皮肤毛细血管减少能可靠预测先兆子痫

旧金山——在美国心脏病学会(ACC)2013年会上，英国伦敦大学的Tarek Antonios博士报告称，妊娠期皮肤毛细血管密度下降是一个新的、独立、可靠且无创的先兆子痫预测因子。

已知可能诱发先兆子痫的心血管危险因素包括原发性高血压、糖尿病和肥胖。Antonios博士及其同事推测这些疾病增加先兆子痫发病风险的机制可能涉及微循环异常和组织灌注受损。于是，他们设计了一种检测手背皮肤毛细血管密度的可重复的方法，并且发现始于妊娠第20周左右的毛细血管密度下降(研究者将其称为“结构性毛细血管稀疏”)可以预测后续出现的先兆子痫。

Antonios博士报告了322例单胎妊娠的连续白人病例，其中13例既往有先兆子痫病史，11例有未经治疗的1期原发性高血压病史，其余孕妇血压正常。受试者分别在妊娠第11~16周、第20~24周、第27~32周、第34~38周以及产后5~15周接受了总共5次结构式毛细血管镜评价。在温度控制的实验室中，采用标准化操作来检测毛细血管密度。

在完成了这项研究的305例受试者中，16例(5%)出现了先兆子痫，其中4例(25%)既往有先兆子痫病史，而在正常妊娠的289例受试者中只有3例(1%)有这样的病史。

在出现了先兆子痫的受试者中，妊娠第20~24周的毛细血管密度相比第11~16周的基线数据平均下降了6.1根/mm²。相比之下，正常妊娠的受试者在这段时间内毛细血管密度只平均下降了1.0根/mm²。此外，在先兆子痫患者中毛细血管稀疏的问题还在随时间进一步加重：妊娠第27~32周的毛细血管密度较之基线平均下降达到11.4根/mm²，而对照组只平均下降了2.1根/mm²。

多因素回归分析显示，先兆子痫的唯一最强预测因子是既往先兆子痫或原发性高血压病史，这与发病风险增加35倍相关。妊娠第20~24周毛细血管密度每降低1根/mm²，发病风险就会增加3%；而第27~32周毛细血管密度每降低1根/mm²，发病风险就会增加26%。

Antonios博士称：“到目前为止，毛细血管密度下降是敏感度和特异度最高的先兆子痫预测因子。妊娠第27~32周出现明显的结构性毛细血管稀疏，其预测后续先兆子痫的敏感度和特异度均达到了77%。如果结合多普勒超声测定的子宫动脉搏动指数上升以及妊娠第27~32周毛细血管密度明显下降，预测先兆子痫的敏感度和特异度可分别提高至86%和80%，这比其他任何已发表的先兆子痫临床预测工具的数据都要高得多。”

他补充道，只要配备了基础设备——可以用于毛细血管镜检查的活体视频显微镜，妊娠期皮肤毛细血管密度的检测费用并不高。

鉴于在这项研究中只有16例受试者出现了先兆子痫，下一步需要开展更大规模的临床试验以验证毛细血管镜检查作为临床风险预测工具的作用，以便最终将其用于日常临床实践。

这项研究由英国心脏基金会资助。Antonios博士声明无相关经济利益冲突。

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By: BRUCE JANCIN, Cardiology News Digital Network

SAN FRANCISCO – A reduction in skin capillary density during pregnancy constitutes a novel independent and reliable noninvasive predictor of preeclampsia, according to Dr. Tarek Antonios of the University of London.

"Capillary density rarefaction is the most sensitive and specific predictor of preeclampsia to date. Combining capillary density rarefaction and the uterine artery Doppler pulsatility index increases the sensitivity of prediction to 86% and the specificity to 80%, figures that are by far more significant than any other published evidence about the clinical prediction of preeclampsia," he declared at the annual meeting of the American College of Cardiology.

Measurement of skin capillary density changes in pregnancy is inexpensive once the essential equipment – an intravital video microscope suitable for capillaroscopy – has been acquired, he added.

Cardiovascular risk factors known to predispose to preeclampsia include essential hypertension, diabetes, and obesity. Dr. Antonios and coworkers have surmised that the mechanism by which these disorders boost the risk of preeclampsia involves microcirculatory abnormalities and impaired tissue perfusion.

The investigators have developed a reproducible method of measuring skin capillary density on the dorsum of the hand. Further, they have demonstrated that reduced capillary density – which they term "structural capillary rarefaction" – beginning at about 20 weeks of gestation is a harbinger of subsequent onset of preeclampsia.

Dr. Antonios reported on 322 consecutive white women with singleton pregnancies, of whom 13 had a history of preeclampsia, 11 had a history of untreated stage 1 essential hypertension, and the rest were normotensive. They underwent five structured capillaroscopy assessments at 11-16 weeks’ of gestation, 20-24 weeks, 27-32 weeks, 34-38 weeks, and finally at 5-15 weeks post partum. The capillary density measurements were done in a temperature-controlled laboratory with a standardized technique.

Among the 305 women who completed the study, 16 (5%) developed preeclampsia. Four of the 16 (25%) had a history of preeclampsia, compared with just 3%  of the 289 (1%) subjects with a normal pregnancy.

The women who became preeclamptic were also set apart by their mean 6.1 capillary/mm2 reduction in density between the weeks 20-24 measurement and the weeks 11-16 baseline. In contrast, the women with normal pregnancies averaged a 1.0 capillary/mm2 decrease during that time frame. Capillary rarefaction further increased over time in women who later developed preeclampsia: their mean reduction in density at the weeks 27-32 measurement was 11.4/mm2, compared with the weeks 11-16 baseline, while the controls averaged a 2.1 capillary/mm2 decrease.

In a multivariate regression analysis, the single strongest predictor of preeclampsia was a history of previous preeclampsia or essential hypertension, which was associated with a 35-fold increase in risk. Each 1 capillary/mm2 reduction in density at 20-24 weeks was associated with a 3% increase in risk, while at 27-32 weeks every 1 capillary/mm2 reduction in density conferred a 26% increase in the risk of preeclampsia.

Significant structural capillary rarefaction at weeks 27-32 had a 77% sensitivity and 77% specificity for subsequent preeclampsia. Combining an increased uterine artery Doppler pulsatility index with a finding of significant capillary density reduction at weeks 27-32 boosted the sensitivity to 86% and the specificity to 80%.

Given that only 16 participants in this study developed preeclampsia, the next step in this research is to conduct a large clinical trial to validate capillaroscopy as a clinical risk prediction tool with an eye toward its eventual integration into routine clinical practice, according to Dr. Antonios.

This study was funded by the British Heart Foundation. Dr. Antonios reported having no financial conflicts.