Author's personal copy Reproductive Toxicology 35 (2013) 25–31 Contents lists available at SciVerse ScienceDirect Reproductive Toxicology jo u r n al hom epa ge: ww w.elsevier.com/locate/reprotox Placental concentrations of mercury, lead, cadmium, and arsenic and the risk of neural tube defects in a Chinese population Lei Jin a,b , Le Zhang a,b , Zhiwen Li a,b , Jian-meng Liu a,b , Rrongwei Ye a,b , Aiguo Ren a,b,∗ a Institute of Reproductive and Child Health/Ministry of Health Key Laboratory of Reproductive Health, Peking University, PR China b Department of Epidemiology and Biostatistics, School of Public Health, Peking University, PR China a r t i c l e i n f o Article history: Received 10 May 2012 Received in revised form 17 October 2012 Accepted 31 October 2012 Available online xxx Keywords: Neural tube defects Anencephaly Spina bifida Birth defects Placenta Heavy metals Mercury Lead Cadmium Arsenic a b s t r a c t To examine whether in utero exposure to mercury (Hg), cadmium (Cd), lead (Pb) and arsenic (As) is asso- ciated with an elevated neural tube defects (NTDs) risk, placental concentrations of total Hg, Cd, Pb and As were measured with an inductively coupled plasma mass spectrometer (ICP-MS) in 36 anencephaly and 44 spina bifida cases as well as in 50 healthy controls. The median Hg concentration in the NTD cases (2.25 ng/g) was higher than that of the controls (1.16 ng/g). The odds ratio (OR) for an Hg concentration above the median was 8.80 (95% CI 3.80–20.36) for the NTD cases. NTD risks increased for the second and third high levels of the concentrations, with ORs of 2.70 (95% CI 1.13–6.43) and 18.20 (95% CI 5.45–60.73), respectively. Therefore, higher placental levels of Hg are associated with an elevated risk of NTDs. © 2012 Elsevier Inc. All rights reserved. 1. Introduction Neural tube defects (NTDs) are among the most common con- genital malformations found in humans. Despite the intensive study of NTDs, their exact etiology remains poorly understood [1]. It is generally agreed that most NTD cases are of multifac- torial origin and that interactions between environmental factors and genetic factors play an important causal role [2]. Environmen- tal factors include maternal folic acid deficiency [3–5], exposure to organic solvents, ionizing radiation, pesticides and maternal smoking, among others [6]. Prenatal exposure to mercury (Hg) or methylmercury (MeHg), lead (Pb), cadmium (Cd) and arsenic (As) can induce NTDs or vertebral malformations or decrease cell proliferation within the embryonic neural tubes of various animal models, such as the chick [7,8], mouse [9,10] and zebrafish [11,12]. However, studies investigating the association between exposure to heavy metals and human fetal NTDs are limited and no con- sistent conclusions have been reached. One epidemiological study ∗ Corresponding author at: Institute of Reproductive and Child Health, 38 Xueyuan Road, Haidian District, Beijing 100191, PR China. Tel.: +86 10 82801140; fax: +86 10 82801141. E-mail address: renag@bjmu.edu.cn (A. Ren). reported elevated urinary Hg levels among women in the highest income group who delivered children with NTDs [13]. Two stud- ies found that maternal whole-blood Pb levels were significantly higher in NTD cases compared to healthy controls [14,15]. How- ever, the findings of an investigation conducted in Glasgow do not support the hypothesis that levels of Pb > 10 g/L in domestic water supplies are associated with a higher prevalence of neural tube defects [16], and a case–control study from a polluted zone in Mexico showed no correlation between NTD occurrence and high levels of Pb or Cd [17]. A study in Bangladesh examined 2006 pregnant women who were chronically exposed to a range of nat- urally occurring concentrations of arsenic in drinking water and found a small but statistically significant increase in birth defect risk [18]. These inconsistent reports indicate the need for further investigations. Neurulation begins on approximately day 17 postfertilization in humans. The entire neurulation process occurs during weeks 3 and 4 postfertilization and is normally completed on approximately day 28 postfertilization [19], before many women are aware that they are pregnant. It is therefore difficult to observe the relationship between risk factor exposure during the time window of neuru- lation and the development of NTDs in humans. The placenta, an organ of nutrient transfer between mother and fetus through which all essential nutrients are delivered to the fetus, may be used to 0890-6238/$ – see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.reprotox.2012.10.015