Epidemiology Branch, Research Triangle Park, National Institute of Environmental Health Sciences, Durham, North Carolina.
Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, North Carolina.
Am J Reprod Immunol. 2018 Oct;80(4):e13017. doi: 10.1111/aji.13017. Epub 2018 Jul 8.
Perturbations in normal fetal growth during pregnancy are associated with poor child and adult health outcomes. Inflammation and oxidative stress are recognized as important mechanisms in preeclampsia and preterm birth but have been examined less in relation to fetal growth. We hypothesized that maternal inflammation and oxidative stress in pregnancy would be associated with reduced fetal growth and sought to identify windows of vulnerability.
In a secondary analysis of 482 women from the LIFECODES birth cohort study, we measured inflammation (C-reactive protein [CRP] and the cytokines IL-1β, IL-6, IL-10, and TNF-α) and oxidative stress (8-isoprostane and 8-hydroxydeoxyguanosine [8-OHdG]) biomarkers in plasma and urine, respectively, at four time points during pregnancy. We examined associations between repeated measures of each marker and ultrasound (head and abdominal circumference, femur length, and a summary measure of estimated fetal weight) as well as delivery (birthweight) metrics of growth.
In adjusted repeated-measures models, an interquartile range (IQR) increase in CRP was associated with a 0.12 standard deviation decrease in fetal weight z-score (95% confidence interval, CI, -0.21, -0.02), which corresponds to approximately 50 g at 40-week gestation. The association was greatest in magnitude (ie, most negative) with CRP measured later in pregnancy. Oxidative stress markers were not associated with fetal weight, although both were inversely associated with head circumference and femur length.
Inflammation and oxidative stress markers measured later in pregnancy were associated with reduced fetal growth as measured by repeated ultrasound scans.
怀孕期间正常胎儿生长的紊乱与儿童和成人健康状况不佳有关。炎症和氧化应激被认为是子痫前期和早产的重要机制，但与胎儿生长的关系研究较少。我们假设孕妇在怀孕期间的炎症和氧化应激与胎儿生长减少有关，并试图确定易损期。
在 LIFECODES 出生队列研究的 482 名女性的二次分析中，我们分别在妊娠四个时间点测量了血浆中的炎症（C 反应蛋白[CRP]和细胞因子 IL-1β、IL-6、IL-10 和 TNF-α）和氧化应激（8-异前列腺素和 8-羟基脱氧鸟苷[8-OHdG]）生物标志物。我们检查了每个标志物的重复测量值与超声（头围和腹围、股骨长度和估计胎儿体重的综合指标）以及生长的分娩（出生体重）指标之间的关联。
在调整后的重复测量模型中，CRP 的四分位距（IQR）增加与胎儿体重 z 分数降低 0.12 个标准差相关（95%置信区间，CI，-0.21，-0.02），这相当于 40 周妊娠时大约 50g。CRP 在妊娠后期测量时，关联幅度最大（即最负）。氧化应激标志物与胎儿体重无关，尽管两者均与头围和股骨长度呈负相关。
妊娠后期测量的炎症和氧化应激标志物与重复超声扫描测量的胎儿生长减少有关。
