Mendola Pauline, Ghassabian Akhgar, Mills James L, Zhang Cuilin, Tsai Michael Y, Liu Aiyi, Yeung Edwina H
Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
Am J Hypertens. 2017 Jun 1;30(6):569-576. doi: 10.1093/ajh/hpx020.
Maternal retinol-binding protein 4 (RBP4) and lipids may relate to preeclampsia and preterm birth risk but longitudinal data are lacking. This study examines these biomarkers longitudinally during pregnancy in relation to preeclampsia and preterm birth risk.
Maternal serum samples from the Calcium for Preeclampsia Prevention (CPEP) trial were analyzed at baseline: average 15 gestational weeks; mid-pregnancy: average 27 weeks; and at >34 weeks. We measured RBP4, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides and lipoprotein (a) (Lp(a)). Cross-sectional logistic regression analyses estimated the odds ratio (OR) and 95% confidence intervals (CI) for preterm preeclampsia (n = 63), term preeclampsia (n = 104), and preterm delivery (n = 160) associated with RBP4 and lipids at baseline and mid-pregnancy compared with controls (n = 136). Longitudinal trajectories across pregnancy were assessed using mixed linear models with fixed effects. Adjusted models included clinical and demographic factors.
RBP4 concentrations at baseline and mid-pregnancy were associated with a 4- to 8-fold increase in preterm preeclampsia risk but were not associated with term preeclampsia. RBP4 measured mid-pregnancy was also associated with preterm birth (OR = 6.67, 95% CI: 1.65, 26.84). Higher triglyceride concentrations in mid-pregnancy were associated with a 2- to 4-fold increased risk for both preeclampsia and preterm birth. Longitudinal models demonstrate that both preterm preeclampsia and preterm birth cases had elevated RBP4 throughout gestation.
Elevated RBP4 is detectable early in pregnancy and its strong relation with preterm preeclampsia merits further investigation and confirmation to evaluate its potential use as a predictor, particularly among high-risk women.
母体视黄醇结合蛋白4(RBP4)和脂质可能与子痫前期及早产风险相关,但缺乏纵向数据。本研究在孕期纵向检测这些生物标志物,以探讨其与子痫前期及早产风险的关系。
对预防子痫前期钙补充(CPEP)试验中的母体血清样本在基线(平均妊娠15周)、孕中期(平均27周)及妊娠34周后进行分析。我们检测了RBP4、总胆固醇、高密度脂蛋白、低密度脂蛋白、甘油三酯和脂蛋白(a)[Lp(a)]。横断面逻辑回归分析估计了与对照组(n = 136)相比,基线和孕中期时RBP4和脂质与早发型子痫前期(n = 63)、晚发型子痫前期(n = 104)及早产(n = 160)相关的比值比(OR)及95%置信区间(CI)。使用具有固定效应的混合线性模型评估孕期的纵向轨迹。校正模型纳入了临床和人口统计学因素。
基线和孕中期时的RBP4浓度与早发型子痫前期风险增加4至8倍相关,但与晚发型子痫前期无关。孕中期检测的RBP4也与早产相关(OR = 6.67,95% CI:1.65,26.84)。孕中期较高的甘油三酯浓度与子痫前期和早产风险增加2至4倍相关。纵向模型显示,早发型子痫前期和早产病例在整个孕期的RBP4均升高。
孕期早期即可检测到RBP4升高,其与早发型子痫前期的密切关系值得进一步研究和验证,以评估其作为预测指标的潜在用途,尤其是在高危女性中。