smokers. The Cd levels registered in the present investigation were far below critical levels. We conclude that the current maternal Cd levels in Austria signify no risk for the breastfed infant of a healthy mother. Further research will have to focus on the specific effects of supplementation and smoking on Cd concentrations.