Association of Placental Weight at Birth with Maternal Whole Blood Concentration of Heavy Metals (Cadmium, Lead, Mercury, Selenium, Manganese): The Japan Environment and Children's Study (JECS)

Background: Lifelong health is dependent on growth and development during pregnancy, as supported by the intrauterine environment of the placenta. The placenta, charged with the dual functions of oxygen and nutrient exchange and a barrier against toxins, is susceptible to environmental exposure and heavy metals. Here we investigated the sensitivity of the placenta, and the use of placenta weight (PW) as a biomarker, in the exposure to heavy metals Cd, Pb and Hg using a large Japanese cohort.Method: Here, the sensitivity of the placenta and the use of placenta weight (PW) as a biomarker in the exposure to heavy metals such as Cd, Pb and Hg were investigated using a large cohort Japan Environment and Children’s Study (JECS). The association between heavy metals in maternal blood levels and PW was estimated by applying Z scores. The essential elements Se and Mn were included as factors directly affecting heavy metals toxicity and fetal growth.Findings: The median concentration values for these in the maternal whole blood were Cd,0.662ng/g; Pb,5.85ng/g; Hg,3.61ng/g; Se,168ng/g; and Mn,15.3ng/g. Regression analysis showed significant correlation between placenta weight Z-scores and metal concentrations in maternal blood: Cd, 0.0660 (standard error (SE) 0.0074, p<0.001); Se, -0.3137 (SE 0.0276, p<0.001); Mn, 0.1483 (SE 0.0110, p<0.001).Interpretation: This study provides a robust examination of the association between heavy metals and PW. Cd and Mn showed positive correlation with significant differences, while Se showed negative. Essential elements have a significant effect on PW, however the effects were different. No significant association existed between Pb, Hg and PW.Funding: This study was funded by the Ministry of the Environment, Japan.Declaration of Interest: The authors explicitly state that there is no conflict of interest in connection with this article.Ethical Approval: The JECS has been conducted based on the Ethical Guidelines for Epidemiological Research proposed by Japan’s Ministry of Health and Welfare (currently the Ministry of Health, Labour and Welfare). The JECS protocol was reviewed and approved by the Ministry of the Environment’s Institutional Review Board on Epidemiological Studies and by the Ethics Committees of all participating institutions. Written informed consent was obtained from all participants.