At Preeclampsia Diagnosis, Total Cell-Free DNA Concentration is Elevated and Correlates With Disease Severity.
At Preeclampsia Diagnosis, Total Cell-Free DNA Concentration is Elevated and Correlates With Disease Severity.
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DOI：
10.1161/jaha.121.021477
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发表时间：
2021-08-03
影响因子：
5.4
通讯作者：
Shree R
中科院分区：
文献类型：
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作者：
Kolarova TR;Gammill HS;Nelson JL;Lockwood CM;Shree R
胎盘来源的无细胞DNA（cfDNA），广泛用于产前筛查，可作为先兆子痫的生物标志物。为了确定cfDNA参数是否在先兆子痫中改变，我们使用我们内部验证的产前筛查测定，使用前瞻性收集的母体血浆（n=20先兆子痫，n=22正常）进行了病例对照研究。对分离的cfDNA进行定量，使用Illumina NextSeq 500测序，并测定胎盘来源的级分。在先兆子痫和对照之间比较临床和测试特征，然后在通过cfDNA浓度二分的先兆子痫群组内进行比较。最后，先兆子痫中的cfDNA参数与疾病严重程度的标志物相关。两组产妇年龄、体重指数、分娩孕周、剖宫产率、新生儿出生体重差异无统计学意义（P≤ 0. 05）。两组之间胎盘来源的cfDNA分数没有差异（21.4%与16.9%，P=0.06）;然而，先兆子痫患者的总cfDNA高出10倍多（1235与106.5 pg/µL，P<0.001）。当控制重要混杂因素时，这种关系仍然存在（OR 1.22，95% CI 1.04-1.43，P=0.01）。具有最高cfDNA浓度的二分先兆子痫组分娩较早（33.2周vs 36.6周，P=0.02），胎盘衍生分数较低（9.1% vs 21.4%，P=0.04）。在先兆子痫病例中，较高的总cfDNA与分娩时较早的胎龄（P=0.01）和较高的最大收缩压（P=0.04）相关。在诊断时，总cfDNA在先兆子痫中显著更高，而胎盘来源的分数保持与健康妊娠相似。在先兆子痫中，较高的总cfDNA与分娩时较早的胎龄和较高的收缩压相关。这些发现可能表明来自母体组织损伤的cfDNA释放增加。
Placental derived cell‐free DNA (cfDNA), widely utilized for prenatal screening, may serve as a biomarker for preeclampsia. To determine whether cfDNA parameters are altered in preeclampsia, we conducted a case‐control study using prospectively collected maternal plasma (n=20 preeclampsia, n=22 normal) using our in‐house validated prenatal screening assay. Isolated cfDNA was quantified, sequenced using Illumina NextSeq 500, and the placental‐derived fraction was determined. Clinical and test characteristics were compared between preeclampsia and controls, followed by comparisons within the preeclampsia cohort dichotomized by cfDNA concentration. Lastly, cfDNA parameters in preeclampsia were correlated with markers of disease severity. Maternal age, body mass index, gestational age at delivery, cesarean rate, and neonatal birthweight were expectedly different between groups (P≤0.05). The placental‐derived cfDNA fraction did not differ between groups (21.4% versus 16.9%, P=0.06); however, total cfDNA was more than 10 times higher in preeclampsia (1235 versus 106.5 pg/µL, P<0.001). This relationship persisted when controlling for important confounders (OR 1.22, 95% CI 1.04–1.43, P=0.01). The dichotomized preeclampsia group with the highest cfDNA concentration delivered earlier (33.2 versus 36.6 weeks, P=0.02) and had lower placental‐derived fractions (9.1% versus 21.4%, P=0.04). Among preeclampsia cases, higher total cfDNA correlated with earlier gestational age at delivery (P=0.01) and higher maximum systolic blood pressure (P=0.04). At diagnosis, total cfDNA is notably higher in preeclampsia, whereas the placental derived fraction remains similar to healthy pregnancies. In preeclampsia, higher total cfDNA correlates with earlier gestational age at delivery and higher systolic blood pressure. These findings may indicate increased release of cfDNA from maternal tissue injury.