Adverse associations between maternal and neonatal cadmium exposure and birth outcomes

Highlights

• Cd concentrations were determined in both umbilical cord blood and maternal urine.

• Associations between Cd exposure and birth outcomes were explored in 1073 mother-newborn pairs.

• Cord blood Cd concentrations were negatively associated with ponderal index of neonates.

• Adverse effects of Cd exposure on birth outcomes differed by neonatal sex.

Abstract

Effects of low-level cadmium (Cd) exposure during early life on fetal growth remain unclear. Our aim was to evaluate whether Cd exposure in maternal urine and umbilical cord blood was associated with birth size parameters. A birth cohort study including 1073 mother-newborn pairs was conducted from 2009 to 2010 in an agricultural population in China. Cd concentrations were analyzed in both cord blood and maternal urine. Generalized linear models were performed to determine associations between maternal and neonatal exposure to Cd and birth indicators, including birth weight, length, head circumference and ponderal index. The median (25th to 75th percentile) value of Cd concentration in maternal urine and umbilical cord blood was 0.19 (0.08, 1.00) μg/L and 0.40 (< LOD ~ 0.62) μg/L, respectively. After adjusting for potential confounders, Cd concentration in cord blood was significantly negatively associated with ponderal index at birth [β = − 0.06 g/cm³, 95% confidence interval (CI): − 0.11, − 0.02; p < 0.01]. Considering sex difference, significant reduction in ponderal index was only observed in males (β = − 0.06 g/cm³, 95%CI: − 0.11, − 0.02; p < 0.01), but not in females (β = − 0.03 g/cm³, 95%CI: − 0.07, 0.01; p = 0.18) (p for interaction term = 0.24). Additionally, no significant associations were observed between maternal urinary Cd levels and birth outcomes. Our findings suggest that adverse effects of neonatal exposure to Cd on fetal growth are of considerable public health importance.

Introduction

Cadmium (Cd) is a toxic heavy metal and has long been considered as a hazardous material to human health. Due to its high volume use from industrial and agricultural sources, Cd was extensively distributed in soil, water, air and even food (Järup and Åkesson, 2009). Environmental contamination by Cd posed a potential threat to human health because of Cd-induced toxicity. Recently, exposure to Cd has attracted growing public concern because Cd has also been suspected to disrupt the endocrine function and may thereby affect reproduction and development in human (Gollenberg et al., 2010). Particularly, pregnant women were highly susceptible due to increased uptake of Cd with low iron status (Akesson et al., 2002). Furthermore, Cd can transfer from mother to fetus through placenta, thus for the developing embryo and fetus in utero, fetal growth could be affected during pregnancy (Di Sant'Agnese et al., 1983). Cd has been detected in several types of biological sample, including maternal blood, maternal urine, placenta, cord tissue, cord blood as well as breast milk (Olszowski et al., 2016, Sakamoto et al., 2013).

Given evidence of relationships between Cd exposure during early life and potential health effects are emerging. In rodent animals, increasing evidence demonstrated that Cd was an embryotoxic and teratogenic metal, namely, offspring malformations and fetal growth restriction could be induced by maternal Cd exposure during gestation (Ji et al., 2011, Paniagua-Castro et al., 2007, Scott et al., 2005). Though several epidemiological studies have suggested that exposure to Cd during pregancy were associated with decrease in birth outcome measures, including birth weight and length, head circumference, ponderal index (PI), chest circumference and small for gestational age (SGA) (Al-Saleh et al., 2014, Kippler et al., 2012a, Llanos and Ronco, 2009, Romano et al., 2016, Wang et al., 2016), the results are still controversial. While some studies observed no associations (Odland et al., 2004, Osman et al., 2000, Tang et al., 2016), either others found positive associations (Bloom et al., 2015), or inverted U-shaped associations (Kippler et al., 2012b). Limited studies are available looking at maternal and fetal Cd exposure in large sample size of mother-newborn pairs.

Once absorbed, Cd can be accumulated in the human body with a half-life of 10–30 years, especially in the kidneys (Järup and Åkesson, 2009). Urinary Cd is a well-documented biomarker of chronic exposure that reflects long-term body burden (Åkesson et al., 2014), while cord blood Cd concentration represents neonatal exposure effectively (Järup et al., 1998). In the present study, Cd exposure in maternal urine and cord blood were evaluated and their associations with birth size measures were explored in a birth cohort from a population living in an agricultural region, China.