ABSTRACT
Prenatal exposure to perfluoroalkyl substances (PFAS), bisphenol A (BPA), lead (Pb), total mercury (THg), and methylmercury (MeHg) can affect fetal development. Factors influencing placental transfer rate of these toxins are poorly investigated. Whether prenatal exposure to pollutants has an effect on birth weight is incompletely understood. We therefore aimed (1) to determine placental transfer rates of PFAS, BPA, Pb, THg, and MeHg, (2) to analyze relationships between fetal exposure and birth outcome and (3) to analyze gene variants as mediators of placental transfer rates and birth outcome. Two hundred healthy pregnant women and their newborns participated in the study. BPA, 16 PFAS, THg, MeHg, and Pb were determined using HPLCMS/MS (BPA, PFAS), HPLC-CV-ICPMS (MeHg), CV-AFS (THg), and GF-AAS (Pb). Questionnaires and medical records were used to survey exposure sources and birth outcome. 20 single nucleotide polymorphisms and two deletion polymorphisms were determined by real-time PCR from both maternal and newborn blood. Genotype-phenotype associations were analyzed by categorical regression and logistic regression analysis. Specific gene variants were associated with altered placental transfer of PFAS (ALAD Lys59Asn, ABCG2 Gln141Lys), THg (UGT Tyr85Asp, GSTT1del, ABCC1 rs246221) and Pb (GSTP1 Ala114Val). A certain combination of three gene polymorphisms (ABCC1 rs246221, GCLM rs41303970, HFE His63Asp) was over-represented in newborns small for gestational age. 36% of Austrian and 75% of Slovakian mothers had levels exceeding the HBM guidance value I (2 µg/L) of the German HBM Commission for PFOA. 13% of newborns and 39% of women had Ery-Pb levels above 24 µg/kg, an approximation for the BMDL01 of 12 µg/L set by the European Food Safety Authority (EFSA). Our findings point to the need to minimize perinatal exposures to protect fetal health, especially those genetically predisposed to increased transplacental exposure.
ABSTRACT
BACKGROUND: Heavy metal pollutants such as cadmium (Cd), lead (Pb), and mercury (Hg) are rarely the subjects of cardiovascular research although they have been suspected for decades to negatively impact the circulatory system. METHODS: Apart from detailed anamnestic data, urinary levels of Cd and full blood levels of Pb and Hg were measured in 53 female (mean age: 68.04±7.03 years) and 111 male (mean age: 60.68±11.43 years) nonsmoking or never-smoking patients with angiographically verified and precisely quantified coronary artery disease (CAD). RESULTS: Although Cd was quantifiable in 68.3% of subjects, only 34.1% of these patients exceeded the critical 1 µg/L Human Biomonitoring (HBM)-I level. Median Pb (20 µg/L) and Hg (0.55 µg/L) levels were lower than the HBM-I, as well as reference levels of Pb. Wine consumption was the main source for Pb, fish and wine consumption for Hg, and previous nicotine abuse for Cd. There was no correlation between Cd, Pb, or Hg and severity of CAD although severity correlated positively with atherosclerosis parameters (uric acid, creatinine, triglycerides, blood urea nitrogen, C-reactive protein) and negatively with high density lipoprotein cholesterol. CONCLUSION: Cd levels detected in CAD patients were high compared to German and European reference levels but it could not be proven that urine levels of Cd and blood levels of Hg or Pb played a major role in the genesis of CAD, particularly when compared to well-known biomarkers such as blood pressure, glucose, and lipids.
