Association of maternal serum copper during early pregnancy with the risk of spontaneous preterm birth: A nested case-control study in China

Background: The effect of maternal copper (Cu) level on the risk of spontaneous preterm birth (SPB) remains debate. Therefore, we conducted a prospective nested case-control study in Shanxi Province to investigate the relationship between maternal serum Cu concentration and SPB risk, as well as the potential mediation effect of lipid metabolism. Method: From an overall cohort of 4229 women, 147 women affected by SPB at 20-36 gestational weeks (cases) and 381 women who delivered at >= 37 gestational weeks (controls) were included in our nested case-control study. Maternal blood samples were collected during 4-22 gestational weeks, and the concentrations of Cu, total cholesterol (TC), and triglycerides (TG) were measured. Information on maternal social demographic characteristics were collected using questionnaires. Unconditional logistic regression models were used to estimate the associations of Cu, TC or TG levels with SPB risk. Linear regressions were used to assess the relationships between concentrations of Cu and TC or TG. Results: Serum Cu concentrations in the case group (median: 184 mu g/dL) were significantly higher than those in the control group (median: 166 mu g/dL, p < 0.0001). Compared to the lowest serum Cu levels, the odds ratios associated with SPB increased to 2.02 (95% confidence interval [CI]: 1.07, 3.82), 3.10 (1.54, 6.22) and 4.18 (2.11, 8.27) in the second, third and fourth quartile respectively, after adjusting for sampling time, maternal age, pre-pregnancy BMI, education, occupation, parity, spontaneous abortion history, folic acid use, medication use, pre-pregnancy passive smoking status, child gender and fasting status. Plasma concentrations of TC and TG were positively associated with SPB risk in a dose-dependent manner. However, when stratified by sampling time, the above-mentioned relationships were significant in the first trimester but not in the second. In addition, plasma concentrations of TC and TG were positively correlated with serum Cu concentrations. Conclusions: High maternal Cu level in the first trimester may increase the risk of SPB, by potentially increasing plasma concentrations of TC and TG.