Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah Health Sciences, Salt Lake City, Utah.
Division of Maternal-Fetal Medicine, Intermountain Health Care, Murray, Utah.
Am J Perinatol. 2024 May;41(S 01):e221-e229. doi: 10.1055/a-1877-6191. Epub 2022 Jun 16.
Delta-like homolog 1 (DLK1) is a growth factor that is reduced in maternal sera in pregnancies with small for gestational age neonates. We sought to determine if DLK1 is associated with stillbirth (SB), with and without placental insufficiency.
A nested case-control study was performed using maternal sera from a multicenter case-control study of SB and live birth (LB). SB and LB were stratified as placental insufficiency cases (small for gestational age <5% or circulatory lesions on placental histopathology) or normal placenta controls (appropriate for gestational age and no circulatory lesions). Enzyme-linked immunosorbent assay (ELISA) was used to measure DLK1. The mean difference in DLK1 was compared on the log scale in an adjusted linear regression model with pairwise differences, stratified by term/preterm deliveries among DLK1 results in the quantifiable range. In exploratory analysis, geometric means were compared among all data and the proportion of "low DLK1" (less than the median value for gestational age) was compared between groups and modeled using linear and logistic regression, respectively.
Overall, 234 SB and 234 LB were analyzed; 246 DLK1 values were quantifiable within the standard curve. Pairwise comparisons of case and control DLK1 geometric means showed no significant differences between groups. In exploratory analysis of all data, adjusted analysis revealed a significant difference for the LB comparison only (SB: 71.9 vs. 99.1 pg/mL, = 0.097; LB: 37.6 vs. 98.1 pg/mL, = 0.005). In exploratory analysis of "low DLK1," there was a significant difference between the odds ratio of having "low DLK1" between preterm cases and controls for both SB and LB. There were no significant differences in geometric means nor "low DLK1" between SB and LB.
In exploratory analysis, more placental insufficiency cases in preterm SB and LB had "low DLK1." However, low DLK1 levels were not associated with SB.
· Maternally circulating DLK1 is correlated with placental insufficiency.. · Maternally circulating DLK1 is not correlated with SB.. · DLK1 is a promising marker for placental insufficiency..
Delta-like 同源物 1（DLK1）是一种生长因子，在胎龄小于正常的新生儿的孕妇血清中减少。我们试图确定 DLK1 是否与死产（SB）相关，包括有无胎盘功能不全。
使用多中心 SB 和活产（LB）病例对照研究的母体血清进行嵌套病例对照研究。SB 和 LB 分为胎盘功能不全病例（胎龄小于正常<5%或胎盘组织病理学上有循环损伤）或正常胎盘对照（胎龄适当且无循环损伤）。采用酶联免疫吸附试验（ELISA）测量 DLK1。在可量化范围内，DLK1 结果呈对数比例，采用调整线性回归模型进行比较，配对差异分层为足月/早产分娩。在探索性分析中，比较了所有数据的几何均数，并分别采用线性和逻辑回归比较了各组之间“低 DLK1”（低于胎龄中位数）的比例。
总体而言，分析了 234 例 SB 和 234 例 LB；246 个 DLK1 值在标准曲线内可量化。病例和对照 DLK1 几何均数的配对比较显示组间无显著差异。在所有数据的探索性分析中，仅 LB 比较的调整分析显示差异有统计学意义（SB：71.9 与 99.1 pg/mL， = 0.097；LB：37.6 与 98.1 pg/mL， = 0.005）。在“低 DLK1”的探索性分析中，SB 和 LB 中，早产病例和对照组之间“低 DLK1”的比值比有显著差异。SB 和 LB 之间的几何均数和“低 DLK1”无显著差异。
在探索性分析中，更多的胎盘功能不全病例在早产 SB 和 LB 中出现“低 DLK1”。然而，低 DLK1 水平与 SB 无关。
·母血循环中的 DLK1 与胎盘功能不全有关。·母血循环中的 DLK1 与 SB 无关。·DLK1 是胎盘功能不全的有前途的标志物。
