Division of Neonatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center and March of Dimes Prematurity Research Center Ohio Collaborative, Cincinnati, Ohio, United States; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center and March of Dimes Prematurity Research Center Ohio Collaborative, Cincinnati, Ohio, United States; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
Am J Clin Nutr. 2024 Jan;119(1):221-231. doi: 10.1016/j.ajcnut.2023.10.011. Epub 2023 Oct 27.
Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB).
This study aimed to determine the association of maternal Cu concentration during pregnancy with PTB risk and gestational duration in a large multicohort study including diverse populations.
Maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal Cu concentrations were determined using inductively coupled plasma mass spectrometry. The associations of maternal Cu with PTB and gestational duration were analyzed using logistic and linear regressions for each cohort. The estimates were then combined using meta-analysis. Associations between maternal Cu and acute-phase reactants (APRs) and infection status were analyzed in 1239 samples from the Malawi cohort.
The maternal prenatal Cu concentration in our study samples followed normal distribution with mean of 1.92 μg/mL and standard deviation of 0.43 μg/mL, and Cu concentrations increased with gestational age up to 20 wk. The random-effect meta-analysis across 18 cohorts revealed that 1 μg/mL increase in maternal Cu concentration was associated with higher risk of PTB with odds ratio of 1.30 (95% confidence interval [CI]: 1.08, 1.57) and shorter gestational duration of 1.64 d (95% CI: 0.56, 2.73). In the Malawi cohort, higher maternal Cu concentration, concentrations of multiple APRs, and infections (malaria and HIV) were correlated and associated with greater risk of PTB and shorter gestational duration.
Our study supports robust negative association between maternal Cu and gestational duration and positive association with risk for PTB. Cu concentration was strongly correlated with APRs and infection status suggesting its potential role in inflammation, a pathway implicated in the mechanisms of PTB. Therefore, maternal Cu could be used as potential marker of integrated inflammatory pathways during pregnancy and risk for PTB.
铜（Cu）是一种必需的微量元素，调节炎症和氧化应激的多种作用，与早产（PTB）的风险有关。
本研究旨在通过包括多种人群的大型多队列研究，确定妊娠期间母体铜浓度与 PTB 风险和妊娠持续时间的关系。
从 18 个地理分布不同的研究队列中获得了 10449 例单胎活产的母体血浆或血清样本。使用电感耦合等离子体质谱法测定母体 Cu 浓度。使用逻辑回归和线性回归分析每个队列中母体 Cu 与 PTB 和妊娠持续时间的关系。然后使用荟萃分析对估计值进行合并。在马拉维队列的 1239 个样本中分析了母体 Cu 与急性期反应物（APRs）和感染状况之间的关系。
我们研究样本中的母体产前 Cu 浓度呈正态分布，平均值为 1.92μg/ml，标准差为 0.43μg/ml，Cu 浓度随着妊娠周数的增加而增加，直到 20 周。18 个队列的随机效应荟萃分析显示，母体 Cu 浓度每增加 1μg/ml，PTB 的风险增加 1.30 倍（95%置信区间[CI]：1.08，1.57），妊娠时间缩短 1.64 天（95%CI：0.56，2.73）。在马拉维队列中，较高的母体 Cu 浓度、多种 APRs 浓度和感染（疟疾和 HIV）呈正相关，与 PTB 风险增加和妊娠时间缩短相关。
本研究支持母体 Cu 与妊娠持续时间呈负相关，与 PTB 风险呈正相关的有力证据。Cu 浓度与 APRs 和感染状态密切相关，提示其在炎症途径中可能发挥作用，炎症途径是 PTB 发生机制的一个途径。因此，母体 Cu 可作为妊娠期间炎症途径和 PTB 风险的潜在标志物。
