Department of Obstetrics and Gynecology, Soroka University Medical Center, School of Medicine, Ben Gurion University of the Negev, Beer Sheva, Israel.
Department of Clinical Biochemistry and Pharmacology, Soroka University Medical Center, School of Medicine, Ben Gurion University of the Negev, Beer Sheva, Israel.
PLoS One. 2018 Jul 12;13(7):e0200360. doi: 10.1371/journal.pone.0200360. eCollection 2018.
Preeclampsia and fetal growth restriction are obstetrical syndromes associated with abnormal placental implantation and changes in the activation status of maternal leukocytes. This study is aimed to determine by a simple, rapid fluorescent assay the changes in maternal serum total cell-free DNA (t-cfDNA) concentrations in women with preeclampsia and those with fetal growth restriction (FGR).
A cross-sectional study was conducted measuring maternal serum t-cfDNA concentrations. Women were classified into the following groups: 1) patients with preeclampsia (n = 21); 2) FGR-estimated fetal weight below the 10thpercentile (n = 28); and 3) normal pregnancy (n = 39). Serum samples were directly assayed for t-cfDNA using a rapid fluorescent SYBR Gold assay. Elevated maternal serum t-cfDNA concentrations were defined as a cutoff>850ng/ml. Nonparametric statistics were used for analysis.
Women with preeclampsia had a higher median maternal serum concentration (802 ng/ml, 400-2272 ng/ml) than women with a normal pregnancy (499 ng/ml, 0-1892 ng/ml, p = 0.004) and those with FGR (484 ng/ml, 72-2187 ng/ml, p = 0.012). Moreover, even patients with FGR <5th percentile and abnormal Doppler had a lower median maternal serum t-cfDNA than those with preeclampsia (median 487 ng/ml, 144-1971 ng/ml, p = 0.022). The median concentration of t-cfDNA did not differ between women with a normal pregnancy and those with FGR (p = 0.54), as well as those with fetuses <5th percentile and abnormal Doppler (p = 0.7). Women with preeclampsia had a higher proportion of elevated t-cfDNA than those with a normal pregnancy (p = 0.015) and patients with FGR (p = 0.025).
Preeclampsia is associated with higher maternal serum t-cfDNA concentration than normal pregnancy or FGR. This observation may reflect an increased systemic activation of the maternal inflammation, rather than placental; this assumption is supported by the fact that we did not observe a significant change in the maternal serum t-cfDNA in patients with placental-mediated FGR.
子痫前期和胎儿生长受限是与胎盘植入异常和母体白细胞激活状态改变相关的产科综合征。本研究旨在通过一种简单、快速的荧光分析方法来确定子痫前期和胎儿生长受限（FGR）患者母体血清总游离 DNA（t-cfDNA）浓度的变化。
这是一项横断面研究，测量了母体血清 t-cfDNA 浓度。将女性分为以下几组：1）子痫前期患者（n=21）；2）估计胎儿体重低于第 10 百分位的 FGR（n=28）；3）正常妊娠（n=39）。使用快速荧光 SYBR Gold 分析直接检测血清 t-cfDNA。将升高的母体血清 t-cfDNA 浓度定义为>850ng/ml 的截断值。采用非参数统计进行分析。
子痫前期患者的中位母体血清浓度（802ng/ml，400-2272ng/ml）高于正常妊娠患者（499ng/ml，0-1892ng/ml，p=0.004）和 FGR 患者（484ng/ml，72-2187ng/ml，p=0.012）。此外，即使是胎儿<第 5 百分位和多普勒异常的 FGR 患者，其母体血清 t-cfDNA 中位数也低于子痫前期患者（中位数 487ng/ml，144-1971ng/ml，p=0.022）。正常妊娠和 FGR（p=0.54）患者、胎儿<第 5 百分位和多普勒异常（p=0.7）患者之间的 t-cfDNA 中位数浓度无差异。子痫前期患者升高 t-cfDNA 的比例高于正常妊娠患者（p=0.015）和 FGR 患者（p=0.025）。
与正常妊娠或 FGR 相比，子痫前期患者母体血清 t-cfDNA 浓度较高。这种观察结果可能反映了母体炎症的全身性激活增加，而不是胎盘；这一假设得到了以下事实的支持，即我们没有观察到胎盘介导的 FGR 患者母体血清 t-cfDNA 有显著变化。
