Heavy metals are defined as metals and metalloids with a density greater than 5 g/cm3, which widely exist in the environmental media such as the air, soil, and water. Concentrations of a wide range of heavy metals have been detected in children [1], [2] and adults [3], [4], including pregnant women from different countries. Some heavy metals play important roles in human biological processes and fetal growth. For example, cobalt (Co) has a role in production of erythrocytes, regeneration and repair of nerves and synthesis of amino acid [4], [5]; molybdenum (Mo) acts as a cofactor for many oxidases and is essential for body growth [6], [7]; strontium (Sr) is mostly deposited in the bone and has a unique mechanism of action increasing pre-osteoblast proliferation, osteoblast differentiation, and inhibiting osteoblast apoptosis in human [8], [9]. Notably, deficiency or over exposure of these metals may threaten human’s health [8], [9]. Moreover, many heavy metals do not have any biological functions and can be toxic even at low concentrations, including arsenic (As) and cadmium (Cd) known as carcinogens [10], [11], lead (Pb) and mercury (Hg) inducing damages on nervous, cardiovascular and endocrine systems [12], [13]. A number of epidemiological studies have reported that exposure to toxic heavy metals during the early stage of pregnancy may have adverse effects on pregnant women’s health and gestational outcomes. For example, Cd was associated with increased risks of low birth weight [14] and decreased head circumference among newborns [15]; As was related to decreased odds of optimal neurodevelopment [16] and chest circumference [17]; Pb was negatively linked with estimated fetal weight [18]. Therefore, to maintain the levels of essential metals in an appropriate range and toxic metals as low as possible is of great importance to pregnant women, especially in early pregnancy.

So far as we know, heavy metals can be produced by various natural processes and anthropogenic activities [19], [20]. Among them, weathering of rocks, soil erosion, forest fire and volcanic eruption are common natural processes [20]. Anthropogenic activities include industries such as mining, metal manufacturing, smelting, and coal combustion [21], [22]; agricultural applications of fertilizers, pesticides and manures; and domestic outputs through sewage and burning of fuel [20], [23]. Heavy metals enter the human body through the intake of food, water, and supplements, and the use of metal-containing products via inhalation, dermal absorption, and incidental ingestion [24]. Previous studies have indicated that the pregnant women’s exposure levels of metals might be associated with their demographic characteristics [25], dietary habits [24], lifestyles [26], [27], [28], and environmental conditions [29]. However, due to the disparities in participants’ characteristics, locations, cultures, exposure levels of various metals and factors screened in different studies, the predictors of heavy metal concentrations reported by different studies were inconsistent. In addition, few studies have included a broad pool of variables covering demographic characteristics, lifestyle habits, food and dietary supplement intake, and residential environment simultaneously when exploring the potential predictors of pregnant women’s exposure levels of heavy metals.

Recently, more attention has been directed towards studying exposures to metal mixtures. Heavy metals Co, Sr, Pb and Hg have some common sources, such as coal combustion, and have been found to be closely related to Mo, Cd, and As in several studies [30], [31], indicating individuals may be co-exposed to such a metal mixture in daily life. Data from a mother-infant cohort in Greece showed that maternal co-exposure to Mo and Pb in the first trimester was associated with offspring’s increased blood pressure in childhood and adolescence [32]. A study from the Tongji Maternal and Child Health Cohort in China observed that exposure to a mixture of nickel (Ni), As, Cd, antimony (Sb), Co, and vanadium (V) in early pregnancy was related to an elevated subsequent risk of gestational diabetes mellitus [33]. Despite the significant effects of co-exposure to heavy metals on maternal and child health, studies to examine the predictors of women’s exposure to heavy metal mixtures in early pregnancy are rare to date.

Jinan is a typical industrial city in Shandong Province, northern China, known for a cluster of heavy industries, such as smelting, caustic soda production, chemical production and machinery, which are important sources of heavy metal emissions. Jinan was one of the twenty most polluted cities in the World Bank list in 2004 [34], suffering severe air pollution, and particulate matter in Jinan was bonded with heavy metals like Hg, Pb, Cd, and Co [35], [36]. Moreover, Shandong ranked in the top 3 provinces in China in terms of heavy metal contamination of farmland soil as reviewed by a study recently [37]. However, there were only a handful of studies on metal exposures among children [38] and general populations [39] in Jinan, and little is known regarding the levels and predictors of pregnant women's heavy metal exposure in this region. Therefore, the aims of the study were to: (1) describe urinary concentrations of seven heavy metals, namely Pb, Hg, Cd, As, Co, Sr and Mo, among pregnant women in the first trimester of pregnancy; (2) identify the factors significantly associated with the levels of heavy metals from variables covering women’s demographics, lifestyle habits, food consumption, dietary supplement and residential environment condition; (3) explore potential predictors of high co-exposure to these heavy metal mixtures.