Associations between toxic and essential trace elements in maternal blood and fetal congenital heart defects

Abstract

Prenatal exposure to toxic trace elements, including heavy metals, is an important public health concern. Few studies have assessed if individual and multiple trace elements simultaneously affect cardiac development. The current study evaluated the association between maternal blood lead (Pb), cadmium (Cd), chromium (Cr), copper (Cu), mercury (Hg), and selenium (Se) levels and congenital heart defects (CHDs) in offspring. This hospital-based case-control study included 112 case and 107 control infants. Maternal peripheral blood draw was made during gestational weeks 17-40 and used to determine trace element levels by inductively coupled plasma mass spectrometry. Multivariable logistic regression was used to assess associations and interactions between individual and multiple trace elements and fetal CHDs, adjusted for maternal age, parity, education, newborn gender, migrant, folic acid or multivitamin intake, cigarette smoking, maternal prepregnancy body mass index, and time of sample collection. Control participants had medians of 2.61μg/dL Pb, 1.76μg/L Cd, 3.57μg/L Cr, 896.56μg/L Cu, 4.17μg/L Hg, and 186.47μg/L Se in blood. In a model including all measured trace elements and adjusted for confounders, high levels of maternal Pb (OR=12.09, 95% CI: 2.81, 51.97) and Se (OR=0.25, 95% CI: 0.08, 0.77) were harmful and protective predictors of CHDs, respectively, with positive and negative interactions suggested for Cd with Pb and Se with Pb, respectively. Similar associations were detected for subgroups of CHDs, including conotruncal defects, septal defects, and right ventricle outflow tract obstruction. Our results suggest that even under the current standard for protecting human health (10μg/dL), Pb exposure poses an important health threat. These data can be used for developing interventions and identifying high-risk pregnancies.

High maternal selenium levels are associated with increased risk of congenital heart defects in the offspring

“…However, different studies have reported varied results. At variance with our findings, a previous hospital‐based case‐control study in China found a protective effect of high maternal blood Se concentrations at 17 to 40 weeks on risk of CHD in infants. This may be because the selected cases were pregnant women from Guangdong Province, which is a relatively Se deficient area in China .…”

“…The strengths of this study include its superior case‐control sample size of pregnant women compared with previous study . The inclusion of multiple centers also expanded the generalizability of the study.…”

“…The strengths of this study include its superior case-control sample size of pregnant women compared with previous study. 19 The inclusion of multiple centers also expanded the generalizability of the study. However, among 2064 pregnant women with available maternal selenium levels, we excluded 1176 pregnant women due to exclusion criteria, missing data on confounding factors.…”

Environmental Contaminants and Congenital Heart Defects: A Re-Evaluation of the Evidence

“…Additionally, hair copper was associated with total CHDs, but particularly conotruncal defects [ 57 ], hair aluminum was associated with total CHDs and particularly septal and conotruncal defects and right ventricular outflow tract obstruction [ 58 ], and hair barium was associated with total CHDs and particularly with septal defects, conotruncal defects, right and left ventricular outflow tract obstruction and anomalous pulmonary venous return [ 59 ]. Only one study has assessed maternal blood metals and found that high blood lead was associated with total CHDs, conotruncal defects, septal defects and right ventricular outflow tract obstruction, while higher blood selenium was protective; cadmium, chromium, copper and mercury were not associated their own but may have had an interactive effect [ 60 ].…”

A novel dual reporter embryonic stem cell line for toxicological assessment of teratogen-induced perturbation of anterior–posterior patterning of the heart

“…Future efforts must focus on testing a larger set of well-characterized reference compounds for their effects on anterior-posterior patterning in shorter time windows. As some non-familial CHD cases could be due to non-medical exposure to environmental pollutants and industrial byproducts, these could also be tested for safety windows in low-cost, highthroughput differentiation assays (Ou et al 2017). Additionally, the same time windows presented here could be tested in other reporter lines which have been developed for toxicological assessment, such as a recently described Wnt/Β-catenin reporter (Kugler et al 2016a, b).…”